Comparative Transcriptomics Unravel Biochemical Specialization of Leaf Tissues of Stevia for Diterpenoid Production1

Science.gov (United States)

Kim, Mi Jung; Jin, Jingjing; Zheng, Junshi

2015-01-01

Stevia (Stevia rebaudiana) produces not only a group of diterpenoid glycosides known as steviol glycosides (SGs), but also other labdane-type diterpenoids that may be spatially separated from SGs. However, their biosynthetic routes and spatial distribution in leaf tissues have not yet been elucidated. Here, we integrate metabolome and transcriptome analyses of Stevia to explore the biosynthetic capacity of leaf tissues for diterpenoid metabolism. Tissue-specific chemical analyses confirmed that SGs were accumulated in leaf cells but not in trichomes. On the other hand, Stevia leaf trichomes stored other labdane-type diterpenoids such as oxomanoyl oxide and agatholic acid. RNA sequencing analyses from two different tissues of Stevia provided a comprehensive overview of dynamic metabolic activities in trichomes and leaf without trichomes. These metabolite-guided transcriptomics and phylogenetic and gene expression analyses clearly identified specific gene members encoding enzymes involved in the 2-C-methyl-d-erythritol 4-phosphate pathway and the biosynthesis of steviol or other labdane-type diterpenoids. Additionally, our RNA sequencing analysis uncovered copalyl diphosphate synthase (SrCPS) and kaurene synthase1 (SrKS1) homologs, SrCPS2 and KS-like (SrKSL), which were specifically expressed in trichomes. In vitro and in planta assays showed that unlike SrCPS and SrKS1, SrCPS2 synthesized labda-13-en-8-ol diphosphate and successively catalyzed the formation of manoyl oxide and epi-manoyl oxide in combination with SrKSL. Our findings suggest that Stevia may have evolved to use distinct metabolic pathways to avoid metabolic interferences in leaf tissues for efficient production of diverse secondary metabolites. PMID:26438788

LC-MS guided isolation of diterpenoids from Sapium insigne with α-glucosidase inhibitory activities.

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Yan, De-Xiu; Geng, Chang-An; Yang, Tong-Hua; Huang, Xiao-Yan; Li, Tian-Ze; Gao, Zhen; Ma, Yun-Bao; Peng, Hua; Zhang, Xue-Mei; Chen, Ji-Jun

2018-04-08

Ten new (1-10) and ten known (11-20) diterpenoids involving ent-atisane, ent-seco-atisane, ent-kaurane and ent-seco-kaurane types were isolated from Sapium insigne under the guidance of LCMS-IT-TOF analyses. Their structures were characterized by extensive spectroscopic analyses (HRESIMS, UV, IR, 1D and 2D NMR). A putative biosynthetic pathway was proposed for ent-seco-atisane diterpenoids. Their inhibitory activities on α-glucosidase in vitro were tested for the first time. Compound 4 showed moderate inhibitory effect on α-glucosidase with an IC 50 value of 0.34 mM via a noncompetitive inhibition mechanism (K i  = 0.27 mM). The preliminary structure-activity relationships of the ent-atisane diterpenoids inhibiting α-glucosidase were discussed. Copyright © 2018 Elsevier B.V. All rights reserved.

Hypophyllins A-D, Labdane-Type Diterpenoids with Vasorelaxant Activity from Hypoestes phyllostachya "Rosea".

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Wu, Xing-De; Luo, Dan; Tu, Wen-Chao; Deng, Zhen-Tao; Chen, Xue-Jiao; Su, Jia; Ji, Xu; Zhao, Qin-Shi

2016-12-16

Three rearranged labdane-type diterpenoids, hypophyllins A-C (1-3), and a caged labdane diterpenoid possessing a 8,9-dioxatricyclic[4.2.1.1 3,7 ]decane moiety, hypophyllin D (4), as well as two new biogenetically related diterpernoids, hypophyllins E (5) and F (6), were isolated from the aerial parts of Hypoestes phyllostachya "Rosea". The absolute configurations of 1-4 were determined by X-ray diffraction analysis. The plausible biogenetic pathway for 1-4 was also proposed. Compounds 4 and 5 showed potent vasorelaxant activity on endothelium-intact thoracic aorta rings precontracted with KCl.

Cytotoxic diterpenoids from Jatropha curcas cv. nigroviensrugosus CY Yang Roots.

Science.gov (United States)

Liu, JieQing; Yang, YuanFeng; Xia, JianJun; Li, XuYang; Li, ZhongRong; Zhou, Lin; Qiu, MingHua

2015-09-01

An investigation of phytochemicals from the roots of Jatropha curcas cv. nigroviensrugosus resulted in the isolation of twenty diterpenoids, including lathyranlactone, an unusual diterpenoid lactone possessing a 5/13/3 tricyclic skeleton, jatrocurcasenones A-E and jatrophodiones B-E, as well as 10 known analogues. All isolates were evaluated for cytotoxicity against the HL-60, SMMC-772, A-549, MCF-7 and SW480 human tumor cell lines using the MTS viability assay. Four of the known analogues showed cytotoxic activity in these cell lines, with IC50 values ranging from 2.0 to 23.0 μM. Moreover, the assessment of their cytotoxic structure-activity relationships showed the epoxy ring between C-5 and C-6 and the hydroxyl group at C-2 were the key functionalities for cytotoxicity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Exploring two plant hosts for expression of diterpenoid pathway genes

DEFF Research Database (Denmark)

Bach, Søren Spanner

Plants produce more than 10.000 diterpenoid compounds of which the large majority is involved in specialized metabolism, while a few are involved in general metabolism. Specialized metabolism diterpenoids have functions in interactions of plants with other organisms and selected ones are utilized....... Since only small changes in the amino acid sequence can influence the roduct outcome of a diterpene synthase (diTPS), prediction of the catalytic activity diTPS of a is not possible purely based on phylogenetic relationship. Thus, functional characterization is required in to determine the catalytic...... and aracterization of diTPSs deriving from the plant kingdom, a plant expression host offers several advantages such as the presence of all relevant compartments (plastids and endoplasmic reticulum) and the universal C5 building blocks for isoprenoid biosynthesis. In addition, a plant based xpression host...

ent-Kaurane diterpenoids from Croton tonkinensis stimulate osteoblast differentiation

DEFF Research Database (Denmark)

Dao, Trong-Tuan; Lee, Kwang-Youl; Jeong, Hyung-Min

2011-01-01

Four new ent-kaurane diterpenoids (1-4) were isolated from the leaves of Croton tonkinensis by bioactivity-guided fractionation using an in vitro osteoblast differentiation assay. Their structures were identified as ent-11β-acetoxykaur-16-en-18-ol (1), ent-11α-hydroxy-18-acetoxykaur-16-ene (2), e...

Fragilisinins A–L, new briarane-type diterpenoids from gorgonian Junceella fragilis

KAUST Repository

Lei, Hui; Sun, Jian Fan; Han, Zhuang; Zhou, Xue Feng; Yang, Bin; Liu, Yonghong

2014-01-01

Our continuous study on the South China Sea gorgonian Junceella fragilis led to the isolation of twelve new briarane type diterpenoids, fragilisinins A-L (1-12), along with seven known analogues (13-19), including four naturally produced organoiodides (9-12), they are the first four iodine-containing briarane diterpenoids from this gorgonian species. Their structures were determined by MS, 1D and 2D NMR spectra analyses and by comparison with those reported in the literature. The configuration of 1 was confirmed by single-crystal X-ray diffraction data. The antifouling test showed that compounds 5, 6, 10, 13, and 15 had potent antifouling activities at nontoxic concentrations with EC50 values of 14.0, 12.6, 11.9, 5.6, and 10.0 μM, respectively. © 2014 The Royal Society of Chemistry.

Taxol: A complex diterpenoid natural product with an evolutionarily ...

African Journals Online (AJOL)

In addition to Taxus sp, taxoids are also synthesized by various endophytic fungi, which often live in association with Taxus trees, thus raising questions about the evolutionary origin of this complex diterpenoid pathway. In the future, it may be possible to improve taxoid synthesis through the genetic modification of Taxus cell ...

Andrographis paniculata: Dissolution investigation and pharmacokinetic studies of four major active diterpenoids after multiple oral dose administration in healthy Thai volunteers.

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Pholphana, Nanthanit; Panomvana, Duangchit; Rangkadilok, Nuchanart; Suriyo, Tawit; Puranajoti, Porranee; Ungtrakul, Teerapat; Pongpun, Wanwisa; Thaeopattha, Saichit; Songvut, Phanit; Satayavivad, Jutamaad

2016-12-24

Andrographis paniculata is included in 'The National List of Essential Herbal Drugs A.D. 1999' of Thailand as an herbal drug for the treatment of common cold symptoms and non-infectious diarrhea. The therapeutic activities of A. paniculata are attributed to four major active diterpenoids: andrographolide (1), 14-deoxy-11, 12-didehydroandrographolide (2), neoandrographolide (3), and 14-deoxyandrographolide (4). However, the pharmacokinetic studies in humans of this plant were performed after a single oral dose administration and reported the parameters related to be of only 1. This study aims to determine the pharmacokinetic parameters of four major active diterpenoids after multiple oral dose administration of A. paniculata capsules in healthy volunteers. The dissolution testing of these four diterpenoids was also performed. The dissolution testing of four major active diterpenoids was conducted in pH 1.2, pH 4.5, and pH 6.8 for 10-100min. The pharmacokinetic study of these active diterpenoids was designed as an open-label, multiple oral dose administration of A. paniculata capsules in 20 healthy Thai volunteers at 1:1 ratio of female and male. Each volunteer was given four A. paniculata capsules each time which contained 1, 2, 3, and 4 in the quantities of 32.64, 5.40, 3.60, and 3.84mg, respectively, three times a day for three consecutive days. On the fourth day, after the first dose of the day was administered, blood samples were collected at the predefined time points. The validated LC-MS/MS method was used to simultaneously determine the concentrations of these diterpenoids in the human plasma samples. The pharmacokinetic parameters of each active diterpenoid were determined. All four major active diterpenoids have been completely dissolved in the simulated pH of gastrointestinal tract within 60min of dissolution. The dissolution profiles were found to be highest in pH 6.8 and lowest in pH 1.2, especially for 3. In the pharmacokinetic study, although 1 was

Two new diterpenoid lactones isolated from Andrographis paniculata.

Science.gov (United States)

Wang, Gui-Yang; Wen, Ting; Liu, Fei-Fei; Tian, Hai-Yan; Chun-Lin, Fan; Huang, Xiao-Jun; Ye, Wen-Cai; Wang, Ying

2017-06-01

In the present study, two new diterpenoid lactones, 3-deoxy-andrographoside (1) and 14-deoxy-15-methoxy-andrographolide (2), were isolated from the aerial parts of Andrographis paniculata. Their structures were elucidated by combination of NMR, MS, and chemical methods. The configurations of 1 and 2 were established based on the analysis of ROESY data and single crystal X-ray diffraction experiment. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Two new grayanane diterpenoids from the flowers of Rhododendron molle.

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Zhang, Zhi-Run; Zhong, Jin-Dong; Li, Hong-Mei; Li, Hai-Zhou; Li, Rong-Tao; Deng, Xu-Liang

2012-01-01

A phytochemical investigation of the flowers of Rhododendron molle has yielded two new grayanane diterpenoids, rhodomolleins F and G (1, 2). Compounds 1 and 2 possessed an oxo-bridge between C-5 and C-9, and their structures were elucidated on the basis of interpretation of spectroscopic data, including 1D and 2D NMR techniques.

Tandem solid-phase extraction followed by HPLC-ESI/QTOF/MS/MS for rapid screening and structural identification of trace diterpenoids in flowers of Rhododendron molle.

Science.gov (United States)

Zou, Hong-Yan; Luo, Jun; Xu, De-Ran; Kong, Ling-Yi

2014-01-01

'Naoyanghua', composed of the flowers of Rhododendron molle G. Don, is a traditional Chinese medicine that is widely known for its toxicity. Grayanane-type diterpenoids are the main active ingredients in R. molle, as well as possibly their toxicity: they are, however, difficult to isolate and analyse using common chromatographic methods, due to their small amounts and absence of conjugated groups, such as phenyl and α, β-unsaturated ketone. To establish a highly sensitive, selective and reliable method for the qualitative evaluation of trace diterpenoids in the flowers of R. molle by using tandem solid-phase extraction followed by high-performance liquid chromatography with electrospray ionisation quadrupole-time-of-flight mass spectrometry (HPLC-ESI/QTOF/MS/MS). Tandem solid phase extraction (SPE) was undertaken using a polyamide cartridge and a C18E cartridge in succession to enrich the trace diterpenoids. HPLC-ESI/QTOF/MS/MS was used to determine the fragmentation patterns of diterpenoids and to tentatively characterise their fragmentation pathways. HPLC-ESI/QTOF/MS/MS detected a total of 14 diterpenoids, eight of which were identified by comparison with literature sources and six based on fragmentation analysis. Among the latter six, rhodojaponin VI-3-glucoside was tentatively identified as a new diterpenoid glycoside and rhodojaponin VII, rhodojaponin IV and rhodojaponin I were reported from R. molle for the first time. By qualitative research of diterpenoids in this plant by HPLC-ESI/QTOF/MS/MS, a reliable methodology for the analysis of these active constituents of R. molle was established for the first time. Copyright © 2014 John Wiley & Sons, Ltd.

Diterpenoids from Azorella compacta (Umbelliferae active on Trypanosoma cruzi

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Araya Jorge E

2003-01-01

Full Text Available The anti-Trypanosoma cruzi activity of natural products isolated from Azorella compacta was evaluated, with particular emphasis on their effect against intracellular amastigotes. Five diterpenoids from A. compacta derived from mulinane and azorellane were isolated and identified. Only two products, named azorellanol (Y-2 and mulin-11,3-dien-20-oic acid (Y-5, showed trypanocidal activity against all stages of T. cruzi including intracellular amastigotes. At 10 µM, these compounds displayed a strong lytic activity. It ranged from 88.4 ± 0.6 to 99.0 ± 1 % for all strains and stages evaluate, with an IC50 /18 h values of 20-84 µM and 41-87 µM, respectively. The development of intracellular amastigotes was also inhibited by nearly 60% at 25 µM. The trypanocidal molecules Y-2 and Y-5 did show different degrees of cytotoxicity depending on the cell line tested, with an IC50 /24 h ranging from 33.2 to 161.2 µM. We evaluated the effect of diterpenoids against intracellular T. cruzi forms by immunofluorescent identification of a specific membrane molecular marker (Ssp-4 antigen of the T. cruzi amastigote forms. The accuracy and reproducibility of the measurements were found to be outstanding when examined by confocal microscopy.

Chemical and biological evaluation on scopadulane-type diterpenoids from Scoparia dulcis of Vietnamese origin.

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Phan, Minh Giang; Phan, Tong Son; Matsunami, Katsuyoshi; Otsuka, Hideaki

2006-04-01

From the aerial parts of Scoparia dulcis L. (Scrophulariaceae) grown in Vietnam, four scopadulane-type diterpenoids (4-7), of which 7 is new and was given the trivial name scopadulcic acid C, together with nine known compounds were isolated. Their structures were elucidated by spectroscopic analyses. The absolute configurations of 4-7 were ascertained by applying the modified Mosher's method to iso-dulcinol (6). The isolation of the lignans nirtetralin and niranthin for the first time from S. dulcis is also of chemotaxonomic interest. The cytotoxic activity in KB cells, inhibitory effect on LPS/IFNgamma-induced NO production, inhibition of multidrug resistance (MDR), and antibacterial and antifungal activities of the scopadulane-type diterpenoids 4-7 were examined in this study.

Briarane Diterpenoids from the Gorgonian Dichotella gemmacea

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Ming-Ping La

2014-12-01

Full Text Available Seven new briarane diterpenoids, gemmacolides AS-AY (1–7, were isolated together with ten known analogues (8–17 from the South China Sea gorgonian Dichotella gemmacea. The structures of the new compounds were elucidated by the detailed analysis of spectroscopic data and comparison with reported data. The absolute configuration of compounds was determined based on electronic circular dichroism (ECD experiments and genetic correlations as well. Compounds 15 and 16 were reported for the first time for the gorgonian. In the preliminary in vitro bioassays, compound 5 showed potential growth inhibitory activity against MG63 cells.

Antifouling Activity of Simple Synthetic Diterpenoids against Larvae of the Barnacle Balanus albicostatus Pilsbry

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Dan-Qing Feng

2010-11-01

Full Text Available Five new pimarane diterpenoids 1-5 were synthesized using ent-8(14-pimarene-15R,16-diol as starting material. The structures were elucidated by means of extensive NMR and MS analysis. The antifouling activity against larval settlement of the barnacle Balanus albicostatus were evaluated using capsaicin as a positive control. Compounds 1-3 and 5 showed more potent antifouling activity than capsaicin. Compound 5, which exhibited almost the same antifouling activity as starting material, showed better stability than starting material. These compounds all showed antifouling activity in a non-toxic way against larval settlement of the barnacle B. albicostatus. Analysis of structure-activity relationships (SAR demonstrated that the substituents on the C-15 and C-16 position of pimarane diterpenoid were responsible for the antifouling activity.

A diterpenoid sugiol from Metasequoia glyptostroboides with α-glucosidase and tyrosinase inhibitory potential

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Vivek K. Bajpai

2014-08-01

Full Text Available Nowadays use of plant derived natural compounds have become a topic of increasing interest in food and medicine industries due to their multitude of biological and therapeutic properties. In this study, a diterpenoid compound sugiol, isolated from Metasequoia glyptostroboides was evaluated for α–glucosidase and tyrosinase inhibitory efficacy in terms of its potent anti-diabetic and anti-melanogenesis potential, respectively. As a result, sugiol at the concentration range of (100-10,000 µg/mL and (20-500 µg/mL showed potent efficacy on inhibiting α-glucosidase and tyrosinase enzymes in vitro ranging from 12.34-63.47% and 28.22-67.43%, respectively. These findings confirm the therapeutic potential of diterpenoid compound sugiol from M. glyptostroboides as a novel candidate for using in food and medicine industry which may have practical potential to cure skin and diabetes mellitus type-2 related disorders.

Isolation of cytotoxic diterpenoids from the Chilean medicinal plant Azorella compacta Phil from the Atacama Desert by high-speed counter-current chromatography.

Science.gov (United States)

Bórquez, Jorge; Bartolucci, Nandy López; Echiburú-Chau, Carlos; Winterhalter, Peter; Vallejos, Javier; Jerz, Gerold; Simirgiotis, Mario J

2016-06-01

Azorella compacta (Apiaceae) is a native Chilean cushion shrub which produces a resin containing mulinane and azorellane diterpenoids. This plant has been used since pre-Colombian times to treat inflammation and dental neuralgias. In this work the first preparative fractionation of diterpenoids present in this plant by means of high-speed counter-current chromatography (HSCCC) was applied, and cytotoxic effects of the isolated compounds were evaluated for the first time against a panel of MCF7 cells. The major compounds isolated were identified by means of spectroscopy as azorellanol, 13α, 14α-dihydroxymulin-11-en-20-oic acid, mulinolic acid, mulin-11,13-dien-20-oic acid, 17-acetoxy-mulin-11,13-dien-20 oic acid, and 17-acetoxy-mulinic acid (compounds 7, 9-11 and 13, respectively), and four minor diterpenoids [7-deacetyl-azorellanol (6), 13-epi-azorellanol, 7-acetoxy-mulin-9,12-diene, and 17-acetoxy-mulin-11,13-dien-20-oic acid (compounds 4, 8 and 12)], together with three new minor diterpenoids: 13β,14β-dihydroxymulin-11-en-20-oic acid (1), 13-epiazorellanone (2) and 13-epi-7-deacetyl-azorellanol (3) were identified. Besides, compounds 4, 6, 7, 8 and 11 displayed good cytotoxic activity (less than 50% cell viability at 100 µM). Among them, compound 7, an acetylated azorellane, was the most active. HSCCC allowed the isolation of 13 diterpenoids present in A. compacta. Three compounds are reported for the first time. Isolated azorellanes are more potent cytotoxic agents than are mulinanes. © 2015 Society of Chemical Industry. © 2015 Society of Chemical Industry.

Bioactive diterpenoids and flavonoids from the aerial parts of Scoparia dulcis.

Science.gov (United States)

Liu, Qing; Yang, Qi-Ming; Hu, Hai-Jun; Yang, Li; Yang, Ying-Bo; Chou, Gui-Xin; Wang, Zheng-Tao

2014-07-25

Six new diterpenoids, 4-epi-7α-O-acetylscoparic acid A (1), 7α-hydroxyscopadiol (2), 7α-O-acetyl-8,17β-epoxyscoparic acid A (3), neo-dulcinol (4), dulcinodal-13-one (5), and 4-epi-7α-hydroxydulcinodal-13-one (6), and a new flavonoid, dillenetin 3-O-(6″-O-p-coumaroyl)-β-D-glucopyranoside (10), along with 12 known compounds, were isolated from the aerial parts of Scoparia dulcis. The 7S absolute configuration of the new diterpenoids 1-4 and 6 was deduced by comparing their NOESY spectra with that of a known compound, (7S)-4-epi-7-hydroxyscoparic acid A (7), which was determined by the modified Mosher's method. The flavonoids scutellarein (11), hispidulin (12), apigenin (15), and luteolin (16) and the terpenoids 4-epi-scopadulcic acid B (9) and betulinic acid (19) showed more potent α-glucosidase inhibitory effects (with IC50 values in the range 13.7-132.5 μM) than the positive control, acarbose. In addition, compounds 1, 11, 12, 15, 16, and acerosin (17) exhibited peroxisome proliferator-activated receptor gamma (PPAR-γ) agonistic activity, with EC50 values ranging from 0.9 to 24.9 μM.

Library construction and biological evaluation of enmein-type diterpenoid analogues as potential anticancer agents.

Science.gov (United States)

Li, Dahong; Xu, Shengtao; Cai, Hao; Pei, Lingling; Wang, Lei; Wu, Xiaoming; Yao, Hequan; Jiang, Jieyun; Sun, Yijun; Xu, Jinyi

2013-05-01

A library of promising enmein-type 14-O-diterpenoid derivatives was constructed from a commercially available kaurene-type oridonin by practical and efficient synthetic methods. These synthetic derivatives were evaluated for their antiproliferative activities against a set of four human cancer cell lines. The IC50 values are similar to or improved over those of the parent molecule and paclitaxel, the latter of which was used as a positive control. Compound 29 was further investigated for its apoptotic properties against human hepatocarcinoma Bel-7402 cells to better understand its mode of action. Moreover, compound 29 was shown to have potent antitumor activity in vivo in studies with a murine model of gastric cancer (MGC-803 mice). These results warrant further preclinical investigations of these diterpenoid-based analogues as potential novel anticancer chemotherapeutics. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Four new ent-kaurane diterpenoids from the fruits of Annona cherimola.

Science.gov (United States)

Miyashita, Hiroyuki; Nishida, Makiko; Okawa, Masafumi; Nohara, Toshihiro; Yoshimitsu, Hitoshi

2010-05-01

Four new ent-kaurane diterpenoids (16R)-ent-kauran-17,19-diol (1), (16R)-17-hydroxy-ent-kauran-19-oic acid (2), (16S)-17-hydroxy-ent-kauran-19-oic acid (3), and (16R)-17-dimethoxy-ent-kauran-19-oic acid (4) have been isolated from the fresh fruits of Annona cherimola together with eight known compounds. Their structures are determined on the basis of spectroscopic data and optical rotation.

Changes in the contents of four active diterpenoids at different growth stages in Andrographis paniculata (Burm.f. Nees (Chuanxinlian

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Pholphana Nanthanit

2013-01-01

Full Text Available Abstract Background The therapeutic activities of Andrographis paniculata are attributed to four major active diterpenoids: andrographolide (AP1, 14-deoxy-11,12-didehydroandrographolide (AP3, neoandrographolide (AP4, and 14-deoxyandrographolide (AP6. This study aims to quantify the four active diterpenoids in various plant organs of A. paniculata at different growth stages in greenhouse and field experiments, with a developed HPLC-diode array detector (HPLC-DAD method for simultaneous determination of these diterpenoids. Methods Plants were grown in greenhouse and in field conditions, harvested at different growth stages, and separated into different organs for determination of the four active diterpenoids by an HPLC-DAD method. Results The most abundant diterpenoid was AP6 between seedling and vegetative stages in the greenhouse experiment (13.38 to 23.71 mg/g in 2006 and 10.67 to 24.54 mg/g in 2007. High levels of AP6 were also detected in leaves at the transfer stage in the greenhouse experiment (36.05 ± 0.69 mg/g and field experiment (30.59 ± 1.39 mg/g. The levels of AP6 then decreased as plants matured. The highest content of AP4 was in cotyledons (16.65 ± 4.48 mg/g at the transfer stage. The highest contents of AP1 were detected in leaves at seed-forming stage in greenhouse experiment (24.72 ± 1.89 mg/g and vegetative stage in field experiment (43.16 ± 0.92 mg/g. Flowers of A. paniculata contained high levels of AP1 (21.42 ± 3.74 mg/g. AP3 and AP4 were at low levels in leaves at all growth stages. Conclusion In A. paniculata, AP6 was at the highest level in leaves at transfer stage in both greenhouse and field experiments. AP1 was at the highest level in leaves at vegetative stage and seed-forming stage in field and greenhouse experiments, respectively. The contents of AP3 and AP4 in leaves were low at all growth stages.

Changes in the contents of four active diterpenoids at different growth stages in Andrographis paniculata (Burm.f.) Nees (Chuanxinlian)

Science.gov (United States)

2013-01-01

Background The therapeutic activities of Andrographis paniculata are attributed to four major active diterpenoids: andrographolide (AP1), 14-deoxy-11,12-didehydroandrographolide (AP3), neoandrographolide (AP4), and 14-deoxyandrographolide (AP6). This study aims to quantify the four active diterpenoids in various plant organs of A. paniculata at different growth stages in greenhouse and field experiments, with a developed HPLC-diode array detector (HPLC-DAD) method for simultaneous determination of these diterpenoids. Methods Plants were grown in greenhouse and in field conditions, harvested at different growth stages, and separated into different organs for determination of the four active diterpenoids by an HPLC-DAD method. Results The most abundant diterpenoid was AP6 between seedling and vegetative stages in the greenhouse experiment (13.38 to 23.71 mg/g in 2006 and 10.67 to 24.54 mg/g in 2007). High levels of AP6 were also detected in leaves at the transfer stage in the greenhouse experiment (36.05 ± 0.69 mg/g) and field experiment (30.59 ± 1.39 mg/g). The levels of AP6 then decreased as plants matured. The highest content of AP4 was in cotyledons (16.65 ± 4.48 mg/g) at the transfer stage. The highest contents of AP1 were detected in leaves at seed-forming stage in greenhouse experiment (24.72 ± 1.89 mg/g) and vegetative stage in field experiment (43.16 ± 0.92 mg/g). Flowers of A. paniculata contained high levels of AP1 (21.42 ± 3.74 mg/g). AP3 and AP4 were at low levels in leaves at all growth stages. Conclusion In A. paniculata, AP6 was at the highest level in leaves at transfer stage in both greenhouse and field experiments. AP1 was at the highest level in leaves at vegetative stage and seed-forming stage in field and greenhouse experiments, respectively. The contents of AP3 and AP4 in leaves were low at all growth stages. PMID:23320627

Rhodomollanol A, a Highly Oxygenated Diterpenoid with a 5/7/5/5 Tetracyclic Carbon Skeleton from the Leaves of Rhododendron molle.

Science.gov (United States)

Zhou, Junfei; Zhan, Guanqun; Zhang, Hanqi; Zhang, Qihua; Li, Ying; Xue, Yongbo; Yao, Guangmin

2017-07-21

A novel diterpenoid with an unprecedented carbon skeleton, rhodomollanol A (1), and a new grayanane diterpenoid, rhodomollein XXXI (2), were isolated from the leaves of Rhododendron molle. Their structures were elucidated using comprehensive spectroscopic methods and single-crystal X-ray diffraction. Compound 1 possesses a unique cis/trans/trans/cis/cis-fused 3/5/7/5/5/5 hexacyclic ring system featuring a rare 7-oxabicyclo[4.2.1]nonane core decorated with three cyclopentane units. The plausible biosynthetic pathway for 1 was proposed. Compound 1 exhibited moderate PTP1B inhibitory activity.

BI- and tricyclic diterpenoids from Halimium viscosum.

Science.gov (United States)

Rodilla, J M; De Mendonça, D I; Ismael, M I; Figueiredo, J A; Silva, M L; Lopes, E

2001-01-01

The study of the acid and neutral parts of the n-hexane extract of Halimium viscosum (S. João da Pesqueira, Portugal) has led to the isolation of various known diterpenoids with the ent-halimane skeleton. Five new compounds have now been isolated, one with the ent-halimane skeleton, and four with the valparane skeleton, two of them with the valparane skeleton degraded. The structures of these compounds, determined by spectroscopic methods using 2D experiments (1H-13C, HMQC and HMBC), were dimethyl 1(10)-halimen-15,18-dioate, dimethyl 3,19-dinor-15-valparen-2,4-dioate, methyl 16-nor-2,3-secovalpara-3,15-dioxo-2-oate, 1,3,5,1 5-valparatetraene and 3R-4alpha-methoxy-15-valparen-2-one.

Bioactive Eunicellin-Based Diterpenoids from the Soft Coral Cladiella krempfi

Science.gov (United States)

Tai, Chi-Jen; Su, Jui-Hsin; Huang, Ming-Shyan; Wen, Zhi-Hong; Dai, Chang-Feng; Sheu, Jyh-Horng

2011-01-01

Four new eunicellin-based diterpenoids, krempfielins A–D (1–4), along with two known compounds (5 and 6) have been isolated from a soft coral Cladiella krempfi. The structures of the new metabolites were elucidated by extensive spectroscopic analysis and by comparison with spectroscopic data of related known compounds. Compounds 5 and 6 were shown to exhibit cytotoxicity against a limited panel of cancer cell lines. Furthermore, compounds 2, 3, 5 and 6 were shown to exert significant in vitro anti-inflammatory activity against LPS-stimulated RAW264.7 macrophage cells. PMID:22073008

α-Glucosidase and tyrosinase inhibitory effects of an abietane type diterpenoid taxoquinone from Metasequoia glyptostroboides.

Science.gov (United States)

Bajpai, Vivek K; Park, Yong-Ha; Na, MinKyun; Kang, Sun Chul

2015-03-26

Nowadays plant derived natural compounds have gained huge amount of research attention especially in food and medicine industries due to their multitude of biological and therapeutic properties as alternative medicines. In this study, a diterpenoid compound taxoquinone, isolated from Metasequoia glyptostroboides was evaluated for its α-glucosidase and tyrosinase inhibitory efficacy in terms of its potent anti-diabetic and depigmentation potential, respectively. As a result, taxoquinone at the concentration range of 100-3,000 μg/mL and 200-1,000 μg/mL showed potent efficacy on inhibiting α-glucosidase and tyrosinase enzymes by 9.24-51.32% and 11.14-52.32%, respectively. The findings of this study clearly evident potent therapeutic efficacy of an abietane diterpenoid taxoquinone isolated from M. glyptostroboides with a possibility for using it as a novel candidate in food and medicine industry as a natural alternative medicine to prevent diabetes mellitus type-2 related disorders and as a depigmentation agent.

Neo-clerodane and abietane diterpenoids with neurotrophic activities from the aerial parts of Salvia leucantha Cav.

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Li, Lai-Wei; Qi, Yan-Yan; Liu, Shi-Xi; Wu, Xing-De; Zhao, Qin-Shi

2018-04-04

Four new neoclerodane diterpenoids, leucansalvialins FI (1-4), and one rare 18(4 → 3)-abeo-abietane diterpenoid, leucansalvialin J (5), were isolated from the aerial part of Salvia leucantha Cav., along with 14 known analogues. Leucansalvialin F (1) represents the first rearranged salvigenane type clerodane-17,12:18,6-diolide. Their structures were elucidated by 1D and 2D NMR spectroscopic data analysis, and the absolute configurations of 1, 2, 3, and 5 were determinded by X-ray diffraction crystal analysis and the ECD technique. All of the isolated components were evaluated for their neurotrophic activities on PC12 cells and all new compounds were evaluated for their cytotoxicity against five human cancer cell lines (HL-60, A-549, SMMC-7721, MCF-7, and SW480). Compounds 2 and 5 showed moderate neuroprotective effects in an in vitro assay. Copyright © 2018. Published by Elsevier B.V.

An ent-kaurane diterpenoid from Isodon japonica var. glaucocalyx

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Su-Ping Bai

2009-08-01

Full Text Available The title compound, 14β-acetoxy-7α-hydroxy-ent-kaur-16-ene-3,15-dione or glaucocalyxin B, C22H30O5, a natural ent-kaurane diterpenoid, is composed of four rings with the expected cis and trans ring junctions. In the crystal structure, there are two molecules in the asymmetric unit related by a noncrystallographic twofold screw axis, and ring A is disordered [ratio occupancies 0.829 (19:0.171 (19], such that both chair and boat conformations are present, but with the boat conformation as the major component. In the crystal, molecules are linked by intermolecular O—H...O hydrogen bonds.

Antiviral potential of a diterpenoid compound sugiol from Metasequoia glyptostroboides.

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Bajpai, Vivek K; Kim, Na-Hyung; Kim, Kangmin; Kang, Sun Chul

2016-05-01

This research reports first time antiviral activity of sugiol, a diterpenoid isolated from Metasequoia glyptostroboides in terms of its ability to inhibit in vitro growth of H1N1 influenza virus. Antiviral potential of sugiol was evaluated through hcytopathogenic reduction assay using Madin-Darby canine kidney (MDCK) cell line. Sugiol (500 μg/ml) was found to exhibit considerable anti-cytopathic effect on MDCK cell line confirming its antiviral efficacy against H1N1 influenza virus. These findings strongly reinforce the suggestion that sugiol could be a candidate of choice in combinational regimen with potential antiviral efficacy.

Proof of the Structure of the Stemodia chilensis Tetracyclic Diterpenoid (+)-19-Acetoxystemodan-12-ol by Synthesis from (+)-Podocarpic Acid: X-ray Structure Determination of a Key Intermediate.

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Leonelli, Francesca; Mostarda, Azzurra; De Angelis, Luca; Lamba, Doriano; Demitri, Nicola; La Bella, Angela; Ceccacci, Francesca; Migneco, Luisa M; Marini Bettolo, Rinaldo

2016-04-22

The first synthesis of (+)-19-acetoxystemodan-12-ol (1), a stemodane diterpenoid isolated from Stemodia chilensis, is described. The structure was supported by an X-ray crystallographic analysis of intermediate (+)-9a, which confirmed the proposed structure and excluded the structure of (-)-19-hydroxystemod-12-ene as a possible candidate for the Chilean Calceolaria diterpenoid to which the (-)-19-hydroxystemar-13-ene structure (9b) had been erroneously assigned.

A Simple and Sensitive LC-MS/MS Method for Determination of Four Major Active Diterpenoids from Andrographis paniculata in Human Plasma and Its Application to a Pilot Study.

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Pholphana, Nanthanit; Panomvana, Duangchit; Rangkadilok, Nuchanart; Suriyo, Tawit; Ungtrakul, Teerapat; Pongpun, Wanwisa; Thaeopattha, Saichit; Satayavivad, Jutamaad

2016-01-01

Andrographis paniculata contains four major active diterpenoids, including andrographolide (1), 14-deoxy-11, 12-didehydroandrographolide (2), neoandrographolide (3), and 14-deoxyandrographolide (4), which exhibit differences in types and/or degrees of their pharmacological activity. Previous pharmacokinetic studies in humans reported only the parameters of compound 1 and its analytical method in human plasma. The purpose of this study was to develop a simple, sensitive, and selective liquid chromatography tandem-mass spectrometry technique for the simultaneous determination of all four major active diterpenoids in the A. paniculata product in human plasma. These four diterpenoids in plasma samples were extracted by a simple protein precipitation method with methanol and separated on a Kinetex C18 column using a gradient system with a mobile phase of acetonitrile and water. The liquid chromatography tandem-mass spectrometry was performed in the negative mode, and the multiple reaction monitoring mode was used for the quantitation. The method showed a good linearity over a wide concentration range of 2.50-500 ng/mL for 1 and over the range of 1.00-500 ng/mL for the other diterpenoids with a correlation coefficient R(2) > 0.995. The lower limit of quantification of 1 was found to be 2.50 ng/mL, while those of the other diterpenoids were 1.00 ng/mL. The intraday and interday accuracy (relative error) ranged from 0.03 % to 10.03 %, and the intraday and interday precisions (relative standard deviation) were in the range of 2.05-9.67 %. The extraction recovery (86.54-111.56 %) with a relative standard deviation of 2.78-8.61 % and the matrix effect (85.15-112.36 %) were within the acceptance criteria. Moreover, these four major active diterpenoids were stable in plasma samples at the studied storage conditions with a relative error ≤-9.79 % and a relative standard deviation ≤ 9.26 %. Hence, this present method was successfully validated

Further Mulinane and Azorellane Diterpenoids Isolated from Mulinum crassifolium and Azorella compacta

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Jorge Bórquez

2014-03-01

Full Text Available The new mulinane diterpenoids 1 and 2 were isolated from the EtOAc extract of Mulinum crassifolium, while the rearranged mulinane 5, which was isolated for the first time from a natural source, was isolated from Azorella compacta. Compounds 1–2 were prepared by semi-synthesis thorough acetylation of the diterpene 17-acetoxymulinic acid (3. A mechanism of reaction was proposed, while the structures of the new compounds were elucidated on the basis of comprehensive spectroscopic analysis and computational methods.

New degraded quinone diterpenoid from the stems of Byrsonima coccolobifolia Kunt (Malpighiaceae)

International Nuclear Information System (INIS)

Sousa, Lorena R.F. de; Santos, Marcos H.F.; Severino, Vanessa G.P.; Severino, Richele P.; Vieira, Paulo C.

2018-01-01

A chemical investigation of two specimens of Byrsonima coccolobifolia collected in the southeast cerrado and from central Brazil was performed. A new degraded diterpenoid, byrsonimaquinone, was isolated from the stems along with known compounds. This is the first study on the roots of B. coccolobifolia, and several triterpenes, such as α-amyrin, β-amyrin, oleanolic acid, and glochidonol, along with a mixture of stigmasterol, β-sitosterol and campesterol, were identified. These compounds were identified by spectroscopic analysis techniques, including 1D and 2D NMR, GC-MS and high-resolution mass spectrometry. (author)

New degraded quinone diterpenoid from the stems of Byrsonima coccolobifolia Kunt (Malpighiaceae)

Energy Technology Data Exchange (ETDEWEB)

Sousa, Lorena R.F. de; Santos, Marcos H.F.; Severino, Vanessa G.P.; Severino, Richele P. [Universidade Federal de Goiás (UFG), GO (Brazil). Unidade Acadêmica Especial de Química; Vieira, Paulo C., E-mail: dpcv@ufscar.br [Universidade Federal de São Carlos (UFSCar), SP (Brazil). Departamehnto de Quimica

2018-02-15

A chemical investigation of two specimens of Byrsonima coccolobifolia collected in the southeast cerrado and from central Brazil was performed. A new degraded diterpenoid, byrsonimaquinone, was isolated from the stems along with known compounds. This is the first study on the roots of B. coccolobifolia, and several triterpenes, such as α-amyrin, β-amyrin, oleanolic acid, and glochidonol, along with a mixture of stigmasterol, β-sitosterol and campesterol, were identified. These compounds were identified by spectroscopic analysis techniques, including 1D and 2D NMR, GC-MS and high-resolution mass spectrometry. (author)

The effects of Andrographis paniculata (Burm.f.) Nees extract and diterpenoids on the CYP450 isoforms' activities, a review of possible herb-drug interaction risks.

Science.gov (United States)

Tan, Mei Lan; Lim, Lin Ee

2015-01-01

Andrographis paniculata (Burm.f.) Nees is a popular medicinal plant and its components are used in various traditional product preparations. However, its herb-drug interactions risks remain unclear. This review specifically discusses the various published studies carried out to evaluate the effects of Andrographis paniculata (Burm.f.) Nees plant extracts and diterpenoids on the CYP450 metabolic enzyme and if the plant components pose a possible herb-drug interaction risk. Unfortunately, the current data are insufficient to indicate if the extracts or diterpenoids can be labeled as in vitro CYP1A2, CYP2C9 or CYP3A4 inhibitors. A complete CYP inhibition assay utilizing human liver microsomes and the derivation of relevant parameters to predict herb-drug interaction risks may be necessary for these isoforms. However, based on the current studies, none of the extracts and diterpenoids exhibited CYP450 induction activity in human hepatocytes or human-derived cell lines. It is crucial that a well-defined experimental design is needed to make a meaningful herb-drug interaction prediction.

Cladielloides A and B: New Eunicellin-Type Diterpenoids from an Indonesian Octocoral Cladiella sp

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Chen, Yung-Husan; Tai, Chia-Ying; Hwang, Tsong-Long; Weng, Ching-Feng; Li, Jan-Jung; Fang, Lee-Shing; Wang, Wei-Hsien; Wu, Yang-Chang; Sung, Ping-Jyun

2010-01-01

Two new eunicellin-type diterpenoids, cladielloides A (1) and B (2), which were found to possess a 2-hydroxybutyroxy group in their structures, were isolated from an Indonesian octocoral identified as Cladiella sp. The structures of eunicellins 1 and 2 were elucidated by spectroscopic methods. Cladielloide B (2) exhibited moderate cytotoxicity toward CCRF-CEM tumor cells and this compound displayed significant inhibitory effects on superoxide anion generation and elastase release by human neutrophils. PMID:21339957

A novel conversion of C(19)-diterpenoid alkaloids into aconane-type diterpenes with eight-membered ring system via skeletal rearrangement of corresponding diazonium derivatives.

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Ji, Hong; Chen, Qiao-Hong; Wang, Feng-Peng

2009-03-01

A new and efficient approach toward the conversion of C(19)-diterpenoid alkaloids into diterpenes with [6+8+5+6] ring system is reported. Treatment of imines 5, 14, and 24 derived from the C(19)-diterpenoid alkaloids with NaNO(2)-NaOAc-HOAc afforded a series of novel rearrangement diterpenes 6-8, 15-19, and 25-27, respectively. The lactone 11 was obtained in 41% yield by treating 5 with NaNO(2)-HBr-Br(2). The formation of diazonium intermediate is postulated, which was subsequently subjected to skeletal rearrangement, leading to the enlargement of B ring. All the new compounds were isolated and fully characterized.

Klymollins T-X, bioactive eunicellin-based diterpenoids from the soft coral Klyxum molle.

Science.gov (United States)

Chang, Fang-Yu; Hsu, Fang-Jung; Tai, Chi-Jen; Wei, Wen-Chi; Yang, Ning-Sun; Sheu, Jyh-Horng

2014-05-22

Five new eunicellin-based diterpenoids, klymollins T-X (1-5), along with two known compounds (6 and 7) have been isolated from the soft coral Klyxum molle. The structures of these new metabolites were elucidated by extensive spectroscopic analysis and by comparison with related known compounds. Compound 5 was found to exert significant in vitro anti-inflammatory activity against LPS-stimulated RAW264.7 macrophage cells. Furthermore, compounds 4 and 7 were shown to exhibit cytotoxicity against a limited panel of human cancer cell lines.

Diterpenoids from Tetraclinis articulata that inhibit various human leukocyte functions.

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Barrero, Alejandro F; Quílez del Moral, José F; Lucas, Rut; Payá, Miguel; Akssira, Mohamed; Akaad, Said; Mellouki, Fouad

2003-06-01

Ten new compounds, eight of them pimarane derivatives (1-8), together with a menthane dimer (9) and a totarane diterpenoid (10), were isolated from the leaves and wood of Tetraclinis articulata. The structures of 1-10 were established by using spectroscopic techniques, including 2D NMR spectra. Pimaranes 1-5 were found to possess an unusual cis interannular union of the B and C rings, which, from a biogenetic perspective, could be derived from the hydration of a carbocation at C-8. Compounds 4-6 and a mixture of 7 and 11 modulated different human leukocyte functions at a concentration of 10 microM, mainly the degranulation process measured as myeloperoxidase release and, to a lesser extent, the superoxide production measured by chemiluminescence.

A new ent-clerodane diterpenoid from Crassocephalum bauchiense Huch. (Asteraceae).

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Tchinda, Alembert T; Mouokeu, Simplice R; Ngono, Rosalie A N; Ebelle, Madeleine R E; Mokale, Aristide L K; Nono, Diane K; Frédérich, Michel

2015-01-01

A phytochemical investigation of the whole plant of Crassocephalum bauchiense Huch. resulted in the isolation of a new clerodane diterpenoid, ent-2β,18,19-trihydroxycleroda-3,13-dien-16,15-olide (1), together with two known flavonoids 3',5-dihydroxy-4',5',6,7,8-pentamethoxyflavone (2) and 4',5-dihydroxy-3',5',6,7,8-pentamethoxyflavone (3). The compounds were tested against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Compound 2 showed weak activity (IC50 = 10.1 g/mL) whilst compounds 1 and 3 were inactive. The structures of the compounds were elucidated by using detailed spectral analyses, especially (1)H and (13)C NMR, (1)H-(1)H COSY, NOESY, HMBC and HR-ESI-MS.

Oridonin, a Promising ent-Kaurane Diterpenoid Lead Compound

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Dahong Li

2016-08-01

Full Text Available Oridonin belongs to ent-kaurane tetracyclic diterpenoid and was first isolated from Isodon species. It exhibits inhibitory activities against a variety of tumor cells, and pharmacological study shows that oridonin could inhibit cell proliferation, DNA, RNA and protein synthesis of cancer cells, induce apoptosis and exhibit an antimutagenic effect. In addition, the large amount of the commercially-available supply is also very important for the natural lead oridonin. Moreover, the good stability, suitable molecular weight and drug-like property guarantee its further generation of a natural-like compound library. Oridonin has become the hot molecule in recent years, and from the year 2010, more than 200 publications can be found. In this review, we summarize the synthetic medicinal chemistry work of oridonin from the first publication 40 years ago and share our research experience of oridonin for about 10 years, which may provide useful information to those who are interested in this research field.

Mollebenzylanols A and B, Highly Modified and Functionalized Diterpenoids with a 9-Benzyl-8,10-dioxatricyclo[5.2.1.01,5]decane Core from Rhododendron molle.

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Zhou, Junfei; Liu, Junjun; Dang, Ting; Zhou, Haofeng; Zhang, Hanqi; Yao, Guangmin

2018-04-06

Two highly modified and functionalized diterpenoids, mollebenzylanols A (1) and B (2), and a known grayanane diterpenoid rhodojaponin III (3) were isolated from Rhododendron molle. Their structures were determined by spectroscopic data analysis, an electronic circular dichroism (ECD) exciton chirality method, ECD calculations, and X-ray diffraction analysis of the p-bromobenzoate ester of 1 (1a). Compounds 1 and 2 possess an unprecedented diterpene carbon skeleton featuring a unique 9-benzyl-8,10-dioxatricyclo[5.2.1.0 1,5 ]decane core, and their plausible biosynthetic pathways are proposed. Their PTP1B inhibitory activity and modes of action were investigated.

Diterpene synthases of the biosynthetic system of medicinally active diterpenoids in Marrubium vulgare

DEFF Research Database (Denmark)

Zerbe, Philipp; Chiang, Angela; Dullat, Harpreet

2014-01-01

Marrubium vulgare (Lamiaceae) is a medicinal plant whose major bioactive compounds, marrubiin and other labdane-related furanoid diterpenoids, have potential applications as anti-diabetics, analgesics or vasorelaxants. Metabolite and transcriptome profiling of M. vulgare leaves identified five...... different candidate diterpene synthases (diTPSs) of the TPS-c and TPS-e/f clades. We describe the in vitro and in vivo functional characterization of the M. vulgare diTPS family. In addition to MvEKS ent-kaurene synthase of general metabolism, we identified three diTPSs of specialized metabolism: MvCPS3...

Klymollins A-H, bioactive eunicellin-based diterpenoids from the formosan soft coral Klyxum molle.

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Hsu, Fang-Jung; Chen, Bo-Wei; Wen, Zhi-Hong; Huang, Chiung-Yao; Dai, Chang-Feng; Su, Jui-Hsin; Wu, Yang-Chang; Sheu, Jyh-Horng

2011-11-28

Eight new eunicellin-based diterpenoids, klymollins A-H (1-8), were isolated during the chemical investigation of the soft coral Klyxum molle from Taiwan waters. Their structures were elucidated by extensive spectroscopic analysis. The absolute configuration of 4 was determined by Mosher's method. Bioassays of the new metabolites showed that compounds 3-8 displayed significant in vitro anti-inflammatory activity by inhibiting the expression of the iNOS protein, and compounds 3, 4, and 6-8 also could effectively reduce the accumulation of COX-2 protein in LPS-stimulated RAW264.7 macrophage cells.

Antifouling briarane type diterpenoids from South China Sea gorgonians Dichotella gemmacea

KAUST Repository

Sun, Jian Fan; Han, Zhuang; Zhou, Xue Feng; Yang, Bin; Lin, Xiuping; Liu, Juan; Peng, Yan; Yang, Xian Wen; Liu, Yonghong

2013-01-01

Our continued investigation on the South China Sea gorgonian Dichotella gemmacea led to the isolation of 16 new briarane-type diterpenoids, dichotellides F-U (1-16), along with 18 known analogues (17-34). Their structures were determined by MS, 1D and 2D NMR spectra analyses and by comparison with those reported in literature. The absolute configuration of 15 was confirmed by single-crystal X-ray diffraction data. The antifouling test showed that compounds 3, 4, 6-11, 16, and 23 had potent antifouling activities at nontoxic concentrations with EC50 values of 4.1, 1.82, 6.3, 7.6, 4.6, 1.2, 5.6, 0.79, 2.0, and 0.2 μg/mL, respectively. © 2012 Elsevier Ltd. All rights reserved.

Krempfielins Q and R, Two New Eunicellin-Based Diterpenoids from the Soft Coral Cladiella krempfi

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Chi-Jen Tai

2014-11-01

Full Text Available Two new eunicellin-based diterpenoids, krempfielins Q and R (1 and 2, and one known compound cladieunicellin K (3 have been isolated from a Formosan soft coral Cladiella krempfi. The structures of these two new metabolites were elucidated by extensive spectroscopic analysis. Anti-inflammatory activity of new metabolites to inhibit the superoxide anion generation and elastase release in N-formyl-methionyl-leucyl phenylalanine/cytochalasin B (FMLP/CB-induced human neutrophil cells and cytotoxicity of both new compounds toward five cancer cell lines were reported.

Cytotoxic and Anti-Inflammatory Eunicellin-Based Diterpenoids from the Soft Coral Cladiella krempfi

Science.gov (United States)

Tai, Chi-Jen; Su, Jui-Hsin; Huang, Chiung-Yao; Huang, Ming-Shyan; Wen, Zhi-Hong; Dai, Chang-Feng; Sheu, Jyh-Horng

2013-01-01

Five new eunicellin-based diterpenoids, krempfielins E–I (1–5) and seven known compounds (6–12) were isolated from the organic extract of a Taiwanese soft coral Cladiella krempfi. The structures of the new metabolites were elucidated on the basis of extensive spectroscopic analysis. Metabolites 5, 6, 10 and 12 were shown to exhibit cytotoxicity against a limited panel of cancer cell lines. Furthermore, compounds 6 and 10 could potently inhibit the accumulation of the pro-inflammatory iNOS protein, and 6 and 12 could significantly reduce the expression of COX-2 protein in LPS-stimulated RAW264.7 macrophage cells. PMID:23481676

Antifeedant Diterpenoids against Tribolium castaneum from the Stems and Twigs of Ceriops tagal (Rhizophoraceae

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Zhi Wei Deng

2011-07-01

Full Text Available The screening of several Chinese mangrove plants for insecticidal principles showed that ethanol extract of Ceriops tagal stems and twigs possessed significant feeding deterrent activity against the red flour beetle, Tribolium castaneum (Family: Rhizophoraceae. From the ethanol extract, three feeding deterrent diterpenoids were isolated by bioassay-guided fractionation. The compounds were identified as tagalsin A, B, and H on the basis of their phytochemical and spectral data. Tagalsin A, B, and H exhibited strong feeding deterrent activity against T. castaneum adults with EC50 values of 375.3 ppm, 277.3 ppm, and 285.45 ppm, respectively.

[Contents of diterpenoid pigments in didifferent parts of fruit from Gardenia jasminoides].

Science.gov (United States)

Zhang, Cun; Xiao, Yongqing; Li, Li; Li, Wen; Yin, Xiaojie

2009-06-01

To compare the contents of diterpenoid pigments among the fruit, seed, and pericarp from Gardenia jasminoides. The separation of Crocin 1, Crocin 2, Crocin 3 were carried out simultaneously on a Kromasil C18 column at 35 degrees C with the methanol-acetonitrile-0.3% formic acid anhydrous in gradient elution as the mobile phrases. The detection wavelength was set at 440 nm and the flow rate was 1.0 mL x min(-1). The obtained linearity of the three components was better over 0.999 5 and the average recoveries were 97.50%, 98.76%, 97.67%, respectively. The results exhibited the remarkable variation among the different parts of the fruit. The contents of three constituents in seed were higher than in pericarp.

[Content comparison of diterpenoid pigments in different processed products of Gardenia jasminoides].

Science.gov (United States)

Zhang, Cun; Xiao, Yong-Qing; Li, Li; Li, Gui-Liu; Pang, Zhen

2008-11-01

To compare the contents of diterpenoid pigments in the different processed products of Gardenia jasminoides. The separation of Crocin 1, Crocin 2, Crocin 3, Crocetin were determined simultaneously by HPLC on a kromasil C18 column at 35 degrees C with the m methanol-acetonitrile-0.3% formic acid anhydrous in gradient elution as the mobile phrase. The detection wavelength was set at 440 nm and the flow rate was 1.0 mL x min(-1). The obtained linearity of the four components was better over 0.9995 and the average recoveries were 97.77%, 100.05% , 98.40%, 101.02%, respectively. The method is simple, accurate with good reproducibility. The results showed that the remarkable variation regulations appear among the different processed products.

Cytotoxic diterpenoids from the roots of Salvia lachnocalyx

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Hossein Hadavand Mirzaei

Full Text Available ABSTRACT Salvia lachnocalyx Hedge, Lamiaceae, is an endemic sage which grows naturally in the Fars Province of Iran. The phytochemical analyses of the roots of S. lachnocalyx led to the isolation of five known diterpenoids: ferruginol (1, taxodione (2, sahandinone (3, 4-dehydrosalvilimbinol (4 and labda-7,14-dien-13-ol (5. Their chemical structures were elucidated using one (1H and 13C and two dimensional (COSY, HSQC and HMBC NMR spectroscopic data as well as electron impact mass spectra. The cytotoxicity of the purified compounds was evaluated against three human cancer cell lines; MOLT-4 (acute lymphoblastic leukemia, HT-29 (colorectal adenocarcinoma and MCF7 (breast adenocarcinoma and all of the isolated compounds showed considerable cytotoxic activity against these cell lines. Compounds 2 and 3 (IC50 range: 0.41–3.87 µg/ml with endocyclic α,β-unsaturated carbonyl functional group, exhibited the highest cytotoxic activities compared to the other compounds (IC50 range: 6.85–17.23 µg/ml. In conclusion, compounds 2 and 3 are presented as compounds that deserve further investigation of their biological activities.

Antioxidant, lipid peroxidation inhibition and free radical scavenging efficacy of a diterpenoid compound sugiol isolated from Metasequoia glyptostroboides.

Science.gov (United States)

Bajpai, Vivek K; Sharma, Ajay; Kang, Sun Chul; Baek, Kwang-Hyun

2014-01-01

To investigate the antioxidant efficacy of a biologically active diterpenoid compound sugiol isolated from Metasequoia glyptostroboides (M. glyptostroboides) in various antioxidant models. An abietane type diterpenoid sugiol, isolated from ethyl acetate extract of M. glyptostroboides cones, was analyzed for its antioxidant efficacy as reducing power ability and lipid peroxidation inhibition as well as its ability to scavenge free radicals such as 1,1-diphenyl-2-picryl hydrazyl, nitric oxide, superoxide and hydroxyl radicals. The sugiol showed significant and concentration-dependent antioxidant and free radical scavenging activities. Consequently, the sugiol exerted lipid peroxidation inhibitory effect by 76.5% as compared to α-tocopherol (80.13%) and butylated hydroxyanisole (76.59%). In addition, the sugiol had significant scavenging activities of 1,1-diphenyl-2-picryl hydrazyl, nitric oxide, superoxide and hydroxyl free radicals in a concentration-dependent manner by 78.83%, 72.42%, 72.99% and 85.04%, when compared to the standard compound ascorbic acid (81.69%, 74.62%, 73.00% and 73.79%) and α-tocopherol/butylated hydroxyanisole (84.09%, 78.61%, 74.45% and 70.02%), respectively. These findings justify the biological and traditional uses of M. glyptostroboides or its secondary metabolites as confirmed by its promising antioxidant efficacy. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

ent-Kaurane Diterpenoids with Neuroprotective Properties from Corn Silk ( Zea mays).

Science.gov (United States)

Qi, Xiao-Li; Zhang, Ying-Ying; Zhao, Peng; Zhou, Le; Wang, Xiao-Bo; Huang, Xiao-Xiao; Lin, Bin; Song, Shao-Jiang

2018-05-25

Thirteen new ent-kaurane diterpenoids, stigmaydenes A-M (1-13), together with two known compounds (14, 15), were isolated from the crude extract of corn silk ( Zea mays). The structures of the compounds were confirmed by comprehensive spectroscopic analyses. The absolute configuration of compound 1 was defined by single-crystal X-ray diffraction. The absolute configurations of the compounds were also confirmed by comparison of experimental and calculated specific rotations. The compounds were evaluated for their neuroprotective effects against H 2 O 2 -induced SH-SY5Y cell injury, and compound 8 was active at 100 μM, as determined by flow cytometry (annexin V-FITC/PI staining) and Hoechst 33258 staining. The results suggested that compound 8 could protect neuronal cells from H 2 O 2 -induced injury by inhibiting apoptosis in SH-SY5Y cells.

Structure determination of two new indole-diterpenoids from Penicillium sp. CM-7 by NMR spectroscopy.

Science.gov (United States)

Zhang, Yu-Hong; Huang, Sheng-Dong; Pan, Hua-Qi; Bian, Xi-Qing; Wang, Zai-Ying; Han, Ai-Hong; Bai, Jiao

2014-06-01

Two new indole-diterpenoids 4b-deoxy-1'-O-acetylpaxilline (1) and 4b-deoxypenijanthine A (2) were isolated from the fermentation broth and the mycelia of the soil fungus Penicillium sp. CM-7, along with three known structurally related compounds, 1'-O-acetylpaxilline (3), paspaline (4) and 3-deoxo-4b-deoxypaxilline (5). The structures of compounds 1 and 2 were elucidated by extensive spectroscopic methods, especially 2D NMR, and their absolute configurations were suggested on the basis of the circular dichroism spectral analysis and the NOESY data. Copyright © 2014 John Wiley & Sons, Ltd.

Further New Diterpenoids as PTP1B Inhibitors from the Xisha Soft Coral Sinularia polydactyla.

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Ye, Fei; Zhu, Zheng-Dan; Gu, Yu-Cheng; Li, Jia; Zhu, Wei-Liang; Guo, Yue-Wei

2018-03-25

A new prenyleudesmane type diterpene, sinupol ( 8 ), and a new capnosane type diterpenoid, sinulacetate ( 9 ), were isolated from the Xisha soft coral Sinularia polydactyla along with five known related diterpenes ( 4 - 7 and 10 ). Their structures, including absolute configurations, were determined by extensive spectroscopic analysis, the comparison of their NMR data with those of related compounds, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD) calculations. Both new compounds ( 8 and 9 ) exhibited promising inhibitory activity against protein tyrosine phosphatase 1B (PTP1B), a potential drug target for the treatment of type II diabetes and obesity.

Indole diterpenoids from the endophytic fungus Drechmeria sp. as natural antimicrobial agents.

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Zhao, Jian-Chao; Wang, Ya-Li; Zhang, Tian-Yuan; Chen, Zhong-Jian; Yang, Tian-Mei; Wu, Ying-Ying; Sun, Cheng-Peng; Ma, Xiao-Chi; Zhang, Yi-Xuan

2018-04-01

A fungal strain, Drechmeria sp., was isolated from the root of Panax notoginseng. Totally, seven new indole diterpenoids, drechmerins A-G (1-7), were isolated from the fermentation broth of Drechmeria sp. together with four known analogues (8-11). Their structures were determined on the basis of 1D and 2D NMR and electronic circular dichroism (ECD) spectroscopic analyses as well as theoretical calculations. All the isolated compounds were evaluated for their antimicrobial activities against Candida albicans, Staphylococcus aureus, Bacillus cereus, B. subtillis, Pseudomonas aeruginosa, and Klebsiella pneumonia, respectively. Drechmerin B (2) displayed antimicrobial activity against C. albicans with an MIC value of 12.5 μg/mL. Molecular docking was used to investigate interactions of peptide deformylase with compounds 1-3, 5-7, 9, and 10. Copyright © 2018 Elsevier Ltd. All rights reserved.

Further New Diterpenoids as PTP1B Inhibitors from the Xisha Soft Coral Sinularia polydactyla

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Fei Ye

2018-03-01

Full Text Available A new prenyleudesmane type diterpene, sinupol (8, and a new capnosane type diterpenoid, sinulacetate (9, were isolated from the Xisha soft coral Sinularia polydactyla along with five known related diterpenes (4–7 and 10. Their structures, including absolute configurations, were determined by extensive spectroscopic analysis, the comparison of their NMR data with those of related compounds, and time-dependent density functional theory electronic circular dichroism (TDDFT ECD calculations. Both new compounds (8 and 9 exhibited promising inhibitory activity against protein tyrosine phosphatase 1B (PTP1B, a potential drug target for the treatment of type II diabetes and obesity.

Serrulatane Diterpenoid from Eremophila neglecta Exhibits Bacterial Biofilm Dispersion and Inhibits Release of Pro-inflammatory Cytokines from Activated Macrophages.

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Mon, Htwe H; Christo, Susan N; Ndi, Chi P; Jasieniak, Marek; Rickard, Heather; Hayball, John D; Griesser, Hans J; Semple, Susan J

2015-12-24

The purpose of this study was to assess the biofilm-removing efficacy and inflammatory activity of a serrulatane diterpenoid, 8-hydroxyserrulat-14-en-19-oic acid (1), isolated from the Australian medicinal plant Eremophila neglecta. Biofilm breakup activity of compound 1 on established Staphylococcus epidermidis and Staphylococcus aureus biofilms was compared to the antiseptic chlorhexidine and antibiotic levofloxacin. In a time-course study, 1 was deposited onto polypropylene mesh to mimic a wound dressing and tested for biofilm removal. The ex-vivo cytotoxicity and effect on lipopolysaccharide-induced pro-inflammatory cytokine release were studied in mouse primary bone-marrow-derived macrophage (BMDM) cells. Compound 1 was effective in dispersing 12 h pre-established biofilms with a 7 log10 reduction of viable bacterial cell counts, but was less active against 24 h biofilms (approximately 2 log10 reduction). Compound-loaded mesh showed dosage-dependent biofilm-removing capability. In addition, compound 1 displayed a significant inhibitory effect on tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) secretion from BMDM cells, but interleukin-1 beta (IL-1β) secretion was not significant. The compound was not cytotoxic to BMDM cells at concentrations effective in removing biofilm and lowering cytokine release. These findings highlight the potential of this serrulatane diterpenoid to be further developed for applications in wound management.

Diterpenoids from the Endophytic Fungus Botryosphaeria sp. P483 of the Chinese Herbal Medicine Huperzia serrata

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Yan-Mei Chen

2015-09-01

Full Text Available Two new tetranorlabdane diterpenoids, named botryosphaerins G (1 and H (2, were isolated from the solid fermentation products of Botryosphaeria sp. P483 along with seven known tetranorlabdane diterpenes (3–9. Their structures were elucidated by extensive analysis, including 1D and 2D nuclear magnetic resonance (NMR spectroscopy, and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS. Their absolute configuration was confirmed by single-crystal X-ray diffraction analyses using the anomalous scattering of Cu Kα radiation. All of the isolated compounds were tested for activity against phytopathogenic fungi and nematodes. Compounds 2 and 3 showed antifungal activity and compound 2 showed weak nematicidal activity.

Mollolide A, a diterpenoid with a new 1,10:2,3-disecograyanane skeleton from the roots of Rhododendron molle.

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Li, Yong; Liu, Yun-Bao; Zhang, Jian-Jun; Li, Yu-Huan; Jiang, Jian-Dong; Yu, Shi-Shan; Ma, Shuang-Gang; Qu, Jing; Lv, Hai-Ning

2013-06-21

Mollolide A (1), a diterpenoid featuring a new 1,10:2,3-disecograyanane skeleton, was isolated from the roots of Rhododendron molle. Its structure was elucidated through extensive MS, IR, and NMR spectroscopy analyses. The absolute configuration was determined by single-crystal X-ray diffraction of its p-bromobenzoate derivative (1b). Compound 1 exhibits a significant analgesic effect at a dose of 20 mg/kg and antiviral activity against the Coxsackie B3 virus with an IC50 value of 27.7 μM.

Sedative and muscle relaxant activities of diterpenoids from Phlomidoschema parviflorum

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Abdur Rauf

Full Text Available Abstract Phlomidoschema parviflorum (Benth. Vved. (Basionym: Stachys parviflora Benth. Lamiaceae, have significance medicinal importance as it is used in number of health disorders including diarrhea, fever, sore mouth and throat, internal bleeding, weaknesses of the liver and heart genital tumors, sclerosis of the spleen, inflammatory tumors and cancerous ulcers. The present contribution deals with the sedative and muscle relaxant like effects of diterpenoids trivially named stachysrosane and stachysrosane, isolated from the ethyl acetate soluble fraction of P. parviflorum. Both compounds (at 5, 10 and 15 mg/kg, i.p were assessed for their in vivo sedative and muscle relaxant activity in open field and inclined plane test, respectively. The geometries of both compounds were optimized with density functional theory. The molecular docking of both compounds were performed with receptor gamma aminobutyric acid. Both compounds showed marked activity in a dose dependent manner. The docking studies showed that both compounds interact strongly with important residues in receptor gamma aminobutyric acid. The reported data demonstrate that both compounds exhibited significant sedative and muscle relaxant-like effects in animal models, which opens a door for novel therapeutic applications.

Extraction of three bioactive diterpenoids from Andrographis paniculata: effect of the extraction techniques on extract composition and quantification of three andrographolides using high-performance liquid chromatography.

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Kumar, Satyanshu; Dhanani, Tushar; Shah, Sonal

2014-10-01

Andrographis paniculata (Burm.f.) wall.ex Nees (Acanthaceae) or Kalmegh is an important medicinal plant finding uses in many Ayurvedic formulations. Diterpenoid compounds andrographolides (APs) are the main bioactive phytochemicals present in leaves and herbage of A. paniculata. The efficiency of supercritical fluid extraction (SFE) using carbon dioxide was compared with the solid-liquid extraction techniques such as solvent extraction, ultrasound-assisted solvent extraction and microwave-assisted solvent extraction with methanol, water and methanol-water as solvents. Also a rapid and validated reverse-phase high-performance liquid chromatography-diode array detection method was developed for the simultaneous determination of the three biologically active compounds, AP, neoandrographolide and andrograpanin, in the extracts of A. paniculata. Under the best SFE conditions tested for diterpenoids, which involved extraction at 60°C and 100 bar, the extractive efficiencies were 132 and 22 µg/g for AP and neoandrographolide, respectively. The modifier percentage significantly affected the extraction efficiency. © The Author [2013]. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Hypofolins A - L, ent-Labdane Diterpenoids from the Roots of Hypoestes phyllostachya 'Pink Splash'.

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Cheng, Bin; Ding, Lin-Fen; Yan, Tong; Xie, Zhang-Qiao; Zhang, Zhi-Jun; Song, Liu-Dong; Wu, Xing-De; Zhao, Qin-Shi

2018-06-01

Twelve new ent-labdane diterpenoids, hypofolins A - F (1 - 6) and hypofolins G - L (7a/7b, 8a/8b, and 9a/9b), were isolated from the roots of Hypoestes phyllostachya 'Pink Splash'. Their structures were elucidated by extensive 1D- and 2D-NMR spectroscopic and HR-MS data. The absolute configurations of 1, 2, 5, and 7a/7b were determined by single crystal X-ray diffraction and ECD analysis, as well as chemical transformations. Compounds 7a/7b, 8a/8b, and 9a/9b were isolated as three pairs of interconverting mixture of two isomers between ketone and hemiketal types. Compound 1 showed weak cytotoxicity against SMMC-7721 cell line with IC 50 value of 31.40 μm. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

Rapid Bioassay-Guided Isolation of Antibacterial Clerodane Type Diterpenoid from Dodonaea viscosa (L. Jaeq.

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Muhammad Khurram

2015-08-01

Full Text Available Plant extracts are complex matrices and, although crude extracts are widely in use, purified compounds are pivotal in drug discovery. This study describes the application of automated preparative-HPLC combined with a rapid off-line bacterial bioassay, using reduction of a tetrazolium salt as an indicator of bacterial metabolism. This approach enabled the identification of fractions from Dodonaea viscosa that were active against Staphylococcus aureus and Escherichia coli, which, ultimately, resulted in the identification of a clerodane type diterpenoid, 6β-hydroxy-15,16-epoxy-5β, 8β, 9β, 10α-cleroda-3, 13(16, 14-trien-18-oic acid, showing bacteriostatic activity (minimum inhibitory concentration (MIC = 64–128 µg/mL against test bacteria. To the best of our knowledge, this is the first report on antibacterial activity of this metabolite from D. viscosa.

Ent-kaurane diterpenoids and other constituents from the stem of Xylopia laevigata (Annonaceae)

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Silva, Dayanne Meneses; Costa, Emmanoel Vilaca; Nogueira, Paulo Cesar de Lima; Moraes, Valeria Regina de Souza [Universidade Federal de Sergipe, Sao Cristovao, SE (Brazil). Dept. de Quimica; Cavalcanti, Socrates Cabral de Holanda [Universidade Federal de Sergipe, Sao Cristovao, SE (Brazil). Dept. de Farmacia; Salvador, Marcos Jose [Universidade Estadual de Campinas, SP (Brazil). Inst. de Biologia. Dept. de Biologia Vegetal; Ribeiro, Luis Henrique Gonzaga; Gadelha, Fernanda Ramos [Universidade Estadual de Campinas, SP (Brazil). Inst. de Biologia. Dept. de Bioquimica; Barison, Andersson [Universidade Federal do Parana, Curitiba, PR (Brazil). Dept. de Quimica; Ferreira, Antonio Gilberto, E-mail: emmanoelvc@gmail.com [Universidade Federal de Sao Carlos, SP (Brazil). Dept. de Quimica

2012-07-01

Phytochemical investigation of the hexane extract from the stem of Xylopia laevigata led to the isolation of the ent-kaurane diterpenoids, ent-kaur-16-en-19-oic acid, 4-epi-kaurenic acid, ent-16{beta}-hydroxy-17-acetoxy-kauran-19-al, ent-3{beta}-hydroxy-kaur-16-en-19-oic acid, and ent-16{beta},17-dihydroxy-kauran-19-oic acid, as well as spathulenol and a mixture of {beta}-sitosterol, stigmasterol and campesterol. The identification of the compounds was performed on the basis of spectrometric methods including GC-MS, IR, and 1D and 2D NMR. Potent larvicidal activity against Aedes aegypti larvae with LC{sub 50} of 62.7 {mu}g mL{sup -1} was found for ent-3{beta}-hydroxy-kaur-16-en-19-oic acid. This compound also showed significant antifungal activity against Candida glabrata and Candida dubliniensis with MIC values of 62.5 {mu}g mL{sup -1}. (author)

Ent-kaurane diterpenoids and other constituents from the stem of Xylopia laevigata (Annonaceae)

International Nuclear Information System (INIS)

Silva, Dayanne Meneses; Costa, Emmanoel Vilaca; Nogueira, Paulo Cesar de Lima; Moraes, Valeria Regina de Souza; Cavalcanti, Socrates Cabral de Holanda; Salvador, Marcos Jose; Ribeiro, Luis Henrique Gonzaga; Gadelha, Fernanda Ramos; Barison, Andersson; Ferreira, Antonio Gilberto

2012-01-01

Phytochemical investigation of the hexane extract from the stem of Xylopia laevigata led to the isolation of the ent-kaurane diterpenoids, ent-kaur-16-en-19-oic acid, 4-epi-kaurenic acid, ent-16β-hydroxy-17-acetoxy-kauran-19-al, ent-3β-hydroxy-kaur-16-en-19-oic acid, and ent-16β,17-dihydroxy-kauran-19-oic acid, as well as spathulenol and a mixture of β-sitosterol, stigmasterol and campesterol. The identification of the compounds was performed on the basis of spectrometric methods including GC-MS, IR, and 1D and 2D NMR. Potent larvicidal activity against Aedes aegypti larvae with LC 50 of 62.7 μg mL -1 was found for ent-3β-hydroxy-kaur-16-en-19-oic acid. This compound also showed significant antifungal activity against Candida glabrata and Candida dubliniensis with MIC values of 62.5 μg mL -1 . (author)

Mitochondrial-mediated apoptosis in lymphoma cells by the diterpenoid lactone Andrographolide, the active component of Andrographis paniculata

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Yang, Shuo; Evens, Andrew M.; Prachand, Sheila; Singh, Amareshwar T.K; Bhalla, Savita; David, Kevin; Gordon, Leo I.

2010-01-01

Purpose Andrographolide is a diterpenoid lactone isolated from Andrographis paniculata (King of Bitters), an herbal medicine used in Asia. It has been reported to have anti-inflammatory, antihypertensive, anti-viral and immune-stimulant properties. Furthermore, it has been shown to inhibit cancer cell proliferation and induce apoptosis in leukemia and solid tumor cell lines. Experimental Design We studied the Burkitt p53 mutated Ramos cell line, the mantle-cell lymphoma (MCL) line Granta, the follicular lymphoma (FL) cell line HF-1 and the diffuse large B-cell lymphoma (DLBCL) cell line SUDHL4, as well as primary cells from patients with FL, DLBCL, and MCL. Results We found that andrographolide resulted in dose- and time-dependent cell death as measured by MTT. Andrographolide significantly increased reactive oxygen species (ROS) production in all cell lines. To determine mechanism of cell death, we measured apoptosis by Annexin-V/propidium iodide (PI) in the presence and absence of the antioxidant N-acetyl-L-cysteine (NAC), the glutathione-depleting agent buthionine sulfoxamine (BSO), or caspase inhibitors. We found that apoptosis was greatly enhanced by BSO, blocked by NAC, and accompanied by PARP cleavage and activation of caspases 3, 8 and 9. We measured BAX conformational change, and mitochondrial membrane potential, and using mouse embryonic fibroblast (MEF) Bax/Bak double knockouts (MEFBax−/−/Bak−/−), we found that apoptosis was mediated through mitochondrial pathways, but dependent on caspases in both cell lines and in patient samples. Conclusions Andrographolide caused ROS-dependent apoptosis in lymphoma cell lines and in primary tumor samples, which was enhanced by depletion of GSH and inhibited by NAC or the pan-caspase inhibitor Z-VAD-FMK. Further studies of diterpenoid lactones in lymphoma are warranted. PMID:20798229

Antibacterial abietane-type diterpenoid, taxodone from Metasequoia glyptostroboides Miki ex Hu.

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Bajpai, Vivek K; Kang, Sun Chul

2010-12-01

In an attempt to isolate bioactive constituents, ethyl acetate cone extract of Metasequoia glyptostroboides was subjected to a column chromatographic analysis that resulted in isolation of an abietane-type diterpenoid, taxodone. Its structure was elucidated by spectroscopic means. Further, taxodone showed potential antibacterial effect as diameters of zones of inhibition against foodborne pathogenic bacteria, such as Listeria monocytogenes ATCC 19166, Salmonella typhimurium KCTC 2515, S. enteritidis KCTC 2021, Escherichia coli ATCC 8739, E. coli O157:H7 ATCC 43888, Enterobacter aerogenes KCTC 2190, Staphylococcus aureus ATCC 6538 and S. aureus KCTC 1916, were found in the range of 9.4 to 14.2 mm. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of taxodone against the employed bacterial pathogens were found in the range of 250 to 1000 and 250 to less than 2000 microg/ml, respectively. Also the compound had a strong antibacterial effect on the viable counts of the tested bacteria. These findings indicate that the bioactive compound taxodone present in M. glyptostroboides could be used as an antibacterial agent in food industry to inhibit the growth of certain important foodborne pathogens.

Inhibition of Helicobacter pylori and Its Associate Urease by Labdane Diterpenoids Isolated from Andrographis paniculata.

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Shaikh, Rafik U; Dawane, Ashwini A; Pawar, Rajendra P; Gond, Dhananjay S; Meshram, Rohan J; Gacche, Rajesh N

2016-03-01

The present study was carried out to evaluate anti-Helicobacter pylori and its associated urease activity of labdane diterpenoids isolated from Andrographis paniculata. A molecular docking analysis was performed by using ArgusLab 4.0.1 software. The results obtained indicate that compound A possesses strong inhibition to H. pylori, 28 ± 2.98 (minimum inhibitory concentration, 9 µg/mL), and its urease, 85.54 ± 2.62% (IC50 , 20.2 µg/mL). Compounds B, C, and D also showed moderate inhibition to H. pylori and its urease. The obtained results were in agreement with the molecular docking analysis of compounds. The phytochemicals under investigation were found to be promising antibacterial agents. Moreover, the isolated compounds can be considered as a resource for searching novel anti-H. pylori agents possessing urease inhibition. Copyright © 2015 John Wiley & Sons, Ltd.

Antimycotic potential of a diterpenoid taxoquinone against Candida species isolated from Metasequoia glyptostroboides

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Vivek K. Bajpai

2014-06-01

Full Text Available The objective of this study was to confirm the antimycotic potential of a diterpenoid compound taxoquinone, isolated from Metasequoia glyptostroboides against pathogenic isolates of Candida species. The taxoquinone (100 μg/disc displayed potential anticandidal effect against Candia albicans KBN06P00076, KBN06P00074, C. glabrata KBN06P00066, KBN06P00068, C. tropicalis KBN06P00682, KBN06P00058, C. parapsilosis KBN06P00060, KBN06P00055, and C. guilliermondii KBN06P00492 and KBN06P00867 as a diameter of zones of inhibition, found in the range of 10 ± 0.6 to 13 ± 1.1 mm. The minimum inhibitory and minimum fungicidal concentrations of taxoquinone against the tested clinical isolates were found in the range of 125 to 500 and 125 to 1,000 μg/mL, respectively. On the viable counts of the tested fungal isolates, the taxoquinone evoked a remarkable anticandidal effect. Elaborative study of SEM revealed potential detrimental effect of taxoquinone on the morphology of C. parapsilosis KBN06P00060 at MIC concentration. These findings confirmed therapeutic potential of taxoquinone.

Eunicellin-based diterpenoids from the Formosan soft coral Klyxum molle with inhibitory activity on superoxide generation and elastase release by neutrophils.

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Lin, Ming-Chang; Chen, Bo-Wei; Huang, Chiung-Yao; Dai, Chang-Feng; Hwang, Tsong-Long; Sheu, Jyh-Horng

2013-09-27

Eleven new eunicellin-based diterpenoids possessing a cladiellane skeleton with a C-2, C-9 ether bridge, klymollins I-S (1-11), have been isolated from the EtOAc extract of the soft coral Klyxum molle from Taiwan waters. The structures of compounds 1-11 were elucidated by extensive spectroscopic analysis, including 2D NMR spectroscopy (COSY, HSQC, HMBC, and NOESY). Compound 5 exhibited cytotoxicity toward several cancer cell lines. Compound 5 is the first eunicellin-based metabolite bearing a phenyl group and displays significant inhibition of both superoxide anion generation and elastase release in N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced human neutrophils.

Characterization and evaluation of an oral microemulsion containing the antitumor diterpenoid compound ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid

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Lu Y

2013-05-01

Full Text Available Yingnian Lu,1,2 Kefeng Wu,2 Li Li,2 Yuhui He,2 Liao Cui,2 Nianci Liang,2 Bozhong Mu11Department of Chemistry, East China University of Science and Technology, Shanghai, 2Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical College, Zhanjiang, People’s Republic of ChinaAbstract: The objective of this study was to develop an oral microemulsion formulation of the antitumor diterpenoid agent, ent-11a-hydroxy-15-oxo-kaur-16-en-19-oic- acid (henceforth referred to as 5F, to enhance its bioavailability and evaluate its hepatotoxicity. Pseudoternary phase diagrams showed that the optimal microemulsion formulation contained 45% water, 10% castor oil as the oil phase, 15% Cremophor EL as the surfactant, and 30% as a cosurfactant mixture of 1,2-propanediol and polyethylene glycol (PEG-400 (2:1, w/w. The microemulsion preparation was characterized and its droplet diameter was within 50 nm. Release of 5F in vitro from the microemulsion was slightly increased compared with a suspension containing the same amount of active drug. Pharmacokinetic parameters in vivo indicated that bioavailability was markedly improved, with the relative bioavailability being 616.15% higher for the microemulsion than for the suspension. Toxicity tests showed that the microemulsion had no hepatotoxicity in mice. These results suggest the potential for 5F microemulsion to be administered by the oral route.Keywords: antitumor, diterpenoid, microemulsion, pharmacokinetics, toxicity

Preparative separation of C19-diterpenoid alkaloids from Aconitum carmichaelii Debx by pH‑zone-refining counter-current chromatography

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Dahui Liu

2013-01-01

Full Text Available The technique of pH-zone-refining counter-current chromatography was successfully applied to preparatively separate three C19-diterpenoid alkaloids from the crude extracts of Aconitum carmichaelii for the first time using a two-phase solvent system of petroleum ether-ethyl acetate-methanol-water (5:5:1:9, v/v/v/v. Mesaconitine (I, hypaconitine (II, and deoxyaconitine (III were obtained from 2.5 g of the crude alkaloids in a one-step separation; the yields were 4.16%, 16.96%, and 5.05%, respectively. The purities of compounds I, II, and III were 93.0%, 95%, and 96%, respectively, as determined by HPLC. The chemical structures of the three compounds were identified by electrospray ionization mass spectrometry (ESI-MS and NMR.

In vivo antimalarial activity of a labdane diterpenoid from the leaves of Otostegia integrifolia Benth.

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Endale, Abyot; Bisrat, Daniel; Animut, Abebe; Bucar, Franz; Asres, Kaleab

2013-12-01

In Ethiopian traditional medicine, the leaves of Otostegia integrifolia Benth. are used for the treatment of several diseases including malaria. In an ongoing search for effective, safe and cheap antimalarial agents from plants, the 80% methanol leaf extract O. integrifolia was tested for its in vivo antimalarial activity, in a 4-day suppressive assay against Plasmodium berghei. Activity-guided fractionation of this extract which showed potent antiplasmodial activity resulted in the isolation of a labdane diterpenoid identified as otostegindiol. Otostegindiol displayed a significant (P antimalarial activity at doses of 25, 50 and 100 mg/kg with chemosuppression values of 50.13, 65.58 and 73.16%, respectively. Acute toxicity studies revealed that the crude extract possesses no toxicity in mice up to a maximum dose of 5000 mg/kg suggesting the relative safety of the plant when administered orally. The results of the present study indicate that otostegindiol is among the antimalarial principles in this medicinal plant, and further support claims for the traditional medicinal use of the plant for the treatment of malaria. Copyright © 2013 John Wiley & Sons, Ltd.

Preparative separation of C{sub 19}-diterpenoid alkaloids from Aconitum carmichaelii Debx by pH zone-refining counter-current chromatography

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Liu, Dahui [Institute of Medicinal Plants, Yunnan Academy of Agricultural Sciences, Kunming (China); Shu, Xikai; Wang, Xiao; Fang, Lei; Huang, Luqi, E-mail: wxjn1998@126.com [Shandong Analysis and Test Center, Shandong Academy of Sciences, Jinan, Shandong (China); Xi, Xingjun; Zheng, Zhenjia [China National institute of Standardization, Beijing (China)

2013-11-01

The technique of pH-zone-refining counter-current chromatography was successfully applied to preparatively separate three C{sub 19}-diterpenoid alkaloids from the crude extracts of Aconitum carmichaelii for the first time using a two-phase solvent system of petroleum ether-ethyl acetate-methanol-water (5:5:1:9, v/v/v/v). Mesaconitine (I), hypaconitine (II), and deoxyaconitine (III) were obtained from 2.5 g of the crude alkaloids in a one-step separation; the yields were 4.16%, 16.96%, and 5.05%, respectively. The purities of compounds I, II, and III were 93.0%, 95%, and 96%, respectively, as determined by HPLC. The chemical structures of the three compounds were identified by electrospray ionization mass spectrometry (ESI-MS) and NMR. (author)

(4aS,10aS-7-Hydroxy-8-isopropyl-1,1,4a-trimethyl-1,2,3,4,4a,9,10,10a-octahydrophenanthrene: a new diterpenoid compound

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Ahmed Benharref

2008-03-01

Full Text Available The new title diterpenoid compound, C20H30O, is a natural product isolated from Tetraclinis articulata wood via chloroform extraction. The asymmetric unit contains four molecules with the same S,S configuration, deduced from the chemical synthesis. Indeed, an overlay analysis, calculated using structure-matching software, shows that the four molecules can be superimposed. The central ring has a half-chair conformation, whereas the saturated ring displays a chair conformation.

Labdane diterpenoids from Curcuma amada rhizomes collected in Myanmar and their antiproliferative activities.

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Win, Nwet Nwet; Ito, Takuya; Ngwe, Hla; Win, Yi Yi; Prema; Okamoto, Yasuko; Tanaka, Masami; Asakawa, Yoshinori; Abe, Ikuro; Morita, Hiroyuki

2017-10-01

Four new labdane diterpenoids, 12β-hydroxy-15-norlabda-8(17),13(14)-dien-16-oic acid (1), (E)-15-ethoxy-15-methoxylabda-8(17),12-dien-16-al (2), (E)-15α-ethoxy-14α-hydroxylabda-8(17),12-dien-16-olide (3), and 15-ethoxy-12β-hydroxylabda-8(17),13(14)-dien-16,15-olide (4) were isolated from the methanol extract of Curcuma amada rhizomes collected in Myanmar, together with 13 known analogs. Their structures were elucidated by extensive spectroscopic techniques. All of the isolates were evaluated for their antiproliferative activities against a small panel of five different human cancer cell lines (A549, human lung cancer; HeLa, human cervical cancer; MCF7, human breast cancer; PANC-1 and PSN-1, human pancreatic cancer). Among the isolates, compounds 2-4, 7, 8, 12, and 17 showed mild antiproliferative activities with IC 50 values ranging from 19.7 to 96.1μM. (E)-14-Hydroxy-15-norlabda-8(17),12-dien-16-al (11) exhibited strong antiproliferative activities selectively against HeLa, PANC-1, and PSN-1 cells, with IC 50 values of 5.88, 1.00, and 3.98μM, respectively. These potencies were comparable to those of the positive control, 5-fluorouracil. Copyright © 2017 Elsevier B.V. All rights reserved.

NO-Releasing Enmein-Type Diterpenoid Derivatives with Selective Antiproliferative Activity and Effects on Apoptosis-Related Proteins

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Dahong Li

2016-09-01

Full Text Available A series of nine enmein-type ent-kaurane diterpenoid and furoxan-based nitric oxide (NO donor hybrids (10a–i were designed and synthesized from commercially available oridonin (1. These hybrids were evaluated for their antiproliferative activity against Bel-7402, K562, MGC-803, and CaEs-17 human cancer cell lines and L-02 normal liver cells. The antiproliferative activity against tumor cells was stronger than the lead compound 1 and parent molecule 9 in most cases. Especially, compound 10f showed the strongest activity against human hepatocarcinoma Bel-7402 cell line with an IC50 of 0.81 μM and could also release 33.7 μmol/L NO at the time point of 60 min. Compounds 10a–i also showed cytotoxic selectivity between tumor and normal liver cells with IC50 ranging from 22.1 to 33.9 μM. Furthermore, the apoptotic properties on Bel-7402 cells revealed that 10f could induce S phase cell cycle arrest and apoptosis at low micromolar concentrations. The effects of 10f on apoptosis-related proteins were also investigated. The potent antiproliferative activities and mechanistic studies warrant further preclinical investigations.

Rhodomollacetals A-C, PTP1B Inhibitory Diterpenoids with a 2,3:5,6-Di-seco-grayanane Skeleton from the Leaves of Rhododendron molle.

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Zhou, Junfei; Sun, Na; Zhang, Hanqi; Zheng, Guijuan; Liu, Junjun; Yao, Guangmin

2017-10-06

Three novel diterpenoids with an unprecedented 2,3:5,6-di-seco-grayanane carbon skeleton, rhodomollacetals A-C (1-3), are isolated from the leaves of Rhododendron molle. Their structures are elucidated by comprehensive spectroscopic techniques and single-crystal X-ray diffraction. Rhodomollacetal A (1) possesses a novel cis/cis/cis/cis-fused 6/6/6/6/5 pentacyclic ring system, featuring an unprecedented 11,13,18-trioxa-pentacyclo [8.7.1.1 5,8 .0 2,8 .0 12,17 ]nonadecane scaffold. Compounds 2 and 3 have a rare 4-oxatricyclo[7.2.1.0 1,6 ]dodecane moiety and a 2,3-dihydro-4H-pyran-4-one unit. Compounds 1-3 showed moderate PTP1B inhibitory activities, and their molecular dockings were investigated.

Cytotoxic activity of abietane diterpenoids from roots of Salvia sahendica by HPLC-based activity profiling

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Fahimeh Moradi-Afrapoli

Full Text Available ABSTRACT Screening of medicinal plants from Iranian flora against human cancer cell-lines have shown that an hexane extract from roots of Salvia sahendica Boiss. & Buhse, Lamiaceae, is active against human cervical cancer (HeLa and colorectal adenocarcinoma (Caco-2 cell-lines at the test concentration of 100 µg/ml (100% inhibition. Cytotoxicity of the extract was localized with the aid of HPLC-time-based activity profiling adapted to the tetrazolium colorimetric bioassay. Four abietane-type diterpenoids in active time-windows were identified as cytotoxic compounds namely: sahandone (1, sahandol (2, 12-deoxy-salvipisone (3 and sahandinone (4. Compound 1 showed the highest toxicity against HeLa cells (IC50 = 5.6 ± 0.1 µg/ml, which was comparable with betulinic acid (IC50 = 4.3 ± 1.2 µg/ml, the positive control. Compound 2 was active against the HeLa cells (IC50 = 8.9 ± 0.7 µg/ml but not the Caco-2 cell-line. Compounds 1, 3 and 4 exhibited moderate activity (IC50 = 22.9–41.4 µg/ml against the Caco-2 cells. This study reveals that the HeLa cells are more sensitive to all tested compounds than the Caco-2 cells. In silico molecular docking study showed a rigid binding of the compounds to tyrosine kinase pp60src, and proved their cytotoxic activity.

Effect of processing on the alkaloids in Aconitum tubers by HPLC-TOF/MS

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Min Liu

2017-06-01

Full Text Available According to the Chinese Pharmacopoeia 2015, only processed Aconitum tubers can be clinically applied, and the effect of processing is unclear. This research aimed to explore the effect of processing on cardiac efficacy of alkaloids in Aconitum tubers. First, the chemical ingredients in unprocessed and processed Aconitum tubers were identified and compared by using high performance liquid chromatography time-of-flight mass spectrometry (HPLC-TOF/MS and multivariate pattern recognition methods. Then the representative alkaloids in Aconitum tubers, aconitine, benzoylaconine, and aconine, which belong to diester-diterpenoid alkaloids, monoester-diterpenoid alkaloids, and amine-diterpenoid alkaloids, respectively, were selected for further validation of attenuated mechanism. Subsequent pharmacological experiments with aconitine, benzoylaconine, and aconine in SD rats were used for validate the effect of processing on cardiac functions. After processing the Aconitum tubers, it was found that the contents of diester-diterpenoid alkaloids were reduced, and those of monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids were increased, suggesting that diester-diterpenoid alkaloids were transformed into monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids. Through further decocting the aconitine in boiling water, it was confirmed that the three alkaloids could be progressively transformed. Pharmacological experiments with aconitine, benzoylaconine, and aconine in SD rats showed that aconitine at a dose of 0.01 mg/kg and aconine at a dose of 10 mg/kg enhanced the cardiac function, while benzoylaconine at a dose of 2 mg/kg weakened the cardiac function. The effect of processing is attributed to the transformation of the most toxic diester-diterpenoid alkaloids into less toxic monoester-diterpenoid alkaloids and amine-diterpenoid alkaloids.

New Pesticidal Diterpenoids from Vellozia gigantea (Velloziaceae, an Endemic Neotropical Plant Living in the Endangered Brazilian Biome Rupestrian Grasslands

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Mariana C. Ferreira

2017-01-01

Full Text Available Vellozia gigantea is a rare, ancient, and endemic neotropical plant present in the Brazilian Rupestrian grasslands. The dichloromethane extract of V. gigantea adventitious roots was phytotoxic against Lactuca sativa, Agrostis stolonifera, and Lemna paucicostata, and showed larvicidal activity against Aedes aegypti. Phytotoxicity bioassay-directed fractionation of the extract revealed one new isopimaradiene, 8(9,15-isopimaradien-1,3,7,11-tetraone, and three new cleistanthane diterpenoids, 7-oxo-8,11,13-cleistanthatrien-3-ol, 3,20-epoxy-7-oxo-8,11,13-cleistanthatrien-3-ol, and 20-nor-3,7-dioxo-1,8,11,13-cleistanthatetraen-10-ol. These new structures are proposed based on interpretation of 1H, 13C, COSY, NOESY, HSQC, and HMBC NMR data. 8(9,15-isopimaradien-1,3,7,11-tetraone was especially phytotoxic with an IC50 value (30 μM comparable to those of commercial herbicides clomazone, EPTC, and naptalam. In addition, 7-oxo-8,11,13-cleistanthatrien-3-ol provided 100% mortality at a concentration of 125 ppm against one-day-old Ae. aegypti larvae. Our results show that ancient and unique plants, like the endangered narrowly endemic neotropical species V. gigantea present in the Rupestrian grasslands, should also be protected because they can be sources of new bioactive compounds.

Characterization and evaluation of an oral microemulsion containing the antitumor diterpenoid compound ent-11alpha-hydroxy-15-oxo-kaur-16-en-19-oic-acid.

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Lu, Yingnian; Wu, Kefeng; Li, Li; He, Yuhui; Cui, Liao; Liang, Nianci; Mu, Bozhong

2013-01-01

The objective of this study was to develop an oral microemulsion formulation of the antitumor diterpenoid agent, ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (henceforth referred to as 5F), to enhance its bioavailability and evaluate its hepatotoxicity. Pseudoternary phase diagrams showed that the optimal microemulsion formulation contained 45% water, 10% castor oil as the oil phase, 15% Cremophor EL as the surfactant, and 30% as a cosurfactant mixture of 1,2-propanediol and polyethylene glycol (PEG)-400 (2:1, w/w). The microemulsion preparation was characterized and its droplet diameter was within 50 nm. Release of 5F in vitro from the microemulsion was slightly increased compared with a suspension containing the same amount of active drug. Pharmacokinetic parameters in vivo indicated that bioavailability was markedly improved, with the relative bioavailability being 616.15% higher for the microemulsion than for the suspension. Toxicity tests showed that the microemulsion had no hepatotoxicity in mice. These results suggest the potential for 5F microemulsion to be administered by the oral route.

A diterpenoid taxodone from Metasequoia glyptostroboides with antimycotic potential against clinical isolates of Candida species.

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Bajpai, V K; Park, Y-H; Kang, S C

2015-03-01

The increasing importance of clinical isolates of Candida species and emerging resistance of Candida species to current synthetic antifungal agents have stimulated the search for safer and more effective alternative drugs from natural sources. This study was directed towards exploring the antimycotic potential of a diterpenoid compound taxodone isolated from Metasequoia glyptostroboides against pathogenic isolates of Candida species. Antimycotic efficacy of taxodone was evaluated by disc diffusion assay, determination of minimum inhibitory (MIC) and minimum fungicidal (MFC) concentrations, and cell viability assay. To confirm a partial antimycotic mode of action of taxodone, the efficacy of taxodone was determined by measuring the release of 260 nm absorbing materials from the selected Candida species as compared to control. The taxodone at the concentration of 400 μg/disc displayed potential antimycotic effect against the tested clinical and pathogenic isolates of Candida species as diameters of zones of inhibitions, which were found in the range of 11 ± 0.0 to 12.6 ± 0.5mm. The MIC and MFC values of taxodone against the tested clinical isolates were found in the range of 250 to 1000 and 500 to 2000μ g/mL, respectively. On the other hand, the MIC and MFC values of positive control (amphotericin B) against the tested Candida isolates were found in the range of 62.5 to 250 and 500 to 2000 μg/mL. On the viable counts of the tested fungal isolates, the taxodone exerted significant antimycotic effect. Elaborative study of partial mode of action conducted onto the release of 260nm materials (DNA and RNA) revealed potential detrimental effect of taxodone on the membrane integrity of the tested pathogens at MIC concentration. With respect to the antimycotic effect of taxodone against pathogenic and clinical isolates of Candida species, it might be confirmed that bioactive compound taxodone present in M. glyptostroboides holds therapeutic value of medicinal

Simultaneous determination of phenolic acids and diterpenoids and their comparative pharmacokinetic study in normal and acute blood stasis rats by UFLC-MS/MS after oral administration of Guan-Xin-Shu-Tong capsules.

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Gao, Xun; Mu, Jingqing; Guan, Shaoyi; Li, Qing; Du, Yiyang; Zhang, Huifen; Bi, Kaishun

2018-01-01

Guan-Xin-Shu-Tong capsules are one of the well-known and first-line Chinese traditional herbal formula for treating coronary heart disease. A validated and sensitive method via ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) was established to simultaneously determinate five phenolic acids and four diterpenoids in rats in order to investigate their pharmacokinetic profiles firstly. Analytes were extracted by ethyl acetate and determined via multiple reaction monitoring mode in both positive and negative ion modes. The values for limit of quantification were in range of 0.025-1.250ng/ml. Inter- and intra-day precisions were no more than 10.9% with accuracy of -11.0%-10.6%, meanwhile the stable and suitable extraction recoveries were also obtained. And finally such excellent method was used to compare the pharmacokinetics of nine compounds in normal and acute blood stasis rats after oral administration of Guan-Xin-Shu-Tong capsules. Copyright © 2017 Elsevier B.V. All rights reserved.

Characterization of Terpenoids from the Root of Ceriops tagal with Antifouling Activity

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Chen, Jun-De; Yi, Rui-Zao; Lin, Yi-Ming; Feng, Dan-Qing; Zhou, Hai-Chao; Wang, Zhan-Chang

2011-01-01

One new dimeric diterpenoid, 8(14)-enyl-pimar-2′(3′)-en-4′(18′)-en-15′(16′)-endolabr- 16,15,2′,3′-oxoan-16-one (1) and five known terpenoids: Tagalsin C (2), Tagalsin I (3), lup-20(29)-ene-3β,28-diol (4), 3-oxolup-20(29)-en-28-oic acid (5) and 28-hydroxylup- 20(29)-en-3-one (6) were isolated from the roots of the mangrove plant Ceriops tagal. Their structures and relative stereochemistry were elucidated by means of extensive NMR, IR and MS analysis. The antifouling activity against larval settlement of the barnacle Balanus albicostatus were evaluated using capsaicin as a positive control. All these terpenoids exhibited antifouling activity against cyprid larvae of the barnacle without significant toxicity. The structure-activity relationship results demonstrated that the order of antifouling activity was diterpenoid (Compound 2) > triterpenoid (Compounds 4, 5 and 6) > dimeric diterpenoid (Compounds 1 and 3). The functional groups on the C-28 position of lupane triterpenoid significantly affect the antifouling activity. The diterpenoid dimmer with two identical diterpenoid subunits might display more potent antifouling activity than one with two different diterpenoid subunits. The stability test showed that Compounds 2, 4, 5 and 6 remained stable over 2-month exposure under filtered seawater. PMID:22072902

The Cyanthin Diterpenoid and Sesterterpene Constituents of Hericium erinaceus Mycelium Ameliorate Alzheimer's Disease-Related Pathologies in APP/PS1 Transgenic Mice.

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Tzeng, Tsai-Teng; Chen, Chien-Chih; Chen, Chin-Chu; Tsay, Huey-Jen; Lee, Li-Ya; Chen, Wan-Ping; Shen, Chien-Chang; Shiao, Young-Ji

2018-02-17

Hericium erinaceus was used in traditional Chinese medicine for physiologically beneficial medicines. Recently, it has become a candidate in causing positive brain health-related activities. We previously reported that Hericium erinaceus mycelium ameliorates Alzheimer's disease (AD)-related pathologies. To reveal the role of the cyanthin diterpenoid and sesterterpene constituents on this effects, erinacine A and S were isolated and their effects on attenuating AD-related pathology in APPswe/PS1dE9 transgenic mice were investigated. A 30 day short-term administration of erinacine A and S were performed to explore the effect of each erinacine on AD-related pathology including amyloid β production and degradation, plaque formation, plaque growth, glial activation and neurogenesis deterioration. Our results indicated the benefit effects of both erinacine A and S in cerebrum of APPswe/PS1dE9 mice, including: (1) attenuating cerebral plaque loading by inhibiting plaque growth; (2) diminishing the activation of glial cells; (3) raising the level of insulin degrading enzyme; and (4) promoting hippocampal neurogenesis. Moreover, erinacine A reduced the level of insoluble amyloid β and C-terminal fragment of amyloid precursor protein which was not mediated by erinacine S. We further performed a long term administration of erinacine A and found that erinacine A recovered the impairment in the tasks including burrowing, nesting, and Morris water maze. Our data pointed out that although both erinacine A and S reduce AD pathology via reducing amyloid deposition and promoting neurogenesis, erinacine A can also inhibit amyloid β production and is worth to be further developed for AD therapeutic use.

The Cyanthin Diterpenoid and Sesterterpene Constituents of Hericium erinaceus Mycelium Ameliorate Alzheimer’s Disease-Related Pathologies in APP/PS1 Transgenic Mice

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Tzeng, Tsai-Teng; Chen, Chien-Chih; Chen, Chin-Chu; Tsay, Huey-Jen; Lee, Li-Ya; Chen, Wan-Ping

2018-01-01

Hericium erinaceus was used in traditional Chinese medicine for physiologically beneficial medicines. Recently, it has become a candidate in causing positive brain health-related activities. We previously reported that Hericium erinaceus mycelium ameliorates Alzheimer’s disease (AD)-related pathologies. To reveal the role of the cyanthin diterpenoid and sesterterpene constituents on this effects, erinacine A and S were isolated and their effects on attenuating AD-related pathology in APPswe/PS1dE9 transgenic mice were investigated. A 30 day short-term administration of erinacine A and S were performed to explore the effect of each erinacine on AD-related pathology including amyloid β production and degradation, plaque formation, plaque growth, glial activation and neurogenesis deterioration. Our results indicated the benefit effects of both erinacine A and S in cerebrum of APPswe/PS1dE9 mice, including: (1) attenuating cerebral plaque loading by inhibiting plaque growth; (2) diminishing the activation of glial cells; (3) raising the level of insulin degrading enzyme; and (4) promoting hippocampal neurogenesis. Moreover, erinacine A reduced the level of insoluble amyloid β and C-terminal fragment of amyloid precursor protein which was not mediated by erinacine S. We further performed a long term administration of erinacine A and found that erinacine A recovered the impairment in the tasks including burrowing, nesting, and Morris water maze. Our data pointed out that although both erinacine A and S reduce AD pathology via reducing amyloid deposition and promoting neurogenesis, erinacine A can also inhibit amyloid β production and is worth to be further developed for AD therapeutic use. PMID:29463001

The Cyanthin Diterpenoid and Sesterterpene Constituents of Hericium erinaceus Mycelium Ameliorate Alzheimer’s Disease-Related Pathologies in APP/PS1 Transgenic Mice

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Tsai-Teng Tzeng

2018-02-01

Full Text Available Hericium erinaceus was used in traditional Chinese medicine for physiologically beneficial medicines. Recently, it has become a candidate in causing positive brain health-related activities. We previously reported that Hericium erinaceus mycelium ameliorates Alzheimer’s disease (AD-related pathologies. To reveal the role of the cyanthin diterpenoid and sesterterpene constituents on this effects, erinacine A and S were isolated and their effects on attenuating AD-related pathology in APPswe/PS1dE9 transgenic mice were investigated. A 30 day short-term administration of erinacine A and S were performed to explore the effect of each erinacine on AD-related pathology including amyloid β production and degradation, plaque formation, plaque growth, glial activation and neurogenesis deterioration. Our results indicated the benefit effects of both erinacine A and S in cerebrum of APPswe/PS1dE9 mice, including: (1 attenuating cerebral plaque loading by inhibiting plaque growth; (2 diminishing the activation of glial cells; (3 raising the level of insulin degrading enzyme; and (4 promoting hippocampal neurogenesis. Moreover, erinacine A reduced the level of insoluble amyloid β and C-terminal fragment of amyloid precursor protein which was not mediated by erinacine S. We further performed a long term administration of erinacine A and found that erinacine A recovered the impairment in the tasks including burrowing, nesting, and Morris water maze. Our data pointed out that although both erinacine A and S reduce AD pathology via reducing amyloid deposition and promoting neurogenesis, erinacine A can also inhibit amyloid β production and is worth to be further developed for AD therapeutic use.

Anti-proliferation activity of terpenoids isolated from Euphorbia kansui in human cancer cells and their structure-activity relationship.

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Hou, Jin-Jun; Shen, Yao; Yang, Zhou; Fang, Lin; Cai, Lu-Ying; Yao, Shuai; Long, Hua-Li; Wu, Wan-Ying; Guo, De-An

2017-10-01

Euphorbia kansui is a commonly used traditional Chinese medicine for the treatment of edema, pleural effusion, and asthma, etc. According to the previous researches, terpenoids in E. kansui possess various biological activities, e.g., anti-virus, anti-allergy, antitumor effects. In this work, twenty five terpenoids were isolated from E. kansui, including thirteen ingenane- and eight jatrophane-type diterpenoids (with two new compounds, kansuinin P and Q) and four triterpenoids. Eighteen of them were analyzed by MTS assay for in vitro anticancer activity in five human cancer cell lines. Structure-activity relationship for 12 ingenane-type diterpenoids in colorectal cancer Colo205 cells were preliminary studied. Significant anti-proliferation activities were observed in human melanoma cells breast cancer MDA-MB-435 cells and Colo205 cells. More than half of the isolated ingenane-type diterpenoids showed inhibitory activities in MDA-MB-435 cells. Eight ingenane- and one jatrophane-type diterpenoids possessed much lower IC 50 values in MDA-MB-435 cells than positive control staurosporine. Preliminary structure-activity relationship analysis showed that substituent on position 20 was important for the activity of ingenane-type diterpenoids in Colo205 cells and substituent on position 3 contributed more significant biological activity of the compounds than that on position 5 in both MDA-MB-435 and Colo205 cells. Copyright © 2017 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

The diterpenoid 7-keto-sempervirol, derived from Lycium chinense, displays anthelmintic activity against both Schistosoma mansoni and Fasciola hepatica.

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Jennifer Edwards

2015-03-01

Full Text Available BACKGROUND: Two platyhelminths of biomedical and commercial significance are Schistosoma mansoni (blood fluke and Fasciola hepatica (liver fluke. These related trematodes are responsible for the chronic neglected tropical diseases schistosomiasis and fascioliasis, respectively. As no vaccine is currently available for anti-flukicidal immunoprophylaxis, current treatment is mediated by mono-chemical chemotherapy in the form of mass drug administration (MDA (praziquantel for schistosomiasis or drenching (triclabendazole for fascioliasis programmes. This overreliance on single chemotherapeutic classes has dramatically limited the number of novel chemical entities entering anthelmintic drug discovery pipelines, raising significant concerns for the future of sustainable blood and liver fluke control. METHODOLOGY/ PRINCIPLE FINDINGS: Here we demonstrate that 7-keto-sempervirol, a diterpenoid isolated from Lycium chinense, has dual anthelmintic activity against related S. mansoni and F. hepatica trematodes. Using a microtiter plate-based helminth fluorescent bioassay (HFB, this activity is specific (Therapeutic index = 4.2, when compared to HepG2 cell lines and moderately potent (LD50 = 19.1 μM against S. mansoni schistosomula cultured in vitro. This anti-schistosomula effect translates into activity against both adult male and female schistosomes cultured in vitro where 7-keto-sempervirol negatively affects motility/behaviour, surface architecture (inducing tegumental holes, tubercle swelling and spine loss/shortening, oviposition rates and egg morphology. As assessed by the HFB and microscopic phenotypic scoring matrices, 7-keto-sempervirol also effectively kills in vitro cultured F. hepatica newly excysted juveniles (NEJs, LD50 = 17.7 μM. Scanning electron microscopy (SEM evaluation of adult F. hepatica liver flukes co-cultured in vitro with 7-keto-sempervirol additionally demonstrates phenotypic abnormalities including breaches in tegumental

[Effects of steaming and baking on content of alkaloids in Aconite Lateralis Radix (Fuzi)].

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Yang, Chang-lin; Huang, Zhi-fang; Zhang, Yi-han; Liu, Yu-hong; Liu, Yun-huan; Chen, Yan; Yi, Jin-hai

2014-12-01

To study the effect of steaming and baking process on contents of alkaloids in Aconite Lateralis Radix (Fuzi), 13 alkaloids were analyzed by UPLC-MS/MS equipped with ESI ion source in MRM mode. In steaming process, the contents of diester-diterpenoid alkaloids decreased rapidly, the contents of monoester-diterpenoid alkaloids firstly increased, reached the peak at 40 min, and then deceased gradually. The contents of aconine alkaloids (mesaconine, aconine and hypaconine) increased all the time during processing, while the contents of fuziline, songorine, karacoline, salsolionl were stable or slightly decreased. In baking process, dynamic variations of alkaloids were different from that in the steaming process. Diester-diterpenoid alkaloids were degraded slightly slower than in steaming process. Monoester-diterpenoid alkaloids, aconine alkaloids and the total alkaloids had been destroyed at different degrees, their contents were significantly lower than the ones in steaming Fuzi at the same processing time. This experiment revealed the dynamic variations of alkaloids in the course of steaming and baking. Two processing methods which can both effectively remove the toxic ingredients and retain the active ingredients are simple and controllable, and are valuable for popularization and application.

In planta functions of cytochrome P450 monooxygenase genes in the phytocassane biosynthetic gene cluster on rice chromosome 2.

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Ye, Zhongfeng; Yamazaki, Kohei; Minoda, Hiromi; Miyamoto, Koji; Miyazaki, Sho; Kawaide, Hiroshi; Yajima, Arata; Nojiri, Hideaki; Yamane, Hisakazu; Okada, Kazunori

2018-06-01

In response to environmental stressors such as blast fungal infections, rice produces phytoalexins, an antimicrobial diterpenoid compound. Together with momilactones, phytocassanes are among the major diterpenoid phytoalexins. The biosynthetic genes of diterpenoid phytoalexin are organized on the chromosome in functional gene clusters, comprising diterpene cyclase, dehydrogenase, and cytochrome P450 monooxygenase genes. Their functions have been studied extensively using in vitro enzyme assay systems. Specifically, P450 genes (CYP71Z6, Z7; CYP76M5, M6, M7, M8) on rice chromosome 2 have multifunctional activities associated with ent-copalyl diphosphate-related diterpene hydrocarbons, but the in planta contribution of these genes to diterpenoid phytoalexin production remains unknown. Here, we characterized cyp71z7 T-DNA mutant and CYP76M7/M8 RNAi lines to find that potential phytoalexin intermediates accumulated in these P450-suppressed rice plants. The results suggested that in planta, CYP71Z7 is responsible for C2-hydroxylation of phytocassanes and that CYP76M7/M8 is involved in C11α-hydroxylation of 3-hydroxy-cassadiene. Based on these results, we proposed potential routes of phytocassane biosynthesis in planta.

Determination of the molecular signature of fossil conifers by experimental palaeochemotaxonomy - Part 1: The Araucariaceae family

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Lu, Y.; Hautevelle, Y.; Michels, R.

2012-08-01

Several extant species of the Araucariaceae family (one of the families of conifers) were invested for the experimental artificial maturation by confined pyrolysis, in order to realize the transformation of biomolecules to geomolecules in laboratory conditions. The experimental study of diagenetized molecular signatures of the Araucariaceae species (common, inter- and infra-generic characteristics) allow to complete our knowledge in botanical palaeochemotaxonomy. Such knowledge is relevant to the reconstitution of palaeoflora and palaeoclimatic reconstruction, archaeology and environmental studies. In this work, major carbon skeleton types of Araucariaceae are detected in the organic solvent extracts of fresh and pyrolyzed plants using gas chromatography-mass spectrometry. The results show that all species of Araucariaceae are firstly characterized by a predominance of saturated tetracyclic diterpenoids. Moreover, the Araucaria genus shows a high relative abundance of bicyclic sesquiterpenoids, particularly compounds of the cadalane-type compounds accompanied by those of eudesmane-type, bisabolane-type as well as chamazulene, pentamethyl-dihydroindenes. Diterpenoids are of the labdane-type, isopimarane, abietane-type (essentially derived from abietanoic acids) as well as isohexyl alkylaromatic hydrocarbons. Compared to the tetracyclic diterpenoids, these compounds show a relatively lower abundance, reaching trace levels in the case of saturated abietanes. Distribution of sesqui- and diterpenoids of Agathis shows some similarities to that of Araucaria, with the exception of one species, in which the tetracyclic compounds are absent and the abietane-type (essentially derived from abietanoic acids) predominant. High similarities between the Wollemia and Araucaria genera are observed. Both are characterized by some high relative abundance of tetracyclic compounds with no predominance of other specific diterpenoids.

Diterpene lactones with labdane, halimane and clerodane frameworks.

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Silva, Lúcia; Gomes, Arlindo C; Rodilla, Jesus M L

2011-04-01

The labdane, halimane and clerodane type diterpenoids are compounds that have been isolated in plants of several families. These molecules and their derivatives with a lactone group on the side chain or on the decaline system, have a great interest because of their biological properties as insect antifeedant, antiviral, cytotoxic and trypanocidal. The scope of this review is lactones diterpenoids with labdane, halimane and clerodane frameworks.

A semisynthetic diterpenoid lactone inhibits NF-κB signalling to ameliorate inflammation and airway hyperresponsiveness in a mouse asthma model

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Lim, J.C.-W.; Goh, F.-Y.; Sagineedu, S.-R.; Yong, A.C.-H.; Sidik, S.M.; Lajis, N.H.; Wong, W.S.F.; Stanslas, J.

2016-01-01

Andrographolide (AGP) and 14-deoxy-11,12-didehydroandrographolide (DDAG), two main diterpenoid constituents of Andrographis paniculata were previously shown to ameliorate asthmatic symptoms in a mouse model. However, due to inadequacies of both compounds in terms of drug-likeness, DDAG analogues were semisynthesised for assessment of their anti-asthma activity. A selected analogue, 3,19-diacetyl-14-deoxy-11,12-didehydroandrographolide (SRS27), was tested for inhibitory activity of NF-κB activation in TNF-α-induced A549 cells and was subsequently evaluated in a mouse model of ovalbumin (OVA)-induced asthma. Female BALB/c mice, 6–8 weeks old were sensitized on days 0 and 14, and challenged on days 22, 23 and 24 with OVA. Compound or vehicle (3% dimethyl sulfoxide) was administered intraperitoneally 1 h before and 11 h after each OVA aerosol challenge. On day 25, pulmonary eosinophilia, airway hyperresponsiveness, mucus hypersecretion, inflammatory cytokines such as IL-4, -5 and -13 in BAL fluid, gene expression of inflammatory mediators such as 5-LOX, E-selectin, VCAM-1, CCL5, TNF-α, AMCase, Ym2, YKL-40, Muc5ac, CCL2 and iNOS in animal lung tissues, and serum IgE were determined. SRS27 at 30 μM was found to suppress NF-κB nuclear translocation in A549 cells. In the ovalbumin-induced mouse asthma model, SRS27 at 3 mg/kg displayed a substantial decrease in pulmonary eosinophilia, BAL fluid inflammatory cytokines level, serum IgE production, mucus hypersecretion and gene expression of inflammatory mediators in lung tissues. SRS27 is the first known DDAG analogue effective in ameliorating inflammation and airway hyperresponsiveness in the ovalbumin-induced mouse asthma model. - Highlights: • SRS27 was synthesised to overcome inadequacies of its parent compound in terms of drug-likeness. • SRS27 was tested in TNF-α-induced A549 lung cells and ovalbumin (OVA)-induced mouse asthma model. • SRS27 suppressed NF-κB nuclear translocation in A549 cells. • SRS27

Andrographis paniculata extracts and major constituent diterpenoids inhibit growth of intrahepatic cholangiocarcinoma cells by inducing cell cycle arrest and apoptosis.

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Suriyo, Tawit; Pholphana, Nanthanit; Rangkadilok, Nuchanart; Thiantanawat, Apinya; Watcharasit, Piyajit; Satayavivad, Jutamaad

2014-05-01

Andrographis paniculata is an important herbal medicine widely used in several Asian countries for the treatment of various diseases due to its broad range of pharmacological activities. The present study reports that A. paniculata extracts potently inhibit the growth of liver (HepG2 and SK-Hep1) and bile duct (HuCCA-1 and RMCCA-1) cancer cells. A. paniculata extracts with different contents of major diterpenoids, including andrographolide, 14-deoxy-11,12-didehydroandrographolide, neoandrographolide, and 14-deoxyandrographolide, exhibited a different potency of growth inhibition. The ethanolic extract of A. paniculata at the first true leaf stage, which contained a high amount of 14-deoxyandrographolide but a low amount of andrographolide, showed a cytotoxic effect to cancer cells about 4 times higher than the water extract of A. paniculata at the mature leaf stage, which contained a high amount of andrographolide but a low amount of 14-deoxyandrographolide. Andrographolide, not 14-deoxy-11,12-didehydroandrographolide, neoandrographolide, or 14-deoxyandrographolide, possessed potent cytotoxic activity against the growth of liver and bile duct cancer cells. The cytotoxic effect of the water extract of A. paniculata at the mature leaf stage could be explained by the present amount of andrographolide, while the cytotoxic effect of the ethanolic extract of A. paniculata at the first true leaf stage could not. HuCCA-1 cells showed more sensitivity to A. paniculata extracts and andrographolide than RMCCA-1 cells. Furthermore, the ethanolic extract of A. paniculata at the first true leaf stage increased cell cycle arrest at the G0/G1 and G2/M phases, and induced apoptosis in both HuCCA-1 and RMCCA-1 cells. The expressions of cyclin-D1, Bcl-2, and the inactive proenzyme form of caspase-3 were reduced by the ethanolic extract of A. paniculata in the first true leaf stage treatment, while a proapoptotic protein Bax was increased. The cleavage of poly (ADP

A semisynthetic diterpenoid lactone inhibits NF-κB signalling to ameliorate inflammation and airway hyperresponsiveness in a mouse asthma model

Energy Technology Data Exchange (ETDEWEB)

Lim, J.C.-W. [Pharmacotherapeutics Unit, Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor (Malaysia); Goh, F.-Y. [Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System (Singapore); Sagineedu, S.-R. [Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor (Malaysia); Yong, A.C.-H. [Faculty of Pharmacy, Segi University, Jalan Teknologi, 47810 Petaling Jaya (Malaysia); Sidik, S.M. [Histopathology Unit, Department of Pathology, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor (Malaysia); Lajis, N.H. [Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor (Malaysia); Wong, W.S.F., E-mail: fred_wong@nuhs.edu.sg [Department of Pharmacology, Yong Loo Lin School of Medicine, National University Health System (Singapore); Immunology Program, Life Science Institute, National University of Singapore (Singapore); Stanslas, J., E-mail: rcxjs@upm.edu.my [Pharmacotherapeutics Unit, Department of Medicine, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, 43400 Serdang, Selangor (Malaysia); Laboratory of Natural Products, Institute of Bioscience, Universiti Putra Malaysia, 43400 Serdang, Selangor (Malaysia)

2016-07-01

Andrographolide (AGP) and 14-deoxy-11,12-didehydroandrographolide (DDAG), two main diterpenoid constituents of Andrographis paniculata were previously shown to ameliorate asthmatic symptoms in a mouse model. However, due to inadequacies of both compounds in terms of drug-likeness, DDAG analogues were semisynthesised for assessment of their anti-asthma activity. A selected analogue, 3,19-diacetyl-14-deoxy-11,12-didehydroandrographolide (SRS27), was tested for inhibitory activity of NF-κB activation in TNF-α-induced A549 cells and was subsequently evaluated in a mouse model of ovalbumin (OVA)-induced asthma. Female BALB/c mice, 6–8 weeks old were sensitized on days 0 and 14, and challenged on days 22, 23 and 24 with OVA. Compound or vehicle (3% dimethyl sulfoxide) was administered intraperitoneally 1 h before and 11 h after each OVA aerosol challenge. On day 25, pulmonary eosinophilia, airway hyperresponsiveness, mucus hypersecretion, inflammatory cytokines such as IL-4, -5 and -13 in BAL fluid, gene expression of inflammatory mediators such as 5-LOX, E-selectin, VCAM-1, CCL5, TNF-α, AMCase, Ym2, YKL-40, Muc5ac, CCL2 and iNOS in animal lung tissues, and serum IgE were determined. SRS27 at 30 μM was found to suppress NF-κB nuclear translocation in A549 cells. In the ovalbumin-induced mouse asthma model, SRS27 at 3 mg/kg displayed a substantial decrease in pulmonary eosinophilia, BAL fluid inflammatory cytokines level, serum IgE production, mucus hypersecretion and gene expression of inflammatory mediators in lung tissues. SRS27 is the first known DDAG analogue effective in ameliorating inflammation and airway hyperresponsiveness in the ovalbumin-induced mouse asthma model. - Highlights: • SRS27 was synthesised to overcome inadequacies of its parent compound in terms of drug-likeness. • SRS27 was tested in TNF-α-induced A549 lung cells and ovalbumin (OVA)-induced mouse asthma model. • SRS27 suppressed NF-κB nuclear translocation in A549 cells. • SRS27

In vitro evaluation of potential bitterness-masking terpenoids from the Canada goldenrod (Solidago canadensis).

Science.gov (United States)

Li, Jie; Pan, Li; Fletcher, Joshua N; Lv, Wei; Deng, Ye; Vincent, Michael A; Slack, Jay P; McCluskey, T Scott; Jia, Zhonghua; Cushman, Mark; Kinghorn, A Douglas

2014-07-25

In a screening of extracts of selected plants native to Ohio against the human bitterness receptor hTAS2R31, a chloroform-soluble extract of the aerial parts of Solidago canadensis (Canada goldenrod) was determined to have hTAS2R31 antagonistic activity and, thus, was fractionated for isolation of potential bitterness-masking agents. One new labdane diterpenoid, solidagol (1), and six known terpenoids, including two labdane diterpenoids (2 and 3), three clerodane diterpenoids (6β-angeloyloxykolavenic acid, 6β-tigloyloxykolavenic acid, and crotonic acid), and a triterpenoid (longispinogenin), were isolated. Among these compounds, 3β-acetoxycopalic acid (2) was found to be the first member of the labdane diterpene class shown to have inhibitory activity against hTAS2R31 activation (IC50 8 μM). A homology model of hTAS2R31 was constructed, and the molecular docking of 2 to this model indicated that this diterpenoid binds well to the active site of hTAS2R31, whereas this was not the case for the closely structurally related compound 3 (sempervirenic acid). The content of 2 in the chloroform-soluble portion of the methanolic extract of S. canadensis was up to 2.24 g/100 g dry weight, as determined by HPLC.

Stereochemistry Structure of Odonicin

Energy Technology Data Exchange (ETDEWEB)

Li, Bao Lin; Li, Jin; Tong, Ling [Shaanxi Normal University, Xian (China); Pan, Yuan Jiang [Zhejiang University, Hangzhou (China); Yu, Kai Bei [Academia Sinica, Chengdu (China)

2004-02-15

Ent-kaurene diterpenoids have various biological activities, such as antitumor, antibacterial, anti-HIV activities etc. The plant of the genus Isodon used in Chinese traditional medicine is a major source of compounds of this structural class. Our investigations on the bitter diterpenoids constituents of the genus Isodon led to the first isolation of odonicin (1) from the leaves and tender branches of Isodon henryi obtained from Taibai Mountain, Shaanxi Province, P. R. China

The conifer biomarkers dehydroabietic and abietic acids are widespread in Cyanobacteria

Science.gov (United States)

Costa, Maria Sofia; Rego, Adriana; Ramos, Vitor; Afonso, Tiago B.; Freitas, Sara; Preto, Marco; Lopes, Viviana; Vasconcelos, Vitor; Magalhães, Catarina; Leão, Pedro N.

2016-01-01

Terpenes, a large family of natural products with important applications, are commonly associated with plants and fungi. The diterpenoids dehydroabietic and abietic acids are defense metabolites abundant in resin, and are used as biomarkers for conifer plants. We report here for the first time that the two diterpenoid acids are produced by members of several genera of cyanobacteria. Dehydroabietic acid was isolated from two cyanobacterial strains and its identity was confirmed spectroscopically. One or both of the diterpenoids were detected in the cells of phylogenetically diverse cyanobacteria belonging to four cyanobacterial ‘botanical orders’, from marine, estuarine and inland environments. Dehydroabietic acid was additionally found in culture supernatants. We investigated the natural role of the two resin acids in cyanobacteria using ecologically-relevant bioassays and found that the compounds inhibited the growth of a small coccoid cyanobacterium. The unexpected discovery of dehydroabietic and abietic acids in a wide range of cyanobacteria has implications for their use as plant biomarkers. PMID:26996104

Triptolide, a diterpenoid triepoxide, induces antitumor proliferation via activation of c-Jun NH2-terminal kinase 1 by decreasing phosphatidylinositol 3-kinase activity in human tumor cells

International Nuclear Information System (INIS)

Miyata, Yoshiki; Sato, Takashi; Ito, Akira

2005-01-01

Triptolide, a diterpenoid triepoxide extracted from the Chinese herb Tripterygium wilfordii Hook f., exerts antitumorigenic actions against several tumor cells, but the intracellular target signal molecule(s) for this antitumorigenesis activity of triptolide remains to be identified. In the present study, we demonstrated that triptolide, in a dose-dependent manner, inhibited the proliferation of human fibrosarcoma HT-1080, human squamous carcinoma SAS, and human uterine cervical carcinoma SKG-II cells. In addition, triptolide was found to decrease phosphatidylinositol 3-kinase (PI3K) activity. A PI3K inhibitor, LY-294002, mimicked the triptolide-induced antiproliferative activity in HT-1080, SAS, and SKG-II cells. There was no change in the activity of Akt or protein kinase C (PKC), both of which are downstream effectors in the PI3K pathway. Furthermore, the phosphorylation of Ras, Raf, and mitogen-activated protein/extracellular signal-regulated kinase 1/2 was not modified in HT-1080 cells treated with triptolide. However, the phosphorylation of c-Jun NH 2 -terminal kinase 1 (JNK1) was found to increase in both triptolide- and LY-294002-treated cells. Furthermore, the triptolide-induced inhibition of HT-1080 cell proliferation was not observed by JNK1 siRNA-treatment. These results provide novel evidence that PI3K is a crucial target molecule in the antitumorigenic action of triptolide. They further suggest a possible triptolide-induced inhibitory signal for tumor cell proliferation that is initiated by the decrease in PI3K activity, which in turn leads to the augmentation of JNK1 phosphorylation via the Akt and/or PKC-independent pathway(s). Moreover, it is likely that the activation of JNK1 is required for the triptolide-induced inhibition of tumor proliferation

Chemical constituents of soft coral Sarcophyton infundibuliforme from the South China Sea

KAUST Repository

Wang, Chang Yun; Chen, An Na; Shao, Chang Lun; Li, Liang; Xu, Ying; Qian, Pei Yuan

2011-01-01

Chemical investigation on soft coral Sarcophyton infundibuliforme collected from the South China Sea led to the isolation and identification of 14 secondary metabolites, including ten cembrene diterpenoids (1-10), one α-tocopheryl quinone derivative (11), one prostaglandin (12), one lipid (13) and one carotinoid (14). Their structures were determined by extensive analysis of their spectroscopic data. All of these metabolites were isolated from this species for the first time. Diterpenoids 1, 2, 7 and 10 showed potent antifouling activity against the larval settlement of barnacle Balanus amphitrite. © 2011 Elsevier Ltd.

Chemical constituents of soft coral Sarcophyton infundibuliforme from the South China Sea

KAUST Repository

Wang, Chang Yun

2011-08-01

Chemical investigation on soft coral Sarcophyton infundibuliforme collected from the South China Sea led to the isolation and identification of 14 secondary metabolites, including ten cembrene diterpenoids (1-10), one α-tocopheryl quinone derivative (11), one prostaglandin (12), one lipid (13) and one carotinoid (14). Their structures were determined by extensive analysis of their spectroscopic data. All of these metabolites were isolated from this species for the first time. Diterpenoids 1, 2, 7 and 10 showed potent antifouling activity against the larval settlement of barnacle Balanus amphitrite. © 2011 Elsevier Ltd.

Liquid shoot culture of Salvia officinalis L. for micropropagation and production of antioxidant compounds; effect of triacontanol

Directory of Open Access Journals (Sweden)

Izabela Grzegorczyk

2011-01-01

Full Text Available Liquid shoot culture of Salvia officinalis L. in MS medium containing IAA (0.1 mg l-1 and BAP (0.45 mg l-1 was developed and evaluated in relation to shoot multiplication and antioxidant compound (carnosic acid, carnosol and rosmarinic acid accumulation. In the liquid medium, on average, 3 new shoots per explant (shoot tip were obtained within 3 weeks. The shoots produced 8.2±0.02 mg of diterpenoids and 31.2±0.29 mg of rosmarinic acid per gram of dry weight. Shoot proliferation and diterpenoid content increased when triacontanol (5, 10 or 20 pg l-1 was added to the liquid medium. In optimum conditions (at 20 pg l-1 TRIA almost 7 shoots were formed per explant after 3 weeks. An increase in diterpenoid production (expressed as the sum of carnosol and carnosic acid ranged from 30% to 50% and dependended on triacontanol concentration tested. The level of diterpenoids in triacontanol-treated shoots was similar to the content of compounds in commercial herbal product (dried leaves of S. officinalis (10-12 mg g-1 dry wt. Triacontanol did not increase rosmarinic acid production, but the content of the phenolic as compound in shoots grown in liquid culture (31 mg g-1 dry wt was even 24 times higher compared to samples of dried leaves of S. officinalis plants. We also demonstrated that the highest amounts of CA, Car and RA were accumulated in young, top parts of sage shoots. This observation could be useful for improving the selection of material for the extraction of natural antioxidants from S. officinalis.

I. Structural studies of termite defense secretions. II. Structural studies of natural products of marine nudibranchs. [Kempene, tridachione

Energy Technology Data Exchange (ETDEWEB)

Solheim, B.A.

1977-12-01

Three families of termites have the ability to produce a sticky secretion that envelopes and immobilizes the enemy. In the family Termitidae the secretion contains the diterpenoid hydrocarbons, kempene I and kempene II. The molecular structure of kempene II from the termite, Nasutitermes kempae, is described in detail. Another species of termite, Cubitermes umbratus, contained the diterpenoid hydrocarbon biflora-4,10-19,15-triene in the secretion and this compound is described. Studies were also conducted on the mucous secretion of the pedal gland of the marine nudibranch, Tidachiella diomedea. Tridachione, a substituted ..gamma..-pyrone, was isolated in the pure state and its molecular structure is described in detail. (HLW)

ANTIMICROBIAL DITERPENOID ALKALOIDS FROM ...

African Journals Online (AJOL)

a

Extraction, isolation and characterization. Air-dried ... aqueous phase was made alkaline with aqueous NH3 and extracted several times with CHCl3. The CHCl3 ... Half of this solid was chromatographed on Sephadex (LH 20) .... Pharmacology (LMP) of the University of Yaoundé I. The strains were activated at 37 °C for 24.

Terpenoid composition and botanical affinity of Cretaceous resins from India and Myanmar

Energy Technology Data Exchange (ETDEWEB)

Dutta, Suryendu; Mallick, Monalisa [Department of Earth Sciences, Indian Institute of Technology-Bombay (India); Kumar, Kishor [Wadia Institute of Himalayan Geology, Uttarakhand (India); Mann, Ulrich [Forschungzentrum Juelich (Germany). Institut fuer Chemie und Dynamik der Geosphaere; Greenwood, Paul F. [John De Laeter Mass Spectrometry and WA Biogeochemistry Centres (M090), University of Western Australia, Crawley (Australia)

2011-01-01

Fossil resins from the Cretaceous sediments of Meghalaya, India and Kachin, Myanmar (Burma) were analysed using Curie point pyrolysis-gas chromatography-mass spectrometry and thermochemolysis gas chromatography-mass spectrometry to help elucidate their botanical source. The major pyrolysis products and methyl-esterified thermochemolysis products of both the resins were abietane and labdane type diterpenoids with minor amount of sesquiterpenoids. The thermochemolysis products also included methyl-16,17-dinor callitrisate, methyl-16,17-dinor dehydroabietate and methyl-8-pimaren-18-oate - the latter two from just the Myanmarese resin. The exclusive presence of both labdane and abietane diterpenoids and the lack of phenolic terpenoids may suggest that the studied Cretaceous resins were derived from Pinaceae (pine family) conifers. (author)

New Lobane and Cembrane Diterpenes from Two Comorian Soft Corals

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Maurice Aknin

2010-02-01

Full Text Available Preliminary biological investigation of a collection of Comorian soft corals resulted in the selection of two specimens, one of Sarcophyton and the other of Lobophytum, on the basis of their toxicity on larvae of the brine shrimp (Artemia salina and inhibition of acetylcholinesterase, respectively. Bioassay-guided fractionations provided a known antitumor promoter cembrane diterpenoid, (+-sarcophytol-A (1, along with a new lobane diterpenoid, carbomethoxyfuscol (2, from Sarcophyton sp., and a new cembranoid, crassumolide E (3, from Lobophytum sp. The structures of compounds 1–3 were determined by spectroscopic analysis and by comparison of the spectral data with previously reported values. The cembranoid 3 was found to exhibit a moderate inhibitory effect on acetylcholinesterase.

Phytochemistry and pharmacology of the genus Leonurus: The herb to benefit the mothers and more.

Science.gov (United States)

Zhang, Rui-Han; Liu, Zhi-Ke; Yang, Da-Song; Zhang, Xing-Jie; Sun, Han-Dong; Xiao, Wei-Lie

2018-03-01

Plants belonging to the genus Leonurus, also named motherwort, are traditionally used for anti-gynecological disorder in East Asia, and for sedative in Europe. Chemical investigation of the genus Leonurus not only enriched the natural products library, but also enlarged the pharmacological application of this traditional herb. In this review, we systematically summarized the structures of 259 compounds isolated from the genus Leonurus, featured with 147 labdane diterpenoids. The reported bioactivity studies up to 2017 are presented in the second part, with the main focus on the isolated compounds and also concerning the extracts. In addition to the traditional uterine contraction and sedative activity, recently the cardiovascular protection effect of leonurine has drawn most attention. Other than that, neuroprotection, anti-inflammation, anti-cancer, anti-platelet aggregation and many other activities have been assigned to various compounds from the genus Leonurus. Among 70 bioactivity references cited in this review, 57% of them were concentrated on two alkaloids (leonurine and stachydrine), whereas only 20% are about the 147 diterpenoids. Anti-inflammation is the major bioactivity discovered so far for the labdane diterpenoids from the genus Leonurus, whose further therapeutic potential still remains for exploration. Copyright © 2017 Elsevier Ltd. All rights reserved.

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African Journals Online (AJOL)

hope&shola

significantly enhanced when Taxus chinensis cell cultures were treated with methyl jasmonate. (MJA) or 2 ... the universal diterpenoid precursor geranylgeranyl ... bifurcations occurring in the taxoid synthetic pathway .... We developed.

Terpenoids for medicine

NARCIS (Netherlands)

Fischedick, Justin

2013-01-01

This thesis is concerns research on monoterpenoids, sesquiterpenoids, and diterpenoids with medicinal properties. Terpenoids from commond herbs as well as Cannabis sativa, Inula britannica, Tanacetum parthenium, and Salvia officinalis were investigated

Prophylactic effects of triptolide on colon cancer development in ...

African Journals Online (AJOL)

tumor development in an azoxymethane (AOM)/dextran sulfate sodium (DSS) mouse model of colon ... pancreas, the expression levels of peroxisome ... diterpenoid molecule [16-18]. Biological investigations of triptolide have revealed its.

Ogunlana et al., Afr J Tradit Complement Altern Med. (2013) 10(6 ...

African Journals Online (AJOL)

AJTCAM

... the plant shows that it contains saponins, alkaloids, flavonoids, triterpenoids, diterpenoids, .... The histopathological study of kidney, liver, spleen and heart removed from the experimental ..... In renal failure, there is an increase in metabolic.

3-Deoxyaconitine from the root of Aconitum Carmichaeli Debx.

Directory of Open Access Journals (Sweden)

Feng Gao

2010-06-01

Full Text Available The title compound (systematic name: 8β-acetoxy-14α-benzoyloxy-N-ethyl-13β,15α-dihydroxy-1α,6α,16β-trimethoxy-4β-methoxymethyleneaconitane, C34H47NO10, is a typical aconitine-type C19-diterpenoid alkaloid, and was isolated from the roots of the Aconitum carmichaeli Debx. The molecule has an aconitine carbon skeleton with four six-membered rings and two five-membered rings, whose geometry is similar to these observed in other C19-diterpenoid alkaloids; both of five-membered rings have the envelope configurations and the six-membered N-containing heterocyclic ring displays a chair conformation. Intramolecular O—H...O hydrogen bonding occurs. Weak intermolecular C—H...O hydrogen bonding is observed in the crystal structure.

Transcription profile data of phorbol esters biosynthetic genes during developmental stages in Jatropha curcas.

Science.gov (United States)

Jadid, Nurul; Mardika, Rizal Kharisma; Purwani, Kristanti Indah; Permatasari, Erlyta Vivi; Prasetyowati, Indah; Irawan, Mohammad Isa

2018-06-01

Jatropha curcas is currently known as an alternative source for biodiesel production. Beside its high free fatty acid content, J. curcas also contains typical diterpenoid-toxic compounds of Euphorbiaceae plant namely phorbol esters. This article present the transcription profile data of genes involved in the biosynthesis of phorbol esters at different developmental stages of leaves, fruit, and seed in Jatropha curcas . Transcriptional profiles were analyzed using reverse transcription-polymerase chain reaction (RT-PCR). We used two genes including GGPPS (Geranylgeranyl diphospate synthase), which is responsible for the formation of common diterpenoid precursor (GGPP) and CS (Casbene Synthase), which functions in the synthesis of casbene. Meanwhile, J. curcas Actin ( ACT ) was used as internal standard. We demonstrated dynamic of GGPPS and CS expression among different stage of development of leaves, fruit and seed in Jatropha .

The terpene synthase gene family in Tripterygium wilfordii harbors a labdane-type diterpene synthase among the monoterpene synthase TPS-b subfamily

DEFF Research Database (Denmark)

Hansen, Nikolaj Lervad; Heskes, Allison Maree; Hamberger, Britta

2017-01-01

Tripterygium wilfordii (Celastraceae) is a medicinal plant with anti-inflammatory and immunosuppressive properties. Identification of a vast array of unusual sesquiterpenoids, diterpenoids and triterpenoids in T. wilfordii has spurred investigations of their pharmacological properties. The tri-ep...

Short Communication Radical Scavenging Activity and Preliminary ...

African Journals Online (AJOL)

Bheema

It is distributed in some regions of Ethiopia such as Tigray, Gondar, Gojam,. Kefa and Shewa ..... Diterpenoids and flavonoids from the fruits of Vitex agnus-castus and antioxidant activity of the fruit extracts and their constituents. Phytotherapy ...

Comparative effectiveness and safety of xiyanping with ribavirin for ...

African Journals Online (AJOL)

Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, ... Methods: Searches included PubMed, Embase, Medline, Cochrane Library, ... Index Medicus, JournalSeek, Journal Citation Reports/Science Edition, ... principle andrographolide, which is a primary labdane diterpenoid. .... Zhaoqing, (2015).

Ent-Abietanoids Isolated from Isodon serra

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Jun Wan

2017-02-01

Full Text Available Four new ent-abietane diterpenoids, along with four known ones were isolated from the aerial parts of Isodon serra, a traditional Chinese folk medicine. The new diterpenoids were named as serrin K (1, xerophilusin XVII (2, and enanderianins Q and R (3 and 4, while the known ones were identified as rubescansin J (5, (3α,14β-3,18-[(1-methylethane-1,1-diyldioxy]-ent-abieta-7,15(17-diene-14,16-diol (6, xerophilusin XIV (7, and enanderianin P (8, respectively. Their structures were elucidated by extensive spectroscopic analysis and comparison with the literature. Compound 1 showed remarkable inhibitory activity towards NO production in LPS-stimulated RAW264.7 cells (IC50 = 1.8 μM and weak cytotoxicity towards five human tumor cell lines (HL-60, SMMC-7721, A-549, MCF-7, SW480.

Identification, Quantification, and Sensory Characterization of Steviol Glycosides from Differently Processed Stevia rebaudiana Commercial Extracts

NARCIS (Netherlands)

Espinoza, M.I.; Vincken, J.P.; Sanders, M.G.; Castro, C.; Stieger, M.A.; Agosin, E.

2014-01-01

Stevia rebaudiana is known for its sweet-tasting ent-kaurene diterpenoid glycosides. Several manufacturing strategies are currently employed to obtain Stevia sweeteners with the lowest possible off-flavors. The chemical composition of four commercial S. rebaudiana extracts, obtained by different

Expanding the landscape of diterpene structural diversity by stereochemically controlled combinatorial biosynthesis

DEFF Research Database (Denmark)

Andersen-Ranberg, Johan; Kongstad, Kenneth Thermann; Nielsen, Morten Thrane

2016-01-01

Plant derived diterpenoids are relevant as pharmaceuticals, food additives and fragrances, yet a broader industrial utilization of these bioproducts is limited due to their low natural abundance and high structural complexity. Mimicking the modularity of diterpene biosynthesis in plants, we const...

Chemosystematics and diagenesis of terpenoids in fossil conifer species and sediment from the Eocene Zeitz formation, Saxony, Germany

Science.gov (United States)

Otto, Angelika; Simoneit, Bernd R. T.

2001-10-01

The biomarker contents of three fossil conifer species (Athrotaxis couttsiae, Taxodium balticum, Pinus palaeostrobus) and the clay sediment from the Eocene Zeitz formation, Germany, have been analyzed by gas chromatography-mass spectrometry. Triterpenoids of the oleanane, ursane and lupane series and aliphatic wax lipids are the major compounds in the total extracts of the sediment indicating a major angiosperm input. In contrast, diterpenoids (abietanes, phenolic abietanes, pimaranes, isopimaranes, kauranes, phyllocladanes, totaranes) and lignin degradation products are predominant in the conifer fossil extracts. Polar diterpenoids (ferruginol and derivatives, dehydroabietic acid) are preserved as major compounds in the conifers, accompained by saturated and aromatic diterpenoid products. The extracts of the fossil conifer species show characteristic biomarker patterns and contain terpenoids of chemosystematic value. The terpenoid composition of the fossil conifers is similar to that of related modern species. Phenolic abietanes (ferruginol, 6,7-dehydroferruginol, hydroxyferruginols, sugiol) which are known from modern species of the Cupressaceae and Podocarpaceae are the major terpenoids in shoots of Athrotaxis couttsiae and a cone of Taxodium balticum (both Cupressaceae). Sesquiterpenoids characteristic for Cupressaceae (cuparene, α-cedrene) are also present in Athrotaxis. Abietane-type acids (dehydroabietic acid, abietic acid) and saturated abietanes [fichtelite, 13α(H)-fichtelite] predominate in the extracts of a Pinus palaeostrobus cone and phenolic abietanes are not detectable. A diagenetic pathway for the degradation of abietic acid is proposed based on the presence of abietane-type acids and a series of their presumed degradation products in the Pinus cone. The formation of diagenetic products from the phenolic abietanes is also discussed.

Journal of Earth System Science | Indian Academy of Sciences

Indian Academy of Sciences (India)

Dihydro-ar-curcumene, cadalene and ionene form the assemblage of sesquiterpenoids which are indicative of higher plant input. Aromatic diterpenoid fraction comprises of simonellite and retene. These compounds are also indicative of higher plants, particularly conifer source which had been a predominant flora during ...

Diterpenoids and phenolics from pseudopanax simplex

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JOHN W. VAN KLINK

2006-02-01

Full Text Available An ethanolic extract of Pseudopanax simplex yielded kaempferol-3,7-di-O-rhamnopyranoside, chlorogenic acid, maltol glucoside, ent-kaur-16-en-18-acid, and 4R,5S,9R,10S,13S-ent-pimara-7,15-dien-19-oic acid. Full NMR data for the last compound are reported for the first time.

TGF-Beta Antibody for Prostate Cancer: Role of ERK

Science.gov (United States)

2012-07-01

flavonoid in soy [84, 85] Long Dan Tan A herbal medicines for chronic liver disease [44] Andrograpgolide A diterpenoid lactone from a...EGCG A natural product of tea extracts [97, 98] Genistein An active flavonoid in soy [88, 89, 96] Lycopene A natural product of tomato

Taxol synthesis | Guo | African Journal of Biotechnology

African Journals Online (AJOL)

Being a complex diterpenoid, the potent anticancer drug, Taxol, requires complicated steps for its biosynthesis. In the present article, recent advances on Taxol biosynthesis pathway are reviewed, including many recently reported genes that regulate Taxol biosynthesis. To meet the urgent need of clinic and scientific ...

Synthesis of ()-albrassitriol and ()-6-epi-albrassitriol from (+)-larixol

NARCIS (Netherlands)

Vlad, P.F.; Ciocarlan, A.; Coltsa, M.; Edu, C.; Biriiac, A.; Barba, A.; Deleanu, C.; Nicolescu, A.; Ambrosio, D' M.; Groot, de Æ.

2013-01-01

A novel synthesis of natural drimanic compounds, ()-albrassitriol (2) and ()-6-epi-albrassitriol (3), has been carried out starting from an easily available labdane diterpenoid, (+)-larixol (1). In a two-step procedure, (+)-larixol (1) was converted into 14,15-bisnorlab-7-ene-6,13-dione (9), which

The effect of triacontanol on shoot multiplication and production of antioxidant compounds in shoot cultures of Salvia officinalis L.

Directory of Open Access Journals (Sweden)

Izabela Grzegorczyk

2011-01-01

Full Text Available This report describes the effect of triacontanol on shoot multiplication and production of antioxidant compounds (carnosic acid, carnosol and rosmarinic acid in S. officinalis cultures grown on MS basal medium (agar solidified medium supplemented with 0.1 mg l-1 IAA, 0.45 mg l-1 BAP. It was found that shoot proliferation significantly increased when triacontanol at concentrations of 5, 10 or 20 µg l-1 was added to the medium. HPLC analysis of acetone and methanolic extracts of sage shoots showed that the production of diterpenoids, carnosic acid/carnosol ratio, as well as, contents of rosmarinic acid were also affected by the treatment with triacontanol. The highest stimulation effect of triacontanol was observed on the production of carnosol, where the treatment with 20 µg l l-1 increased the content of this diterpenoid 4.5-fold compared to that in the control (sage shoots growing on MS basal medium, only.

In vitro cultures of Salvia officinalis L. as a source of antioxidant compounds

Directory of Open Access Journals (Sweden)

Izabela Grzegorczyk

2011-01-01

Full Text Available The concentrations of carnosic acid, carnosol and rosmarinic acid in different materials from differentiated (multiple shoot cultures and regenerated plants and undifferentiated (callus and cell suspension in vitro cultures of Salvia officinalis were determined by HPLC. The results suggested that diterpenoid (carnosic acid and carnosol production is closely related to shoot differentiation. The highest diterpenoid yield (11.4 mg g-1 for carnosic acid and 1.1 mg g-1 for carnosol was achieved in shoots of 10-week-old micropropagated plants. The levels were comparable to those found in shoots of naturally growing plants. Undifferentiated callus and cell suspension cultures produced only very low amounts of carnosol (ca. 0.05 mg g-1 of dry weight. In contrast, content of rosmarinic acid in callus and suspension cultures as well as shoots growing in vitro and in vivo was similar and ranged between 11.2 and 18.6 mg g-1 of dry weight.

Molecular fossils in Cretaceous condensate from western India

Science.gov (United States)

Bhattacharya, Sharmila; Dutta, Suryendu; Dutta, Ratul

2014-06-01

The present study reports the biomarker distribution of condensate belonging to the early Cretaceous time frame using gas chromatography-mass spectrometry (GC-MS). The early Cretaceous palaeoenvironment was inscribed into these molecular fossils which reflected the source and conditions of deposition of the condensate. The saturate fraction of the condensate is characterized by normal alkanes ranging from n-C9 to n-C29 (CPI-1.13), cycloalkanes and C14 and C15 sesquiterpanes. The aromatic fraction comprises of naphthalene, phenanthrene, their methylated derivatives and cyclohexylbenzenes. Isohexylalkylnaphthalenes, a product of rearrangement process of terpenoids, is detected in the condensate. Several aromatic sesquiterpenoids and diterpenoids have been recorded. Dihydro- ar-curcumene, cadalene and ionene form the assemblage of sesquiterpenoids which are indicative of higher plant input. Aromatic diterpenoid fraction comprises of simonellite and retene. These compounds are also indicative of higher plants, particularly conifer source which had been a predominant flora during the Cretaceous time.

Chemical Constituents and Biological Properties of the Marine Soft ...

African Journals Online (AJOL)

methyldihydroxy steroid from the soft coral. Nephthea chabroli in Indian coast. Journal of the Indian Chemical Society, 1994; 71(6-8):. 523-525. 10. Anjaneyulu ASR, Prakash CVS. New sesqui and diterpenoids from the soft coral Nephthea chabroli of Indian Coast. Indian Journal of. Chemistry, Section B: Organic Chemistry.

Maoecrystal V: A formidable synthetic challenge

Indian Academy of Sciences (India)

Maoecrystal V; synthesis; Diels–Alder reaction; dearomatization. 1. Introduction. There is continuing search for ... of ailments, is known to be a rich source of biologi- cally active diterpenoids.5 Maoecrystal V (figure 1) ... ever, only two groups have succeeded in the synthesis of maoecrystal V since its isolation a decade ago.

Effect of Xylopic Acid on Paclitaxel-induced Neuropathic pain in rats ...

African Journals Online (AJOL)

Xylopic acid, a diterpenoid isolated from the fruits of Xylopia aethiopica has demonstrated analge-sic properties in acute pain models. It was therefore evaluated for its analgesic properties in paclitaxel-induced neuropathic pain, a type of pain difficult to treat clinically. Neuropathic pain was induced in rats by injecting 2 mg ...

Author Details

African Journals Online (AJOL)

Obikeze, KC. Vol 61 (2008) - Articles Characterization and Cardiovascular Effects of (13S)-9α,13α-epoxylabda-6β(19),15(14)diol Dilactone, a Diterpenoid Isolated from Leonotis leonurus. Abstract PDF. ISSN: 0379-4350. AJOL African Journals Online. HOW TO USE AJOL... for Researchers · for Librarians · for Authors ...

Characterization and evolutionary analysis of ent-kaurene synthase like genes from the wild rice species Oryza rufipogon.

Science.gov (United States)

Toyomasu, Tomonobu; Miyamoto, Koji; Shenton, Matthew R; Sakai, Arisa; Sugawara, Chizu; Horie, Kiyotaka; Kawaide, Hiroshi; Hasegawa, Morifumi; Chuba, Masaru; Mitsuhashi, Wataru; Yamane, Hisakazu; Kurata, Nori; Okada, Kazunori

2016-11-18

Cultivated rice (Oryza sativa) possesses various labdane-related diterpene synthase genes, homologs of ent-copalyl diphosphate synthase (CPS) and ent-kaurene synthase (KS) that are responsible for the biosynthesis of phytohormone gibberellins. The CPS homologs and KS like (KSL) homologs successively converted geranylgeranyl diphosphate to cyclic diterpene hydrocarbons via ent-copalyl diphosphate or syn-copalyl diphosphate in O. sativa. Consequently, a variety of labdane-related diterpenoids, including phytoalexin phytocassanes, momilactones and oryzalexins, have been identified from cultivated rice. Our previous report indicated that the biosynthesis of phytocassanes and momilactones is conserved in Oryza rufipogon, the progenitor of Asian cultivated rice. Moreover, their biosynthetic gene clusters, containing OsCPS2 and OsKSL7 for phytocassane biosynthesis and OsCPS4 and OsKSL4 for momilactone biosynthesis, are also present in the O. rufipogon genome. We herein characterized O. rufipogon homologs of OsKSL5, OsKSL6, OsKSL8 responsible for oryzalexin S biosynthesis, and OsKSL10 responsible for oryzalexins A-F biosynthesis, to obtain more evolutionary insight into diterpenoid biosynthesis in O. sativa. Our phytoalexin analyses showed that no accumulation of oryzalexins was detected in extracts from O. rufipogon leaf blades. In vitro functional analyses indicated that unlike OsKSL10, O. rufipogon KSL10 functions as an ent-miltiradiene synthase, which explains the lack of accumulation of oryzalexins A-F in O. rufipogon. The different functions of KSL5 and KSL8 in O. sativa japonica to those in indica are conserved in each type of O. rufipogon, while KSL6 functions (ent-isokaurene synthases) are well conserved. Our study suggests that O. sativa japonica has evolved distinct specialized diterpenoid metabolism, including the biosynthesis of oryzalexins. Copyright © 2016 Elsevier Inc. All rights reserved.

Antifouling Activity of Secondary Metabolites Isolated from Chinese Marine Organisms

KAUST Repository

Li, Yong Xin

2013-04-25

Biofouling results in tremendous economic losses to maritime industries around the world. A recent global ban on the use of organotin compounds as antifouling agents has further raised demand for safe and effective antifouling compounds. In this study, 49 secondary metabolites, including diterpenoids, steroids, and polyketides, were isolated from soft corals, gorgonians, brown algae, and fungi collected along the coast of China, and their antifouling activity was tested against cyprids of the barnacle Balanus (Amphibalanus) amphitrite. Twenty of the compounds were found to inhibit larval settlement significantly at a concentration of 25 μg ml-1. Two briarane diterpenoids, juncin O (2) and juncenolide H (3), were the most promising non-toxic antilarval settlement candidates, with EC50 values less than 0.13 μg ml-1 and a safety ratio (LC50/EC50) higher than 400. A preliminary structure-activity relationships study indicated that both furanon and furan moieties are important for antifouling activity. Intriguingly, the presence of hydroxyls enhanced their antisettlement activity. © 2013 Springer Science+Business Media New York.

Characterization of ent-kaurene synthase and kaurene oxidase involved in gibberellin biosynthesis from Scoparia dulcis.

Science.gov (United States)

Yamamura, Yoshimi; Taguchi, Yukari; Ichitani, Kei; Umebara, Io; Ohshita, Ayako; Kurosaki, Fumiya; Lee, Jung-Bum

2018-03-01

Gibberellins (GAs) are ubiquitous diterpenoids in higher plants, whereas some higher plants produce unique species-specific diterpenoids. In GA biosynthesis, ent-kaurene synthase (KS) and ent-kaurene oxidase (KO) are key players which catalyze early step(s) of the cyclization and oxidation reactions. We have studied the functional characterization of gene products of a KS (SdKS) and two KOs (SdKO1 and SdKO2) involved in GA biosynthesis in Scoparia dulcis. Using an in vivo heterologous expression system of Escherichia coli, we found that SdKS catalyzed a cyclization reaction from ent-CPP to ent-kaurene and that the SdKOs oxidized ent-kaurene to ent-kaurenoic acid after modification of the N-terminal region for adaptation to the E. coli expression system. The real-time PCR results showed that the SdKS, SdKO1 and SdKO2 genes were mainly expressed in the root and lateral root systems, which are elongating tissues. Based on these results, we suggest that these three genes may be responsible for the metabolism of GAs in S. dulcis.

Chemical constituents of marine mangrove-derived endophytic fungus Alternaria tenuissima EN-192

Science.gov (United States)

Sun, Hong; Gao, Shushan; Li, Xiaoming; Li, Chunshun; Wang, Bingui

2013-03-01

A chemical investigation of the ethyl acetate extract of the fermentation broth of Alternaria tenuissima EN-192, an endophytic fungus obtained from the stems of the marine mangrove plant Rhizophora stylosa, resulted in the isolation of nine known secondary metabolites, including four indole-diterpenoids: penijanthine A ( 1), paspaline ( 2), paspalinine ( 3), and penitrem A ( 4); three tricycloalternarene derivatives: tricycloalternarene 3a ( 5), tricycloalternarene 1b ( 6), and tricycloalternarene 2b ( 7); and two alternariol congeners: djalonensone ( 8) and alternariol ( 9). The chemical structures of these metabolites were characterized through a combination of detailed spectroscopic analyses and their comparison with reports from the literature. The inhibitory activities of each isolated compound against four bacteria were evaluated and compounds 5 and 8 displayed moderate activity against the aquaculture pathogenic bacterium Vibrio anguillarum, with inhibition zone diameters of 8 and 9 mm, respectively, at 100 μg/disk. To the best of our knowledge, this is the first report on the secondary metabolites of mangrove-derived A lternaria tenuissima and also the first report of the isolation of indole-diterpenoids from fungal genus A lternaria.

Inhibitory Effect of Inflexinol on Nitric Oxide Generation and iNOS Expression via Inhibition of NF-κB Activation

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Jae Woong Lee

2007-01-01

Full Text Available Inflexinol, an ent-kaurane diterpenoid, was isolated from the leaves of Isodon excisus. Many diterpenoids isolated from the genus Isodon (Labiatae have antitumor and antiinflammatory activities. We investigated the antiinflammatory effect of inflexinol in RAW 264.7 cells and astrocytes. As a result, we found that inflexinol (1, 5, 10 μM suppressed the expression of inducible nitric oxide synthase (iNOS and cyclooxygenase-2 (COX-2 as well as the production of nitric oxide (NO in LPS-stimulated RAW 264.7 cells and astrocytes. Consistent with the inhibitory effect on iNOS and COX-2 expression, inflexinol also inhibited transcriptional and DNA binding activity of NF-κB via inhibition of IκB degradation as well as p50 and p65 translocation into nucleus. These results suggest that inflexinol inhibits iNOS and COX-2 expression through inhibition of NF-κB activation, thereby inhibits generation of inflammatory mediators in RAW 264.7 cells and astrocytes, and may be useful for treatment of inflammatory diseases.

Antifouling Activity of Secondary Metabolites Isolated from Chinese Marine Organisms

KAUST Repository

Li, Yong Xin; Wu, Hui Xian; Xu, Ying; Shao, Chang Lun; Wang, Chang Yun; Qian, Pei Yuan

2013-01-01

Biofouling results in tremendous economic losses to maritime industries around the world. A recent global ban on the use of organotin compounds as antifouling agents has further raised demand for safe and effective antifouling compounds. In this study, 49 secondary metabolites, including diterpenoids, steroids, and polyketides, were isolated from soft corals, gorgonians, brown algae, and fungi collected along the coast of China, and their antifouling activity was tested against cyprids of the barnacle Balanus (Amphibalanus) amphitrite. Twenty of the compounds were found to inhibit larval settlement significantly at a concentration of 25 μg ml-1. Two briarane diterpenoids, juncin O (2) and juncenolide H (3), were the most promising non-toxic antilarval settlement candidates, with EC50 values less than 0.13 μg ml-1 and a safety ratio (LC50/EC50) higher than 400. A preliminary structure-activity relationships study indicated that both furanon and furan moieties are important for antifouling activity. Intriguingly, the presence of hydroxyls enhanced their antisettlement activity. © 2013 Springer Science+Business Media New York.

Indole-diterpenes and ergot alkaloids in Cynodon dactylon (Bermuda grass) infected with Claviceps cynodontis from an outbreak of tremors in cattle.

Science.gov (United States)

Uhlig, Silvio; Botha, Christo J; Vrålstad, Trude; Rolén, Elin; Miles, Christopher O

2009-12-09

Tremorgenic syndromes in mammals are commonly associated with indole-diterpenoid alkaloids of fungal origin. Cattle are sometimes affected by tremors (also called "staggers") when they graze on toxic grass pastures, and Bermuda grass ( Cynodon dactylon , kweek) has been known to be associated with tremors for several decades. This study reports the identification of paspalitrems and paspaline-like indole-diterpenes in the seedheads of Claviceps cynodontis -infected Bermuda grass collected from a pasture that had caused a staggers syndrome in cattle in South Africa and thereby links the condition to specific mycotoxins. The highest concentration (about 150 mg/kg) was found for paspalitrem B. Ergonovine and ergine (lysergic acid amide), together with their C-8 epimers, were found to co-occur with the indole-diterpenes at concentrations of about 10 microg/kg. The indole-diterpene profile of the extract from the ergotized Bermuda grass was similar to that of Claviceps paspali sclerotia. However, the C. paspali sclerotia contained in addition agroclavine and elymoclavine. This is the first study linking tremors associated with grazing of Bermuda grass to specific tremorgenic indole-diterpenoid mycotoxins.

ISOLATION OF ENT-KAUR-16-EN-19-OIC AND ENT-TRACHILOBAN-19-OIC ACIDS FROM THE SUNFLOWER HELIANTHUS ANNUUS L.DRY WASTE

Directory of Open Access Journals (Sweden)

Nicon Ungur

2008-12-01

Full Text Available A relatively simple method for isolation of the mixture of ent-kaur-16-en-19-oic (1 and ent-trachiloban-19-oic (2 acids from dry waste of sunflower processing has been elaborated, and it has been shown that the waste can serve as an accessible source of ent-kauranic and ent-trachilobanic diterpenoids.

Nicotiana tabacum as model for ozone - plant surface reactions

Science.gov (United States)

Jud, Werner; Fischer, Lukas; Wohlfahrt, Georg; Tissier, Alain; Canaval, Eva; Hansel, Armin

2015-04-01

Elevated tropospheric ozone concentrations are considered a toxic threat to plants, responsible for global crop losses with associated economic costs of several billion dollars per year. The ensuing injuries have been related to the uptake of ozone through the stomatal pores and oxidative effects damaging the internal leaf tissue. A striking question of current research is the environment and plant specific partitioning of ozone loss between gas phase, stomatal or plant surface sink terms. Here we show results from ozone fumigation experiments using various Nicotiana Tabacum varieties, whose surfaces are covered with different amounts of unsaturated diterpenoids exuded by their glandular trichomes. Exposure to elevated ozone levels (50 to 150 ppbv) for 5 to 15 hours in an exceptionally clean cuvette system did neither result in a reduction of photosynthesis nor caused any visible leaf damage. Both these ozone induced stress effects have been observed previously in ozone fumigation experiments with the ozone sensitive tobacco line Bel-W3. In our case ozone fumigation was accompanied by a continuous release of oxygenated volatile organic compounds, which could be clearly associated to their condensed phase precursors for the first time. Gas phase reactions of ozone were avoided by choosing a high enough gas exchange rate of the plant cuvette system. In the case of the Ambalema variety, that is known to exude only the diterpenoid cis-abienol, ozone fumigation experiments yield the volatiles formaldehyde and methyl vinyl ketone (MVK). The latter could be unequivocally separated from isomeric methacrolein (MACR) by the aid of a Selective Reagent Ion Time-of-Flight Mass Spectrometer (SRI-ToF-MS), which was switched every six minutes from H3O+ to NO+ primary ion mode and vice versa. Consistent with the picture of an ozone protection mechanism caused by reactive diterpenoids at the leaf surface are the results from dark-light experiments. The ozone loss obtained from the

Semisynthetic Esters of 17-Hydroxycativic Acid with in Vitro Cytotoxic Activity against Leukemia Cell Lines

Czech Academy of Sciences Publication Activity Database

Cavallaro, V.; Řezníčková, Eva; Jorda, Radek; Alza, N.P.; Murray, A.P.; Kryštof, Vladimír

2017-01-01

Roč. 40, č. 11 (2017), s. 1923-1928 ISSN 0918-6158 R&D Projects: GA MŠk(CZ) LO1204 Institutional support: RVO:61389030 Keywords : biological evaluation * derivatives * andrographolide * apoptosis * cancer * agents * diterpenes * inhibition * activation * chemistry * diterpenoid * 17-hydroxycativic acid * cytotoxic activity * human cancer cell * apoptosis Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Hematology Impact factor: 1.683, year: 2016

4R-cembranoid protects against diisopropylfluorophosphate-mediated neurodegeneration

OpenAIRE

Ferchmin, P.A.; Andino, Myrna; Salaman, Rebeca Reyes; Alves, Janaina; Velez-Roman, Joyce; Cuadrado, Brenda; Carrasco, Marimeé; Torres-Rivera, Wilmarie; Segarra, Annabell; Martins, Antonio Henrique; Lee, Jae Eun; Eterovic, Vesna A.

2014-01-01

Many organophosphorous esters synthesized for applications in industry, agriculture, or warfare irreversibly inhibit acetylcholinesterase, and acute poisoning with these compounds causes life-threatening cholinergic overstimulation. Following classical emergency treatment with atropine, an oxime, and a benzodiazepine, surviving victims often suffer brain neurodegeneration. Currently, there is no pharmacological treatment to prevent this brain injury. Here we show that a cyclic diterpenoid, (1...

Engineering metabolic pathways in Amycolatopsis japonicum for the optimization of the precursor supply for heterologous brasilicardin congeners production

Directory of Open Access Journals (Sweden)

Paul N. Schwarz

2018-03-01

Full Text Available The isoprenoid brasilicardin A is a promising immunosuppressant compound with a unique mode of action, high potency and reduced toxicity compared to today's standard drugs. However, production of brasilicardin has been hampered since the producer strain Nocardia terpenica IFM0406 synthesizes brasilicardin in only low amounts and is a biosafety level 2 organism. Previously, we were able to heterologously express the brasilicardin gene cluster in the nocardioform actinomycete Amycolatopsis japonicum. Four brasilicardin congeners, intermediates of the BraA biosynthesis, were produced. Since chemical synthesis of the brasilicardin core structure has remained elusive we intended to produce high amounts of the brasilicardin backbone for semi synthesis and derivatization. Therefore, we used a metabolic engineering approach to increase heterologous production of brasilicardin in A. japonicum. Simultaneous heterologous expression of genes encoding the MVA pathway and expression of diterpenoid specific prenyltransferases were used to increase the provision of the isoprenoid precursor isopentenyl diphosphate (IPP and to channel the precursor into the direction of diterpenoid biosynthesis. Both approaches contributed to an elevated heterologous production of the brasilicardin backbone, which can now be used as a starting point for semi synthesis of new brasilicardin congeners with better properties.

The genus Vitex: A review

OpenAIRE

Rani, Anita; Sharma, Anupam

2013-01-01

The review includes 161 references on the genus Vitex, and comprises ethnopharmacology, morphology and microscopy, phytoconstituents, pharmacological reports, clinical studies, and toxicology of the prominent species of Vitex. Essential oils, flavonoids, iridoid glycosides, diterpenoides and ligans constitute major classes of phytoconstituents of the genus. A few species of this genus have medicinal value, among these, leaves and fruits of V. agnus-castus Linn. (Verbenaceae) has been traditio...

Phytotherapeutics oridonin and ponicidin show additive effects combined with irradiation in pancreatic cancer in vitro

Directory of Open Access Journals (Sweden)

Liermann Jakob

2017-11-01

Full Text Available Chemoradiation of locally advanced non-metastatic pancreatic cancer can lead to secondary operability by tumor mass reduction. Here, we analyzed radiomodulating effects of oridonin and ponicidin in pancreatic cancer in vitro. Both agents are ent-kaurane diterpenoids, extracted from Isodon rubescens, a plant that is well known in Traditional Chinese Medicine. Cytotoxic effects have recently been shown in different tumor entities for both agents.

A non-cytotoxic N-dehydroabietylamine derivative with potent antimalarial activity.

Science.gov (United States)

Sadashiva, Maralinganadoddi P; Gowda, Raghavendra; Wu, Xianzhu; Inamdar, Gajanan S; Kuzu, Omer F; Rangappa, Kanchugarakoppal S; Robertson, Gavin P; Gowda, D Channe

2015-08-01

Malaria caused by the Plasmodium parasites continues to be an enormous global health problem owing to wide spread drug resistance of parasites to many of the available antimalarial drugs. Therefore, development of new classes of antimalarial agents is essential to effectively treat malaria. In this study, the efficacy of naturally occurring diterpenoids, dehydroabietylamine and abietic acid, and their synthetic derivatives was assessed for antimalarial activity. Dehydroabietylamine and its N-trifluoroacetyl, N-tribromoacetyl, N-benzoyl, and N-benzyl derivatives showed excellent activity against P. falciparum parasites with IC50 values of 0.36 to 2.6 µM. Interestingly, N-dehydroabietylbenzamide showed potent antimalarial activity (IC50 0.36), and negligible cytotoxicity (IC50 >100 µM) to mammalian cells; thus, this compound can be an important antimalarial drug. In contrast, abietic acid was only marginally effective, exhibiting an IC50 value of ~82 µM. Several carboxylic group-derivatives of abietic acid were moderately active with IC50 values of ~8.2 to ~13.3 µM. These results suggest that a detailed understanding of the structure-activity relationship of abietane diterpenoids might provide strategies to exploit this class of compounds for malaria treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

Anti-inflammatory effects of glaucocalyxin B in microglia cells

Directory of Open Access Journals (Sweden)

Ping Gan

2015-05-01

Full Text Available Over-activated microglia is involved in various kinds of neurodegenerative process including Parkinson, Alzheimer and HIV dementia. Suppression of microglial over activation has emerged as a novel strategy for treatment of neuroinflammation-based neurodegeneration. In the current study, anti-inflammatory and neuroprotective effects of the ent-kauranoid diterpenoids, which were isolated from the aerial parts of Rabdosia japonica (Burm. f. var. glaucocalyx (Maxim. Hara, were investigated in cultured microglia cells. Glaucocalyxin B (GLB, one of five ent-kauranoid diterpenoids, significantly decreased the generation of nitric oxide (NO, tumor necrosis factor (TNF-α, interleukin (IL-1β, cyclooxygenase (COX-2 and inducible nitric oxide synthase (iNOS in the lipopolysaccharide (LPS-activated microglia cells. In addition, GLB inhibited activation of nuclear factor-κB (NF-κB, p38 mitogen-activated protein kinase (MAPK and generation of reactive oxygen species (ROS in LPS-activated microglia cells. Furthermore, GLB strongly induced the expression of heme oxygenase (HO-1 in BV-2 microglia cells. Finally, GLB exhibited neuroprotective effect by preventing over-activated microglia induced neurotoxicity in a microglia/neuron co-culture model. Taken together, the present study demonstrated that the GLB possesses anti-nueroinflammatory activity, and might serve as a potential therapeutic agent for treating neuroinflammatory diseases.

Identification of PTP1B and α-Glucosidase Inhibitory Serrulatanes from Eremophila spp. by Combined use of Dual High-Resolution PTP1B and α-Glucosidase Inhibition Profiling and HPLC-HRMS-SPE-NMR.

Science.gov (United States)

Wubshet, Sileshi G; Tahtah, Yousof; Heskes, Allison M; Kongstad, Kenneth T; Pateraki, Irini; Hamberger, Björn; Møller, Birger L; Staerk, Dan

2016-04-22

According to the International Diabetes Federation, type 2 diabetes (T2D) has reached epidemic proportions, affecting more than 382 million people worldwide. Inhibition of protein tyrosine phosphatase-1B (PTP1B) and α-glucosidase is a recognized therapeutic approach for management of T2D and its associated complications. The lack of clinical drugs targeting PTP1B and side effects of the existing α-glucosidase drugs, emphasize the need for new drug leads for these T2D targets. In the present work, dual high-resolution PTP1B and α-glucosidase inhibition profiles of Eremophila gibbosa, E. glabra, and E. aff. drummondii "Kalgoorlie" were used for pinpointing α-glucosidase and/or PTP1B inhibitory constituents directly from the crude extracts. A subsequent targeted high-performance liquid chromatography-high-resolution mass spectrometry-solid-phase extraction-nuclear magnetic resonance spectroscopy (HPLC-HRMS-SPE-NMR) analysis and preparative-scale HPLC isolation led to identification of 21 metabolites from the three species, of which 16 were serrulatane-type diterpenoids (12 new) associated with either α-glucosidase and/or PTP1B inhibition. This is the first report of serrulatane-type diterpenoids as potential α-glucosidase and/or PTP1B inhibitors.

Experimental and Theoretical Vibrational Spectra of Sideridiol Isolated from Sideritis Species

Science.gov (United States)

Kilic, Turgut; Sagir, Züleyha Ozer; Carikci, Sema; Azizoğlu, Akın

2017-12-01

Sideridiol ( ent-7α,18β-dihydroxykaur-15-ene) one of the ent-kaurene diterpenoid, is isolated from the genus Sideritis L. belongs to the family of Lamiaceae. The vibrational frequencies of sideridiol in the ground state have been calculated using the Density Functional Theory (DFT) method with the 6-31G( d) and 6 31+G( d, p) basis sets. The calculated vibrational frequencies have been compared with that of obtained experimental IR spectrum.

Functional Characterization of Gibberellin-Regulated Genes in Rice Using Microarray System

OpenAIRE

Jan, Asad; Komatsu, Setsuko

2006-01-01

Gibberellin (GA) is collectively referred to a group of diterpenoid acids, some of which act as plant hormones and are essential for normal plant growth and development. DNA microarray technology has become the standard tool for the parallel quantification of large numbers of messenger RNA transcripts. The power of this approach has been demonstrated in dissecting plant physiology and development, and in unraveling the underlying cellular signaling pathways. To understand the molecular mechan...

Biotransformation of steviol derivatives by Aspergillus niger and Fusarium moniliforme

Energy Technology Data Exchange (ETDEWEB)

Oliveira, Bras H. de; Leal, Paulo C. [Parana Univ., Curitiba, PR (Brazil). Dept. de Quimica]. E-mail: bho@ufpr.br; Souza Filho, Jose Dias [Minas Gerais Univ., Belo Horizonte, MG (Brazil). Dept. de Quimica

2005-04-01

Steviol derivatives have been submitted to biotransformations by fungi. Methyl ent-11{beta},13-dihydroxy-15,16-epoxikauran-19-oate was hydroxylated at C-11 by Aspergillus niger, whereas ent-16{beta}-hydroxybeyeran-19-oic acid was hydroxylated at C-6 and C-7 by Fusarium moniliforme. The hydroxylation at non-activated positions at the carbon skeleton is discussed in connection with the properties of important polyhydroxylated diterpenoids described in the literature. (author)

Biotransformation of steviol derivatives by Aspergillus niger and Fusarium moniliforme

International Nuclear Information System (INIS)

Oliveira, Bras H. de; Leal, Paulo C.; Souza Filho, Jose Dias

2005-01-01

Steviol derivatives have been submitted to biotransformations by fungi. Methyl ent-11β,13-dihydroxy-15,16-epoxikauran-19-oate was hydroxylated at C-11 by Aspergillus niger, whereas ent-16β-hydroxybeyeran-19-oic acid was hydroxylated at C-6 and C-7 by Fusarium moniliforme. The hydroxylation at non-activated positions at the carbon skeleton is discussed in connection with the properties of important polyhydroxylated diterpenoids described in the literature. (author)

STRUCTURE MODIFICATION OF ANDROGRAPHOLIDE TO IMPROVE ITS POTENCY AS ANTICANCER

OpenAIRE

Hadi Poerwono; Yoshiyuki Hattori; Hajime Kubo; Kimio Higashiyama

2010-01-01

Andrographolide, a diterpenoid lactone isolated from the herb of Andrographis paniculata and known to possess antitumor activity in breast cancer models was subjected to semisynthesis leading to the preparation of a number of derivatives. After protection of the two hydroxyl groups present at C-3 and C-19 to give 3,19-isopropylidene and 3,19-benzylidene andrographolides, the remaining hydroxyl group at C-14 of andrographolide was treated with acid anhydride or acid chloride under base conditi...

Qualitative and Quantitative Analysis of Andrographis paniculata by Rapid Resolution Liquid Chromatography/Time-of-Flight Mass Spectrometry

Directory of Open Access Journals (Sweden)

Jian-Fei Qin

2013-09-01

Full Text Available A rapid resolution liquid chromatography/time-of-flight tandem mass spectrometry (RRLC-TOF/MS method was developed for qualitative and quantitative analysis of the major chemical constituents in Andrographis paniculata. Fifteen compounds, including flavonoids and diterpenoid lactones, were unambiguously or tentatively identified in 10 min by comparing their retention times and accurate masses with standards or literature data. The characteristic fragmentation patterns of flavonoids and diterpenoid lactones were summarized, and the structures of the unknown compounds were predicted. Andrographolide, dehydroandrographolide and neoandrographolide were further quantified as marker substances. It was found that the calibration curves for all analytes showed good linearity (R2 > 0.9995 within the test ranges. The overall limits of detection (LODs and limits of quantification (LOQs were 0.02 μg/mL to 0.06 μg/mL and 0.06 μg/mL to 0.2 μg/mL, respectively. The relative standard deviations (RSDs for intra- and inter-day precisions were below 3.3% and 4.2%, respectively. The mean recovery rates ranged from 96.7% to 104.5% with the relative standard deviations (RSDs less than 2.72%. It is concluded that RRLC-TOF/MS is powerful and practical in qualitative and quantitative analysis of complex plant samples due to time savings, sensitivity, precision, accuracy and lowering solvent consumption.

Crystal structure, phytochemical study and enzyme inhibition activity of Ajaconine and Delectinine

Science.gov (United States)

Ahmad, Shujaat; Ahmad, Hanif; Khan, Hidayat Ullah; Shahzad, Adnan; Khan, Ezzat; Ali Shah, Syed Adnan; Ali, Mumtaz; Wadud, Abdul; Ghufran, Mehreen; Naz, Humera; Ahmad, Manzoor

2016-11-01

The Crystal structure, comparative DFT study and phytochemical investigation of atisine type C-20 diterpenoid alkaloid ajaconine (1) and lycoctonine type C-19 diterpenoid alkaloid delectinine (2) is reported here. These compounds were isolated from Delphinium chitralense. Both the natural products 1 and 2 crystallize in orthorhombic crystal system with identical space group of P212121. The geometric parameters of both compounds were calculated with the help of DFT using B3LYP/6-31+G (p) basis set and HOMO-LUMO energies, optimized band gaps, global hardness, ionization potential, electron affinity and global electrophilicity are calculated. The compounds 1 and 2 were screened for acetyl cholinesterase and butyryl cholinesterase inhibition activities in a dose dependent manner followed by molecular docking to explore the possible inhibitory mechanism of ajaconine (1) and delectinine (2). The IC50 values of tested compounds against AChE were observed as 12.61 μM (compound 1) and 5.04 μM (compound 2). The same experiments were performed for inhibition of BChE and IC50 was observed to be 10.18 μM (1) and 9.21 μM (2). Promising inhibition activity was shown by both the compounds against AChE and BChE in comparison with standard drugs available in the market such as allanzanthane and galanthamine. The inhibition efficiency of both the natural products was determined in a dose dependent manner.

Genomic and transcriptomic analyses reveal differential regulation of diverse terpenoid and polyketides secondary metabolites in Hericium erinaceus.

Science.gov (United States)

Chen, Juan; Zeng, Xu; Yang, Yan Long; Xing, Yong Mei; Zhang, Qi; Li, Jia Mei; Ma, Ke; Liu, Hong Wei; Guo, Shun Xing

2017-08-31

The lion's mane mushroom Hericium erinaceus is a famous traditional medicinal fungus credited with anti-dementia activity and a producer of cyathane diterpenoid natural products (erinacines) useful against nervous system diseases. To date, few studies have explored the biosynthesis of these compounds, although their chemical synthesis is known. Here, we report the first genome and tanscriptome sequence of the medicinal fungus H. erinaceus. The size of the genome is 39.35 Mb, containing 9895 gene models. The genome of H. erinaceus reveals diverse enzymes and a large family of cytochrome P450 (CYP) proteins involved in the biosynthesis of terpenoid backbones, diterpenoids, sesquiterpenes and polyketides. Three gene clusters related to terpene biosynthesis and one gene cluster for polyketides biosynthesis (PKS) were predicted. Genes involved in terpenoid biosynthesis were generally upregulated in mycelia, while the PKS gene was upregulated in the fruiting body. Comparative genome analysis of 42 fungal species of Basidiomycota revealed that most edible and medicinal mushroom show many more gene clusters involved in terpenoid and polyketide biosynthesis compared to the pathogenic fungi. None of the gene clusters for terpenoid or polyketide biosynthesis were predicted in the poisonous mushroom Amanita muscaria. Our findings may facilitate future discovery and biosynthesis of bioactive secondary metabolites from H. erinaceus and provide fundamental information for exploring the secondary metabolites in other Basidiomycetes.

Biological Activities of a Macrocyclic Diterpenoid Isolated from the ...

African Journals Online (AJOL)

www.jaaps.aapsnet.org. Research Article .... Melting points were determined on a capillary melting point apparatus (M-560, Buchi labtechnik ... increasing polarity with ethyl acetate up to 60% ethyl acetate at 2% increment. A total of 150 fractions ...

Antitumor-promoting activity of scopadulcic acid B, isolated from the medicinal plant Scoparia dulcis L.

Science.gov (United States)

Nishino, H; Hayashi, T; Arisawa, M; Satomi, Y; Iwashima, A

1993-01-01

Scopadulcic acid B (SDB), a tetracyclic diterpenoid isolated from a medicinal plant, Scoparia dulcis L., inhibited the effects of tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in vitro and in vivo; SDB inhibited TPA-enhanced phospholipid synthesis in cultured cells, and also suppressed the promoting effect of TPA on skin tumor formation in mice initiated with 7,12-dimethylbenz[a]anthracene. The potency of SDB proved to be stronger than that of other natural antitumor-promoting terpenoids, such as glycyrrhetinic acid.

Responses of Synechocystis sp. PCC 6803 to heterologous biosynthetic pathways

DEFF Research Database (Denmark)

Vavitsas, Konstantinos; Rue, Emil Østergaard; Stefánsdóttir, Lára Kristín

2017-01-01

BACKGROUND: There are an increasing number of studies regarding genetic manipulation of cyanobacteria to produce commercially interesting compounds. The majority of these works study the expression and optimization of a selected heterologous pathway, largely ignoring the wholeness and complexity...... different compounds, the cyanogenic glucoside dhurrin and the diterpenoid 13R-manoyl oxide in Synechocystis PCC 6803. We used genome-scale metabolic modelling to study fluxes in individual reactions and pathways, and we determined the concentrations of key metabolites, such as amino acids, carotenoids...

Ácido ent-16a,17-diidroxicauran-19-óico isolado de Ouratea semiserrata e os desafios estereoquímicos dos carbonos quirais C-4 e C-16

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Velandia Javier Rincón

1998-01-01

Full Text Available Phytochemical investigation of the leaves and branches of a specimen of Ouratea semiserrata led to the isolation and characterization of ent-16alpha,17-dihydroxykauran-19-oic acid, along with other natural products. This diterpenoid and its derivatives were used to unambiguous ¹H and 13C chemical shifts assignments and to indicate some mistake data described in the literature as consequence mainly of the stereochemicals of the chiral carbons C-4 and C-16. The HRMS spectra were also analysed.

Pharmacokinetics and Metabolism of 4R-Cembranoid

OpenAIRE

V?lez-Carrasco, Wanda; Green, Carol E.; Catz, Paul; Furimsky, Anna; O?Loughlin, Kathleen; Eterovi?, Vesna A.; Ferchmin, P. A.

2015-01-01

4R-cembranoid (4R) is a natural cyclic diterpenoid found in tobacco leaves that displays neuroprotective activity. 4R protects against NMDA, paraoxon (POX), and diisopropylfluorophosphate (DFP) damage in rat hippocampal slices and against DFP in rats in vivo. The purpose of this study was to examine the metabolism and pharmacokinetics of 4R as part of its preclinical development as a neuroprotective drug. 10 µM 4R was found to be very stable in plasma for up to 1 hr incubation. 4R metabolism ...

6β-Acetoxy-1α,7β,11β,15β-tetrahydroxy-7α,20-epoxy-ent-kaur-16-ene

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Fu-Lin Yan

2010-02-01

Full Text Available The title compound, C22H32O7, a natural ent-kaurane diterpenoid also referred to as Maoyecrystal F, was obtained from the medicinal plant Isodon nervosa. There are four rings with the expected cis and trans junctions. Cyclohexane ring A adopts a chair conformation, rings B and C adopt boat conformations, while the five-membered ring has an envelope conformation. The molecules stack along the a axis in the crystal and are linked together by intermolecular O—H...O hydrogen bonds.

Rapid quality assessment of Radix Aconiti Preparata using direct analysis in real time mass spectrometry.

Science.gov (United States)

Zhu, Hongbin; Wang, Chunyan; Qi, Yao; Song, Fengrui; Liu, Zhiqiang; Liu, Shuying

2012-11-08

This study presents a novel and rapid method to identify chemical markers for the quality control of Radix Aconiti Preparata, a world widely used traditional herbal medicine. In the method, the samples with a fast extraction procedure were analyzed using direct analysis in real time mass spectrometry (DART MS) combined with multivariate data analysis. At present, the quality assessment approach of Radix Aconiti Preparata was based on the two processing methods recorded in Chinese Pharmacopoeia for the purpose of reducing the toxicity of Radix Aconiti and ensuring its clinical therapeutic efficacy. In order to ensure the safety and effectivity in clinical use, the processing degree of Radix Aconiti should be well controlled and assessed. In the paper, hierarchical cluster analysis and principal component analysis were performed to evaluate the DART MS data of Radix Aconiti Preparata samples in different processing times. The results showed that the well processed Radix Aconiti Preparata, unqualified processed and the raw Radix Aconiti could be clustered reasonably corresponding to their constituents. The loading plot shows that the main chemical markers having the most influence on the discrimination amongst the qualified and unqualified samples were mainly some monoester diterpenoid aconitines and diester diterpenoid aconitines, i.e. benzoylmesaconine, hypaconitine, mesaconitine, neoline, benzoylhypaconine, benzoylaconine, fuziline, aconitine and 10-OH-mesaconitine. The established DART MS approach in combination with multivariate data analysis provides a very flexible and reliable method for quality assessment of toxic herbal medicine. Copyright © 2012 Elsevier B.V. All rights reserved.

Three New Cytotoxic ent-Kaurane Diterpenes from Isodon excisoides

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Li-Ping Dai

2015-09-01

Full Text Available Three types of ent-kaurane diterpenoids were isolated from the aerial parts of Isodon excisoides, including three new diterpenoids, 1α,7α,14β-trihydroxy-20-acetoxy-ent-kaur-15-one (1; 1α,7α,14β,18-tetrahydroxy-20-acetoxy-ent-kaur-15-one (2; and 1α-acetoxy-14β-hydroxy-7α,20-epoxy-ent-kaur-16-en-15-one (3; together with six known diterpenes henryin (4; kamebanin (5; reniformin C (6; kamebacetal A (7; kamebacetal B (8; and oridonin (9. The structures of the isolated compounds were elucidated by means of nuclear magnetic resonance spectroscopy and high-resolution mass spectrometry in conjunction with published data for their analogs, as well as their fragmentation patterns. Compounds 5 and 9 were isolated from Isodon excisoides for the first time. To explore the structure-activity relationships of the isolated compounds, they were tested for their cytotoxic effects against five human cancer cell lines: HCT-116, HepG2, A2780, NCI-H1650, and BGC-823. Most of the isolated compounds showed certain cytotoxic activity against the five cancer cell lines with IC50 values ranging from 1.09–8.53 µM. Among the tested compounds, compound 4 exhibited the strongest cytotoxic activity in the tested cell lines, with IC50 values ranging from 1.31–2.07 µM. Compounds 1, 6, and 7 exhibited selective cytotoxic activity.

Trigocherrierin A, a Potent Inhibitor of Chikungunya Virus Replication

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Mélanie Bourjot

2014-03-01

Full Text Available Trigocherrierin A (1 and trigocherriolide E (2, two new daphnane diterpenoid orthoesters (DDOs, and six chlorinated analogues, trigocherrins A, B, F and trigocherriolides A–C, were isolated from the leaves of Trigonostemon cherrieri. Their structures were identified by mass spectrometry, extensive one- and two-dimensional NMR spectroscopy and through comparison with data reported in the literature. These compounds are potent and selective inhibitors of chikungunya virus (CHIKV replication. Among the DDOs isolated, compound 1 exhibited the strongest anti-CHIKV activity (EC50 = 0.6 ± 0.1 µM, SI = 71.7.

Discovery of New Eunicellins from an Indonesian Octocoral Cladiella sp.

Science.gov (United States)

Chen, Yung-Husan; Tai, Chia-Ying; Su, Yin-Di; Chang, Yu-Chia; Lu, Mei-Chin; Weng, Ching-Feng; Su, Jui-Hsin; Hwang, Tsong-Long; Wu, Yang-Chang; Sung, Ping-Jyun

2011-01-01

Two new 11-hydroxyeunicellin diterpenoids, cladieunicellin F (1) and (–)-solenopodin C (2), were isolated from an Indonesian octocoral Cladiella sp. The structures of eunicellins 1 and 2 were established by spectroscopic methods, and eunicellin 2 was found to be an enantiomer of the known eunicellin solenopodin C (3). Eunicellin 2 displayed inhibitory effects on the generation of superoxide anion and the release of elastase by human neutrophils. The previously reported structures of two eunicellin-based compounds, cladielloides A and B, are corrected in this study. PMID:21747739

1α,6β,7β,11α,15β-Pentahydroxy-7α,20-epoxy-ent-kaur-16-ene

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Chuang Feng

2010-02-01

Full Text Available The title compound, C20H30O6, a natural ent-kaurane diterpenoid, named nervosanin B, was obtained from the medicinal plant Isodon serra. It is composed of four rings with the expected trans and cis junctions. One of the six-membered rings is in a chair conformation, the other two are in boat conformations and the five-membered ring adopts an evenlope conformation. The molecules stack along the a axis and are linked together by intermolecular O—H...O hydrogen bonds. Two intramolecular O—H...O interactions also occur.

Absolute Configuration of Andrographolide and Its Proliferation of Osteoblast Cell Lines

Science.gov (United States)

Chantrapromma, S.; Boonnak, N.; Pitakpornpreecha, T.; Yordthong, T.; Chidan Kumar, C. S.; Fun, H. K.

2018-05-01

Andrographolide, C20H30O5, is a labdane diterpenoid which was isolated from the leave of Andrographis paniculata. Its crystal structure is determined by single crystal X-ray diffraction: monoclinic, sp. gr. P21, Z = 2. Absolute configuration is determined by the refinement of the Flack parameter to 0.21(19). In the crystal, molecules are linked by O-H···O hydrogen bonds and C-H···O interactions into two dimensional network parallel to the (001) plane. Its proliferation of osteoblast cell lines is reported.

Antiproliferative Compounds of Cyphostemma greveana from a Madagascar Dry Forest[1

OpenAIRE

Cao, Shugeng; Hou, Yanpeng; Brodie, Peggy; Miller, James S.; Randrianaivo, Richard; Rakotobe, Etienne; Rasamison, Vincent E.; Kingston, David G. I.

2011-01-01

Bioassay-guided fractionation of the EtOH extracts obtained from a plant identified as Cyphostemma greveana Desc. (Vitaceae) led to the identification of one macrolide, lasiodiplodin (1), three sesquiterpenoids, 12-hydroxy-15-oxo-selina-4,1l-diene (2), 1β,6α-dihydroxyeudesm-4(15)-ene (3), and (7R*)-opposit-4(15)-ene-1β,7-diol (5), and the new diterpenoid, 16,18-dihydroxykolavenic acid lactone (4). All the isolates were tested against the A2780 human ovarian cancer cell line, and compound 4 an...

Synthetic routes to some isotopically labelled intermediates for diterpenoid biosynthesis

International Nuclear Information System (INIS)

Dawson, R.M.; Godfrey, I.M.; Hogg, R.W.; Knox, J.R.

1989-01-01

The exo-15-hydrogen of ent-kaurene can be exchanged through a reversible ene reaction in a convenient and efficient procedure which has the potential for giving high specific activity 3 H-labelling. Copalol, the (Z)-double bond stereoisomer, and the allylic alcohol isomers ent-manool and ent-epimanool have been obtained through divergent synthetic pathways involving a 15,16-bisnor ketone intermediate. These pathways have also allowed the four compounds to be obtained with 14 C-labelling. A method, involving a Wittig reaction to form a vinyl bromide intermediate, has been developed for obtaining copalol, as the trityl ether derivative, with stereospecific isotopic labelling of one or the other of the hydrogens of the exocyclic methylene group. 27 refs., figs

Identity, regulation, and activity of inducible diterpenoid phytoalexins in maize

Science.gov (United States)

Phytoalexins constitute a broad category of pathogen and insect-inducible biochemicals that locally protect plant tissues. Due to their agronomic significance, maize and rice have been extensively investigated for their terpenoid-based defenses which include insect-inducible monoterpene and sesquite...

A New Diterpenoid from the Seeds of Caesalpinia sappan Linn

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Yong-Jiang Xu

2013-03-01

Full Text Available A new cassane-type d iterpene, named Phangininoxy A (1 and one known Phanginin A (2 were isolated from the exact of seeds of Caesalpinia sappan Linn. Their structures were elucidated by spectroscopic methods, mainly 1D and 2D NMR.

First enantiocontrolled formal synthesis of (+)-neovibsanin B, a neurotrophic diterpenoid.

Science.gov (United States)

Esumi, Tomoyuki; Mori, Takehiro; Zhao, Ming; Toyota, Masao; Fukuyama, Yoshiyasu

2010-02-19

An enantiocontrolled formal synthesis of (+)-neovibsanin B has been achieved by a sequence that applies an asymmetric 1,4-addition of (H(2)C=CH)(2)Cu(CN)Li(2) to trisubstituted alpha,beta-carboxylic acid derivative 1 to induce the chirality at the C-11 all-carbon quaternary center. Together with a modified Negishi cyclic carbopalladation-carbonylative esterification tandem reaction for constructing the A-ring, the synthesis was completed.

Naturally occurring Vpr inhibitors from medicinal plants of Myanmar.

Science.gov (United States)

Win, Nwet Nwet; Ngwe, Hla; Abe, Ikuro; Morita, Hiroyuki

2017-10-01

Human immunodeficiency virus type-1 (HIV-1) is a lentiviral family member that encodes the retroviral Gag, Pol, and Env proteins, along with six additional accessory proteins, Tat, Rev, Vpu, Vif, Nef, and Vpr. The currently approved anti-HIV drugs target the Pol and Env encoded proteins. However, these drugs are only effective in reducing viral replication. Furthermore, the drugs' toxicities and the emergence of drug-resistant strains have become serious worldwide problems. Resistance eventually arises to all of the approved anti-HIV drugs, including the newly approved drugs that target HIV integrase (IN). Drug resistance likely emerges because of spontaneous mutations that occur during viral replication. Therefore, new drugs that effectively block other viral components must be developed to reduce the rate of resistance and suppress viral replication with little or no long-term toxicity. The accessory proteins may expand treatment options. Viral protein R (Vpr) is one of the promising drug targets among the HIV accessory proteins. However, the search for inhibitors continues in anti-HIV drug discovery. In this review, we summarize the naturally occurring compounds discovered from two Myanmar medicinal plants as well as their structure-activity relationships. A total of 49 secondary metabolites were isolated from Kaempferia pulchra rhizomes and Picrasama javanica bark, and the types of compounds were identified as isopimarane diterpenoids and picrasane quassinoids, respectively. Among the isolates, 7 diterpenoids and 15 quassinoids were found to be Vpr inhibitors lacking detectable toxicity, and their potencies varied according to their respective functionalities.

A practical strategy for the characterization of ponicidin metabolites in vivo and in vitro by UHPLC-Q-TOF-MS based on nontargeted SWATH data acquisition.

Science.gov (United States)

Xie, Weiwei; Jin, Yiran; Hou, Ludan; Ma, Yinghua; Xu, Huijun; Zhang, Kerong; Zhang, Lantong; Du, Yingfeng

2017-10-25

Ponicidin is an active natural ent-kaurane diterpenoid ingredient originating from many Isondon herbs and is expected to become a new anticancer agent. In this study, a practical strategy was developed for the identification of ponicidin metabolites in vivo and in vitro utilizing ultra-high-performance liquid chromatography coupled with hybrid triple quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS). The analytical strategy was as follows: potential ponicidin metabolites were detected by a novel on-line data acquisition approach, i.e., sequential window acquisition of all theoretical fragment-ion spectra (SWATH™). Compared to the traditional information-dependent acquisition (IDA) method, SWATH™ significantly improved the hit rate of low-level or trace metabolites because it could obtain all MS/MS spectra. Moreover, many data post-processing methods were used to deduce the metabolites structures. As a result, a total of 20 metabolites were characterized in vivo and in vitro. The results showed that ponicidin could undergo general metabolic reactions, such as oxidation, reduction, hydrolysis, methylation and glucuronidation. Furthermore, there was an obvious difference in the ponicidin metabolites among four species in vitro. This is the first time that the SWATH™ data acquisition mode has been used to characterize ponicidin metabolites in trace amounts or in a biological matrix. These results not only provided a better understanding of the safety and efficacy of ponicidin but also showed a valuable methodology for the identification of other ent-kaurane diterpenoid metabolites. Copyright © 2017 Elsevier B.V. All rights reserved.

Gas chromatography/mass spectrometry characterization of historical varnishes of ancient Italian lutes and violin.

Science.gov (United States)

Echard, J P; Benoit, C; Peris-Vicente, J; Malecki, V; Gimeno-Adelantado, J V; Vaiedelich, S

2007-02-12

The organic constituents of historical vanishes from two ancient Italian lutes and a Stradivari violin, kept in the Musée de la musique in Paris, have been characterized using gas chromatography-mass spectrometry. Results have been compared with the chromatograms and mass spectra of recent as well as old naturally aged reference materials. The three historical varnishes analyzed have been shown to be oil varnishes, probably mixtures of linseed oil with resins. Identification of diterpenoids and triterpenoids compounds, and of the resins that may have been ingredients of the varnishes, are discussed in this paper.

Microtropins Q-W, ent-Labdane Glucosides: Microtropiosides G-I, Ursane-Type Triterpene Diglucoside and Flavonol Glycoside from the Leaves of Microtropis japonica.

Science.gov (United States)

Terazawa, Saori; Uemura, Yuka; Koyama, Yuka; Kawakami, Susumu; Sugimoto, Sachiko; Matsunami, Katsuyoshi; Otsuka, Hideaki; Shinzato, Takakazu; Kawahata, Masatoshi; Yamaguchi, Kentaro

2017-01-01

Microtropins Q-W, (2S,3R)-2-ethyl-2,3-dihydroxybutyrate of various glucosides and glucose, as well as three ent-labdane diterpenoid glucosides, named microtropiosides G, H and I, an ursane-type triterpene diglucoside and a flavonoid glycoside were isolated from the MeOH extract of the leaves of Microtropis japonica. The structure of microtropioside A, also isolated from the branches of M. japonica, was elucidated spectroscopically in a previous experiment and was found to possess a rare seven-membered oxyrane ring. Its structure was confirmed by X-ray crystallographic analysis of its pentaacetate.

Total synthesis of (+/-)-taiwaniaquinol B via a domino intramolecular friedel-crafts acylation/carbonyl alpha-tert-alkylation reaction.

Science.gov (United States)

Fillion, Eric; Fishlock, Dan

2005-09-28

The first synthesis of taiwaniaquinol B, a 6-nor-5(6-->7)abeoabietane-type diterpenoid exhibiting the uncommon fused 6-5-6 tricyclic carbon skeleton, was accomplished in 15 steps. A Lewis acid-promoted tandem intramolecular Friedel-Crafts/carbonyl alpha-tert-alkylation reaction was exploited as the core strategy for the synthesis of the sterically congested 1-indanone-containing tricyclic structure. This multiple carbon-carbon bond forming reaction exploits the unique reactivity of Meldrum's acid. The facile precursor synthesis makes this a useful methodology for the expedient modification and assembly of sterically congested 1-indanone-containing ring systems.

Terpenoids from the Octocoral Sinularia gaweli

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Wun-Jie Lin

2015-08-01

Full Text Available Two eudesmane sesquiterpenoids, verticillatol (1 and 5α-acetoxy-4(14-eudesmene-1β-ol (2 and two cembrane diterpenoids, (–-leptodiol acetate (3 and sinulacembranolide A (4 were isolated from the octocoral Sinularia gaweli and compounds 2–4 are new isolates. The structures of new terpenoids 2–4 were elucidated by spectroscopic methods and by comparison the spectral data with those of known analogues. Terpenoid 4 was found to inhibit the accumulation of the pro-inflammatory inducible nitric oxide synthase (iNOS protein of the lipopolysaccharide (LPS-stimulated RAW264.7 marcophage cells.

Structure–function relationships of inhibition of mosquito cytochrome P450 enzymes by flavonoids of Andrographis paniculata.

Science.gov (United States)

Kotewong, Rattanawadee; Duangkaew, Panida; Srisook, Ekaruth; Sarapusit, Songklod; Rongnoparut, Pornpimol

2014-09-01

The cytochrome P450 monooxygenases are known to play a major role in pyrethroid resistance, by means of increased rate of insecticide detoxification as a result of their overexpression. Inhibition of detoxification enzymes may help disrupting insect detoxifying defense system. The Anopheles minimus CYP6AA3 and CYP6P7 have shown pyrethroid degradation activity and been implicated in pyrethroid resistance. In this study inhibition of the extracts and constituents of Andrographis paniculata Nees. leaves and roots was examined against benzyloxyresorufin O-debenzylation (BROD) of CYP6AA3 and CYP6P7. Four purified flavones (5,7,4′-trihydroxyflavone, 5-hydroxy-7,8-dimethoxyflavone, 5-hydroxy-7,8,2′,3′-tetramethoxyflavone, and 5,4′-dihydroxy-7,8,2′,3′-tetramethoxyflavone), one flavanone (5-hydroxy-7,8-dimethoxyflavanone) and a diterpenoid (14-deoxy-11,12-didehydroandrographolide) containing inhibitory effects toward both enzymes were isolated from A. paniculata. Structure–function relationships were observed for modes and kinetics of inhibition among flavones, while diterpenoid and flavanone were inferior to flavones. Docking of flavones onto enzyme homology models reinforced relationships on flavone structures and inhibition modes. Cell-based inhibition assays employing 3-(4,5-dimethylthiazol-2-y-l)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assays revealed that these flavonoids efficiently increased susceptibility of CYP6AA3- and CYP6P7-expressing Spodoptera frugiperda (Sf9) cells to cypermethrin toxicity, due to inhibition effects on mosquito enzymes. Thus synergistic effects on cypermethrin toxicity of A. paniculata compounds as a result of enzyme inhibition could be useful for mosquito vector control and insecticide resistance management in the future.

SIRT1 inhibitory diterpenoids from the Vietnamese medicinal plant Croton tonkinensis

DEFF Research Database (Denmark)

Dao, Trong Tuan; Le, Thi Van; Nguyen, Phi Hung

2010-01-01

Silent information regulator two ortholog 1 (SIRT1) is a member of the sirtuin deacetylase family of enzymes that removes acetyl groups from the lysine residues in histones and other proteins. It has been suggested that SIRT1 inhibitors might be beneficial in the treatment of cancer and neurodege...

Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus-castus

DEFF Research Database (Denmark)

Heskes, Allison Maree; Sundram, Tamil C M; Boughton, Berin Alain

2018-01-01

Vitex agnus-castus L. (Lamiaceae) is a medicinal plant historically used throughout the Mediterranean region to treat menstrual cycle disorders and is still used today as a clinically effective treatment for premenstrual syndrome. The pharmaceutical activity of the plant extract is linked to its ...

An antibacterial ortho-quinone diterpenoid and its derivatives from Caryopteris mongolica.

Science.gov (United States)

Saruul, Erdenebileg; Murata, Toshihiro; Selenge, Erdenechimeg; Sasaki, Kenroh; Yoshizaki, Fumihiko; Batkhuu, Javzan

2015-06-15

To identify antibacterial components in traditional Mongolian medicinal plant Caryopteris mongolica, an ortho-quinone abietane caryopteron A (1) and three its derivatives caryopteron B-D (2-4) were isolated from the roots of the plant together with three known abietanes demethylcryptojaponol (5), 6α-hydroxydemethyl cryptojaponol (6), and 14-deoxycoleon U (7). The chemical structures of these abietane derivatives were elucidated on the basis of spectroscopic data. Compounds 1-4 had C-13 methylcyclopropane substructures, and 2-4 had a hexanedioic anhydride ring C instead of ortho-quinone in 1. The stereochemistry of these compound was assumed from NOE spectra and ECD Cotton effects. Compounds 1 and 5-7 showed antibacterial activities against the Gram-positive bacteria Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, and Micrococcus luteus, being 1 the more potent. Copyright © 2015 Elsevier Ltd. All rights reserved.

Briarane Diterpenes from the South China Sea Gorgonian Coral, Junceella gemmacea

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Wei Zhou

2014-01-01

Full Text Available Four new briarane diterpenoids, junceellolides M–P (1–4, were isolated together with seven known analogs (5–11 from the South China Sea gorgonian, Junceella gemmacea. The structures of these compounds were elucidated by detailed spectroscopic analysis and comparison with the reported data. The absolute configuration of compounds 1–3 were determined based on an ECD experiment, while the absolute configuration of compound 4 was genetically determined. All the compounds were isolated for the first time from J. gemmacea. These compounds showed no growth inhibitory activity against A549, MG63 and SMMC-7721 cell lines in an in vitro bioassay.

A New Asymmetric ent-Kauranoid Dimer from Rabdosia rubescens

Institute of Scientific and Technical Information of China (English)

LU Hai-ying; LIANG Jing-yu

2012-01-01

Objective To study the ent-kaurane diterpenoids from Rabdosia rubescens.Methods The compounds were isolated by chromatographies and their structures were identified by spectral analyses.Results Four compounds were isolated,and they were identified as bisrubescensin E (1),2α,3α,24-trihydroxyurs-12-en-28-oic acid (2),2α,3α,24-trihydroxyurs-12,20-(30)-dien-28-oic acid (3),and 6,7-dihydroxycoumarin (4).Conclusion Compound 1 is a new asymmetric ent-kauranoid dimer.Compound 2 is isolated from the plant for the first time.Compounds 3 and 4 are isolated from the plants ofRabdosia (B1.) Hassk for the first time.

15α,20β-Dihydroxy-6β-methoxy-6,7-seco-6,20-epoxy-1,7-olide-ent-kaur-16-ene

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Fu-Lin Yan

2010-04-01

Full Text Available The title compound, C21H30O6, a natural ent-kaurane diterpenoid, was obtained from the medicinal plant Isodon serra. The five rings in the molecule exhibit the expected cis and trans junctions. The three six-membered rings adopt chair, twist-boat and boat conformations, while two five-membered rings adopt envelope conformations. There are two molecules in the asymmetric unit, related by a non-crystallographic twofold screw axis; the main difference is in the different degrees of distortion of ring B. In the crystal, the molecules are linked by intermolecular O—H...O hydrogen bonds, forming chains along the b axis.

Briarenols C–E, New Polyoxygenated Briaranes from the Octocoral Briareum excavatum

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Nan-Fu Chen

2017-03-01

Full Text Available Three new polyoxygenated briarane diterpenoids, briarenols C–E (1–3, were isolated from the octocoral Briareum excavatum. The structures of briaranes 1–3 were elucidated by interpretation of spectroscopic data, and the methylenecyclohexane ring in 1 was found to exist in a twisted boat conformation. Briarenol D (2 displayed an inhibitory effect on the release of elastase by human neutrophils with an IC50 value of 4.65 μM. Briarenol E (3 was found to inhibit the protein expression of pro-inflammatory inducible nitric oxide synthase (iNOS in a murine macrophage-like cell line, RAW 264.7, stimulated with lipopolysaccharides (LPS.

Molecular characterization of primary humic-like substances in fine smoke particles by thermochemolysis-gas chromatography-mass spectrometry

Science.gov (United States)

Fan, Xingjun; Wei, Siye; Zhu, Mengbo; Song, Jianzhong; Peng, Ping'an

2018-05-01

In this study, the molecular structures of primary humic-like substances (HULIS) in fine smoke particles emitted from the combustion of biomass materials (including rice straw, corn straw, and pine branches) and coal, and atmospheric HULIS were determined by off-line tetramethylammonium hydroxide thermochemolysis coupled with gas chromatography and mass spectrometry (TMAH-GC/MS). A total of 89 pyrolysates were identified by the thermochemolysis of primary and atmospheric HULIS. The main groups were polysaccharide derivatives, N-containing compounds, lignin derivatives, aromatic acid methyl ester, aliphatic acid methyl ester, and diterpenoid derivatives. Both the type and distribution of pyrolysates among primary HULIS were comparable to those in atmospheric HULIS. This indicates that primary HULIS from combustion processes are important contributors to atmospheric HULIS. Some distinct differences were also observed. The aromatic compounds, including lignin derivatives and aromatic acid methyl ester, were the major pyrolysates (53.0%-84.9%) in all HULIS fractions, suggesting that primary HULIS significantly contributed aromatic structures to atmospheric HULIS. In addition, primary HULIS from biomass burning (BB) contained a relatively high abundance of lignin and polysaccharide derivatives, which is consistent with the large amounts of lignin and cellulose structures contained in biomass materials. Aliphatic acid methyl ester and benzyl methyl ether were prominent pyrolysates in atmospheric HULIS. Moreover, some molecular markers of specific sources were obtained from the thermochemolysis of primary and atmospheric HULIS. For example, polysaccharide derivatives, pyridine and pyrrole derivatives, and lignin derivatives can be used as tracers of fresh HULIS emitted from BB. Diterpenoid derivatives are important markers of HULIS from pine wood combustion sources. Finally, the differences in pyrolysate types and the distributions between primary and atmospheric HULIS

Rapid quality assessment of Radix Aconiti Preparata using direct analysis in real time mass spectrometry

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Zhu Hongbin; Wang Chunyan; Qi Yao [Changchun Center of Mass Spectrometry and Chemical Biology Laboratory, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); University of Chinese Academy of Sciences, Beijing 100039 (China); Song Fengrui, E-mail: songfr@ciac.jl.cn [Changchun Center of Mass Spectrometry and Chemical Biology Laboratory, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China); Liu Zhiqiang; Liu Shuying [Changchun Center of Mass Spectrometry and Chemical Biology Laboratory, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022 (China)

2012-11-08

Highlights: Black-Right-Pointing-Pointer DART MS combined with PCA and HCA was used to rapidly identify markers of Radix Aconiti. Black-Right-Pointing-Pointer The DART MS behavior of six aconitine-type alkaloids was investigated. Black-Right-Pointing-Pointer Chemical markers were recognized between the qualified and unqualified samples. Black-Right-Pointing-Pointer DART MS was shown to be an effective tool for quality control of Radix Aconiti Preparata. - Abstract: This study presents a novel and rapid method to identify chemical markers for the quality control of Radix Aconiti Preparata, a world widely used traditional herbal medicine. In the method, the samples with a fast extraction procedure were analyzed using direct analysis in real time mass spectrometry (DART MS) combined with multivariate data analysis. At present, the quality assessment approach of Radix Aconiti Preparata was based on the two processing methods recorded in Chinese Pharmacopoeia for the purpose of reducing the toxicity of Radix Aconiti and ensuring its clinical therapeutic efficacy. In order to ensure the safety and effectivity in clinical use, the processing degree of Radix Aconiti should be well controlled and assessed. In the paper, hierarchical cluster analysis and principal component analysis were performed to evaluate the DART MS data of Radix Aconiti Preparata samples in different processing times. The results showed that the well processed Radix Aconiti Preparata, unqualified processed and the raw Radix Aconiti could be clustered reasonably corresponding to their constituents. The loading plot shows that the main chemical markers having the most influence on the discrimination amongst the qualified and unqualified samples were mainly some monoester diterpenoid aconitines and diester diterpenoid aconitines, i.e. benzoylmesaconine, hypaconitine, mesaconitine, neoline, benzoylhypaconine, benzoylaconine, fuziline, aconitine and 10-OH-mesaconitine. The established DART MS approach in

Rapid quality assessment of Radix Aconiti Preparata using direct analysis in real time mass spectrometry

International Nuclear Information System (INIS)

Zhu Hongbin; Wang Chunyan; Qi Yao; Song Fengrui; Liu Zhiqiang; Liu Shuying

2012-01-01

Highlights: ► DART MS combined with PCA and HCA was used to rapidly identify markers of Radix Aconiti. ► The DART MS behavior of six aconitine-type alkaloids was investigated. ► Chemical markers were recognized between the qualified and unqualified samples. ► DART MS was shown to be an effective tool for quality control of Radix Aconiti Preparata. - Abstract: This study presents a novel and rapid method to identify chemical markers for the quality control of Radix Aconiti Preparata, a world widely used traditional herbal medicine. In the method, the samples with a fast extraction procedure were analyzed using direct analysis in real time mass spectrometry (DART MS) combined with multivariate data analysis. At present, the quality assessment approach of Radix Aconiti Preparata was based on the two processing methods recorded in Chinese Pharmacopoeia for the purpose of reducing the toxicity of Radix Aconiti and ensuring its clinical therapeutic efficacy. In order to ensure the safety and effectivity in clinical use, the processing degree of Radix Aconiti should be well controlled and assessed. In the paper, hierarchical cluster analysis and principal component analysis were performed to evaluate the DART MS data of Radix Aconiti Preparata samples in different processing times. The results showed that the well processed Radix Aconiti Preparata, unqualified processed and the raw Radix Aconiti could be clustered reasonably corresponding to their constituents. The loading plot shows that the main chemical markers having the most influence on the discrimination amongst the qualified and unqualified samples were mainly some monoester diterpenoid aconitines and diester diterpenoid aconitines, i.e. benzoylmesaconine, hypaconitine, mesaconitine, neoline, benzoylhypaconine, benzoylaconine, fuziline, aconitine and 10-OH-mesaconitine. The established DART MS approach in combination with multivariate data analysis provides a very flexible and reliable method for quality

Biosynthesis of the oxygenated diterpene nezukol in the medicinal plant Isodon rubescens is catalyzed by a pair of diterpene synthases.

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Kyle A Pelot

Full Text Available Plants produce an immense diversity of natural products (i.e. secondary or specialized metabolites that offer a rich source of known and potentially new pharmaceuticals and other desirable bioproducts. The Traditional Chinese Medicinal plant Isodon rubescens (Lamiaceae contains an array of bioactive labdane-related diterpenoid natural products. Of these, the ent-kauranoid oridonin is the most prominent specialized metabolite that has been extensively studied for its potent antimicrobial and anticancer efficacy. Mining of a previously established transcriptome of I. rubescens leaf tissue identified seven diterpene synthase (diTPSs candidates. Here we report the functional characterization of four I. rubescens diTPSs. IrTPS5 and IrTPS3 were identified as an ent-copalyl diphosphate (CPP synthase and a (+-CPP synthase, respectively. Distinct transcript abundance of IrTPS5 and the predicted ent-CPP synthase IrTPS1 suggested a role of IrTPS5 in specialized ent-kaurene metabolism possibly en route to oridonin. Nicotiana benthamiana co-expression assays demonstrated that IrTPS4 functions sequentially with IrTPS3 to form miltiradiene. In addition, IrTPS2 converted the IrTPS3 product (+-CPP into the hydroxylated tricyclic diterpene nezukol not previously identified in I. rubescens. Metabolite profiling verified the presence of nezukol in I. rubescens leaf tissue. The proposed IrTPS2-catalyzed reaction mechanism proceeds via the common ionization of the diphosphate group of (+-CPP, followed by formation of an intermediary pimar-15-en-8-yl+ carbocation and neutralization of the carbocation by water capture at C-8 to yield nezukol, as confirmed by nuclear magnetic resonance (NMR analysis. Oxygenation activity is rare for the family of class I diTPSs and offers new catalysts for developing metabolic engineering platforms to produce a broader spectrum of bioactive diterpenoid natural products.

Selection for high oridonin yield in the Chinese medicinal plant Isodon (Lamiaceae using a combined phylogenetics and population genetics approach.

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Eric S J Harris

Full Text Available Oridonin is a diterpenoid with anti-cancer activity that occurs in the Chinese medicinal plant Isodon rubescens and some related species. While the bioactivity of oridonin has been well studied, the extent of natural variation in the production of this compound is poorly known. This study characterizes natural variation in oridonin production in order to guide selection of populations of Isodon with highest oridonin yield. Different populations of I. rubescens and related species were collected in China, and their offspring were grown in a greenhouse. Samples were examined for oridonin content, genotyped using 11 microsatellites, and representatives were sequenced for three phylogenetic markers (ITS, rps16, trnL-trnF. Oridonin production was mapped on a molecular phylogeny of the genus Isodon using samples from each population as well as previously published Genbank sequences. Oridonin has been reported in 12 out of 74 species of Isodon examined for diterpenoids, and the phylogeny indicates that oridonin production has arisen at least three times in the genus. Oridonin production was surprisingly consistent between wild-collected parents and greenhouse-grown offspring, despite evidence of gene flow between oridonin-producing and non-producing populations of Isodon. Additionally, microsatellite genetic distance between individuals was significantly correlated with chemical distance in both parents and offspring. Neither heritability nor correlation with genetic distance were significant when the comparison was restricted to only populations of I. rubescens, but this result should be corroborated using additional samples. Based on these results, future screening of Isodon populations for oridonin yield should initially prioritize a broad survey of all species known to produce oridonin, rather than focusing on multiple populations of one species, such as I. rubescens. Of the samples examined here, I. rubescens or I. japonicus from Henan province

Anti-inflammatory and anti-angiogenic activities in vitro of eight diterpenes from Daphne genkwa based on hierarchical cluster and principal component analysis.

Science.gov (United States)

Wang, Ling; Lan, Xin-Yi; Ji, Jun; Zhang, Chun-Feng; Li, Fei; Wang, Chong-Zhi; Yuan, Chun-Su

2018-06-01

Rheumatoid arthritis (RA) is one of the most prevalent chronic inflammatory and angiogenic diseases. The aim of this study was to evaluate the anti-inflammatory and anti-angiogenic activities in vitro of eight diterpenoids isolated from Daphne genkwa. LC-MS was used to identify diterpenes isolated from D. genkwa. The anti-inflammatory and anti-angiogenic activities of eight diterpenoids were evaluated on LPS-induced macrophage RAW264.7 cells and TNF-α-stimulated human umbilical vein endothelial cells (HUVECs) using hierarchical cluster analysis (HCA) and principal component analysis (PCA). The eight diterpenes isolated from D. genkwa were identified as yuanhuaphnin, isoyuanhuacine, 12-O-(2'E,4'E-decadienoyl)-4-hydroxyphorbol-13-acetyl, yuanhuagine, isoyuanhuadine, yuanhuadine, yuanhuaoate C and yuanhuacine. All the eight diterpenes significantly down-regulated the excessive secretion of TNF-α, IL-6, IL-1β and NO in LPS-induced RAW264.7 macrophages. However, only 12-O-(2'E,4'E-decadienoyl)-4-hydroxyphorbol-13-acetyl markedly reduced production of VEGF, MMP-3, ICAM and VCAM in TNF-α-stimulated HUVECs. HCA obtained 4 clusters, containing 12-O-(2'E,4'E-decadienoyl)-4-hydroxyphorbol-13-acetyl, isoyuanhuacine, isoyuanhuadine and five other compounds. PCA showed that the ranking of diterpenes sorted by efficacy from highest to lowest was 12-O-(2'E,4'E-decadienoyl)-4-hydroxyphorbol-13-acetyl, yuanhuaphnin, isoyuanhuacine, yuanhuacine, yuanhuaoate C, yuanhuagine, isoyuanhuadine, yuanhuadine. In conclusion, eight diterpenes isolated from D. genkwa showed different levels of activity in LPS-induced RAW264.7 cells and TNF-α-stimulated HUVECs. The comprehensive evaluation of activity by HCA and PCA indicated that of the eight diterpenes, 12-O-(2'E,4'E-decadienoyl)-4-hydroxyphorbol-13-acetyl was the best, and can be developed as a new drug for RA therapy.

Production of cyathane type secondary metabolites by submerged cultures of Hericium erinaceus and evaluation of their antibacterial activity by direct bioautography.

Science.gov (United States)

Shen, T; Morlock, G; Zorn, H

2015-01-01

Fungi of the phylum Basidiomycota are well-known to form a broad spectrum of biologically active secondary metabolites, especially low molecular weight compounds such as terpenoids. Hericium erinaceus produces various cyathane type diterpenoids including erinacines. However, no quantitative data and production kinetics have been reported on the biosynthesis of the erinacines C and P in submerged cultures. In the present study, the production of erinacine C was optimized, and the product formation kinetics as well as the antimicrobial activity were studied by high-performance liquid chromatography (HPLC), high-performance thin-layer chromatography (HPTLC) and direct bioautography. Oatmeal and Edamin ® K were identified to be crucial media components for an efficient production of erinacine C. The highest concentrations of erinacine C were obtained in the optimized culture medium on the 9 th culture day (approximately 260 mg L -1 ). The production of erinacine P was strongly time dependent. The maximum concentration of erinacine P of 184 mg L -1 was observed on the third culture day. Afterwards, the concentrations of erinacine P decreased while the concentrations of erinacine C steadily increased. Comparable results were obtained by HPTLC with UV detection and HPLC with diode-array detection (DAD) analyses. Direct bioautography allowed for an additional analysis of the antimicrobial activity of the secondary metabolites. The C and N sources oatmeal and Edamin ® K induced the formation of erinacine C. Detailed product formation kinetics of the erinacines C and P have been reported for the first time. HPTLC combined with the Aliivibrio fischeri bioassay allowed for an instant detection of cyathane diterpenoids in crude extracts and for an evaluation of the antimicrobial activity of the secondary metabolites directly on the plate.

Screening Some Plants for their Antiproliferative Compounds

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Ufuk Kolak

2012-03-01

Full Text Available This paper covers the screening of the secondary plant products to find a cure against cancer which were piled up during the years. In early stages of these studies highly active antitumor glycoproteins were obtained from native Arizona (USA plants. Later smaller molecules were isolated showing antitumor activity in different test systems. Among these compounds sesquiterpene lactones with an exo-methylene group in the lactone ring, unsaturated diterpenoids and some triterpenoids exhibited activity in vivo and in vitro test systems. A few Colchicum alkaloids showed high activity against murine lymphocytic leukemia (P388. Activity also established in some flavonoidal compounds. Today all around the world research on Natural Products is still going on.

A NEW CYTOTOXIC DOLABELLANE FROM THE INDONESIAN SOFT CORAL Anthelia sp.

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Anggia Murni

2013-12-01

Full Text Available One new dolabellane (1 and two known diterpenoids stolonidiol (2 and clavinflol B (3 have been isolated from the ethyl acetate extract of the Indonesian soft coral Anthelia sp. A new compound 1 exhibited a moderate cytotoxicity against NBT-T2 cells at 10 µg/mL, while known compounds 2 and 3 showed cytotoxicity at 1 and 0.5 µg/mL, respectively. Structure of the new compound 1 was elucidated by interpretation of NMR spectroscopic data (1D and 2D NMR data and mass spectrometry (ESIMS data as well as comparison with those of related ones. This finding should be useful for anti cancer drug development of the promising dolabellane-types compound.

New Abietane and Kaurane Type Diterpenoids from the Stems of Tripterygium regelii

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Dongsheng Fan

2017-01-01

Full Text Available Eleven new abietane type (1‒11, and one new kaurane (12, diterpenes, together with eleven known compounds (13–23, were isolated and identified from the stems of Tripterygium regelii, which has been used as a traditional folk Chinese medicine for the treatment of rheumatoid arthritis in China. The structures of new compounds were characterized by means of the interpretation of high-resolution electrospray ionization mass spectrometry (HRESIMS, extensive nuclear magnetic resonance (NMR spectroscopic data and comparisons of their experimental CD spectra with calculated electronic circular dichroism (ECD spectra. Compound 1 is the first abietane type diterpene with an 18→1 lactone ring. Compound 19 was isolated from the plants of the Tripterygium genus for the first time, and compounds 14–17 were isolated from T. regelii for the first time. Triregelin I (9 showed significant cytotoxicity against A2780 and HepG2 with IC50 values of 5.88 and 11.74 µM, respectively. It was found that this compound was inactive against MCF-7 cells. The discovery of these twelve new diterpenes not only provided information on chemical substances of T. regelii, but also contributed to the chemical diversity of natural terpenoids.

Microbial transformation of isosteviol and inhibitory effects on Epstein-Barr virus activation of the transformation products.

Science.gov (United States)

Akihisa, Toshihiro; Hamasaki, Yusuke; Tokuda, Harukuni; Ukiya, Motohiko; Kimura, Yumiko; Nishino, Hoyoku

2004-03-01

Microbial transformation of isosteviol (2), a beyerane-type diterpenoid obtained from stevioside (1) by acid hydrolysis, yielded 7beta-hydroxyisosteviol (3), 11beta-hydroxyisosteviol (5), and 12beta-hydroxyisosteviol (6) by the fungus Aspergillus niger, 17-hydroxyisosteviol (7) by the fungus Glomerella cingulata, and 3 and 7-oxoisosteviol (4) by the fungus Mortierella elongate. The five metabolites, 3-7, along with 1 and 2 were evaluated for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) in Raji cells as a primary screening test for inhibitors of tumor promoters. All the diterpenes tested showed potent inhibitory effects, with the five metabolites 3-7 exhibiting more potent effects.

Casbane diterpenes and acetophenones of Croton nepetaefolius (Euphorbiaceae)

International Nuclear Information System (INIS)

Santos, Helcio Silva; Mesquita, Francisca Maria Rodrigues; Lemos, Telma Leda G.; Monte, Francisco Jose Queiroz; Braz-Filho, Raimundo

2008-01-01

Croton nepetaefolius is an aromatic plant native to the northeast of Brazil where it is extensively used in folk medicine as a sedative, orexigen and antispasmodic agent. The present work deals with the chromatographic analysis of the ethanolic extract of Croton nepetaefolius stalk. It allowed the isolation and characterization of two diterpenoids named 1,4-dihydroxy-2E,6E,12E-trien-5-one-casbane and 4-hydroxy- 2E,6E,12E-5-one-casbane, two acetophenones named 2-hydroxy-4,6-dimethoxyacetophenone and 2-hydroxy-3,4,6- trimethoxyacetophenone and the steroids 3-O-beta-D-glucopiranosylsitosterol and a mixture of beta-sitosterol and stigmasterol. Structural elucidation was done on the basis of spectral data, mainly high field NMR and EIMS. (author)

Trogopterins A–C: Three new neolignans from feces of Trogopterus xanthipes

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Soyoon Baek

2014-12-01

Full Text Available Seven compounds, including three neolignans 1–3, a norlignan 4, and three diterpenoids 5–7, were isolated from the feces of Trogopterus xanthipes. Structures of these compounds were identified by 1D and 2D NMR as well as MS. The absolute configurations of compounds 1, 2, and 4 were determined by comparing CD spectra and optical rotations. Among the isolated compounds, 1–3 were novel and subsequently named trogopterins A, B, and C, respectively. Likewise, compound 4 was isolated from nature for the first time. Cytotoxic activities of compounds 1–4 were evaluated. Compounds 1–3 exhibited moderate cytotoxic activities against HL-60 cells with IC50 values of 34.77–45.68 μM.

A Dereplication and Bioguided Discovery Approach to Reveal New Compounds from a Marine-Derived Fungus Stilbella fimetaria

DEFF Research Database (Denmark)

Kildgaard, Sara; Subko, Karolina; Phillips, Emma

2017-01-01

towards various cancer cell lines. Further media optimization led to increased production followed by the purification and bioactivity screening of several new and known pimarane-type diterpenoids. A known broad-spectrum antifungal compound, ilicicolin H, was purified along with two new analogues......A marine-derived Stilbella fimetaria fungal strain was screened for new bioactive compounds based on two different approaches: (i) bio-guided approach using cytotoxicity and antimicrobial bioassays; and (ii) dereplication based approach using liquid chromatography with both diode array detection...... aid in the dereplication process, since separate fractions displaying different bioactivities allowed a quick tentative identification of known antimicrobial compounds and of potential new analogues. A new pimarane-type diterpene, myrocin F, was discovered in trace amounts and displayed cytotoxicity...

Metabolic engineering of the diterpenoid sclareol in the moss Physcomitrella patens

DEFF Research Database (Denmark)

Pan, Xiwu

Plant terpenoids play indispensable roles in primary metabolism as the vital constituents in photosynthesis (chlorophylls, carotenoids and plastoquinones), respiration (ubiquinone) and development regulation (gibberellins, abscisic acid, cytokinin and brassinosteroids). They are also the membrane...

New labdane-type diterpenoids from Leonotis leonurus support circumscription of Lamiaceae s.l.

CSIR Research Space (South Africa)

Naidoo, D

2010-08-01

Full Text Available , with Leonotis nepetifolia (L.) R.Br. naturalised in the tropics (Harley et al., 2004). Leonotis leonurus (L.) R.Br., commonly referred to as Wild dagga or Lion’s ear, is a robust perennial shrub which grows usually to 2 m tall and is widespread throughout...

Characterization and quantification of biomarkers from biomass burning at a recent wildfire site in northern Alberta, Canada

Energy Technology Data Exchange (ETDEWEB)

Otto, A.; Gondokusumo, R.; Simpson, M.J. [University of Toronto (Canada). Scarborough College

2006-01-15

The composition of organic matter (OM) in pine vegetation and soil samples from a pine forest which was charred by a wildfire was analyzed using solid-state nuclear magnetic resonance ({sup 13}C NMR) and gas chromatography-mass spectrometry (GC-MS) of solvent extracts to study the effects of thermal alteration on soil organic matter (SOM). The NMR data revealed the presence of unaltered biomolecules (cellulose, proteins) and low contents of aromatic C (15%) in the charred pine wood and cones while the charred soil samples exhibited higher contents of aromatic C (39-56%). The solvent extraction of charred and uncharred plant and soil samples yielded diterpenoids, triterpenoids, steroids, a series of aliphatic lipids, phenols and carbohydrates indicating the predominant input of higher plant OM and minor contributions from microorganisms and/or fauna. The lower yield of solvent extractable aliphatic lipids in the charred samples versus the uncharred samples suggests that these compounds are thermally degraded during a wildfire. Molecular markers for the burning of cellulose (levoglucosan, mannosan, galactosan) were detected in all charred samples. The comparison of charred and uncharred samples allowed the identification of unaltered pine derived biomolecules and their thermal alteration products in the charred samples. Terpenoid and steroid biomolecules were in part altered during incomplete combustion to aromatic, unsaturated and polar derivatives (pyromolecules'') that still retained the characteristic skeleton of their precursors. Since some of the polar degradation products found in the charred soils can be generated either from thermal or microbial degradation, the aromatic and unsaturated hydrocarbon products are preferred as molecular markers for SOM burning. Ratios of biological precursors to aromatic (diterpenoids) or unsaturated products (steroids) indicate that the cyclic lipids in the pine wood and the soil surface horizon were highly altered

Andrographolide inhibits adipogenesis of 3T3-L1 cells by suppressing C/EBPβ expression and activation

International Nuclear Information System (INIS)

Chen, Ching-Chu; Chuang, Wei-Ting; Lin, Ai-Hsuan; Tsai, Chia-Wen; Huang, Chin-Shiu; Chen, Yun-Ting; Chen, Haw-Wen; Lii, Chong-Kuei

2016-01-01

Andrographolide, a diterpenoid, is the most abundant terpenoid in Andrographis paniculata, a popular Chinese herbal medicine. Andrographolide displays diverse biological activities including hypoglycemia, hypolipidemia, anti-inflammation, and anti-tumorigenesis. Recent evidence indicates that andrographolide displays anti-obesity property by inhibiting lipogenic gene expression, however, the underlying mechanisms remain to be elucidated. In this study, the effects of andrographolide on transcription factor cascade and mitotic clonal expansion in 3T3-L1 preadipocyte differentiation into adipocyte were determined. Andrographolide dose-dependently (0–15 μM) inhibited CCAAT/enhancer-binding protein α (C/EBPα) and C/EBPβ mRNA and protein expression as well as peroxisome proliferator-activated receptor γ (PPARγ) protein level during the adipogenesis of 3T3-L1 cells. Concomitantly, fatty acid synthase and stearoyl-CoA desaturase expression and lipid accumulation were attenuated by andrographolide. Oil-red O staining further showed that the first 48 h after the initiation of differentiation was critical for andrographolide inhibition of adipocyte formation. Andrographolide inhibited the phosphorylation of PKA and the activation of cAMP response element-binding protein (CREB) in response to a differentiation cocktail, which led to attenuated C/EBPβ expression. In addition, ERK and GSK3β-dependent C/EBPβ phosphorylation was attenuated by andrographolide. Moreover, andrographolide suppressed cyclin A, cyclin E, and CDK2 expression and impaired the progression of mitotic clonal expansion (MCE) by arresting the cell cycle at the Go/G1 phase. Taken together, these results indicate that andrographolide has a potent anti-obesity action by inhibiting PKA-CREB-mediated C/EBPβ expression as well as C/EBPβ transcriptional activity, which halts MCE progression and attenuates C/EBPα and PPARγ expression. - Highlights: • Andrographolide is a diterpenoid phytochemical. �

Andrographolide inhibits adipogenesis of 3T3-L1 cells by suppressing C/EBPβ expression and activation

Energy Technology Data Exchange (ETDEWEB)

Chen, Ching-Chu [Division of Endocrinology and Metabolism, Department of Medicine, China Medical University Hospital, Taichung, Taiwan (China); Division of Endocrinology and Metabolism, Department of Chinese Medicine, China Medical University, China Medical University, Taichung, Taiwan (China); Chuang, Wei-Ting; Lin, Ai-Hsuan; Tsai, Chia-Wen [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Huang, Chin-Shiu [Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China); Chen, Yun-Ting [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Chen, Haw-Wen, E-mail: chenhw@mail.cmu.edu.tw [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Lii, Chong-Kuei, E-mail: cklii@mail.cmu.edu.tw [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China)

2016-09-15

Andrographolide, a diterpenoid, is the most abundant terpenoid in Andrographis paniculata, a popular Chinese herbal medicine. Andrographolide displays diverse biological activities including hypoglycemia, hypolipidemia, anti-inflammation, and anti-tumorigenesis. Recent evidence indicates that andrographolide displays anti-obesity property by inhibiting lipogenic gene expression, however, the underlying mechanisms remain to be elucidated. In this study, the effects of andrographolide on transcription factor cascade and mitotic clonal expansion in 3T3-L1 preadipocyte differentiation into adipocyte were determined. Andrographolide dose-dependently (0–15 μM) inhibited CCAAT/enhancer-binding protein α (C/EBPα) and C/EBPβ mRNA and protein expression as well as peroxisome proliferator-activated receptor γ (PPARγ) protein level during the adipogenesis of 3T3-L1 cells. Concomitantly, fatty acid synthase and stearoyl-CoA desaturase expression and lipid accumulation were attenuated by andrographolide. Oil-red O staining further showed that the first 48 h after the initiation of differentiation was critical for andrographolide inhibition of adipocyte formation. Andrographolide inhibited the phosphorylation of PKA and the activation of cAMP response element-binding protein (CREB) in response to a differentiation cocktail, which led to attenuated C/EBPβ expression. In addition, ERK and GSK3β-dependent C/EBPβ phosphorylation was attenuated by andrographolide. Moreover, andrographolide suppressed cyclin A, cyclin E, and CDK2 expression and impaired the progression of mitotic clonal expansion (MCE) by arresting the cell cycle at the Go/G1 phase. Taken together, these results indicate that andrographolide has a potent anti-obesity action by inhibiting PKA-CREB-mediated C/EBPβ expression as well as C/EBPβ transcriptional activity, which halts MCE progression and attenuates C/EBPα and PPARγ expression. - Highlights: • Andrographolide is a diterpenoid phytochemical. �

Broad-spectrum antiviral properties of andrographolide.

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Gupta, Swati; Mishra, K P; Ganju, Lilly

2017-03-01

Andrographolide, a diterpenoid, is known for its anti-inflammatory effects. It can be isolated from various plants of the genus Andrographis, commonly known as 'creat'. This purified compound has been tested for its anti-inflammatory effects in various stressful conditions, such as ischemia, pyrogenesis, arthritis, hepatic or neural toxicity, carcinoma, and oxidative stress, Apart from its anti-inflammatory effects, andrographolide also exhibits immunomodulatory effects by effectively enhancing cytotoxic T cells, natural killer (NK) cells, phagocytosis, and antibody-dependent cell-mediated cytotoxicity (ADCC). All these properties of andrographolide form the foundation for the use of this miraculous compound to restrain virus replication and virus-induced pathogenesis. The present article covers antiviral properties of andrographolide in variety of viral infections, with the hope of developing of a new highly potent antiviral drug with multiple effects.

Synthesis and biological evaluation of new C-12(α/β)-(N-) sulfamoyl-phenylamino-14-deoxy-andrographolide derivatives as potent anti-cancer agents.

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Kandanur, Sai Giridhar Sarma; Nanduri, Srinivas; Golakoti, Nageswara Rao

2017-07-01

Andrographolide, the major diterpenoidal constituent of Andrographis paniculata (Acanthaceae) and its derivatives have been reported to possess plethora of biological properties including potent anti-cancer activity. In this work, synthesis and in-vitro anti-cancer evaluation of new C-12-substituted aryl amino 14-deoxy-andrographolide derivatives (III a-f) are reported. The substitutions include various sulfonamide moieties -SO 2 -NH-R 1 . The new derivatives (III a-e) exhibited improved cytotoxicity (GI 50 , TGI and LC 50 ) compared to andrographolide (I) and the corresponding 3,14,19-O-triacetyl andrographolide (II) when evaluated against 60 NCI cell line panel. Compounds III c and III e are found to be non-toxic to normal human dermal fibroblasts (NHDF) cells compared to reference drug THZ-1. Copyright © 2017 Elsevier Ltd. All rights reserved.

Scopadulciol, an inhibitor of gastric H+, K(+)-ATPase from Scoparia dulcis, and its structure-activity relationships.

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Hayashi, T; Asano, S; Mizutani, M; Takeguchi, N; Kojima, T; Okamura, K; Morita, N

1991-01-01

A new tetracyclic diterpenoid, scopadulciol [3], together with 6-methoxybenzoxazolinone, glutinol, and acacetin, was isolated from the 70% EtOH extract of Scoparia dulcis collected in Taiwan. Its structure was elucidated to be 6 beta-benzoyl-12-methyl-13-oxo-9(12)a,9(12)b-dihomo-18-podocarpanol on the basis of spectral data. It mildly inhibited hog gastric H+, K(+)-ATPase. Examination of the inhibitory activities of derivatives of scopadulcic acid B [2], including 3, revealed that methylation of the carboxyl group and introduction of an acetyl group or oxime at C-13 or C-18 markedly enhanced the inhibitory activity, while debenzoylation reduced the activity. Among the 30 compounds tested, compound 12, a methyl ester of scopadulcic acid B [2], showed the most potent activity.

Antimalarial activity of abietane ferruginol analogues possessing a phthalimide group.

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González, Miguel A; Clark, Julie; Connelly, Michele; Rivas, Fatima

2014-11-15

The abietane-type diterpenoid (+)-ferruginol, a bioactive compound isolated from New Zealand's Miro tree (Podocarpus ferruginea), displays relevant pharmacological properties, including antimicrobial, cardioprotective, anti-oxidative, anti-plasmodial, leishmanicidal, anti-ulcerogenic, anti-inflammatory and anticancer. Herein, we demonstrate that ferruginol (1) and some phthalimide containing analogues 2-12 have potential antimalarial activity. The compounds were evaluated against malaria strains 3D7 and K1, and cytotoxicity was measured against a mammalian cell line panel. A promising lead, compound 3, showed potent activity with an EC50 = 86 nM (3D7 strain), 201 nM (K1 strain) and low cytotoxicity in mammalian cells (SI>290). Some structure-activity relationships have been identified for the antimalarial activity in these abietane analogues. Copyright © 2014 Elsevier Ltd. All rights reserved.

New volatile constituents from leaves of Stemodia trifoliata (Link.) Reichb. (Schrophulariaceae)

International Nuclear Information System (INIS)

Silva, Wildson Max B. da; Assuncao, Joao Carlos da C.; Araujo, Renata M.; Silveira, Edilberto R.; Pessoa, Otilia D.L.

2009-01-01

The leaf essential oils of Stemodia trifoliata (Scrophulariaceae), collected at the same month of two different years (August 2005 and 2006), were analyzed by GC-MS and GC-FID. A total of 22 volatile components represented by sesquiterpenes and diterpenes was identified. β-Caryophyllene (9.4-15.4%) and caryophyllene oxide (6.2-9.0%) were the major compounds identified in the sesquiterpene fraction, while the diterpenoids 6α-acetoxymanoyl oxide (13.9-23.2%) and 6α-hydroxymanoyl oxide (25.1-29.7%) were the main constituents of the diterpene fraction. The two novel manoyl oxide derivatives had their structures established by means of spectroscopic methods, particularly 1D and 2D NMR. This work describes for the first time the chemical investigation on the volatile composition of S. trifoliata. (author)

New volatile constituents from leaves of Stemodia trifoliata (Link.) Reichb. (Schrophulariaceae)

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Silva, Wildson Max B. da; Assuncao, Joao Carlos da C.; Araujo, Renata M.; Silveira, Edilberto R.; Pessoa, Otilia D.L. [Universidade Federal do Ceara (UFC), Fortaleza, CE (Brazil). Dept. de Quimica Organica e Inorganica]. E-mail: opessoa@ufc.br

2009-07-01

The leaf essential oils of Stemodia trifoliata (Scrophulariaceae), collected at the same month of two different years (August 2005 and 2006), were analyzed by GC-MS and GC-FID. A total of 22 volatile components represented by sesquiterpenes and diterpenes was identified. {beta}-Caryophyllene (9.4-15.4%) and caryophyllene oxide (6.2-9.0%) were the major compounds identified in the sesquiterpene fraction, while the diterpenoids 6{alpha}-acetoxymanoyl oxide (13.9-23.2%) and 6{alpha}-hydroxymanoyl oxide (25.1-29.7%) were the main constituents of the diterpene fraction. The two novel manoyl oxide derivatives had their structures established by means of spectroscopic methods, particularly 1D and 2D NMR. This work describes for the first time the chemical investigation on the volatile composition of S. trifoliata. (author)

Preliminary correlation of organic molecular tracers in residential wood smoke with the source of fuel

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Standley, Laurel J.; Simoneit, Bernd R. T.

Polar cyclic di- and triterpenoids were analyzed in the extracts of residential wood combustion aerosols collected in suburban sections of Eugene, Oakridge and Corvallis, Oregon. Additional samples collected included alder wood, smoke from two wood stoves burning only alder or pine as fuel, soot from a stove burning alder and a fireplace where oak was the predominant fuel. Due to the relatively cooler temperatures present under the smoldering conditions of residential wood combustion, as compared to the active burning of forest fires and slash burns, incomplete combustion resulted in the preservation of high levels of the natural products. There were three distinct signatures which could be used to trace relative input from coniferous, alder and oak combustion products, i.e. diterpenoids, lupane-derived triterpenoids and friedelin, respectively. Conifer combustion products dominated the suburban smoke aerosols.

Isolation and identification of bioactive compounds in Andrographis paniculata (Chuanxinlian

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Lin Bi-Fong

2010-05-01

Full Text Available Abstract Andrographis paniculata (Burm. f. Nees (Acanthaceae is a medicinal plant used in many countries. Its major constituents are diterpenoids, flavonoids and polyphenols. Among the single compounds extracted from A. paniculata, andrographolide is the major one in terms of bioactive properties and abundance. Among the andrographolide analogues, 14-deoxy-11,12-didehydroandrographolide is immunostimulatory, anti-infective and anti-atherosclerotic; neoandrographolide is anti-inflammatory, anti-infective and anti-hepatotoxic; 14-deoxyandrographolide is immunomodulatory and anti-atherosclerotic. Among the less abundant compounds from A. paniculata, andrograpanin is both anti-inflammatory and anti-infective; 14-deoxy-14,15-dehydroandrographolide is anti-inflammatory; isoandrographolide, 3,19-isopropylideneandrographolide and 14-acetylandrographolide are tumor suppressive; arabinogalactan proteins are anti-hepatotoxic. The four flavonoids from A. paniculata, namely 7-O-methylwogonin, apigenin, onysilin and 3,4-dicaffeoylquinic acid are anti-atherosclerotic.

Transcript Quantification of Genes Involved in Steviol Glycoside Biosynthesis in Stevia rebaudiana Bertoni by Real-Time Polymerase Chain Reaction (RT-PCR).

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Modi, Arpan; Kumar, Nitish; Narayanan, Subhash

2016-01-01

Stevia (Stevia rebaudiana Bertoni) is a medicinal plant having sweet, diterpenoid glycosides known as steviol glycosides which are 200-300 times sweeter than sucrose (0.4 % solution). They are synthesized mainly in the leaves via plastid localized 2-C-methyl-D-erythrose-4-phosphate pathway (MEP pathway). Fifteen genes are involved in the formation of these glycosides. In the present protocol, a method for the quantification of transcripts of these genes is shown. The work involves RNA extraction and cDNA preparation, and therefore, procedures for the confirmation of DNA-free cDNA preparation have also been illustrated. Moreover, details of plant treatments are not mentioned as this protocol may apply to relative gene expression profile in any medicinal plant with any treatment. The treatments are numbered as T0 (Control), T1, T2, T3, and T4.

PHYTOCHEMICAL ASSESSMENT ON N-HEXANE EXTRACT AND FRACTIONS OF Marsilea crenata Presl. LEAVES THROUGH GC-MS

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Burhan Ma'arif

2016-08-01

Full Text Available Estrogen deficiency causes various health problems in postmenopausal women, including osteoporosis. Phytoestrogen emerged as a potential alternative of estrogen with minimum side effects. Green clover (Marsilea crenata Presl. is a typical plant in East Java which suspected contains estrogen-like substances. The aim of this research was to report the phytochemical properties of M. crenata using GC-MS as a preliminary study. M. crenata leaves were dried and extracted with n-hexane, then separated using vacuum column chromatography to get four fractions, after that the n-hexane extract and four fractions were identified with GC-MS. The results of GC-MS analysis showed some compounds contained in M. crenata leaves like monoterpenoid, diterpenoid, fatty acid compounds, and other unknown compounds. The results obtained in this research indicated a promising potential of M. crenata as medicinal plants, especially as antiosteoporotic agent.

Semi-Empirical Predictions on the Structure and Properties of ent-Kaurenoic Acid and Derivatives

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Jose Isagani B. Janairo

2011-01-01

Full Text Available The physicochemical properties of ent- kaurenoic acid model derivatives, which possibly influence its therapeutic application, were calculated. Results revealed that the molecule possess favourable attributes which renders it possible to be considered as a drug lead only that its very hydrophobic nature can result to poor bioavailabilty, low absorption and poor systemic circulation. In silico simulations revealed that this setback can be overcome by introduction of hydroxyl group to the tertiary carbon of ent-kaurenoic acid employing m-CPBA catalyzed hydroxylation, thus, unleashing its full drug potency. Moreover, molecular similarity analyses derived from semi-empirical calculations between ent-kaurenoic acid and a set of kaurane diterpenoids showed differences in hydrophobic complementarity, size and electronic properties despite possessing nearly identical molecular frameworks, thus, arriving in a generalization for their observed mechanistic differences on acting on different targets.

Microtropiosides A-F: ent-Labdane diterpenoid glucosides from the leaves of Microtropis japonica (Celastraceae).

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Koyama, Yuka; Matsunami, Katsuyoshi; Otsuka, Hideaki; Shinzato, Takakazu; Takeda, Yoshio

2010-04-01

From a 1-BuOH-soluble fraction of a MeOH extract of the leaves of Microtropis japonica, collected in the Okinawa islands, six ent-labdane glucosides, named microtropiosides A-F, were isolated together with one known acyclic sesquiterpene glucoside. Their structures were elucidated by a combination of spectroscopic analyses, and their absolute configurations determined by application of the beta-D-glucopyranosylation-induced shift-trend rule in (13)C NMR spectroscopy and the modified Mosher's method. Copyright 2010 Elsevier Ltd. All rights reserved.

Three New Indole Diterpenoids from the Sea-Anemone-Derived Fungus Penicillium sp. AS-79.

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Hu, Xue-Yi; Meng, Ling-Hong; Li, Xin; Yang, Sui-Qun; Li, Xiao-Ming; Wang, Bin-Gui

2017-05-12

Three new indolediterpenoids, namely, 22-hydroxylshearinine F ( 1 ), 6-hydroxylpaspalinine ( 2 ), and 7- O -acetylemindole SB ( 3 ), along with eight related known analogs ( 4 - 11 ), were isolated from the sea-anemone-derived fungus Penicillium sp. AS-79. The structures and relative configurations of these compounds were determined by a detailed interpretation of the spectroscopic data, and their absolute configurations were determined by ECD calculations ( 1 and 2 ) and single-crystal X-ray diffraction ( 3 ). Some of these compounds exhibited prominent activity against aquatic and human pathogenic microbes.

Chemical characteristics of Upper Cretaceous (Turonian) jet of the Gosau Group of Gams/Hieflau (Styria, Austria)

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Bechtel, A.; Gratzer, R.; Sachsenhofer, R.F. [Institut fuer Geowissenschaften, Prospektion und Angewandte Sedimentologie, Montanuniversitaet Leoben, Peter-Tunner-Str. 5, A-8700 Leoben (Austria)

2001-03-01

Jet and coaly sediments within the Upper Cretaceous (Gosau) Schoenleiten Formation were collected from two outcrops near Gams/Hieflau (Styria, Austria). For comparison, additional jet and coal samples from different Gosau localities were included in the study. The identification of jet as bituminous driftwood (collotelinite) has been provided by microscopical examination of organic matter [Kollmann, H.A. and Sachsenhofer, R.F., Mitt. Ref. Geol. und Palaeont. Landesmuseum Joanneum SH 2 (1998) 223]. Rock-Eval analyses revealed enhanced HI and lower T{sub max} values of jet compared with the coals and coaly shales. The results reflect the higher contents of bituminous organic matter compared to vitrain-rich coals of similar maturity. In comparison with the coals and coaly shales, high amounts of liberated hydrocarbons (mg HC/g C{sub org}) are in contrast to generally lower yields of soluble organic matter during extraction with dichloromethane, indicating that portions of the hydrocarbons are liberated from lipids loosely bound to kerogen during pyrolysis. Further differences in n-alkane distribution patterns, odd over even predominance, pristane/phytane, and pristane/n-C{sub 17} ratios exist between jet, coals and coaly shales. The microbial origin of short-chain n-alkanes presumably resulted from the degradation of the predominant odd-numbered long-chain n-alkanes within the jet. The occurrence of biological markers (sesqui and diterpenoids) within the sediments (coaly shales), coals and jet samples indicates the origin of terrestrial organic matter from conifers. Biomarker composition of jet samples indicates enhanced aromatisation of sesqui and diterpenoids. These results correspond to enhanced aromatisation of steranes, as reflected by generally higher relative contents of triaromatic steroids in the jet. Because of comparable maturation (0.5-0.6% R{sub r}) of the coals, coaly shales and the jet samples, confirmed by the isomerisation of {alpha}{beta} C{sub 31

Storage method, drying processes and extraction procedures strongly affect the phenolic fraction of rosemary leaves: an HPLC/DAD/MS study.

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Mulinacci, N; Innocenti, M; Bellumori, M; Giaccherini, C; Martini, V; Michelozzi, M

2011-07-15

The Rosmarinus officinalis L. is widely known for its numerous applications in the food field but also for the increasing interest in its pharmaceutical properties. Two groups of compounds are mainly responsible for the biological activities of the plant: the volatile fraction and the phenolic constituents. The latter group is mainly constituted by rosmarinic acid, by a flavonoidic fraction and by some diterpenoid compounds structurally derived from the carnosic acid. The aim of our work was to optimize the extractive and analytical procedure for the determination of all the phenolic constituents. Moreover the chemical stability of the main phenols, depending on the storage condition, the different drying procedures and the extraction solvent, have been evaluated. This method allowed to detect up to 29 different constituents at the same time in a relatively short time. The described procedure has the advantage to being able to detect and quantify several classes of compounds, among them numerous minor flavonoids, thus contributing to improving knowledge of the plant. The findings from this study have demonstrated that storing the raw fresh material in the freezer is not appropriate for rosemary, mainly due to the rapid disappearing of the rosmarinic acid during the freezing/thawing process. Regarding the flavonoidic fraction, consistent decrements, were highlighted in the dried samples at room temperature if compared with the fresh leaf. Rosmarinic acid, appeared very sensitive also to mild drying processes. The total diterpenoidic content undergoes to little changes when the leaves are freeze dried or frozen and limited losses are observed working on dried leaves at room temperature. Nevertheless it can be taken in account that this fraction is very sensitive to the water presence during the extraction that favors the conversion of carnosic acid toward it oxidized form carnosol. From our findings, it appear evident that when evaluating the phenolic content in

Ontology-based systematic representation and analysis of traditional Chinese drugs against rheumatism.

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Liu, Qingping; Wang, Jiahao; Zhu, Yan; He, Yongqun

2017-12-21

Rheumatism represents any disease condition marked with inflammation and pain in the joints, muscles, or connective tissues. Many traditional Chinese drugs have been used for a long time to treat rheumatism. However, a comprehensive information source for these drugs is still missing, and their anti-rheumatism mechanisms remain unclear. An ontology for anti-rheumatism traditional Chinese drugs would strongly support the representation, analysis, and understanding of these drugs. In this study, we first systematically collected reported information about 26 traditional Chinese decoction pieces drugs, including their chemical ingredients and adverse events (AEs). By mostly reusing terms from existing ontologies (e.g., TCMDPO for traditional Chinese medicines, NCBITaxon for taxonomy, ChEBI for chemical elements, and OAE for adverse events) and making semantic axioms linking different entities, we developed the Ontology of Chinese Medicine for Rheumatism (OCMR) that includes over 3000 class terms. Our OCMR analysis found that these 26 traditional Chinese decoction pieces are made from anatomic entities (e.g., root and stem) from 3 Bilateria animals and 23 Mesangiospermae plants. Anti-inflammatory and antineoplastic roles are important for anti-rheumatism drugs. Using the total of 555 unique ChEBI chemical entities identified from these drugs, our ChEBI-based classification analysis identified 18 anti-inflammatory, 33 antineoplastic chemicals, and 9 chemicals (including 3 diterpenoids and 3 triterpenoids) having both anti-inflammatory and antineoplastic roles. Furthermore, our study detected 22 diterpenoids and 23 triterpenoids, including 16 pentacyclic triterpenoids that are likely bioactive against rheumatism. Six drugs were found to be associated with 184 unique AEs, including three AEs (i.e., dizziness, nausea and vomiting, and anorexia) each associated with 5 drugs. Several chemical entities are classified as neurotoxins (e.g., diethyl phthalate) and allergens (e

STRUCTURE MODIFICATION OF ANDROGRAPHOLIDE TO IMPROVE ITS POTENCY AS ANTICANCER

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Hadi Poerwono

2010-06-01

Full Text Available Andrographolide, a diterpenoid lactone isolated from the herb of Andrographis paniculata and known to possess antitumor activity in breast cancer models was subjected to semisynthesis leading to the preparation of a number of derivatives. After protection of the two hydroxyl groups present at C-3 and C-19 to give 3,19-isopropylidene and 3,19-benzylidene andrographolides, the remaining hydroxyl group at C-14 of andrographolide was treated with acid anhydride or acid chloride under base condition. Unfortunately, the reactions gave only 14-dehydroandrographolide as well as unidentified diacyl compounds in replace of the target molecule 14-O-acyl andrographolide. An alternative procedure using neat acetic anhydride under reflux gave the acetyl derivatives. The resulted compounds exhibited cytotoxic activity against MCF-7 breast cancer cells with better growth inhibition than the parent compound andrographolide.   Keywords: andrographolide, acylation, anticancer, cytotoxic, breast cancer cells.

Analysis of Taiwan patents for the medicinal mushroom "Niu-Chang- Chih".

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Chen, Yu-Fen; Lu, Wen-Ling; Wu, Ming-Der; Yuan, Gwo-Fang

2013-04-01

"Niu-Chang-Chih" (Antrodia cinnanomea) is a medicinal mushroom that has only been collected from the aromatic tree, Cinnamomum kanehirai, which is native to Taiwan. A total of 105 Taiwan patent applications and patents for "Niu-Chang-Chih" were collected and analyzed. Patent applications and granted patents claiming newly identified functional components from "Niu-Chang-Chih," biologically pure cultures of the mushroom strain, and cultivation of "Niu-Chang-Chih" were examined. Several applications and patents claim identified active compounds from "Niu-Chang- Chih," which provide better patent protection. These newly identified functional compounds include cyclohexanones, maleic and succinic acid derivatives, labdane diterpenoids, and benzenoids. Newly identified functional proteins include a glutathione-dependent formaldehyde dehydrogenase (GFD), a glycoprotein named ACA1, and a laccase. Newly identified functional polysaccharides include ACP1, ACP2, and ACP3. The number of patents for newly identified compounds and their uses are expected to continue growing.

In vitro and in vivo antiviral activity of scopadulcic acid B from Scoparia dulcis, Scrophulariaceae, against herpes simplex virus type 1.

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Hayashi, K; Niwayama, S; Hayashi, T; Nago, R; Ochiai, H; Morita, N

1988-09-01

The antiviral activity of five diterpenoids isolated from Scoparia dulcis L., Scrophulariaceae, was examined in vitro against herpes simplex virus type 1. Among these compounds, only scopadulcic acid B was found to inhibit the viral replication with the in vitro therapeutic index of 16.7. The action of scopadulcic acid B was not due to a direct virucidal effect or inhibition of virus attachment to host cells. Single-cycle replication experiments indicated that the compound interfered with considerably early events of virus growth. The influence of scopadulcic acid B on the course of the primary corneal herpes simplex virus infection was investigated by means of a hamster test model. When the treatment was initiated immediately after virus inoculation, scopadulcic acid B, when applied orally or intraperitoneally, effectively prolonged both the appearance of herpetic lesions and the survival time at the dose of 100 and 200 mg/kg per day.

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems.

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Kemper, Katarina; Hirte, Max; Reinbold, Markus; Fuchs, Monika; Brück, Thomas

2017-01-01

With over 50.000 identified compounds terpenes are the largest and most structurally diverse group of natural products. They are ubiquitous in bacteria, plants, animals and fungi, conducting several biological functions such as cell wall components or defense mechanisms. Industrial applications entail among others pharmaceuticals, food additives, vitamins, fragrances, fuels and fuel additives. Central building blocks of all terpenes are the isoprenoid compounds isopentenyl diphosphate and dimethylallyl diphosphate. Bacteria like Escherichia coli harbor a native metabolic pathway for these isoprenoids that is quite amenable for genetic engineering. Together with recombinant terpene biosynthesis modules, they are very suitable hosts for heterologous production of high value terpenes. Yet, in contrast to the number of extracted and characterized terpenes, little is known about the specific biosynthetic enzymes that are involved especially in the formation of highly functionalized compounds. Novel approaches discussed in this review include metabolic engineering as well as site-directed mutagenesis to expand the natural terpene landscape. Focusing mainly on the validation of successful integration of engineered biosynthetic pathways into optimized terpene producing Escherichia coli , this review shall give an insight in recent progresses regarding manipulation of mostly diterpene synthases.

HPTLC analysis of hepatoprotective diterpenoid andrographolide from Andrographis paniculata nees (kalmegh)

OpenAIRE

Raina Archana; Kumar A; Pareek S

2007-01-01

A rapid, accurate and simple high performance thin layer chromatography method for quantitative estimation of andrographolide in Andrographis paniculata is described here. The assay combines separation of andrographolide on silica gel 60 F 254 HPTLC plates followed by scanning of the spots at 232 nm using a Camag Scanner 3. Thirty germplasm collections of Andrographis paniculata were evaluated for andrographolide content by this method. Andrographolide content ranged from 1.14% to...

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

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Katarina Kemper

2017-05-01

Full Text Available With over 50.000 identified compounds terpenes are the largest and most structurally diverse group of natural products. They are ubiquitous in bacteria, plants, animals and fungi, conducting several biological functions such as cell wall components or defense mechanisms. Industrial applications entail among others pharmaceuticals, food additives, vitamins, fragrances, fuels and fuel additives. Central building blocks of all terpenes are the isoprenoid compounds isopentenyl diphosphate and dimethylallyl diphosphate. Bacteria like Escherichia coli harbor a native metabolic pathway for these isoprenoids that is quite amenable for genetic engineering. Together with recombinant terpene biosynthesis modules, they are very suitable hosts for heterologous production of high value terpenes. Yet, in contrast to the number of extracted and characterized terpenes, little is known about the specific biosynthetic enzymes that are involved especially in the formation of highly functionalized compounds. Novel approaches discussed in this review include metabolic engineering as well as site-directed mutagenesis to expand the natural terpene landscape. Focusing mainly on the validation of successful integration of engineered biosynthetic pathways into optimized terpene producing Escherichia coli, this review shall give an insight in recent progresses regarding manipulation of mostly diterpene synthases.

Antioxidant compounds in Salvia officinalis L. shoot and hairy root cultures in the nutrient sprinkle bioreactor

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Izabela Grzegorczyk

2011-01-01

Full Text Available The study focused on the production of compounds with antioxidant activity in hairy root and shoot cultures of Salvia officinalis grown in laboratory-scale sprinkle nutrient bioreactors. HPLC analysis showed that production of rosmarinic acid in transformed roots (34.65 ±1.07 mg l-1 was higher that in shoot culture (26.24 ±0.48 mg l-1. In the latter diterpenoids: carnosic acid (1.74 ±0.02 mg l-1 and carnosol (1.34 ±0.01 mg l-1 were also found. Biomass accumulation after a growth period in the bioreactor was also studied. An 18-fold increase in hairy root biomass was recorded after 40 days of culture. In sage shoot culture, biomass increased 43 times after 21 days of bioreactor run. The current operating conditions of the bioreactor were not suitable for the propagation of Salvia officinalis mainly due to the hyperhydricity problem of leaves and stems.

Isolation and Identification of Secondary Metabolites from the Aerial Parts of Stachys lavandulifolia Vahl.

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Sajjadi, Seyed Ebrahim; Ghanadian, Seyed Mustafa; Rabbani, Mohammad; Tahmasbi, Fateme

2017-01-01

Stachys lavandulifolia Vahl is an herbaceous wild plant native to Iran which is traditionally used in Iranian folk medicine as a mild sedative tea for reducing anxiety and for treatment of gastrointestinal disorders. Our previous study on ethyl acetate extract of S. lavandulifolia proved anti-anxiolytic activity and so the present study was designed to determine chemical components of this biologically active fraction. The extract was prepared using maceration method. Column chromatography and medium pressure liquid chromatography (MPLC) was used respectively to separate the fractions. Finally, some evaluated fractions were used for high pressure liquid (HPLC) and peak shaving recycle technique to achieve more purification. Separated compounds were determined using NMR analysis and mass spectroscopy. Six compounds have been isolated from ethylacetate extract of aerial parts of S. lavandulifolia including four flavonoids (apigenin, kumatakenin, penduletin and 4', 7-dihyroxy- 3, 5, 6-trimethoxy flavon), a labdan diterpenoid (labda-13-en-8, 15-diol), and an iridoid.

Synthesis and in vitro cytotoxicity of novel C-12 substituted-14-deoxy-andrographolide derivatives as potent anti-cancer agents.

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Kandanur, Sai Giridhar Sarma; Golakoti, Nageswara Rao; Nanduri, Srinivas

2015-12-15

Andrographolide, the major labdane diterpenoid from Andrographis paniculata has been reported to be cytotoxic against various cancer cells in vitro. Our research efforts led to the discovery of novel 12-phenyl thio and 12-aryl amino-14-deoxy-andrographolide derivatives (III q and III r) with potent cytotoxic activity, 12-benzyl amino-14-deoxy-andrographolide analogues showing broad range of cytotoxic activity against most of the cell lines and 12-alkyl amino-14-deoxy-andrographolide derivatives being selective to few cell lines (PC-3 and HOP-92), when the selected analogues were evaluated against 60 human cancer cell line panel at National Cancer Institute (N.C.I.), USA. The SAR (structure activity relationship) studies demonstrated potent activity for the compounds containing the following functionalities at C-12: substituted aryl amino/phenyl thio>benzylamine>alkyl amine. The significant cytotoxic activity observed for compounds III q and III r suggest that these could serve as templates for further optimization. Copyright © 2015 Elsevier Ltd. All rights reserved.

Polar compounds isolated from the leaves of Calea prunifolia H.B.K. and their anti-adrenergic related vasodilator activity

International Nuclear Information System (INIS)

Puebla, Pilar; San Feliciano, Arturo; Aranguren, Nataly; Rincon, Javier; Rojas, Maritza; Guerrero, Mario

2011-01-01

The leaves of Calea prunifolia H.B.K., medicinal specie used in Colombian folk medicine for hypertension have been analysed for their chemical constituents, resulting in the isolation of one flavonoid glycoside, one quinic acid derivative and one kaurane diterpenoid glycoside. Their chemical structures were elucidated on the basis of spectral analysis, including HRMS, 1D- and 2D-NMR data. The vasodilator effect related to anti adrenergic activity of the three compounds was evaluated in isolated aortic rings from Wistar rats contracted cumulatively with phenylephrine (from 1 x 10 -9 to 5 x 10 -5 mol L -1 ). Although these compounds were devoid of significant vasodilator activity when they were tested alone (1 μg mL-1), mixtures of them (1:1:1) and the own EtOH extract exerted preventive anti-adrenergic activity increasing the phenylephrine CE 50 from 2.3 x 10 -8 to 1.3 x 10 -7 and 8.0 x 10 -7 mol L -1 , respectively. (author)

Pekinenin E Inhibits the Growth of Hepatocellular Carcinoma by Promoting Endoplasmic Reticulum Stress Mediated Cell Death

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Lu Fan

2017-06-01

Full Text Available Hepatocellular carcinoma (HCC is a malignant primary liver cancer with poor prognosis. In the present study, we report that pekinenin E (PE, a casbane diterpenoid derived from the roots of Euphorbia pekinensis, has a strong antitumor activity against human HCC cells both in vitro and in vivo. PE suppressed the growth of human HCC cells Hep G2 and SMMC-7721. In addition, PE-mediated endoplasmic reticulum (ER stress caused increasing expressions of C/EBP homologous protein (CHOP, leading to apoptosis in HCC cells both in vitro and in vivo. Inhibition of ER stress with CHOP small interfering RNA or 4-phenyl-butyric acid partially reversed PE-induced cell death. Furthermore, PE induced S cell cycle arrest, which could also be partially reversed by CHOP knockdown. In all, these findings suggest that PE causes ER stress-associated cell death and cell cycle arrest, and it may serve as a potent agent for curing human HCC.

An In-Silico Investigation of Phytochemicals as Antiviral Agents Against Dengue Fever.

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Powers, Chelsea N; Setzer, William N

2016-01-01

A virtual screening analysis of our library of phytochemical structures with dengue virus protein targets has been carried out using a molecular docking approach. A total of 2194 plant-derived secondary metabolites have been docked. This molecule set comprised of 290 alkaloids (68 indole alkaloids, 153 isoquinoline alkaloids, 5 quinoline alkaloids, 13 piperidine alkaloids, 14 steroidal alkaloids, and 37 miscellaneous alkaloids), 678 terpenoids (47 monoterpenoids, 169 sesquiterpenoids, 265 diterpenoids, 81 steroids, and 96 triterpenoids), 20 aurones, 81 chalcones, 349 flavonoids, 120 isoflavonoids, 74 lignans, 58 stilbenoids, 169 miscellaneous polyphenolic compounds, 100 coumarins, 28 xanthones, 67 quinones, and 160 miscellaneous phytochemicals. Dengue virus protein targets examined included dengue virus protease (NS2B-NS3pro), helicase (NS3 helicase), methyltransferase (MTase), RNA-dependent RNA polymerase (RdRp), and the dengue virus envelope protein. Polyphenolic compounds, flavonoids, chalcones, and other phenolics were the most numerous of the strongly docking ligands for dengue virus protein targets.

The genus Vitex: A review.

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Rani, Anita; Sharma, Anupam

2013-07-01

The review includes 161 references on the genus Vitex, and comprises ethnopharmacology, morphology and microscopy, phytoconstituents, pharmacological reports, clinical studies, and toxicology of the prominent species of Vitex. Essential oils, flavonoids, iridoid glycosides, diterpenoides and ligans constitute major classes of phytoconstituents of the genus. A few species of this genus have medicinal value, among these, leaves and fruits of V. agnus-castus Linn. (Verbenaceae) has been traditionally used in treatment of women complaints. V. agnus-castus has also been included in herbal remedies, which are in clinical use to regulate the menstrual cycle, reduce premenstrual symptom tension and anxiety, treat some menopausal symptoms as well as to treat hormonally induced acne. Despite a long tradition of use of some species, the genus has not been explored properly. In the concluding part, the future scope of Vitex species has been emphasized with a view to establish their multifarious biological activities and mode of action.

Identification, quantification, and sensory characterization of steviol glycosides from differently processed Stevia rebaudiana commercial extracts.

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Espinoza, María Inés; Vincken, Jean-Paul; Sanders, Mark; Castro, Cristian; Stieger, Markus; Agosin, Eduardo

2014-12-10

Stevia rebaudiana is known for its sweet-tasting ent-kaurene diterpenoid glycosides. Several manufacturing strategies are currently employed to obtain Stevia sweeteners with the lowest possible off-flavors. The chemical composition of four commercial S. rebaudiana extracts, obtained by different technologies, was characterized using UHPLC-ESI-MS(n). The composition of one of the ethanol-crystallized extracts (EC2) was entirely rebaudioside A, whereas the enzymatically modified (EM) extract contained the lowest concentration of this compound (2.7 mg/100 mg). The membrane-purified (MP) extract had the highest content of minor natural steviol glycosides (23.7 mg/100 mg total extract) versus an average of 2.4 mg/100 mg total extract for the EC samples. Thirteen trained panelists evaluated sweetness, bitterness, licorice, and metallic attributes of all four extracts. The highest licorice intensity (p ≤ 0.05) was found for MP. Both samples EC1 and EC2, despite their different chemical compositions, showed no significant differences in sensory perception.

Characterization of Stevia leaves by LC-QTOF MS/MS analysis of polar and non-polar extracts.

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Molina-Calle, M; Priego-Capote, F; Luque de Castro, M D

2017-03-15

Stevia is currently a well-known plant thanks to its sweeting power. Numerous studies that elucidate its composition were exclusively focused on determination of steviol and its glycosides. Untargeted analysis was applied to obtain a profile of main compounds present in extracts from Stevia (Stevia rebaudiana Bertoni) leaves using LC-MS in high resolution mode with a quadrupole-time of flight analyzer. Eighty-nine compounds were tentatively identified and classified into different families: flavonoids; quinic and caffeic acids and derivatives; diterpenoids (including steviol and glycosides); sesquiterpenoids; amino acids and derivatives; fatty amides and derivatives; fatty acids and derivatives; oligosaccharides; glycerolipids; purines; and retinoids. New steviol glycosides were tentatively identified and their possible structures proposed. Other compounds were tentatively identified in Stevia for the first time, such as fatty acid amides. These results reveal the wide range of compounds present in Stevia, which could be responsible for the nutraceutical effects ascribed to their leaves. Copyright © 2016 Elsevier Ltd. All rights reserved.

Tyrosinase inhibitors from Calceolaria integrifolia s.l.: Calceolaria talcana aerial parts.

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Muñoz, Evelyn; Avila, Jose G; Alarcón, Julio; Kubo, Isao; Werner, Enrique; Céspedes, Carlos L

2013-05-08

As a defense mechanism of the aerial parts of Calceolaria talcana (Calceolariaceae; formerly Scrophulariaceae) against herbivore offenses and insect pest attack, diterpenoids, triterpenoids, phenylethanoids, flavonoids, and iridoids are rapidly accumulated along the aerial parts, resulting in a unique natural biopesticide complex from this plant. In addition to verbascoside a series of known compounds were screened for their inhibitory activity against mushroom tyrosinase and protease enzymes. Ethyl acetate and n-hexane extracts, together with cyclopropyl-7,15-ent-pimaradiene (1), abietatriene (2), ursolic acid (3), α-lupeol (4), β-sitosterol (5), 2-hydroxy-3-(1,1-dimethylallyl)-1,4-naphthoquinone (6), α-dunnione (7), verbascoside (8), martynoside (9), and some known model compounds proved to be inhibitors of oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) catalyzed by tyrosinase (EC 1.14.18.1) with an IC50 between 10.0 and 200 ppm or μM, respectively, suggesting that phenolic moieties in the molecules assayed are important for the activity.

Antitumor and Antibacterial Derivatives of Oridonin: A Main Composition of Dong-Ling-Cao

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Dahong Li

2016-04-01

Full Text Available Isodon rubescens has been used as a traditional green tea for more than 1000 years and many medicinal functions of I. rubescens are also very useful, such as its well-known antitumor and antibacterial activities. Oridonin, a bioactive ent-kaurane diterpenoid, is the major ingredient of this medicinal tea. Herein, 22 novel oridonin derivatives were designed and synthesized. The antibacterial activity was evaluated for the first time. Compound 12 was the most promising one with MIC of 2.0 μg/mL against B. subtilis, which was nearly 3-fold stronger than positive control chloromycetin. The antiproliferative property was also assayed and compound 19 showed stronger activity than taxol. The apoptosis-inducing ability, cell cycle arrest effect at S phase and influence of mitochondrial membrane potential by 19 in CaEs-17 cancer cells were first disclosed. Based on the above results, the cell apoptosis induced by compound 19 in CaEs-17 cells was most probably involved in the intrinsic apoptotic pathway.

ent-Jungermannenone C Triggers Reactive Oxygen Species-Dependent Cell Differentiation in Leukemia Cells.

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Yue, Zongwei; Xiao, Xinhua; Wu, Jinbao; Zhou, Xiaozhou; Liu, Weilong; Liu, Yaxi; Li, Houhua; Chen, Guoqiang; Wu, Yingli; Lei, Xiaoguang

2018-02-23

Acute myeloid leukemia (AML) is a hematologic malignancy that is characterized by clonal proliferation of myeloid blasts. Despite the progress that has been made in the treatment of various malignant hematopoietic diseases, the effective treatment of AML remains very challenging. Differentiation therapy has emerged as a promising approach for leukemia treatment, and new and effective chemical agents to trigger the differentiation of AML cells, especially drug-resistant cells, are urgently required. Herein, the natural product jungermannenone C, a tetracyclic diterpenoid isolated from liverworts, is reported to induce cell differentiation in AML cells. Interestingly, the unnatural enantiomer of jungermannenone C (1) was found to be more potent than jungermannenone C in inducing cell differentiation. Furthermore, compound 1 targets peroxiredoxins I and II by selectively binding to the conserved cysteine residues and leads to cellular reactive oxygen species accumulation. Accordingly, ent-jungermannenone C (1) shows potential for further investigation as an effective differentiation therapy against AML.

Chemical Constituents from Hericium erinaceus Promote Neuronal Survival and Potentiate Neurite Outgrowth via the TrkA/Erk1/2 Pathway.

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Zhang, Cheng-Chen; Cao, Chen-Yu; Kubo, Miwa; Harada, Kenichi; Yan, Xi-Tao; Fukuyama, Yoshiyasu; Gao, Jin-Ming

2017-07-30

Hericium erinaceus is a culinary-medicinal mushroom used traditionally in Eastern Asia to improve memory. In this work, we investigated the neuroprotective and neuritogenic effects of the secondary metabolites isolated from the MeOH extract of cultured mycelium of H. erinaceus and the primary mechanisms involved. One new dihydropyridine compound ( 6 ) and one new natural product ( 2 ) together with five known compounds ( 1 , 3 - 5 , 7 ) were obtained and their structures were elucidated by spectroscopic analysis, including 2D NMR and HRMS. The cell-based screening for bioactivity showed that 4-chloro-3,5-dimethoxybenzoic methyl ester ( 1 ) and a cyathane diterpenoid, erincine A ( 3 ), not only potentiated NGF-induced neurite outgrowth but also protected neuronally-differentiated cells against deprivation of NGF in PC12 pheochromocytoma cells. Additionally, compound 3 induced neuritogenesis in primary rat cortex neurons. Furthermore, our results revealed that TrkA-mediated and Erk1/2-dependant pathways could be involved in 1 and 3 -promoted NGF-induced neurite outgrowth in PC12 cells.

Antiproliferative Compounds of Cyphostemma greveana from a Madagascar Dry Forest[1

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Cao, Shugeng; Hou, Yanpeng; Brodie, Peggy; Miller, James S.; Randrianaivo, Richard; Rakotobe, Etienne; Rasamison, Vincent E.

2011-01-01

Bioassay-guided fractionation of the EtOH extracts obtained from a plant identified as Cyphostemma greveana Desc. (Vitaceae) led to the identification of one macrolide, lasiodiplodin (1), three sesquiterpenoids, 12-hydroxy-15-oxo-selina-4,1l-diene (2), 1β,6α-dihydroxyeudesm-4(15)-ene (3), and (7R*)-opposit-4(15)-ene-1β,7-diol (5), and the new diterpenoid, 16,18-dihydroxykolavenic acid lactone (4). All the isolates were tested against the A2780 human ovarian cancer cell line, and compound 4 and a fraction containing 5 as the major constituent showed antiproliferative activities with IC50 values of 0.44 μM (0.14 μg/mL) and 0.045 μg/mL, respectively. A semisynthesis of compound 5 was carried out, but the pure synthetic compound was inactive, indicating that the activity of the fraction containing it must be due to a very minor and as yet unidentified substance. PMID:21480509

Aphadilactones A-D, four diterpenoid dimers with DGAT inhibitory and antimalarial activities from a Meliaceae plant.

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Liu, Jia; He, Xiu-Feng; Wang, Gai-Hong; Merino, Emilio F; Yang, Sheng-Ping; Zhu, Rong-Xiu; Gan, Li-She; Zhang, Hua; Cassera, Maria B; Wang, He-Yao; Kingston, David G I; Yue, Jian-Min

2014-01-17

Aphadilactones A-D (1-4), four diastereoisomers possessing an unprecedented carbon skeleton, were isolated from the Meliaceae plant Aphanamixis grandifolia. Their challenging structures and absolute configurations were determined by a combination of spectroscopic data, chemical degradation, fragment synthesis, experimental CD spectra, and ECD calculations. Aphadilactone C (3) with the 5S,11S,5'S,11'S configuration showed potent and selective inhibition against the diacylglycerol O-acyltransferase-1 (DGAT-1) enzyme (IC50 = 0.46 ± 0.09 μM, selectivity index > 217) and is the strongest natural DGAT-1 inhibitor discovered to date. In addition, compounds 1-4 showed significant antimalarial activities with IC50 values of 190 ± 60, 1350 ± 150, 170 ± 10, and 120 ± 50 nM, respectively.

Abietane-Type Diterpenoid Amides with Highly Potent and Selective Activity against Leishmania donovani and Trypanosoma cruzi.

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Pirttimaa, Minni; Nasereddin, Abedelmajeed; Kopelyanskiy, Dmitry; Kaiser, Marcel; Yli-Kauhaluoma, Jari; Oksman-Caldentey, Kirsi-Marja; Brun, Reto; Jaffe, Charles L; Moreira, Vânia M; Alakurtti, Sami

2016-02-26

Dehydroabietylamine (1) was used as a starting material to synthesize a small library of dehydroabietyl amides by simple and facile methods, and their activities against two disease-causing trypanosomatids, namely, Leishmania donovani and Trypanosoma cruzi, were assayed. The most potent compound, 10, an amide of dehydroabietylamine and acrylic acid, was found to be highly potent against these parasites, displaying an IC50 value of 0.37 μM against L. donovani axenic amastigotes and an outstanding selectivity index of 63. Moreover, compound 10 fully inhibited the growth of intracellular amastigotes in Leishmania donovani-infected human macrophages with a low IC50 value of 0.06 μM. This compound was also highly effective against T. cruzi amastigotes residing in L6 cells with an IC50 value of 0.6 μM and high selectivity index of 58, being 3.5 times more potent than the reference compound benznidazole. The potent activity of this compound and its relatively low cytotoxicity make it attractive for further development in pursuit of better drugs for patients suffering from leishmaniasis and Chagas disease.

Rhodomollins A and B, two Diterpenoids with an Unprecedented Backbone from the Fruits of Rhododendron molle

Science.gov (United States)

Li, Yong; Liu, Yun-Bao; Yan, Hui-Min; Liu, Yang-Lan; Li, Yu-Huan; Lv, Hai-Ning; Ma, Shuang-Gang; Qu, Jing; Yu, Shi-Shan

2016-11-01

Two new grayanoids, rhodomollin A (1) and rhodomollin B (2), possessing an unprecedented D-homo grayanane carbon skeleton, were isolated from the fruits of Rhododendron molle. The structures of 1 and 2 were fully characterized using a combination of spectroscopic analyses and X-ray crystallography. Rhodomollin B (2) exhibited modest activity against influenza virus A/95-359, with an IC50 value of 19.24 μM.

Apparent Contradiction: Psychrotolerant Bacteria from Hydrocarbon-Contaminated Arctic Tundra Soils That Degrade Diterpenoids Synthesized by Trees

Science.gov (United States)

Yu, Zhongtang; Stewart, Gordon R.; Mohn, William W.

2000-01-01

Resin acids are tricyclic terpenoids occurring naturally in trees. We investigated the occurrence of resin acid-degrading bacteria on the Arctic tundra near the northern coast of Ellesmere Island (82°N, 62°W). According to most-probable-number assays, resin acid degraders were abundant (103 to 104 propagules/g of soil) in hydrocarbon-contaminated soils, but they were undetectable (soil) in pristine soils from the nearby tundra. Plate counts indicated that the contaminated and the pristine soils had similar populations of heterotrophs (106 to 107 propagules/g of soil). Eleven resin acid-degrading bacteria belonging to four phylogenetically distinct groups were enriched and isolated from the contaminated soils, and representative isolates of each group were further characterized. Strains DhA-91, IpA-92, and IpA-93 are members of the genus Pseudomonas. Strain DhA-95 is a member of the genus Sphingomonas. All four strains are psychrotolerant, with growth temperature ranges of 4°C to 30°C (DhA-91 and DhA-95) or 4°C to 22°C (IpA-92 and IpA-93) and with optimum temperatures of 15 to 22°C. Strains DhA-91 and DhA-95 grew on the abietanes, dehydroabietic and abietic acids, but not on the pimaranes, isopimaric and pimaric acids. Strains IpA-92 and IpA-93 grew on the pimaranes but not the abietanes. All four strains grew on either aliphatic or aromatic hydrocarbons, which is unusual for described resin acid degraders. Eleven mesophilic resin acid degraders did not use hydrocarbons, with the exception of two Mycobacterium sp. strains that used aliphatic hydrocarbons. We conclude that hydrocarbon contamination in Arctic tundra soil indirectly selected for resin acid degraders, selecting for hydrocarbon degraders that coincidentally use resin acids. Psychrotolerant resin acid degraders are likely important in the global carbon cycle and may have applications in biotreatment of pulp and paper mill effluents. PMID:11097882

Engineered andrographolide nanosystems for smart recovery in hepatotoxic conditions

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Roy, Partha; Das, Suvadra; Auddy, Runa Ghosh; Mukherjee, Arup

2014-01-01

Andrographolide (AG) is one of the most potent labdane diterpenoid-type free radical scavengers available from plant sources. The compound is the principal bioactive component in Andrographis paniculata leaf extracts, and is responsible for anti-inflammatory, anticancer, and immunomodulatory activity. The application of AG in therapeutics, however, is severely constrained, due to its low aqueous solubility, short biological half-life, and poor cellular permeability. Engineered nanoparticles in biodegradable polymer systems were therefore conceived as one solution to aid in further drug-like applications of AG. In this study, a cationic modified poly(lactic-co-glycolic) acid nanosystem was applied for evaluation against experimental mouse hepatotoxic conditions. Biopolymeric nanoparticles of hydrodynamic size of 229.7±17.17 nm and ζ-potential +34.4±1.87 mV facilitated marked restoration in liver functions and oxidative stress markers. Superior dissolution for bioactive AG, hepatic residence, and favorable cytokine regulation in the liver tissues are some of the factors responsible for the newer nanosystem-assisted rapid recovery. PMID:25336950

Isolasi dan Identifikasi Andrografolida dari Herba Andrographis paniculata Ness

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Suharmiati Suharmiati

2012-09-01

Full Text Available Andrographolide is the main constituent of Andrographis paniculata Ness (AP which was poorly soluble in water and bitter taste. As diterpenoid lactone andrographolide has many biological activities, some of them are immunostimulant, anti malaria, hepatoproccctor and anti mutagenic. The objective of this study were isolation and identification andrographolide from AP. In this study AP metanol extracted by percolation. Filtrate was collected and congealed ad viscous and was snaked by ethylacetate - water (1:1. Ethylacetate fraction was congealed until crystal formed. Recrystallization with hot metanol repeatedly until pure andrographolide isolate. Identification of andrographolide isolate by thin layer chromatography (TLC, UV spectrophotometer, Nuclear Magnetic Resonance (NMR and Fourier Transform Infra Red. Result of this study showed that from one kilogram AP herbs dried is produced 0,43% andrographolide isolate as identic as andrographolide standard (Sigma. The continued research to develop phytopharmaca product that consist andrographolide or AP herbs is needed to minimize taste bitter or to increase solubility is water so that its useful in health services.

Terpenoid Compositions and Botanical Origins of Late Cretaceous and Miocene Amber from China

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Shi, Gongle; Dutta, Suryendu; Paul, Swagata; Wang, Bo; Jacques, Frédéric M. B.

2014-01-01

The terpenoid compositions of the Late Cretaceous Xixia amber from Central China and the middle Miocene Zhangpu amber from Southeast China were analyzed by gas chromatography-mass spectrometry (GC-MS) to elucidate their botanical origins. The Xixia amber is characterized by sesquiterpenoids, abietane and phyllocladane type diterpenoids, but lacks phenolic abietanes and labdane derivatives. The molecular compositions indicate that the Xixia amber is most likely contributed by the conifer family Araucariaceae, which is today distributed primarily in the Southern Hemisphere, but widely occurred in the Northern Hemisphere during the Mesozoic according to paleobotanical evidence. The middle Miocene Zhangpu amber is characterized by amyrin and amyrone-based triterpenoids and cadalene-based sesquiterpenoids. It is considered derived from the tropical angiosperm family Dipterocarpaceae based on these compounds and the co-occurring fossil winged fruits of the family in Zhangpu. This provides new evidence for the occurrence of a dipterocarp forest in the middle Miocene of Southeast China. It is the first detailed biomarker study for amber from East Asia. PMID:25354364

Determination of Terpenoid Content in Pine by Organic Solvent Extraction and Fast-GC Analysis

Energy Technology Data Exchange (ETDEWEB)

Harman-Ware, Anne E., E-mail: anne.ware@nrel.gov; Sykes, Robert [National Bioenergy Center, National Renewable Energy Laboratory, Golden, CO (United States); Peter, Gary F. [School of Forest Resources and Conservation, University of Florida, Gainesville, FL (United States); Davis, Mark [National Bioenergy Center, National Renewable Energy Laboratory, Golden, CO (United States)

2016-01-25

Terpenoids, naturally occurring compounds derived from isoprene units present in pine oleoresin, are a valuable source of chemicals used in solvents, fragrances, flavors, and have shown potential use as a biofuel. This paper describes a method to extract and analyze the terpenoids present in loblolly pine saplings and pine lighter wood. Various extraction solvents were tested over different times and temperatures. Samples were analyzed by pyrolysis-molecular beam mass spectrometry before and after extractions to monitor the extraction efficiency. The pyrolysis studies indicated that the optimal extraction method used a 1:1 hexane/acetone solvent system at 22°C for 1 h. Extracts from the hexane/acetone experiments were analyzed using a low thermal mass modular accelerated column heater for fast-GC/FID analysis. The most abundant terpenoids from the pine samples were quantified, using standard curves, and included the monoterpenes, α- and β-pinene, camphene, and δ-carene. Sesquiterpenes analyzed included caryophyllene, humulene, and α-bisabolene. Diterpenoid resin acids were quantified in derivatized extractions, including pimaric, isopimaric, levopimaric, palustric, dehydroabietic, abietic, and neoabietic acids.

Polar compounds isolated from the leaves of Calea prunifolia H.B.K. and their anti-adrenergic related vasodilator activity

Energy Technology Data Exchange (ETDEWEB)

Puebla, Pilar; San Feliciano, Arturo [Laboratory of Organic and Pharmaceutical Chemistry, Faculty of Pharmacy, Campus Miguel de Unamuno, Salamanca University (Spain); Aranguren, Nataly; Rincon, Javier; Rojas, Maritza; Guerrero, Mario, E-mail: mfguerrerop@unal.edu.co [Pharmacy Department, School of Sciences, National University of Colombia, Bogota D.C. (Colombia)

2011-09-15

The leaves of Calea prunifolia H.B.K., medicinal specie used in Colombian folk medicine for hypertension have been analysed for their chemical constituents, resulting in the isolation of one flavonoid glycoside, one quinic acid derivative and one kaurane diterpenoid glycoside. Their chemical structures were elucidated on the basis of spectral analysis, including HRMS, 1D- and 2D-NMR data. The vasodilator effect related to anti adrenergic activity of the three compounds was evaluated in isolated aortic rings from Wistar rats contracted cumulatively with phenylephrine (from 1 x 10{sup -9} to 5 x 10{sup -5} mol L{sup -1}). Although these compounds were devoid of significant vasodilator activity when they were tested alone (1 {mu}g mL-1), mixtures of them (1:1:1) and the own EtOH extract exerted preventive anti-adrenergic activity increasing the phenylephrine CE{sub 50} from 2.3 x 10{sup -8} to 1.3 x 10{sup -7} and 8.0 x 10{sup -7} mol L{sup -1}, respectively. (author)

Characterization of a Newly Isolated Marine Fungus Aspergillus dimorphicus for Optimized Production of the Anti-Tumor Agent Wentilactones

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Rui Xu

2015-11-01

Full Text Available The potential anti-tumor agent wentilactones were produced by a newly isolated marine fungus Aspergillus dimorphicus. This fungus was derived from deep-sea sediment and identified by polyphasic approach, combining phenotypic, molecular, and extrolite profiles. However, wentilactone production was detected only under static cultures with very low yields. In order to improve wentilactone production, culture conditions were optimized using the response surface methodology. Under the optimal static fermentation conditions, the experimental values were closely consistent with the prediction model. The yields of wentilactone A and B were increased about 11-fold to 13.4 and 6.5 mg/L, respectively. The result was further verified by fermentation scale-up for wentilactone production. Moreover, some small-molecule elicitors were found to have capacity of stimulating wentilactone production. To our knowledge, this is first report of optimized production of tetranorlabdane diterpenoids by a deep-sea derived marine fungus. The present study might be valuable for efficient production of wentilactones and fundamental investigation of the anti-tumor mechanism of norditerpenoids.

Synthesis facilitates an understanding of the structural basis for translation inhibition by the lissoclimides

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Könst, Zef A.; Szklarski, Anne R.; Pellegrino, Simone; Michalak, Sharon E.; Meyer, Mélanie; Zanette, Camila; Cencic, Regina; Nam, Sangkil; Voora, Vamsee K.; Horne, David A.; Pelletier, Jerry; Mobley, David L.; Yusupova, Gulnara; Yusupov, Marat; Vanderwal, Christopher D.

2017-11-01

The lissoclimides are unusual succinimide-containing labdane diterpenoids that were reported to be potent cytotoxins. Our short semisynthesis and analogue-oriented synthesis approaches provide a series of lissoclimide natural products and analogues that expand the structure-activity relationships (SARs) in this family. The semisynthesis approach yielded significant quantities of chlorolissoclimide (CL) to permit an evaluation against the National Cancer Institute's 60-cell line panel and allowed us to obtain an X-ray co-crystal structure of the synthetic secondary metabolite with the eukaryotic 80S ribosome. Although it shares a binding site with other imide-based natural product translation inhibitors, CL engages in a particularly interesting and novel face-on halogen-π interaction between the ligand's alkyl chloride and a guanine residue. Our analogue-oriented synthesis provides many more lissoclimide compounds, which were tested against aggressive human cancer cell lines and for protein synthesis inhibitory activity. Finally, computational modelling was used to explain the SARs of certain key compounds and set the stage for the structure-guided design of better translation inhibitors.

Determination of Terpenoid Content in Pine by Organic Solvent Extraction and Fast-GC Analysis

International Nuclear Information System (INIS)

Harman-Ware, Anne E.; Sykes, Robert; Peter, Gary F.; Davis, Mark

2016-01-01

Terpenoids, naturally occurring compounds derived from isoprene units present in pine oleoresin, are a valuable source of chemicals used in solvents, fragrances, flavors, and have shown potential use as a biofuel. This paper describes a method to extract and analyze the terpenoids present in loblolly pine saplings and pine lighter wood. Various extraction solvents were tested over different times and temperatures. Samples were analyzed by pyrolysis-molecular beam mass spectrometry before and after extractions to monitor the extraction efficiency. The pyrolysis studies indicated that the optimal extraction method used a 1:1 hexane/acetone solvent system at 22°C for 1 h. Extracts from the hexane/acetone experiments were analyzed using a low thermal mass modular accelerated column heater for fast-GC/FID analysis. The most abundant terpenoids from the pine samples were quantified, using standard curves, and included the monoterpenes, α- and β-pinene, camphene, and δ-carene. Sesquiterpenes analyzed included caryophyllene, humulene, and α-bisabolene. Diterpenoid resin acids were quantified in derivatized extractions, including pimaric, isopimaric, levopimaric, palustric, dehydroabietic, abietic, and neoabietic acids.

Analysis of Helichrysum oligocephalum DC. essential oil

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N. Ghassemi-Dehkordi

2015-12-01

Full Text Available Background and objectives: Helichrysum oligocephalum DC. (Compositae  is an endemic plant in Iran that has been recommended by Iranian traditional and folk medicine practitioners for gastrointestinal complaints. The plant is rich in essential oil and in the present investigation, the volatile composition of the species has been determined. Methods: The light yellow essential oil from the aerial parts of the plant was prepared according to the method which was recommended in British Pharmacopoeia by using hydrodistillation. The chemical composition of the oil was investigated by gas chromatography mass spectroscopy (GC/MS. Results: Thirty-seven compounds were identified; among them β-caryophyllene, α-humulene and epimanoyl oxide were dominant. Sesquiterpenoids were the most dominant compounds in the essential oil while monoterpenoides, fatty acids and diterpenoides were found to be less. These outcomes are a little bit different from what has been reported before. Conclusion: The differences between the results of the present study with previous works could be due to the diversity of variety, polymorphism, stage of plant growth and environmental factors.

Experimental and NMR theoretical methodology applied to geometric analysis of the bioactive clerodane trans-dehydrocrotonin

Energy Technology Data Exchange (ETDEWEB)

Soares, Breno Almeida; Firme, Caio Lima, E-mail: firme.caio@gmail.com, E-mail: caiofirme@quimica.ufrn.br [Universidade Federal do Rio Grande do Norte (UFRN), Natal, RN (Brazil). Instituto de Quimica; Maciel, Maria Aparecida Medeiros [Universidade Potiguar, Natal, RN (Brazil). Programa de Pos-graduacao em Biotecnologia; Kaiser, Carlos R. [Universidade Federal do Rio de Janeiro (UFRJ), RJ (Brazil). Instituto de Quimica; Schilling, Eduardo; Bortoluzzi, Adailton J. [Universidade Federal de Santa Catarina (UFSC), Florianopolis, SC (Brazil). Departamento de Quimica

2014-04-15

trans-Dehydrocrotonin (t-DCTN) a bioactive 19-nor-diterpenoid clerodane type isolated from Croton cajucara Benth, is one of the most investigated clerodane in the current literature. In this work, a new approach joining X-ray diffraction data, nuclear magnetic resonance (NMR) data and theoretical calculations was applied to the thorough characterization of t-DCTN. For that, the geometry of t-DCTN was reevaluated by X-ray diffraction as well as {sup 1}H and {sup 13}C NMR data, whose geometrical parameters where compared to those obtained from B3LYP/6-311G++(d,p) level of theory. From the evaluation of both calculated and experimental values of {sup 1}H and {sup 13}C NMR chemical shifts and spin-spin coupling constants, it was found very good correlations between theoretical and experimental magnetic properties of t-DCTN. Additionally, the delocalization indexes between hydrogen atoms correlated accurately with theoretical and experimental spin-spin coupling constants. An additional topological analysis from quantum theory of atoms in molecules (QTAIM) showed intramolecular interactions for t-DCTN. (author)

Oridonin inhibits breast cancer growth and metastasis through blocking the Notch signaling

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Shixin Xia

2017-05-01

Full Text Available Background: Oridonin is a diterpenoid isolated from Rabdosia rubescens with potent anticancer activity. The aim of our study is to investigate the role of oridonin to inhibit growth and metastasis of human breast cancer cells. Methods: The effect of oridonin on proliferation was evaluated by MTT assay, cell migration and invasion were evaluated by transwell migration and invasion assays in human breast cancer cells. The inhibitive effect of oridonin in vivo was determined by using xenografted nude mice. In addition, the expression of Notch receptors (Notch 1–4 was detected by western blot. Results: Oridonin inhibited human breast cancer cells in vitro and in vivo. In addition, oridonin significantly induced human breast cancer cells apoptosis. Furthermore, the oridonin treatment not only inhibited cancer cell migration and invasion, but more significantly, decreased the expression of Notch 1-4 protein. Conclusion: Our results suggest that the inhibitive effect of oridonin is likely to be driven by the inhibition of Notch signaling pathway and the resulting increased apoptosis.

Solicitation of HPLC and HPTLC Techniques for Determination of Rutin from Polyalthia longifolia Thwaites

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Doshi, Gaurav Mahesh; Zine, Sandeep Prabhakar; Chaskar, Pratip Kashinath; Une, Hemant Devidas

2014-01-01

Background: Polyalthia longifolia Thwaites is an important traditional plant in India. Rutin, an active constituent has been reported to possess good amount of pharmacological as well as therapeutic potential. Objective: The aim of the present study was to find out by analytical techniques how much percentage of rutin is present in the plant leaves’ ethanolic extract by analytical techniques. Materials and Methods: Shade dried leaves of Polyalthia longifolia were subjected to cold ethanolic extraction followed by monitoring the isolated rutin high-pressure liquid chromatography (HPLC) and high performance thin layer chromatography (HPTLC) after carrying out preliminary phytochemical screening. Results: Extraction yield was found to be 13.94% w/w. Phytochemical screening of the extract showed the presence of flavonoids, steroids, diterpenoids, alkaloids, saponins, tannins and phenolic compounds and mucilage. From the Rf value, the ethanolic extract was found to be having constituent identical to rutin. By HPTLC and HPLC the amount of rutin was found to be 11.60% w/w and 4.03% w/v, respectively. Conclusion: The active constituent isolated was found to be equal to rutin. PMID:25002804

Andrographolide Induces Apoptosis of C6 Glioma Cells via the ERK-p53-Caspase 7-PARP Pathway

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Shih-Hung Yang

2014-01-01

Full Text Available Background. Glioma is the most malignant tumor of the central nervous system. Efforts on the development of new chemotherapy are mandatory. Andrographolide (AND, a diterpenoid lactone isolated from the Andrographis paniculata, has been shown to have antitumor activities in several types of cancer cells. Whether AND can exert its antitumor activity in glioblastoma cells remains unknown. This study examined the anticancer effects of AND, both in vitro and in vivo. Methods. Cell apoptosis was assayed by flow cytometry and nuclear staining. The signaling pathway for AND was determined by western blotting. The effects of AND on tumor growth was evaluated in a mouse model. Results and Conclusion. In vitro, with application of specific inhibitors and siRNA, AND-induced apoptosis was proven through ROS-ERK-P53-caspase 7-PARP signaling pathway. In vivo, AND significantly retarded tumor growth and caused regression of well-formed tumors in vivo. Furthermore, AND did not induce apoptosis or activate ERK and p53 in primary cultured astrocyte cells, and it may serve as a potential therapeutic candidate for the treatment of glioma.

PENGARUH POLIVINILPIROLIDON K-30 TERHADAP PENINGKATAN LAJU DISOLUSI ANDROGRAFOLIDA DENGAN SISTEM DISPERSI SOLIDA

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Suharmiati Suharmiati

2012-11-01

Full Text Available Andrographolide is the main constituent of Andrographis paniculata Ness which was poorly soluble in water. As diterpenoid lactone andrographolide has many biological activity, some of them ara immunostimulant, antimalaria, hepatoprotector and anti mutagenic. The objectives of this study were to find out influence of polyvinylpirrolidon (PVP K-30 to increase dissolution rate of andrographolide by solid dispersion in water and dissolution media pH 8,0. In this research andrographolide were divided in 6 groups that are physical mixture and solid dispersion by ratio 1:3; 1:5 and 1:9. Result of these study showed that the X-ray difraction patterns of physical mixture have crystal intensity as same as andrographolide crystal. But solid dispersion showed lower intensity. The solid dispersion system increase dissolution rate of andrographolide isolate. Increasing of dissolution rate a function of the ratio of drug to PVP used. Studies of dissolution rate have shown that coprecipitate of andrographolide-PVP K-30 (1:9 is better combination than 1:5 and 1:3.   Keywords: andrographolide, PVP K-30, solid dispersion and dissolution rate

Chemical Constituents from Hericium erinaceus Promote Neuronal Survival and Potentiate Neurite Outgrowth via the TrkA/Erk1/2 Pathway

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Cheng-Chen Zhang

2017-07-01

Full Text Available Hericium erinaceus is a culinary-medicinal mushroom used traditionally in Eastern Asia to improve memory. In this work, we investigated the neuroprotective and neuritogenic effects of the secondary metabolites isolated from the MeOH extract of cultured mycelium of H. erinaceus and the primary mechanisms involved. One new dihydropyridine compound (6 and one new natural product (2 together with five known compounds (1,3–5,7 were obtained and their structures were elucidated by spectroscopic analysis, including 2D NMR and HRMS. The cell-based screening for bioactivity showed that 4-chloro-3,5-dimethoxybenzoic methyl ester (1 and a cyathane diterpenoid, erincine A (3, not only potentiated NGF-induced neurite outgrowth but also protected neuronally-differentiated cells against deprivation of NGF in PC12 pheochromocytoma cells. Additionally, compound 3 induced neuritogenesis in primary rat cortex neurons. Furthermore, our results revealed that TrkA-mediated and Erk1/2-dependant pathways could be involved in 1 and 3-promoted NGF-induced neurite outgrowth in PC12 cells.

Antiproliferative compounds of Cyphostemma greveana from a Madagascar dry forest.

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Cao, Shugeng; Hou, Yanpeng; Brodie, Peggy; Miller, James S; Randrianaivo, Richard; Rakotobe, Etienne; Rasamison, Vincent E; Kingston, David G I

2011-04-01

Bioassay-guided fractionation of the EtOH extracts obtained from a plant identified as Cyphostemma greveana Desc. (Vitaceae) led to the identification of one macrolide, lasiodiplodin (1), three sesquiterpenoids, 12-hydroxy-15-oxoselina-4,11-diene (2), 1β,6α-dihydroxyeudesm-4(15)-ene (3), and (7R*)-opposit-4(15)-ene-1β,7-diol (5), and a new diterpenoid, 16,18-dihydroxykolavenic acid lactone (4). All the isolates were tested against the A2780 human ovarian cancer cell line, and compound 4 and a fraction containing 5 as the major constituent showed antiproliferative activities with IC(50) values of 0.44 μM (0.14 μg/ml) and 0.045 μg/ml, respectively. A partial synthesis of compound 5 was carried out, but the pure synthetic compound was inactive, indicating that the activity of the fraction containing it must be due to a very minor and as yet unidentified substance. Copyright © 2011 Verlag Helvetica Chimica Acta AG, Zürich.

Experimental and NMR theoretical methodology applied to geometric analysis of the bioactive clerodane trans-dehydrocrotonin

International Nuclear Information System (INIS)

Soares, Breno Almeida; Firme, Caio Lima; Maciel, Maria Aparecida Medeiros; Kaiser, Carlos R.; Schilling, Eduardo; Bortoluzzi, Adailton J.

2014-01-01

trans-Dehydrocrotonin (t-DCTN) a bioactive 19-nor-diterpenoid clerodane type isolated from Croton cajucara Benth, is one of the most investigated clerodane in the current literature. In this work, a new approach joining X-ray diffraction data, nuclear magnetic resonance (NMR) data and theoretical calculations was applied to the thorough characterization of t-DCTN. For that, the geometry of t-DCTN was reevaluated by X-ray diffraction as well as 1 H and 13 C NMR data, whose geometrical parameters where compared to those obtained from B3LYP/6-311G++(d,p) level of theory. From the evaluation of both calculated and experimental values of 1 H and 13 C NMR chemical shifts and spin-spin coupling constants, it was found very good correlations between theoretical and experimental magnetic properties of t-DCTN. Additionally, the delocalization indexes between hydrogen atoms correlated accurately with theoretical and experimental spin-spin coupling constants. An additional topological analysis from quantum theory of atoms in molecules (QTAIM) showed intramolecular interactions for t-DCTN. (author)

Structural studies and antimicrobial properties of norcembrane diterpenoid from an Indian soft coral Sinularia inelegans Tixier-Durivault

Digital Repository Service at National Institute of Oceanography (India)

Singh, K.S.; Kaminsky, W.H.; Rodrigues, C; Naik, C

SARJIT SINGH 1, *, WERNER H KAMINSKY 2 , CELINA RODRIGUES 1 and C G NAIK 1 1 Bioorganic Chemistry Laboratory, National Institute of Oceanography (CSIR), Goa 403 004 2 Department of Chemistry, University of Washington, Seattle, Washington 98195, USA... from marine organisms, 21 here, we wish to report the isolation of two norcembranoid diterpenes (1 and 2) that are epimer at one carbon atom (C-9) from the soft coral of the genus sinularia. Bioassay of the compounds against some micro- organisms...

(-)-6 alpha hydroxy polyanthellian A - A novel antifouling diterpenoid from the Indian soft coral Cladiella krempfi (Hickson)

Digital Repository Service at National Institute of Oceanography (India)

LimnaMol, V.P.; Raveendran, T.V.; Parameswaran, P.S.; Kunnath, R.J.; Rajamohanan, P.R.

shifts of (-)-6α-hydroxy polyanthellin A and polyanthellin A C- No (-)-6α-hydroxy polyanthellin A Polyanthellin A δ c δ h δ c δ h 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 41... 3 4 5 6 7 8 9 1011 12 13 14 15 16 17 18 19 20 H H O CH 3 CH 3 Fig.3. (-)-6α-hydroxy polyanthellin A A 0 20 40 60 80 100 Control 6.25 12.5 25 50 100 Concentration (μg/ml) % A c t i v i t y B 0 20 40 60 80 100 Control 6.25 12.5 25 50 100...

Antihyperglycemic effect ofJuniperus phoenicea L. on alloxan-induced diabetic rats and diterpenoids isolated from the fruits

Institute of Scientific and Technical Information of China (English)

Salma Ahmed El-Sawi; Hemaia Mohamed Motawae; Abdel-Rahman Omar El-Shabrawy; Mohamed Aboul-Fotouh Sleem; Amani Ameen Sleem; Maii Abdel Naby Ismail Maamoun

2015-01-01

Objective:To explore the traditional use ofJuniperus phoenicea L. (J. phoenicea) growing in Egypt as antidiabetic herb. Methods: The antihyperglycemic activities of the crude 80% ethanol and successive extracts of leaves and fruits of the plant were investigated in alloxan-induced diabetic rats after collecting blood samples through retro-orbital puncture technique. As a consequence of the biological results, phytochemical investigation of the chloroform fraction of fruits was carried out by column chromatography and thin layer chromatography. Results: Results revealed the reduction in blood glucose levels in rats, which were significantly different from control at 4 and 8 weeks (P Conclusions: It has become clear that leaves and fruits of the EgyptianJ. phoenicea provide effective antihyperglycemic action in diabetic rats as was reported in folk medicine. The high contents of terpenoids in the non-polar fractions may attribute to the antidiabetic effect of the plant.

Spectroscopy and crystal structures of natural stereoisomers of neoclerodane diterpenoids from Teucrium yemense of Saudi medicinal plant

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Nur-e-Alam, Mohammad; Kanthasamy, Gopikkaa; Yousaf, Muhammad; Alqahtani, Ali S.; Ghabbour, Hazem A.; Al-Rehaily, Adnan J.

2017-11-01

3-O-deacetylteugracilin (1) and teugracilin B (2), two natural stereoisomers, are isolated from Teucrium yemense (Defl). These two compounds are almost identical to each other, differing only at the C6 stereocenter. We now crystallise these two compounds and for the first time, determine the crystal structure through single crystal X-ray diffraction, and the stereochemistry for all positions using spectroscopic data. These techniques enable us to establish the difference between the two compounds. Careful interpretation of the results indicates that HRMS and 1 and 2D NMR spectroscopy, are in agreement with single crystal X-ray diffraction data.

Organic geochemistry of resins from modern Agathis australis and Eocene resins from New Zealand: Diagenetic and taxonomic implications

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Lyons, P.C.; Mastalerz, Maria; Orem, W.H.

2009-01-01

A maturation series of resins and fossil resins from New Zealand, ranging in age from Modern to Eocene and ranging from uncoalified to high volatile C bituminous coal, were analyzed by elemental, pyrolysis-gas chromatography (Py-GC), Fourier Transform infrared (FTir), and solid-state 13C nuclear magnetic resonance (13C NMR) techniques. For comparison, four resin samples from the Latrobe Valley, Australia, were analyzed. All of the resins and fossil resins of this study show very high H/C atomic ratios, and are characterized by dominant peaks in the 10-60??ppm range of solid-state 13C NMR spectra and prominent bands in the aliphatic stretching region (2800-3000??cm- 1) of FTir spectra, all indicating a highly aliphatic molecular structure. The 13C NMR and FTir data indicate a diterpenoid structure for these resins. There is an abrupt loss of oxygen that occurs at the Lignite A/Subbituminous C stage, which is attributed to a dramatic loss of carboxyl (COOH) from the diterpenoid molecule. This is a new finding in the diagenesis of resins. This important loss in oxygenated functional groups is attributed to a maturation change. Also, there is a progressive loss of exomethylene (CH2) groups with increasing degree of maturation, as shown by both 13C NMR and FTir data. This change has been noted by previous investigators. Exomethylene is absent in the fossil resins from the Eocene high volatile C bituminous coals. This progressive loss is characteristic of Class I resinites. FTir data indicate that the oxygenated functional groups are strong in all the resin samples except the fossil resin from high volatile C bituminous coal. This important change in oxygenated functional groups is attributed to maturation changes. The 13C NMR and FTir data indicate there are minor changes in the Agathis australis resin from the living tree and soil, which suggests that alteration of A. australis resins begins shortly after deposition in the soil for as little as 1000??years. The Morwell

Organic geochemistry of resins from modern Agathis australis and Eocene resins from New Zealand: Diagenetic and taxonomic implications

Energy Technology Data Exchange (ETDEWEB)

Lyons, Paul C. [Lyons and Associates Consultants, 206 Amber Road, Middleboro, MA 02346 (United States); Mastalerz, Maria [Indiana Geological Survey, Indiana University, 611 North Walnut Grove, Bloomington, IN 47405 (United States); Orem, William H. [U.S. Geological Survey, MS 956 National Center, Reston, VA 20192 (United States)

2009-10-01

A maturation series of resins and fossil resins from New Zealand, ranging in age from Modern to Eocene and ranging from uncoalified to high volatile C bituminous coal, were analyzed by elemental, pyrolysis-gas chromatography (Py-GC), Fourier Transform infrared (FTir), and solid-state {sup 13}C nuclear magnetic resonance ({sup 13}C NMR) techniques. For comparison, four resin samples from the Latrobe Valley, Australia, were analyzed. All of the resins and fossil resins of this study show very high H/C atomic ratios, and are characterized by dominant peaks in the 10-60 ppm range of solid-state {sup 13}C NMR spectra and prominent bands in the aliphatic stretching region (2800-3000 cm{sup -} {sup 1}) of FTir spectra, all indicating a highly aliphatic molecular structure. The {sup 13}C NMR and FTir data indicate a diterpenoid structure for these resins. There is an abrupt loss of oxygen that occurs at the Lignite A/Subbituminous C stage, which is attributed to a dramatic loss of carboxyl (COOH) from the diterpenoid molecule. This is a new finding in the diagenesis of resins. This important loss in oxygenated functional groups is attributed to a maturation change. Also, there is a progressive loss of exomethylene (CH{sub 2}) groups with increasing degree of maturation, as shown by both {sup 13}C NMR and FTir data. This change has been noted by previous investigators. Exomethylene is absent in the fossil resins from the Eocene high volatile C bituminous coals. This progressive loss is characteristic of Class I resinites. FTir data indicate that the oxygenated functional groups are strong in all the resin samples except the fossil resin from high volatile C bituminous coal. This important change in oxygenated functional groups is attributed to maturation changes. The {sup 13}C NMR and FTir data indicate there are minor changes in the Agathis australis resin from the living tree and soil, which suggests that alteration of A. australis resins begins shortly after deposition

Bifunctional cis-Abienol Synthase from Abies balsamea Discovered by Transcriptome Sequencing and Its Implications for Diterpenoid Fragrance Production*

Science.gov (United States)

Zerbe, Philipp; Chiang, Angela; Yuen, Macaire; Hamberger, Björn; Hamberger, Britta; Draper, Jason A.; Britton, Robert; Bohlmann, Jörg

2012-01-01

The labdanoid diterpene alcohol cis-abienol is a major component of the aromatic oleoresin of balsam fir (Abies balsamea) and serves as a valuable bioproduct material for the fragrance industry. Using high-throughput 454 transcriptome sequencing and metabolite profiling of balsam fir bark tissue, we identified candidate diterpene synthase sequences for full-length cDNA cloning and functional characterization. We discovered a bifunctional class I/II cis-abienol synthase (AbCAS), along with the paralogous levopimaradiene/abietadiene synthase and isopimaradiene synthase, all of which are members of the gymnosperm-specific TPS-d subfamily. The AbCAS-catalyzed formation of cis-abienol proceeds via cyclization and hydroxylation at carbon C-8 of a postulated carbocation intermediate in the class II active site, followed by cleavage of the diphosphate group and termination of the reaction sequence without further cyclization in the class I active site. This reaction mechanism is distinct from that of synthases of the isopimaradiene- or levopimaradiene/abietadiene synthase type, which employ deprotonation reactions in the class II active site and secondary cyclizations in the class I active site, leading to tricyclic diterpenes. Comparative homology modeling suggested the active site residues Asp-348, Leu-617, Phe-696, and Gly-723 as potentially important for the specificity of AbCAS. As a class I/II bifunctional enzyme, AbCAS is a promising target for metabolic engineering of cis-abienol production. PMID:22337889

Mollanol A, a diterpenoid with a new C-nor-D-homograyanane skeleton from the fruits of Rhododendron molle.

Science.gov (United States)

Li, Yong; Liu, Yun-Bao; Liu, Yang-Lan; Wang, Chen; Wu, Lian-Qiu; Li, Li; Ma, Shuang-Gang; Qu, Jing; Yu, Shi-Shan

2014-08-15

Two new grayanoids, mollanol A (1) and rhodomollein XXV (2), were isolated from the fruits of Rhododendron molle. Their structures were elucidated by spectroscopic methods and X-ray diffraction analyses. Mollanol A (1) possesses a new C-nor-D-homograyanane carbon skeleton, while rhodomollein XXV (2) is the first example of an 11,16-epoxygrayanane and features a caged oxa-tricyclo[3.3.1.0(3.7)]nonane ring system. Plausible biogenetic pathways for 1 were proposed. Compound 1 exhibited transcriptional activation effects on the xbp1 upstream promoter in IEC-6, 293T, and RAW264.7 cells.

Specificity and inhibitory mechanism of andrographolide and its analogues as antiasthma agents on NF-κB p50.

Science.gov (United States)

Nguyen, Van Sang; Loh, Xin Yi; Wijaya, Hadhi; Wang, Jigang; Lin, Qingsong; Lam, Yulin; Wong, Wai-Shiu Fred; Mok, Yu Keung

2015-02-27

Andrographolide (1) is a diterpenoid lactone with an α,β-unsaturated lactone group that inhibits NF-κB DNA binding. Andrographolide reacts with the nucleophilic Cys62 of NF-κB p50 through a Michael addition at the Δ(12(13)) exocylic double bond to form a covalent adduct. Using computer docking, site-directed mutagenesis, and mass spectrometry, the noncovalent interactions between andrographolide and additional binding site residues other than Cys62 were found to be essential for the covalent incorporation of andrographolide. Furthermore, the addition reaction of andrographolide on Cys62 was highly dependent on the redox conditions and on the vicinity of nearby, positively charged Arg residues in the conserved RxxRxR motif. The reaction mechanisms of several of the analogues were determined, showing that 14-deoxy-11,12-didehydroandrographolide (8) reacts with NF-κB p50 via a novel mechanism distinct from andrographolide. The noncovalent interaction and redox environment of the binding site should be considered, in addition to the electrophilicity, when designing a covalent drug. Analogues similar in structure appear to use distinct reaction mechanisms and may have very different cytotoxicities, e.g., compound 6.

Estimation for origin of coals on biomaker analysis; Jinko sekitan oyobi tennen sekitan no biomaker bunseki ni yoru sekitan kigen busshitsu no suitei

Energy Technology Data Exchange (ETDEWEB)

Suzuki, Y. [Geological Survey of Japan, Tsukuba (Japan); Sugimoto, Y. [National Institute of Materials and Chemical Research, Tsukuba (Japan); Okada, K. [Coal Mining Research Center, Tokyo (Japan)

1996-10-28

In order to study coal production processes, an estimation study was carried out on coal originating materials by using biomaker analysis. Test samples are original coals collected directly from a mine in Hokkaido (not having been subjected cleaning). Mixing and solvent extraction were performed after pulverization, and then tests were given on saturated hydrocarbon components divided by using a silicagel column chromatograph for the present study. It can be known from n-alkane distribution in the coal that low molecular alkane increases with increasing degree of coalification. Artificial coal made by wet-heating Metasequoia leaves contains only little n-alkane. Diterpenoid compound exists in the Taiheiyo and Akabira coals. Tetra-cyclic diterpernoid is contained abundantly in subtropical coniferous trees, serving as a parameter for warm environment. The compound is contained also in the Fushun coal, but not in Indonesian coals. Hopanoid constitution shows very high similarity, but H/C atomic ratio may vary largely even if the coalification is at the same degree. This is likely to be caused from difference in originating materials. Hopanoids are bacteria attributed substances, whose activities are not affected by the originating materials. 2 figs., 1 tab.

Antidiabetic effects of scoparic acid D isolated from Scoparia dulcis in rats with streptozotocin-induced diabetes.

Science.gov (United States)

Latha, Muniappan; Pari, Leelavinothan; Ramkumar, Kunga Mohan; Rajaguru, Palanisamy; Suresh, Thangaraj; Dhanabal, Thangavel; Sitasawad, Sandhya; Bhonde, Ramesh

2009-01-01

We evaluated the antihyperglycaemic effect of scoparic acid D (SAD), a diterpenoid isolated from the ethanol extract of Scoparia dulcis in streptozotocin (STZ)-induced diabetic male Wistar rats. SAD was administered orally at a dose of 10, 20 and 40 mg kg(-1) bodyweight for 15 days. At the end of the experimental period, the SAD-treated STZ diabetic rats showed decreased levels of glucose as compared with diabetic control rats. The improvement in blood glucose levels of SAD-treated rats was associated with a significant increase in plasma insulin levels. SAD at a dose of 20 mg kg(-1) bodyweight exhibited a significant effect when compared with other doses. Further, the effect of SAD was tested on STZ-treated rat insulinoma cell lines (RINm5F cells) and isolated islets in vitro. SAD at a dose of 20 microg mL(-1) evoked two-fold stimulation of insulin secretion from isolated islets, indicating its insulin secretagogue activity. Further, SAD protected STZ-mediated cytotoxicity and nitric oxide (NO) production in RINm5F cells. The present study thus confirms the antihyperglycaemic effect of SAD and also demonstrated the consistently strong cytoprotective properties of SAD.

Differences in phytoalexin response among rice cultivars of different resistance to blast

International Nuclear Information System (INIS)

Dillon, V.M.; Overton, J.; Grayer, R.J.; Harborne, J.B.

1997-01-01

he production of both flavonoid and diterpenoid phytoalexins after induction by UV irradiation was studied in five rice genotypes of different susceptibility to the rice blast fungus Pyricularia oryzae. Consistent qualitative and quatitative differences were found between the rice cultivars in the phytoalexins produced, and there was a strong correlation between the accumulation of the phytoalexins, sakuranetin, momilactone A and oryzalexin S, and rice resistance to blast. Production of phytoalexins was also investigated in rice genotype Tetep after inoculation with an incompatible race of P. oryzae. Similar levels of sakuranetin and oryzalexin E were formed 3 days after both inoculation and UV irradiation of the leaves, but there were different levels of momilactone A and the other oryzalexins. Although a given rice genotype may respond quite differently in its production of phytoalexins depending on whether it has been irradiated or inoculated with a fungus, and in the latter case on whether a compatible race of the pathogen has been used, the present results indicate that genetic differences in phytoalexin response between rice cultivars are likely to play an important role among the many factors that determine differences in blast resistance between different rice genotypes. (author)

Stevia preferences in Wistar rats.

Science.gov (United States)

Núñez Martínez, Paula; Argüelles Luis, Juan; Perillán Méndez, Carmen

2016-11-01

The Stevia rebaudiana plant is likely to become a major source of high-potency sweetener for the growing natural-food market. S. rebaudiana is the source of a number of sweet diterpenoid glycosides, but the major sweet constituents are rebaudioside A and stevioside. These two constituents have similar pharmacokinetic and metabolic profiles in rats and humans, and thus, studies carried out with either steviol glycoside are relevant to both. Other studies illustrate the diversity of voluntary sweet intake in mammals. This study was done using a series of two-bottle tests that compared a wide range of sweetener concentrations versus saccharin concentrations and versus water. Wistar rats displayed preferences for stevia extract and pure rebaudioside A solutions over water at a range of concentrations (0.001% to 0.3%), and their intake peak occurred at 0.1% concentration. They also preferred solutions prepared with a commercial rebaudioside A plus erythritol mixture to water, and their peak was at 2% concentration. The present study provides new information about the responses of Wistar rats to stevia compounds and commercial stevia products such as Truvia. These results could help with the appropriate dosage selection for focused behavioral and physiological studies on stevia.

In-silico Leishmania Target Selectivity of Antiparasitic Terpenoids

Directory of Open Access Journals (Sweden)

Ifedayo Victor Ogungbe

2013-07-01

Full Text Available Neglected Tropical Diseases (NTDs, like leishmaniasis, are major causes of mortality in resource-limited countries. The mortality associated with these diseases is largely due to fragile healthcare systems, lack of access to medicines, and resistance by the parasites to the few available drugs. Many antiparasitic plant-derived isoprenoids have been reported, and many of them have good in vitro activity against various forms of Leishmania spp. In this work, potential Leishmania biochemical targets of antiparasitic isoprenoids were studied in silico. Antiparasitic monoterpenoids selectively docked to L. infantum nicotinamidase, L. major uridine diphosphate-glucose pyrophosphorylase and methionyl t-RNA synthetase. The two protein targets selectively targeted by germacranolide sesquiterpenoids were L. major methionyl t-RNA synthetase and dihydroorotate dehydrogenase. Diterpenoids generally favored docking to L. mexicana glycerol-3-phosphate dehydrogenase. Limonoids also showed some selectivity for L. mexicana glycerol-3-phosphate dehydrogenase and L. major dihydroorotate dehydrogenase while withanolides docked more selectively with L. major uridine diphosphate-glucose pyrophosphorylase. The selectivity of the different classes of antiparasitic compounds for the protein targets considered in this work can be explored in fragment- and/or structure-based drug design towards the development of leads for new antileishmanial drugs.

Molecular cloning and characterization of a cDNA encoding the gibberellin biosynthetic enzyme ent-kaurene synthase B from pumpkin (Cucurbita maxima L.).

Science.gov (United States)

Yamaguchi, S; Saito, T; Abe, H; Yamane, H; Murofushi, N; Kamiya, Y

1996-08-01

The first committed step in the formation of diterpenoids leading to gibberellin (GA) biosynthesis is the conversion of geranylgeranyl diphosphate (GGDP) to ent-kaurene. ent-Kaurene synthase A (KSA) catalyzes the conversion of GGDP to copalyl diphosphate (CDP), which is subsequently converted to ent-kaurene by ent-kaurene synthase B (KSB). A full-length KSB cDNA was isolated from developing cotyledons in immature seeds of pumpkin (Cucurbita maxima L.). Degenerate oligonucleotide primers were designed from the amino acid sequences obtained from the purified protein to amplify a cDNA fragment, which was used for library screening. The isolated full-length cDNA was expressed in Escherichia coli as a fusion protein, which demonstrated the KSB activity to cyclize [3H]CDP to [3H]ent-kaurene. The KSB transcript was most abundant in growing tissues, but was detected in every organ in pumpkin seedlings. The deduced amino acid sequence shares significant homology with other terpene cyclases, including the conserved DDXXD motif, a putative divalent metal ion-diphosphate complex binding site. A putative transit peptide sequence that may target the translated product into the plastids is present in the N-terminal region.

Andrographis paniculata (Burm. f.) Wall. ex Nees: A Review of Ethnobotany, Phytochemistry, and Pharmacology

Science.gov (United States)

Sule, Abubakar; Rahman, K. M. Hafizur

2014-01-01

As aboriginal sources of medications, medicinal plants are used from the ancient times. Andrographis paniculata is one of the highly used potential medicinal plants in the world. This plant is traditionally used for the treatment of common cold, diarrhoea, fever due to several infective cause, jaundice, as a health tonic for the liver and cardiovascular health, and as an antioxidant. It is also used to improve sexual dysfunctions and serve as a contraceptive. All parts of this plant are used to extract the active phytochemicals, but the compositions of phytoconstituents widely differ from one part to another and with place, season, and time of harvest. Our extensive data mining of the phytoconstituents revealed more than 55 ent-labdane diterpenoids, 30 flavonoids, 8 quinic acids, 4 xanthones, and 5 rare noriridoids. In this review, we selected only those compounds that pharmacology has already reported. Finally we focused on around 46 compounds for further discussion. We also discussed ethnobotany of this plant briefly. Recommendations addressing extraction process, tissue culture, and adventitious rooting techniques and propagation under abiotic stress conditions for improvement of phytoconstituents are discussed concisely in this paper. Further study areas on pharmacology are also proposed where needed. PMID:25950015

Pseudolaric acid B extracted from the Chinese medicinal herb Cortex Pseudolaricis ameliorates DNFB-induced atopic dermatitis-like skin lesions in BALB/c mice

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Yi-Teng Wang

2017-10-01

Full Text Available Objective: Pseudolaric acid B (PB is a newly identified diterpenoid isolated from Tujinpi (Cortex Pseudolaricis. In the present study, we aimed to explore the anti-inflammatory effects of PB on atopic dermatitis (AD, as well as the molecular mechanisms underlying its effects. Methods: BALB/c mice treated with 2,4-dinitrofluorobenzene were orally administered with PB (10 mg∙kg-1∙d-1. After evaluating the AD score, serum levels of IgE and the mRNA expression of NLRP3 inflammasome and IL-1β were measured by ELISA and qRT-PCR respectively. Results: The results showed that PB treatment significantly ameliorated the development of AD-like clinical symptoms and effectively suppressed the infiltration of inflammatory cells. Furthermore, PB inhibited the expression of NLRP3 inflammasome and IL-1β in skin lesions, and downregulated serum IgE levels. Conclusion: The anti-inflammatory properties of PB were demonstrated using the 2,4-dinitrofluorobenzene-induced mouse model of AD-like skin lesions. Our study highlighted the potential use of PB as a novel therapeutic agent for the treatment of inflammation-associated skin diseases.

Natural Product Vibsanin A Induces Differentiation of Myeloid Leukemia Cells through PKC Activation.

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Yu, Zu-Yin; Xiao, He; Wang, Li-Mei; Shen, Xing; Jing, Yu; Wang, Lin; Sun, Wen-Feng; Zhang, Yan-Feng; Cui, Yu; Shan, Ya-Jun; Zhou, Wen-Bing; Xing, Shuang; Xiong, Guo-Lin; Liu, Xiao-Lan; Dong, Bo; Feng, Jian-Nan; Wang, Li-Sheng; Luo, Qing-Liang; Zhao, Qin-Shi; Cong, Yu-Wen

2016-05-01

All-trans retinoic acid (ATRA)-based cell differentiation therapy has been successful in treating acute promyelocytic leukemia, a unique subtype of acute myeloid leukemia (AML). However, other subtypes of AML display resistance to ATRA-based treatment. In this study, we screened natural, plant-derived vibsane-type diterpenoids for their ability to induce differentiation of myeloid leukemia cells, discovering that vibsanin A potently induced differentiation of AML cell lines and primary blasts. The differentiation-inducing activity of vibsanin A was mediated through direct interaction with and activation of protein kinase C (PKC). Consistent with these findings, pharmacological blockade of PKC activity suppressed vibsanin A-induced differentiation. Mechanistically, vibsanin A-mediated activation of PKC led to induction of the ERK pathway and decreased c-Myc expression. In mouse xenograft models of AML, vibsanin A administration prolonged host survival and inhibited PKC-mediated inflammatory responses correlated with promotion of skin tumors in mice. Collectively, our results offer a preclinical proof of concept for vibsanin A as a myeloid differentiation-inducing compound, with potential application as an antileukemic agent. Cancer Res; 76(9); 2698-709. ©2016 AACR. ©2016 American Association for Cancer Research.

Two novel creatinine adducts of andrographolide in human urine.

Science.gov (United States)

Qiu, Feng; Cui, Liang; Chen, Lixia; Sun, Jiawen; Yao, Xinsheng

2012-09-01

Andrographolide is a major labdane diterpenoid of the traditional Chinese and Ayurvedic medicine. Andrographis paniculate (Burm) Nees, is used in clinical situations in China mainly to treat fever, cold, and inflammation. In our previous study, fifteen metabolites of andrographolide were identified in human urine. However, there are still two other unknown metabolites. The aim of this study was to elucidate the structures of these two metabolites. 3. The two metabolites which are probably epimers were identified as creatinine adducts, and their structures were determined to be 14-deoxy-12-(creatinine-5-yl)-andrographolide-19-O-β-D-glucuronide A (Metabolite 1) and 14-deoxy-12-(creatinine-5-yl)-andrographolide-19-O-β-D-glucuronide B (Metabolite 2) by means of spectroscopic evidences. 4. It is for the first time that the formation of creatinine adducts as a novel metabolic pathway is reported. The mechanism was presumed that β-carbon (C-12) of α, β-unsaturated carbonyl was attacked by a 5-anion intermediate of creatinine formed through elimination of a proton, followed by the double bond migration from 12(13) to 13(14) and elimination of the hydroxyl group at C-14.

Andrographis paniculata (Burm. f.) Wall. ex Nees: a review of ethnobotany, phytochemistry, and pharmacology.

Science.gov (United States)

Hossain, Md Sanower; Urbi, Zannat; Sule, Abubakar; Hafizur Rahman, K M

2014-01-01

As aboriginal sources of medications, medicinal plants are used from the ancient times. Andrographis paniculata is one of the highly used potential medicinal plants in the world. This plant is traditionally used for the treatment of common cold, diarrhoea, fever due to several infective cause, jaundice, as a health tonic for the liver and cardiovascular health, and as an antioxidant. It is also used to improve sexual dysfunctions and serve as a contraceptive. All parts of this plant are used to extract the active phytochemicals, but the compositions of phytoconstituents widely differ from one part to another and with place, season, and time of harvest. Our extensive data mining of the phytoconstituents revealed more than 55 ent-labdane diterpenoids, 30 flavonoids, 8 quinic acids, 4 xanthones, and 5 rare noriridoids. In this review, we selected only those compounds that pharmacology has already reported. Finally we focused on around 46 compounds for further discussion. We also discussed ethnobotany of this plant briefly. Recommendations addressing extraction process, tissue culture, and adventitious rooting techniques and propagation under abiotic stress conditions for improvement of phytoconstituents are discussed concisely in this paper. Further study areas on pharmacology are also proposed where needed.

New phytotoxic diterpenoids from Vellozia gigantea (Velloziaceae), an endemic neotropical plant living in the endangered Brazilian biome Rupestrian grasslands

Science.gov (United States)

Vellozia gigantea is a rare, ancient and endemic neotropical plant present in the Brazilian Rupestrian grasslands. The dichloromethane extract of V. gigantea adventitious roots was phytotoxic against Lactuca sativa, Agrostis stolonifera and Lemna paucicostata, and showed larvicidal activity against ...

Regio- and stereoselective synthesis of (+)-6-ketoeuryfuran, (+)-6-ketowinterin, and (-)-7-ketoeuryfuran from accessible labdane diterpenoids (+)-larixol and (-)-sclareol

NARCIS (Netherlands)

Vlad, P.E.; Ciocarlan, A.; Edu, C.; Aricu, A.; Biriiac, A.; Coltsa, M.; Ambrosio, D' M.; Deleanu, C.; Nicolescu, A.; Shova, S.; Vornicu, N.; Groot, de Æ.

2013-01-01

Starting from (+)-larixol and (-)-sclareol, new syntheses of (+)-6-ketoeuryfuran, (+)-6-ketowinterin, and (-)-7-ketoeuryfuran have been elaborated in high yields. (+)-6-Ketowinterin was synthesized for the first time. Both euryfurans are excellent starting materials for the synthesis of important

An Effective Vacuum Assisted Extraction Method for the Optimization of Labdane Diterpenoids from Andrographis paniculata by Response Surface Methodology

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Ya-Qi Wang

2014-12-01

Full Text Available An effective vacuum assisted extraction (VAE technique was proposed for the first time and applied to extract bioactive components from Andrographis paniculata. The process was carefully optimized by response surface methodology (RSM. Under the optimized experimental conditions, the best results were obtained using a boiling temperature of 65 °C, 50% ethanol concentration, 16 min of extraction time, one extraction cycles and a 12:1 liquid-solid ratio. Compared with conventional ultrasonic assisted extraction and heat reflux extraction, the VAE technique gave shorter extraction times and remarkable higher extraction efficiency, which indicated that a certain degree of vacuum gave the solvent a better penetration of the solvent into the pores and between the matrix particles, and enhanced the process of mass transfer. The present results demonstrated that VAE is an efficient, simple and fast method for extracting bioactive components from A. paniculata, which shows great potential for becoming an alternative technique for industrial scale-up applications.

An effective vacuum assisted extraction method for the optimization of labdane diterpenoids from Andrographis paniculata by response surface methodology.

Science.gov (United States)

Wang, Ya-Qi; Wu, Zhen-Feng; Ke, Gang; Yang, Ming

2014-12-31

An effective vacuum assisted extraction (VAE) technique was proposed for the first time and applied to extract bioactive components from Andrographis paniculata. The process was carefully optimized by response surface methodology (RSM). Under the optimized experimental conditions, the best results were obtained using a boiling temperature of 65 °C, 50% ethanol concentration, 16 min of extraction time, one extraction cycles and a 12:1 liquid-solid ratio. Compared with conventional ultrasonic assisted extraction and heat reflux extraction, the VAE technique gave shorter extraction times and remarkable higher extraction efficiency, which indicated that a certain degree of vacuum gave the solvent a better penetration of the solvent into the pores and between the matrix particles, and enhanced the process of mass transfer. The present results demonstrated that VAE is an efficient, simple and fast method for extracting bioactive components from A. paniculata, which shows great potential for becoming an alternative technique for industrial scale-up applications.

Two New Cyathane Diterpenoids from Mycelial Cultures of the Medicinal Mushroom Hericium erinaceus and the Rare Species, Hericium flagellum

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Zeljka Rupcic

2018-03-01

Full Text Available Basidiomycetes of the genus Hericium are among the most praised medicinal and edible mushrooms, which are known to produce secondary metabolites with the potential to treat neurodegenerative diseases. This activity has been attributed to the discovery of various terpenoids that can stimulate the production of nerve growth factor (NGF or (as established more recently brain-derived neurotrophic factor (BDNF in cell-based bioassays. The present study reports on the metabolite profiles of a Lion’s Mane mushroom (Hericium erinaceus strain and a strain of the rare species, Hericium flagellum (synonym H. alpestre. While we observed highly similar metabolite profiles between the two strains that were examined, we isolated two previously undescribed metabolites, given the trivial names erinacines Z1 and Z2. Their chemical structures were elucidated by means of nuclear magnetic resonance (NMR spectroscopy and high resolution mass spectrometry. Along with six further, previously identified cyathane diterpenes, the novel erinacines were tested for neurotrophin inducing effects. We found that erinacines act on BDNF, which is a neurotrophic factor that has been reported recently by us to be induced by the corallocins, but as well on NGF expression, which is consistent with the literature.

Two New Cyathane Diterpenoids from Mycelial Cultures of the Medicinal Mushroom Hericium erinaceus and the Rare Species, Hericium flagellum.

Science.gov (United States)

Rupcic, Zeljka; Rascher, Monique; Kanaki, Sae; Köster, Reinhard W; Stadler, Marc; Wittstein, Kathrin

2018-03-06

Basidiomycetes of the genus Hericium are among the most praised medicinal and edible mushrooms, which are known to produce secondary metabolites with the potential to treat neurodegenerative diseases. This activity has been attributed to the discovery of various terpenoids that can stimulate the production of nerve growth factor ( NGF ) or (as established more recently) brain-derived neurotrophic factor ( BDNF ) in cell-based bioassays. The present study reports on the metabolite profiles of a Lion's Mane mushroom ( Hericium erinaceus ) strain and a strain of the rare species, Hericium flagellum (synonym H. alpestre ). While we observed highly similar metabolite profiles between the two strains that were examined, we isolated two previously undescribed metabolites, given the trivial names erinacines Z1 and Z2. Their chemical structures were elucidated by means of nuclear magnetic resonance (NMR) spectroscopy and high resolution mass spectrometry. Along with six further, previously identified cyathane diterpenes, the novel erinacines were tested for neurotrophin inducing effects. We found that erinacines act on BDNF , which is a neurotrophic factor that has been reported recently by us to be induced by the corallocins, but as well on NGF expression, which is consistent with the literature.

Two New Cyathane Diterpenoids from Mycelial Cultures of the Medicinal Mushroom Hericium erinaceus and the Rare Species, Hericium flagellum

OpenAIRE

Rupcic, Zeljka; Rascher, Monique; Kanaki, Sae; Köster, Reinhard W.; Stadler, Marc; Wittstein, Kathrin

2018-01-01

Basidiomycetes of the genus Hericium are among the most praised medicinal and edible mushrooms, which are known to produce secondary metabolites with the potential to treat neurodegenerative diseases. This activity has been attributed to the discovery of various terpenoids that can stimulate the production of nerve growth factor (NGF) or (as established more recently) brain-derived neurotrophic factor (BDNF) in cell-based bioassays. The present study reports on the metabolite profiles of a Li...

Seasonal Variation, Chemical Composition and Antioxidant Activity of Brazilian Propolis Samples

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Érica Weinstein Teixeira

2010-01-01

Full Text Available Total phenolic contents, antioxidant activity and chemical composition of propolis samples from three localities of Minas Gerais state (southeast Brazil were determined. Total phenolic contents were determined by the Folin–Ciocalteau method, antioxidant activity was evaluated by DPPH, using BHT as reference, and chemical composition was analyzed by GC/MS. Propolis from Itapecerica and Paula Cândido municipalities were found to have high phenolic contents and pronounced antioxidant activity. From these extracts, 40 substances were identified, among them were simple phenylpropanoids, prenylated phenylpropanoids, sesqui- and diterpenoids. Quantitatively, the main constituent of both samples was allyl-3-prenylcinnamic acid. A sample from Virginópolis municipality had no detectable phenolic substances and contained mainly triterpenoids, the main constituents being α- and β-amyrins. Methanolic extracts from Itapecerica and Paula Cândido exhibited pronounced scavenging activity towards DPPH, indistinguishable from BHT activity. However, extracts from Virginópolis sample exhibited no antioxidant activity. Total phenolic substances, GC/MS analyses and antioxidant activity of samples from Itapecerica collected monthly over a period of 1 year revealed considerable variation. No correlation was observed between antioxidant activity and either total phenolic contents or contents of artepillin C and other phenolic substances, as assayed by CG/MS analysis.

Antidiarrheal Activity of 19-Deoxyicetexone Isolated from Salvia ballotiflora Benth in Mice and Rats

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Ernesto Sánchez-Mendoza

2013-07-01

Full Text Available The antidiarrheal properties of 19-deoxyicetexone, a diterpenoid isolated from Salvia ballotiflora were evaluated on castor oil-, arachidonic acid (AA- and prostaglandin (PGE2-induced diarrhea in rodent models. The structure of 19-deoxyicetexone was determined by X-ray crystallography, mass spectrometry (EI-MS, as well as ultraviolet (UV-Vis, infrared (FT-IR and nuclear magnetic resonance (NMR spectroscopies. This compound significantly and dose-dependently reduced frequency of stooling in castor oil-induced diarrhea, and at dose of 25 mg/kg it also inhibited diarrhea induced with AA, while it had no effect on PGE2-induced diarrhea. This compound at doses of 25 mg/kg also diminished castor oil-induced enteropooling and intestinal motility, and inhibited the contraction of the rats’ ileum induced by carbachol chloride at a concentration of 100 µg/mL. 19-Deoxyicetexone did not present acute toxicity at doses of 625 mg/kg. Its antidiarrheal activity may be due to increased reabsorption of NaCl and water and inhibition of the release of prostaglandins, gastrointestinal motility and fluid accumulation in the intestinal tracts of rats. These findings suggest that 19-deoxyicetexone may be used in the treatment of diarrhea, although more studies must be carried out to confirm this.

Gaschromatographic and mass spectroscopic investigations of tall oil rosin acids and diterpenioc compounds and modified diterpene acids

International Nuclear Information System (INIS)

Mayr, M.

1984-12-01

Diterpene resin acids are important constituents of the coniferous wood. The composition of these nonvolatile extractives have been studied by a number of investigations; both naturally occurring resins (oleoresin) and distillation products of the alkaline sulfate pulping process (tall oil) were analyzed. These mixtures find important uses in chemical intermediates, paper sizes, ester gums, coatings and numerous other applications. Owing to the more ameliorate physical properties a major part of tall oil resin acids is chemically modified and is used in intermediate chemicals. Such modifications are the disproportionation in the presence of certain catalysts and the formation of Diels-Alder adducts. The present study was undertaken to obtain detailed information of the overall composition of diterpenoid compounds and to achieve a separation of the complex natural and tall oil mixtures using high resolution glass capillary columns. Furthermore, one objective was to characterize the identified diterpene compounds and Diels-Alder adducts by relative retention values. Additionally the presence of some major adduct components in the modified samples was checked by comparison with pure specimens, independently synthesized or purified by crystallization and the mechanism of the Diels-Alder reaction was investigated. A compilation of the mass spectra of the substances detected in the different samples closes this work. (Author)

Direct suppression of a rice bacterial blight (Xanthomonas oryzae pv. oryzae) by monoterpene (S)-limonene.

Science.gov (United States)

Lee, Gun Woong; Chung, Moon-Soo; Kang, Mihyung; Chung, Byung Yeoup; Lee, Sungbeom

2016-05-01

Rice bacterial blight, caused by Xanthomonas oryzae pv. oryzae (Xoo), is a severe disease of rice plants. Upon pathogen infection, rice biosynthesizes phytoalexins, including diterpenoids such as momilactones, phytocassanes, and oryzalexins. However, information on headspace volatiles in response to Xoo infection is limited. We have examined headspace volatile terpenes, induced by the infection of Xoo, and investigated their biological roles in the rice plant. Monoterpenes α-thujene, α-pinene, sabinene, myrcene, α-terpene, and (S)-limonene and sesquiterpenes cyclosativene, α-copaene, and β-elemene were detected from 1-week-old Xoo-infected rice seedlings, by solid-phase microextraction-gas chromatography-mass spectrometry. All monoterpenes were constitutively released from rice seedlings before Xoo infection. However, (S)-limonene emission was further elicited after exposure of the seedlings to Xoo in coincidence with upregulation of limonene synthase gene (OsTPS20) transcripts. Only the stereospecific (S)-limonene [and not (R)-limonene or other monoterpenes] severely inhibited Xoo growth, as confirmed by disc diffusion and liquid culture assays. Rice seedlings showed suppressed pathogenic symptoms suggestive of resistance to Xoo infection after foliar treatment with (S)-limonene. Collectively, our findings suggest that (S)-limonene is a volatile phytoanticipin, which plays a significant role in suppressing Xoo growth in rice seedlings.

Andrographolide induces Nrf2 and heme oxygenase 1 in astrocytes by activating p38 MAPK and ERK.

Science.gov (United States)

Wong, Siew Ying; Tan, Michelle G K; Wong, Peter T H; Herr, Deron R; Lai, Mitchell K P

2016-09-23

Andrographolide is the major labdane diterpenoid originally isolated from Andrographis paniculata and has been shown to have anti-inflammatory and antioxidative effects. However, there is a dearth of studies on the potential therapeutic utility of andrographolide in neuroinflammatory conditions. Here, we aimed to investigate the mechanisms underlying andrographolide's effect on the expression of anti-inflammatory and antioxidant heme oxygenase-1 (HO-1) in primary astrocytes. Measurements of the effects of andrograholide on antioxidant HO-1 and its transcription factor, Nrf2, include gene expression, protein turnover, and activation of putative signaling regulators. Andrographolide potently activated Nrf2 and also upregulated HO-1 expression in primary astrocytes. Andrographolide's effects on Nrf2 seemed to be biphasic, with acute (within 1 h) reductions in Nrf2 ubiquitination efficiency and turnover rate, followed by upregulation of Nrf2 mRNA between 8 and 24 h. The acute regulation of Nrf2 by andrographolide seemed to be independent of Keap1 and partly mediated by p38 MAPK and ERK signaling. These data provide further insights into the mechanisms underlying andrographolide's effects on astrocyte-mediated antioxidant, and anti-inflammatory responses and support the further assessment of andrographolide as a potential therapeutic for neurological conditions in which oxidative stress and neuroinflammation are implicated.

Feeding preferences of the endemic gastropod Astraea latispina in relation to chemical defenses of Brazilian tropical seaweeds

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PEREIRA R. C.

2002-01-01

Full Text Available Seaweed preference by the Brazilian endemic gastropod Astraea latispina was examined in the laboratory to evaluate the role of secondary metabolites in determining food choice. Of three species of seaweeds examined, Plocamium brasiliense was highly preferred; less so were Sargassum furcatum and Dictyota cervicornis were preferred less. Extracts and/or pure major metabolites of the two potentially chemically-defended seaweeds (P. brasiliense and D. cervicornis were tested as feeding deterrents against A. latispina. Algal extract assays demonstrated that three concentrations of crude organic extract of the red alga P. brasiliense (50%, 100%: natural concentration, and 200% of dry weight: dw did not affect feeding of this gastropod. In contrast, the three concentrations of crude organic extract of the brown alga D. cervicornis (50%, 100% and 200% dw inhibited feeding by A. latispina. The chemical deterrent property of D. cervicornis extract against the gastropod A. latispina occurred due to a mixture of the secodolastane diterpenes isolinearol/linearol (4:1 -- 0.08% dry weight. This is the first report showing that Dictyota cervicornis produces a chemical defense against herbivores using secodolastane diterpenoid. In addition, these results widen the action spectrum of secondary metabolites found in seaweed belonging to this brown algal genus.

The role of bioactive substances in controlling foodborne pathogens derived from Metasequoia glyptostroboides Miki ex Hu.

Science.gov (United States)

Bajpai, Vivek K; Na, Minkyun; Kang, Sun Chul

2010-07-01

In an attempt to isolate bioactive substances, ethyl acetate cone extract of Metasequoia glyptostroboides was subjected to a column chromatographic analysis that resulted in isolation of an abietane type diterpenoid, taxoquinone. Its structure was elucidated by spectroscopic means. In further, taxoquinone showed potential antibacterial effect as diameters of zones of inhibition against foodborne pathogenic bacteria such as Listeria monocytogenes ATCC 19166, Salmonella typhimurium KCTC 2515, Salmonella enteritidis KCTC 2021, Escherichia coli ATCC 8739, E. coli O157:H7 ATCC 43888, Enterobacter aerogenes KCTC2190, Staphylococcus aureus ATCC 6538 and S. aureus KCTC 1916, which were found in the range of 10.6-15.8mm. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values of taxoquinone against the employed bacterial pathogens were found in the range of 62.5-250 and 125-500 microg/ml. Also the compound had strong antibacterial effect on the viable counts of the tested bacteria. Further, scanning electron microscopic study demonstrated potential detrimental effect of taxoquinone on the morphology of E. coli ATCC 8739. These findings indicate that bioactive compound taxoquinone present in M. glyptostroboides could be used as a promising antibacterial agent in food industry to inhibit the growth of certain important foodborne pathogens. 2010 Elsevier Ltd. All rights reserved.

Feeding preferences of the endemic gastropod Astraea latispina in relation to chemical defenses of Brazilian tropical seaweeds

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R. C. PEREIRA

Full Text Available Seaweed preference by the Brazilian endemic gastropod Astraea latispina was examined in the laboratory to evaluate the role of secondary metabolites in determining food choice. Of three species of seaweeds examined, Plocamium brasiliense was highly preferred; less so were Sargassum furcatum and Dictyota cervicornis were preferred less. Extracts and/or pure major metabolites of the two potentially chemically-defended seaweeds (P. brasiliense and D. cervicornis were tested as feeding deterrents against A. latispina. Algal extract assays demonstrated that three concentrations of crude organic extract of the red alga P. brasiliense (50%, 100%: natural concentration, and 200% of dry weight: dw did not affect feeding of this gastropod. In contrast, the three concentrations of crude organic extract of the brown alga D. cervicornis (50%, 100% and 200% dw inhibited feeding by A. latispina. The chemical deterrent property of D. cervicornis extract against the gastropod A. latispina occurred due to a mixture of the secodolastane diterpenes isolinearol/linearol (4:1 -- 0.08% dry weight. This is the first report showing that Dictyota cervicornis produces a chemical defense against herbivores using secodolastane diterpenoid. In addition, these results widen the action spectrum of secondary metabolites found in seaweed belonging to this brown algal genus.

An Ingenol Derived from Euphorbia kansui Induces Hepatocyte Cytotoxicity by Triggering G0/G1 Cell Cycle Arrest and Regulating the Mitochondrial Apoptosis Pathway in Vitro

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Xiaojing Yan

2016-06-01

Full Text Available Natural product lingenol, a purified diterpenoid compound derived from the root of Euphorbia kansui, exerts serious hepatotoxicity; however, the molecular mechanisms remain to be defined. In the present study, cell counting Kit-8 (CCK-8, inverted phase contrast microscope and flow cytometry were used to demonstrate that lingenol significantly inhibited L-O2 cells proliferation, and induced cell cycle arrest and apoptosis. Moreover, the results investigated that lingenol markedly disrupted mitochondrial functions by high content screening (HCS. In addition, the up-regulation of cytochrome c, AIF and Apaf-1 and activation of caspases were found in L-O2 cells detected by Western blotting and ELISA assay, which was required for lingenol activation of cytochrome c-mediated caspase cascades and AIF-mediated DNA damage. Mechanistic investigations revealed that lingenol significantly down-regulated the Bcl-2/Bax ratio and enhanced the reactive oxygen species (ROS in L-O2 cells. These data collectively indicated that lingenol modulation of ROS and Bcl-2/Bax ratio led to cell cycle arrest and mitochondrial-mediated apoptosis in L-O2 cells in vitro. All of these results will be helpful to reveal the hepatotoxicity mechanism of Euphorbia kansui and to effectively guide safer and better clinical application of this herb.

2C-Methyl- D- erythritol 2,4-cyclodiphosphate synthase from Stevia rebaudiana Bertoni is a functional gene.

Science.gov (United States)

Kumar, Hitesh; Singh, Kashmir; Kumar, Sanjay

2012-12-01

Stevia [Stevia rebaudiana (Bertoni)] is a perennial herb which accumulates sweet diterpenoid steviol glycosides (SGs) in its leaf tissue. SGs are synthesized by 2C-methyl-D-erythritol 4-phosphate (MEP) pathway. Of the various enzymes of the MEP pathway, 2C-methyl-D-erythritol 2,4-cyclodiphosphate synthase (MDS) (encoded by MDS) catalyzes the cyclization of 4-(cytidine 5' diphospho)-2C-methyl-D-erythritol 2-phosphate into 2C-methyl-D-erythritol 2,4-cyclodiphosphate. Complementation of the MDS knockout mutant strain of Escherichia coli, EB370 with putative MDS of stevia (SrMDS) rescued the lethal mutant, suggesting SrMDS to be a functional gene. Experiments conducted in plant growth chamber and in the field suggested SrMDS to be a light regulated gene. Indole 3-acetic acid (IAA; 50, 100 μM) down-regulated the expression of SrMDS at 4 h of the treatment, whereas, abscisic acid did not modulate its expression. A high expression of SrMDS was observed during the light hours of the day as compared to the dark hours. The present work established functionality of SrMDS and showed the role of light and IAA in regulating expression of SrMDS.

Glycosides from Stevia rebaudiana Bertoni Possess Insulin-Mimetic and Antioxidant Activities in Rat Cardiac Fibroblasts

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Cecilia Prata

2017-01-01

Full Text Available Stevia rebaudiana Bertoni is a shrub having a high content of sweet diterpenoid glycosides in its leaves, mainly stevioside and rebaudioside A, which are used as noncaloric, natural sweeteners. The aim of this study was to deepen the knowledge about the insulin-mimetic effect exerted by four different mixtures of steviol glycosides, rich in stevioside and rebaudioside A, in neonatal rat cardiac fibroblasts. The potential antioxidant activity of these steviol glycosides was also assessed, as oxidative stress is associated with diabetes. Likewise the insulin effect, steviol glycosides caused an increase in glucose uptake into rat fibroblasts by activating the PI3K/Akt pathway, thus inducing Glut4 translocation to the plasma membrane. The presence of S961, an insulin antagonist, completely abolished these effects, allowing to hypothesize that steviol glycosides could act as ligands of the same receptor engaged by insulin. Moreover, steviol glycosides counteracted oxidative stress by increasing reduced glutathione intracellular levels and upregulating expression and activity of the two antioxidant enzymes superoxide dismutase and catalase. The present work unravels the insulin-mimetic effect and the antioxidant property exerted by steviol glycosides, suggesting their potential beneficial role in the cotreatment of diabetes and in health maintenance.

Glycosides from Stevia rebaudiana Bertoni Possess Insulin-Mimetic and Antioxidant Activities in Rat Cardiac Fibroblasts

Science.gov (United States)

Prata, Cecilia; Zambonin, Laura; Rizzo, Benedetta; Vieceli Dalla Sega, Francesco

2017-01-01

Stevia rebaudiana Bertoni is a shrub having a high content of sweet diterpenoid glycosides in its leaves, mainly stevioside and rebaudioside A, which are used as noncaloric, natural sweeteners. The aim of this study was to deepen the knowledge about the insulin-mimetic effect exerted by four different mixtures of steviol glycosides, rich in stevioside and rebaudioside A, in neonatal rat cardiac fibroblasts. The potential antioxidant activity of these steviol glycosides was also assessed, as oxidative stress is associated with diabetes. Likewise the insulin effect, steviol glycosides caused an increase in glucose uptake into rat fibroblasts by activating the PI3K/Akt pathway, thus inducing Glut4 translocation to the plasma membrane. The presence of S961, an insulin antagonist, completely abolished these effects, allowing to hypothesize that steviol glycosides could act as ligands of the same receptor engaged by insulin. Moreover, steviol glycosides counteracted oxidative stress by increasing reduced glutathione intracellular levels and upregulating expression and activity of the two antioxidant enzymes superoxide dismutase and catalase. The present work unravels the insulin-mimetic effect and the antioxidant property exerted by steviol glycosides, suggesting their potential beneficial role in the cotreatment of diabetes and in health maintenance. PMID:28947927

Transcriptional effect of an Aframomum angustifolium seed extract on human cutaneous cells using low-density DNA chips.

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Bonnet-Duquennoy, Mathilde; Dumas, Marc; Debacker, Adeline; Lazou, Kristell; Talbourdet, Sylvie; Franchi, Jocelyne; Heusèle, Catherine; André, Patrice; Schnebert, Sylvianne; Bonté, Frédéric; Kurfürst, Robin

2007-06-01

Studying photoexposed and photoprotected skin biopsies from young and aged women, it has been found that a specific zone, composed of the basal layers of the epidermis, the dermal epidermal junction, and the superficial dermis, is major target of aging and reactive oxygen species. We showed that this zone is characterized by significant variations at a transcriptional and/or protein levels. Using low-density DNA chip technology, we evaluated the effect of a natural mixture of Aframomum angustifolium seed extract containing labdane diterpenoids on these aging markers. Expression profiles of normal human fibroblasts (NHF) were studied using a customized cDNA macroarray system containing genes covering dermal structure, inflammatory responses, and oxidative stress defense mechanisms. For normal human keratinocyte (NHK) investigations, we chose OLISA technique, a sensitive and quantitative method developed by BioMérieux specifically designed to investigate cell death, proliferation, epidermal structure, differentiation, and oxidative stress defense response. We observed that this extract strongly modified gene expression profiles of treated NHK, but weakly for NHF. This extract regulated antioxidant defenses, dermal-epidermal junction components, and epidermal renewal-related genes. Using low-density DNA chip technology, we identified new potential actions of A. angustifolium seed extract on skin aging.

Yuanhuapine-induced intestinal and hepatotoxicity were correlated with disturbance of amino acids, lipids, carbohydrate metabolism and gut microflora function: A rat urine metabonomic study.

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Chen, Yanyan; Duan, Jin-Ao; Guo, Jianming; Shang, Erxin; Tang, Yuping; Qian, Yefei; Tao, Weiwei; Liu, Pei

2016-07-15

This research was designed to study metabonomic characteristics of the toxicity induced by yuanhuapine, a major bioactive diterpenoid in a well-known traditional Chinese medicine-Genkwa Flos. General observation, blood biochemistry and histopathological examination were used to reflect yuanhuapine-induced toxicity. Urine samples from rats in control and yuanhuapine treated rats were analyzed by ultra-performance liquid chromatography tandem quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Pattern recognition methods including principal components analysis (PCA), partial least-squared discriminant analysis (PLS-DA), orthogonal partial least-squared discriminant analysis (OPLS-DA) and computational system analysis were integrated to obtain comprehensive metabonomic profiling and pathways of the biological data sets. The results suggested that yuanhuapine could induce intestinal and liver damage. And 14 endogenous metabolites as biomarkers related to the amino acids metabolism, lipids metabolism, carbohydrate metabolism and gut microflora were significantly changed in the urine of yuanhuapine treated rats, which were firstly constructed the metabolomic feature profiling and metabolite interaction network of yuanhuapine-induced injury using pattern recognition methods and Ingenuity Pathway Analysis (IPA) approach. The present study showed that yuanhuapine-induced intestinal and hepatic toxicity were correlated with disturbance of amino acids metabolism, lipids metabolism, carbohydrate metabolism and gut microflora. Copyright © 2015 Elsevier B.V. All rights reserved.

Alepidea amatymbica Eckl. & Zeyh.: A Review of Its Traditional Uses, Phytochemistry, Pharmacology, and Toxicology

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O. A. Wintola

2014-01-01

Full Text Available Alepidea amatymbica is an important medicinal plant in Southern Africa with a long history of traditional use for the management of conditions like colds, coughs, sore throat, influenza, asthma, and abdominal cramps. Despite the much acclaimed traditional uses of the plant, there is a dearth of scientific information on the review of this plant. Hence, this review is aimed at providing information on the botany, phytochemistry, pharmacology, and toxicology of A. amatymbica. This review uses all the synonyms of the plant obtained from the plant list. Google scholar, Science Direct, PubMed, and Scopus were made use of in addition to the University of Fort Hare’s online databases. All the phytochemical studies on Alepidea amatymbica obtained from the literature reported the presence of kaurene-type diterpenoids and their derivatives. Pharmacological areas identified on A. amatymbica fresh and dried extract include antibacterial, antifungal, sedative, astringent, antimalarial, anti-inflammatory, antihelminthes, antihypertensive, anti-HIV, and diuretic activities. Literature search on A. amatymbica revealed the use of cell line, brine shrimps, and rats for the determination of the toxicity in the plant. Clinical trials and product development to fully exploit the medicinal value are also required to validate its folklore use in traditional medicine.

Oridonin inhibits tumor growth and metastasis through anti-angiogenesis by blocking the Notch signaling.

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Yanmin Dong

Full Text Available While significant progress has been made in understanding the anti-inflammatory and anti-proliferative effects of the natural diterpenoid component Oridonin on tumor cells, little is known about its effect on tumor angiogenesis or metastasis and on the underlying molecular mechanisms. In this study, Oridonin significantly suppressed human umbilical vascular endothelial cells (HUVECs proliferation, migration, and apillary-like structure formation in vitro. Using aortic ring assay and mouse corneal angiogenesis model, we found that Oridonin inhibited angiogenesis ex vivo and in vivo. In our animal experiments, Oridonin impeded tumor growth and metastasis. Immunohistochemistry analysis further revealed that the expression of CD31 and vWF protein in xenografts was remarkably decreased by the Oridonin. Furthermore, Oridonin reinforced endothelial cell-cell junction and impaired breast cancer cell transendothelial migration. Mechanistically, Oridonin not only down-regulated Jagged2 expression and Notch1 activity but also decreased the expression of their target genes. In conclusion, our results demonstrated an original role of Oridonin in inhibiting tumor angiogenesis and propose a mechanism. This study also provides new evidence supporting the central role of Notch in tumor angiogenesis and suggests that Oridonin could be a potential drug candidate for angiogenesis related diseases.

Andrographis paniculata (Burm. f. Wall. ex Nees: A Review of Ethnobotany, Phytochemistry, and Pharmacology

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Md. Sanower Hossain

2014-01-01

Full Text Available As aboriginal sources of medications, medicinal plants are used from the ancient times. Andrographis paniculata is one of the highly used potential medicinal plants in the world. This plant is traditionally used for the treatment of common cold, diarrhoea, fever due to several infective cause, jaundice, as a health tonic for the liver and cardiovascular health, and as an antioxidant. It is also used to improve sexual dysfunctions and serve as a contraceptive. All parts of this plant are used to extract the active phytochemicals, but the compositions of phytoconstituents widely differ from one part to another and with place, season, and time of harvest. Our extensive data mining of the phytoconstituents revealed more than 55 ent-labdane diterpenoids, 30 flavonoids, 8 quinic acids, 4 xanthones, and 5 rare noriridoids. In this review, we selected only those compounds that pharmacology has already reported. Finally we focused on around 46 compounds for further discussion. We also discussed ethnobotany of this plant briefly. Recommendations addressing extraction process, tissue culture, and adventitious rooting techniques and propagation under abiotic stress conditions for improvement of phytoconstituents are discussed concisely in this paper. Further study areas on pharmacology are also proposed where needed.

Inhibition of autophagy by andrographolide resensitizes cisplatin-resistant non-small cell lung carcinoma cells via activation of the Akt/mTOR pathway

International Nuclear Information System (INIS)

Mi, Shanwei; Xiang, Gang; Yuwen, Daolu; Gao, Jian; Guo, Wenjie; Wu, Xuefeng; Wu, Xudong; Sun, Yang; Su, Yongqian; Shen, Yan; Xu, Qiang

2016-01-01

Resistance to cisplatin is a major obstacle for the success of non-small cell lung cancer therapy. The mechanisms underlying cisplatin resistance are not fully understood. In this study, we found that the increase of basal auotophagy accompanied the development of cisplatin resistance. Meanwhile the blockade of the Akt/mTOR pathway occurred in the process. Inhibition of this pathway was induced by cisplatin treatment in the resistant non-small cell lung carcinoma cells. Andrographolide, a natural diterpenoid, promoted the activation of the Akt/mTOR signaling by downregulating PTEN and suppressed autophagy, which subsequently resensitized the resistant cells to cisplatin-mediated apoptosis. Cisplatin treatment in combination with andrographolide significantly prevented the growth of the resistant cells in vivo. These results highlight the involvement of autophagy in cisplatin-resistance development and suggest that inhibition of autophagy via tuning the Akt/mTOR signaling could be a promising strategy in the therapy for cisplatin-resistant non-small cell lung cancer. - Highlights: • The increase of basal auotophagy accompanied the development of cisplatin resistance in NSCLC cells. • Cisplatin induced the blockade of the Akt/mTOR pathway. • Andrographolide promoted the activation of the Akt/mTOR signaling. • Andrographolide downregulated PTEN expression. • Cisplatin treatment in combination with andrographolide resensitized the resistant cells to cisplatin.

Inhibition of autophagy by andrographolide resensitizes cisplatin-resistant non-small cell lung carcinoma cells via activation of the Akt/mTOR pathway

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Mi, Shanwei; Xiang, Gang [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Yuwen, Daolu [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 (China); Gao, Jian; Guo, Wenjie; Wu, Xuefeng; Wu, Xudong; Sun, Yang [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Su, Yongqian [Department of Clinical Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029 (China); Shen, Yan, E-mail: shenyan@nju.edu.cn [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China); Xu, Qiang, E-mail: molpharm@163.com [State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093 (China)

2016-11-01

Resistance to cisplatin is a major obstacle for the success of non-small cell lung cancer therapy. The mechanisms underlying cisplatin resistance are not fully understood. In this study, we found that the increase of basal auotophagy accompanied the development of cisplatin resistance. Meanwhile the blockade of the Akt/mTOR pathway occurred in the process. Inhibition of this pathway was induced by cisplatin treatment in the resistant non-small cell lung carcinoma cells. Andrographolide, a natural diterpenoid, promoted the activation of the Akt/mTOR signaling by downregulating PTEN and suppressed autophagy, which subsequently resensitized the resistant cells to cisplatin-mediated apoptosis. Cisplatin treatment in combination with andrographolide significantly prevented the growth of the resistant cells in vivo. These results highlight the involvement of autophagy in cisplatin-resistance development and suggest that inhibition of autophagy via tuning the Akt/mTOR signaling could be a promising strategy in the therapy for cisplatin-resistant non-small cell lung cancer. - Highlights: • The increase of basal auotophagy accompanied the development of cisplatin resistance in NSCLC cells. • Cisplatin induced the blockade of the Akt/mTOR pathway. • Andrographolide promoted the activation of the Akt/mTOR signaling. • Andrographolide downregulated PTEN expression. • Cisplatin treatment in combination with andrographolide resensitized the resistant cells to cisplatin.

Mallotus philippinensis Muell. Arg (Euphorbiaceae: Ethnopharmacology and Phytochemistry Review

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Mayank Gangwar

2014-01-01

Full Text Available Mallotus philippinensis Muell. Arg (Euphorbiaceae are widely distributed perennial shrub or small tree in tropical and subtropical region in outer Himalayas regions with an altitude below 1,000 m and are reported to have wide range of pharmacological activities. Mallotus philippinensis species are known to contain different natural compounds, mainly phenols, diterpenoids, steroids, flavonoids, cardenolides, triterpenoids, coumarins, isocoumarins, and many more especially phenols; that is, bergenin, mallotophilippinens, rottlerin, and isorottlerin have been isolated, identified, and reported interesting biological activities such as antimicrobial, antioxidant, antiviral, cytotoxicity, antioxidant, anti-inflammatory, immunoregulatory activity protein inhibition against cancer cell. We have selected all the pharmacological aspects and toxicological and all its biological related studies. The present review reveals that Mallotus philippinensis is a valuable source of medicinally important natural molecules and provides convincing support for its future use in modern medicine. However, the existing knowledge is very limited about Mallotus philippinensis and its different parts like steam, leaf, and fruit. Further, more detailed safety data pertaining to the acute and subacute toxicity and cardio- and immunotoxicity also needs to be generated for crude extracts or its pure isolated compounds. This review underlines the interest to continue the study of this genus of the Euphorbiaceae.

Supercritical carbon dioxide extraction of antioxidants from rosemary (Rosmarinus officinalis L. and sage (Salvia officinalis L.

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JASNA IVANOVIĆ

2009-07-01

Full Text Available The aim of the present study was to isolate and characterize antioxidant extracts obtained from dried leaves of rosemary (Rosmarinus officinalis L. and sage (Salvia officinalis L., originating from the southern Balkan Region. The antioxidant fraction was isolated from the plant material by supercritical carbon dioxide (SC-CO2 fractional extraction under a pressure of 30 MPa and at temperatures of 40 and 100 °C. In the present study, kinetic data and yields of antioxidant extracts obtained from dried leaves of rosemary and sage under different conditions were determined. Electron spin resonance (ESR spectroscopy assay on the ability of the extracts to scavenge stable 2,2-diphenyl-1-picrylhydrazyl (DPPH free radicals and reactive hydroxyl radicals during the Fenton reaction trapped by 5,5-dimethyl-1-pyrroline-N-oxide (DMPO showed that the investigated extracts had antioxidant activity comparable to that of butylated hydroxyanisole (BHA and commercial rosemary extract. The antioxidant fractions isolated at the higher temperature had higher antioxidant activities. A tentative analysis of the chemical composition of the antioxidant fractions obtained at the higher temperature was accomplished by LC-DAD and LC-MS analytical methods. Abietane-type diterpenoids, flavonoids and fatty acids were identified in the SC-CO2 extract of rosemary and sage.

Plant-derived immunomodulators: An insight on their preclinical evaluation and clinical trials

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Ibrahim eJantan

2015-08-01

Full Text Available The phagocyte-microbe interactions in the immune system is a defence mechanism but when excessively or inappropriately deployed can harm host tissues and participate in the development of different non-immune and immune chronic inflammatory diseases such as autoimmune problems, allergies, some rheumatoid disorders, cancers and others. Immunodrugs include organic synthetics, biological agents such as cytokines and antibodies acting on single targets or pathways have been used to treat immune-related diseases but with limited success. Most of immunostimulants and immunosuppressants in clinical use are the cytotoxic drugs which possess serious side effects. There is a growing interest to use herbal medicines as multi-component agents to modulate the complex immune system in the prevention of infections rather than treating the immune-related diseases. Many therapeutic effects of plant extracts have been suggested to be due to their wide array of immunomodulatory effects and influence on the immune system of the human body. Phytochemicals such as flavonoids, polysaccharides, lactones, alkaloids, diterpenoids and glycosides, present in several plants, have been reported to be responsible for the plants immunomodulating properties. Thus the search for natural products of plant origin as new leads for development of potent and safe immunosuppressant and immunostimulant agents is gaining much major research

Leishmanicidal, antiplasmodial, and cytotoxic activity of novel diterpenoid 1,2-quinones from Perovskia abrotanoides: new source of tanshinones

DEFF Research Database (Denmark)

Sairafianpour, M; Christensen, J; Staerk, D

2001-01-01

provide a rationale for traditional use of the roots in Iran as a constituent of poultices for treatment of cutaneous leishmaniasis. The isolated tanshinones also inhibited growth of cultured malaria parasites (3D7 strain of Plasmodium falciparum), drug-sensitive KB-3-1 human carcinoma cell line...

Diterpenoids and flavonoids from the fruits of Vitex agnus-castus and antioxidant activity of the fruit extracts and their constituents.

Science.gov (United States)

Hajdú, Zsuzsanna; Hohmann, Judit; Forgo, Peter; Martinek, Tamás; Dervarics, Máté; Zupkó, István; Falkay, György; Cossuta, Daniel; Máthé, Imre

2007-04-01

From the n-hexane fraction of the fruits of Vitex agnus-castus, two labdane-type diterpenes, vitetrifolin B and C, were isolated by means of multiple chromatographic separations, together with the previously identified rotundifuran, vitexilactone and the sesquiterpene spathulenol. From the EtOAc fraction, eupatorin was identified for the first time, besides the known casticin, penduletin, vitexin and orientin. The n-hexane, EtOAc and MeOH-H(2)O fractions of the MeOH extract of Agni-casti fructus were subjected to in vitro antioxidant assays. The EtOAc extract displayed a significant concentration-dependent effect when tested by 1,1-diphenyl-2-picrylhydrasyl (DPPH) free radical assay (IC(50) = 68 microg/mL) and against the autooxidation of a standard rat brain homogenate (IC(50) = 14 microg/mL). The MeOH-H(2)O fraction was less active with 3643 microg/mL (DPPH test) and IC(50) = 125 microg/mL (rat brain homogenate), while the n-hexane phase proved to be inactive. The main flavonoid constituents of the EtOAc extract, casticin, vitexin and orientin were assayed for antioxidant activity and found that only casticin possesses a marked lipid peroxidation inhibitory effect (IC(50) = 0.049 mm) compared with that of the positive control ascorbic acid (IC(50) = 0.703 mm).

Synthesis of antimalarial amide analogues based on the plant serrulatane diterpenoid 3,7,8-trihydroxyserrulat-14-en-19-oic acid.

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Kumar, Rohitesh; Duffy, Sandra; Avery, Vicky M; Davis, Rohan A

2017-09-01

A plant-derived natural product scaffold, 3,7,8-trihydroxyserrulat-14-en-19-oic acid (1) was isolated in high yield from the aerial parts of the endemic Australian desert plant Eremophila microtheca. This scaffold (1) was subsequently used in the generation of a series of new amide analogues via a one-pot mixed anhydride amidation using pivaloyl chloride. The structures of all analogues were characterized using MS, NMR, and UV data. The major serrulatane natural products (1-3), isolated from the plant extract, and all amide analogues (6-15) together with several pivaloylated derivatives of 3,7,8-trihydroxyserrulat-14-en-19-oic acid (16-18) were evaluated for their antimalarial activity against 3D7 (chloroquine sensitive) and Dd2 (chloroquine resistant) Plasmodium falciparum strains, and preliminary cytotoxicity data were also acquired using the human embryonic kidney cell line HEK293. The natural product scaffold (1) did not display any antimalarial activity at 10µM. Replacing the carboxylic acid of 1 with various amides resulted in moderate activity against the P. falciparum 3D7 strain with IC 50 values ranging from 1.25 to 5.65µM. Copyright © 2017 Elsevier Ltd. All rights reserved.

Phytochemical Profiling of Flavonoids, Phenolic Acids, Terpenoids, and Volatile Fraction of a Rosemary (Rosmarinus officinalis L. Extract

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Pedro Mena

2016-11-01

Full Text Available This paper presents a comprehensive analysis of the phytochemical profile of a proprietary rosemary (Rosmarinus officinalis L. extract rich in carnosic acid. A characterization of the (polyphenolic and volatile fractions of the extract was carried out using mass spectrometric techniques. The (polyphenolic composition was assessed by ultra-high performance liquid chromatography-electrospray ionization-mass spectrometry (UHPLC-ESI-MSn and a total of 57 compounds were tentatively identified and quantified, 14 of these being detected in rosemary extract for the first time. The rosemary extract contained 24 flavonoids (mainly flavones, although flavonols and flavanones were also detected, 5 phenolic acids, 24 diterpenoids (carnosic acid, carnosol, and rosmanol derivatives, 1 triterpenoid (betulinic acid, and 3 lignans (medioresinol derivatives. Carnosic acid was the predominant phenolic compound. The volatile profile of the rosemary extract was evaluated by head space solid-phase microextraction (HS-SPME linked to gas chromatography-mass spectrometry (GC-MS. Sixty-three volatile molecules (mainly terpenes, alcohols, esters, aldehydes, and ketones were identified. This characterization extends the current knowledge on the phytochemistry of Rosmarinus officinalis and is, to our knowledge, the broadest profiling of its secondary metabolites to date. It can assist in the authentication of rosemary extracts or rosemary-containing products or in testing its bioactivity. Moreover, this methodological approach could be applied to the study of other plant-based food ingredients.

In vitro tests and ethnopharmacological investigations: wound healing as an example.

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Houghton, P J; Hylands, P J; Mensah, A Y; Hensel, A; Deters, A M

2005-08-22

In vitro tests are now widely employed in ethnopharmacological research because of ethical reasons and their usefulness in bioactive-guided fractionation and determination of active compounds. For many disease conditions, a variety of in vitro tests can now be employed as the biochemical mechanisms underlying disease and healing processes are understood. Approaches to the in vitro investigations of wound healing processes are exemplified by studies on extracts of Buddleja species and three Ghanaian species Spathodea campanulata, Commelina diffusa and Secamone afzelii. Most studies have been carried out on Buddleja officinalis or Buddleja globosa. The extracts have been shown to have anti-inflammatory and antioxidant properties due to flavonoids, triterpenoids, diterpenoids and caffeic acid derivatives. There appears to a slight effect on proliferation of fibroblasts at lower concentrations, but this was not significant, and higher concentrations appeared to be cytotoxic. Novel findings are the ability of Buddleja globosa leaf extracts to induce differentiation in keratinocytes and to alter the profile of proteins produced by cultured fibroblasts. Extracts also had some effect on lattice contraction. The three Ghanaian species examined show a mixture of antimicrobial and antioxidant activities. The evolution over recent years of tests for wound healing, from in vivo tests to cell-based systems and chemical reactions and on to investigations into effects on secondary messengers and protein expression, is described.

Andrographolide Activates Keap1/Nrf2/ARE/HO-1 Pathway in HT22 Cells and Suppresses Microglial Activation by Aβ42 through Nrf2-Related Inflammatory Response.

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Seo, Ji Yeon; Pyo, Euisun; An, Jin-Pyo; Kim, Jinwoong; Sung, Sang Hyun; Oh, Won Keun

2017-01-01

Therapeutic approach of Alzheimer's disease (AD) has been gradually diversified. We examined the therapeutic and preventive potential of andrographolide, which is a lactone diterpenoid from Andrographis paniculata , and focused on the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated heme oxygenase (HO)-1-inducing effects and the inhibitory activity of amyloid beta (A β ) 42 -induced microglial activation related to Nrf2 and nuclear factor κ B (NF- κ B)-mediated inflammatory responses. Andrographolide induced the expression and translocation of Nrf2 from the cytoplasm to the nucleus, thereby activating antioxidant response element (ARE) gene transcription and HO-1 expression in murine hippocampal HT22 cells. Andrographolide eliminated intracellular A β 42 in BV-2 cells and decreased the production of interleukin (IL)-6, IL-1 β , prostaglandin (PG)E 2 , and nitric oxide (NO) because of artificial phagocytic A β 42 . It decreased pNF- κ B accumulation in the nucleus and the expression of inducible nitric oxide synthase (i-NOS) and cyclooxygenase II (COX-II) in the microglial BV-2 cell line. In summary, andrographolide activates Nrf2-mediated HO-1 expression and inhibits A β 42 -overexpressed microglial BV-2 cell activation. These results suggested that andrographolide might have the potential for further examination of the therapeutics of AD.

Inhibitory effects of andrographolide on activated macrophages and adjuvant-induced arthritis.

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Gupta, Swati; Mishra, Kamla Prasad; Singh, Shashi Bala; Ganju, Lilly

2018-04-01

Andrographolide, a diterpenoid lactone obtained from plant Andrographis paniculata, is used in South Asian countries to relieve various inflammatory symptoms. To study the effects of this agent, the impact of andrographolide on production of inflammatory mediators were delineated in mouse peritoneal macrophages (PMϕ). Inflammatory mediators like nitric oxide (NO), tumor necrosis factor (TNF)-α, interleukin-6 and related molecular mechanisms of andrographolide-mediated inhibition of enzymes/transcription factors were studied. In addition, the in vivo anti-inflammatory activity of andrographolide was evaluated in an adjuvant-induced arthritis rat model. The results indicated that andrographolide clearly inhibited the production of NO and TNF-α in lipopolysaccharide-activated PMϕ in a dose-related manner. Immunoblot analyses revealed that andrographolide suppressed activation of both inducible NO synthase and cyclo-oxygenase-2 by directly targeting nuclear transcription factor (NF)-κB. Complete Freund's Adjuvant-induced paw edema in rats was also significantly inhibited by andrographolide treatment. From the data, we concluded that andrographolide imparted anti-inflammatory effects by suppressing two key inflammatory enzymes and a signaling pathway that mediates expression of variety of inflammatory cytokines/agents in situ. It is plausible that eventually, after further toxicologic characterization, andrographolide might be useful as a drug for the clinical treatment of various inflammatory diseases like rheumatoid arthritis or diseases associated with joint pain.

Andrographolide Activates Keap1/Nrf2/ARE/HO-1 Pathway in HT22 Cells and Suppresses Microglial Activation by Aβ42 through Nrf2-Related Inflammatory Response

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Ji Yeon Seo

2017-01-01

Full Text Available Therapeutic approach of Alzheimer’s disease (AD has been gradually diversified. We examined the therapeutic and preventive potential of andrographolide, which is a lactone diterpenoid from Andrographis paniculata, and focused on the Kelch-like ECH-associated protein 1 (Keap1/nuclear factor (erythroid-derived 2-like 2 (Nrf2-mediated heme oxygenase (HO-1-inducing effects and the inhibitory activity of amyloid beta (Aβ42-induced microglial activation related to Nrf2 and nuclear factor κB (NF-κB-mediated inflammatory responses. Andrographolide induced the expression and translocation of Nrf2 from the cytoplasm to the nucleus, thereby activating antioxidant response element (ARE gene transcription and HO-1 expression in murine hippocampal HT22 cells. Andrographolide eliminated intracellular Aβ42 in BV-2 cells and decreased the production of interleukin (IL-6, IL-1β, prostaglandin (PGE2, and nitric oxide (NO because of artificial phagocytic Aβ42. It decreased pNF-κB accumulation in the nucleus and the expression of inducible nitric oxide synthase (i-NOS and cyclooxygenase II (COX-II in the microglial BV-2 cell line. In summary, andrographolide activates Nrf2-mediated HO-1 expression and inhibits Aβ42-overexpressed microglial BV-2 cell activation. These results suggested that andrographolide might have the potential for further examination of the therapeutics of AD.

Pharmacology and Phytochemistry of Oleo-Gum Resin of Commiphora wightii (Guggulu

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Prerna Sarup

2015-01-01

Full Text Available Guggulu is an oleo-gum resin which exudes out as a result of injury from the bark of Commiphora wightii (Arnott Bhandari [syn.  Commiphora mukul (Hook. Ex Stocks Engl; Balsamodendron mukul (Hook. Ex Stocks; Family, Burseraceae]. It has been used in the Ayurveda since time immemorial for the treatment of variety of disorders such as inflammation, gout, rheumatism, obesity, and disorders of lipids metabolism. It is a mixture of phytoconstituents like volatile oil which contains terpenoidal constituents such as monoterpenoids, sesquiterpenoids, diterpenoids, and triterpenoids; steroids; flavonoids; guggultetrols; lignans; sugars; and amino acids. This review is an effort to compile all the information available on all of its chemical constituents which are responsible for its therapeutic potential. The wild occurrence of this species is restricted mainly to the dry regions of Rajasthan and Gujarat States of India, and the bordering regions of Pakistan. Oleo-gum resin, guggulu, tapped from the stems of this species, is consumed in high volumes by the Indian herbal industries. There has been a decline in its wild population over the last several decades, as a result of habitat loss and degradation, coupled with unregulated harvesting and tapping of oleo-gum resin. This species is consequently assessed as Critically Endangered and enlisted in the IUCN red list of threatened species.

Phytochemical Profiling of Flavonoids, Phenolic Acids, Terpenoids, and Volatile Fraction of a Rosemary (Rosmarinus officinalis L.) Extract.

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Mena, Pedro; Cirlini, Martina; Tassotti, Michele; Herrlinger, Kelli A; Dall'Asta, Chiara; Del Rio, Daniele

2016-11-19

This paper presents a comprehensive analysis of the phytochemical profile of a proprietary rosemary ( Rosmarinus officinalis L.) extract rich in carnosic acid. A characterization of the (poly)phenolic and volatile fractions of the extract was carried out using mass spectrometric techniques. The (poly)phenolic composition was assessed by ultra-high performance liquid chromatography-electrospray ionization-mass spectrometry (UHPLC-ESI-MS n ) and a total of 57 compounds were tentatively identified and quantified, 14 of these being detected in rosemary extract for the first time. The rosemary extract contained 24 flavonoids (mainly flavones, although flavonols and flavanones were also detected), 5 phenolic acids, 24 diterpenoids (carnosic acid, carnosol, and rosmanol derivatives), 1 triterpenoid (betulinic acid), and 3 lignans (medioresinol derivatives). Carnosic acid was the predominant phenolic compound. The volatile profile of the rosemary extract was evaluated by head space solid-phase microextraction (HS-SPME) linked to gas chromatography-mass spectrometry (GC-MS). Sixty-three volatile molecules (mainly terpenes, alcohols, esters, aldehydes, and ketones) were identified. This characterization extends the current knowledge on the phytochemistry of Rosmarinus officinalis and is, to our knowledge, the broadest profiling of its secondary metabolites to date. It can assist in the authentication of rosemary extracts or rosemary-containing products or in testing its bioactivity. Moreover, this methodological approach could be applied to the study of other plant-based food ingredients.

Proteomic Analysis of the Endosperm Ontogeny of Jatropha curcas L. Seeds.

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Shah, Mohibullah; Soares, Emanoella L; Carvalho, Paulo C; Soares, Arlete A; Domont, Gilberto B; Nogueira, Fábio C S; Campos, Francisco A P

2015-06-05

Seeds of Jatropha curcas L. represent a potential source of raw material for the production of biodiesel. However, this use is hampered by the lack of basic information on the biosynthetic pathways associated with synthesis of toxic diterpenes, fatty acids, and triacylglycerols, as well as the pattern of deposition of storage proteins during seed development. In this study, we performed an in-depth proteome analysis of the endosperm isolated from five developmental stages which resulted in the identification of 1517, 1256, 1033, 752, and 307 proteins, respectively, summing up 1760 different proteins. Proteins with similar label free quantitation expression pattern were grouped into five clusters. The biological significance of these identifications is discussed with special focus on the analysis of seed storage proteins, proteins involved in the metabolism of fatty acids, carbohydrates, toxic components and proteolytic processing. Although several enzymes belonging to the biosynthesis of diterpenoid precursors were identified, we were unable to find any terpene synthase/cyclase, indicating that the synthesis of phorbol esters, the main toxic diterpenes, does not occur in seeds. The strategy used enabled us to provide a first in depth proteome analysis of the developing endosperm of this biodiesel plant, providing an important glimpse into the enzymatic machinery devoted to the production of C and N sources to sustain seed development.

Scopadulciol, Isolated from Scoparia dulcis, Induces β-Catenin Degradation and Overcomes Tumor Necrosis Factor-Related Apoptosis Ligand Resistance in AGS Human Gastric Adenocarcinoma Cells.

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Fuentes, Rolly G; Toume, Kazufumi; Arai, Midori A; Sadhu, Samir K; Ahmed, Firoj; Ishibashi, Masami

2015-04-24

Scopadulciol (1), a scopadulan-type diterpenoid, was isolated from Scoparia dulcis along with three other compounds (2-4) by an activity-guided approach using the TCF reporter (TOP) luciferase-based assay system. A fluorometric microculture cytotoxicity assay (FMCA) revealed that compound 1 was cytotoxic to AGS human gastric adenocarcinoma cells. The treatment of AGS cells with 1 decreased β-catenin levels and also inhibited its nuclear localization. The pretreatment of AGS cells with a proteasome inhibitor, either MG132 or epoxomicin, protected against the degradation of β-catenin induced by 1. The 1-induced degradation of β-catenin was also abrogated in the presence of pifithrin-α, an inhibitor of p53 transcriptional activity. Compound 1 inhibited TOP activity in AGS cells and downregulated the protein levels of cyclin D1, c-myc, and survivin. Compound 1 also sensitized AGS cells to tumor necrosis factor-related apoptosis ligand (TRAIL)-induced apoptosis by increasing the levels of the death receptors, DR4 and DR5, and decreasing the level of the antiapoptotic protein Bcl-2. Collectively, our results demonstrated that 1 induced the p53- and proteasome-dependent degradation of β-catenin, which resulted in the inhibition of TCF/β-catenin transcription in AGS cells. Furthermore, 1 enhanced apoptosis in TRAIL-resistant AGS when combined with TRAIL.

An operon for production of bioactive gibberellin A4 phytohormone with wide distribution in the bacterial rice leaf streak pathogen Xanthomonas oryzae pv. oryzicola.

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Nagel, Raimund; Turrini, Paula C G; Nett, Ryan S; Leach, Jan E; Verdier, Valérie; Van Sluys, Marie-Anne; Peters, Reuben J

2017-05-01

Phytopathogens have developed elaborate mechanisms to attenuate the defense response of their host plants, including convergent evolution of complex pathways for production of the GA phytohormones, which were actually first isolated from the rice fungal pathogen Gibberella fujikuroi. The rice bacterial pathogen Xanthomonas oryzae pv. oryzicola (Xoc) has been demonstrated to contain a biosynthetic operon with cyclases capable of producing the universal GA precursor ent-kaurene. Genetic (knock-out) studies indicate that the derived diterpenoid serves as a virulence factor for this rice leaf streak pathogen, serving to reduce the jasmonic acid-mediated defense response. Here the functions of the remaining genes in the Xoc operon are elucidated and the distribution of the operon in X. oryzae is investigated in over 100 isolates. The Xoc operon leads to production of the bioactive GA 4 , an additional step beyond production of the penultimate precursor GA 9 mediated by the homologous operons recently characterized from rhizobia. Moreover, this GA biosynthetic operon was found to be widespread in Xoc (> 90%), but absent in the other major X. oryzae pathovar. These results indicate selective pressure for production of GA 4 in the distinct lifestyle of Xoc, and the importance of GA to both fungal and bacterial pathogens of rice. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

Ovatodiolide of Anisomeles indica Exerts the Anticancer Potential on Pancreatic Cancer Cell Lines through STAT3 and NF-κB Regulation

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Ya-Ju Hsieh

2016-01-01

Full Text Available Pancreatic cancer is the eighth leading cause of cancer death worldwide. Patients with pancreatic cancer are normally diagnosed at an advanced stage and present poor survival rate. Ovatodiolide (OV, a bioactive macrocyclic diterpenoid isolated from Anisomeles indica, showed cytotoxicity effects in pancreatic cancer cells by inhibiting cell proliferation and inducing apoptosis. Moreover, not only were cell adhesion and invasion markedly suppressed in a dose-dependent manner, but the mRNA expression of matrix metalloproteinase-9 (MMP-9 and focal adhesion kinase (FAK was also significantly decreased. Western blot analysis indicated that OV potently suppressed the phosphorylation of STAT-3 and its upstream kinase including ERK1/2, P38, and AKT Ser473. Meanwhile, OV inactivated the nuclear factor kappa B (NF-κB by inhibiting IκB kinase (IKK α/β activation and the subsequent suppression of inhibitor of kappa B (IκB phosphorylation. These results demonstrated that OV could potentially inhibit Mia-PaCa2 cancer cells proliferation and induce apoptosis through modulation of NF-κB and STAT3 pathway. Moreover, OV suppressed cell invasiveness and interfered with cell-matrix adhesion in Mia-PaCa2 cancer cells by reducing MMP-9 and FAK transcription through suppressing NF-κB and STAT3 pathway. Taken together, our findings reveal a new therapeutic and antimetastatic potential of ovatodiolide for pancreatic cancer remedy.

Andrographolide-loaded nanoparticles for brain delivery: Formulation, characterisation and in vitro permeability using hCMEC/D3 cell line.

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Guccione, Clizia; Oufir, Mouhssin; Piazzini, Vieri; Eigenmann, Daniela Elisabeth; Jähne, Evelyn Andrea; Zabela, Volha; Faleschini, Maria Teresa; Bergonzi, Maria Camilla; Smiesko, Martin; Hamburger, Matthias; Bilia, Anna Rita

2017-10-01

Andrographolide (AG) is a major diterpenoid of the Asian medicinal plant Andrographis paniculata which has shown exciting pharmacological potential for the treatment of inflammation-related pathologies including neurodegenerative disorders. Conversely, the low bioavailability of AG still represents a limiting factor for its use. To overcome these limitations, AG was loaded into human serum albumin based nanoparticles (HSA NPs) and poly ethylcyanoacrylate nanoparticles (PECA NPs). HSA NPs were prepared by thermal (HSAT AG NPs) and chemical cross-linking (HSAC AG NPs), while PECA AG NPs were produced by emulsion-polymerization. NPs were characterized in terms of size, zeta (ζ)-potential, polydispersity, and release studies of AG. In addition, the ability of free AG and AG-loaded in PECA and HSAT NPs to cross the blood-brain barrier (BBB) was assessed using an in vitro BBB model based on human cerebral microvascular endothelial cell line (hCMEC/D3). For BBB drug permeability assays, a quantitative UPLC-MS/MS method for AG in Ringer HEPES buffer was developed and validated according to international regulatory guidelines for industry. Free AG did not permeate the BBB model, as also predicted by in silico studies. HSAT NPs improved by two-fold the permeation of AG while maintaining the integrity of the cell layer, while PECA NPs temporarily disrupted BBB integrity. Copyright © 2017 Elsevier B.V. All rights reserved.

Inhibition of proliferation and energy metabolism of Cloudman melanoma cells by aphidicolin and X-ray irradiation in vitro. Hemmung der Proliferation und des Energiestoffwechsels von Cloudman-Melanomzellen in vitro durch Aphidicolin und Gammastrahlung

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Merte, H [Marburg Univ. (Germany). Abt. fuer Strahlentherapie, Medizinisches Zentrum fuer Radiologie; Schachtschabel, D O [Marburg Univ. (Germany). Inst. fuer Physiologische Chemie; Plamper, G [Marburg Univ. (Germany). Abt. fuer Strahlentherapie, Medizinisches Zentrum fuer Radiologie; Pfab, R [Marburg Univ. (Germany). Abt. fuer Strahlentherapie, Medizinisches Zentrum fuer Radiologie

1994-06-01

Purpose: The present investigation is concerned with the effect of aphidicolin (a tetracyclic diterpenoid) and X-ray irradiation - alone or in combination - on cell proliferation, protein production, glucose consumption and lactate production of in vitro cultured Cloudman melanoma cells. Methods: Monolayer cultures of Cloudman melanoma cells in exponential growth phase were irradiated with 2, 4 or 6 Gy (Cobalt-60) or treated for 96 h with 0.1, 0.2 or 1.0 [mu]g/ml aphidicolin. Further, the combination of 0.1 or 0.2 [mu]g/ml aphidicolin with the above mentioned radiation doses were investigated. Measurements were performed in regard to changes of cell number, protein content, glucose consumption and lactate production. Results: Single treatments resulted in a dose-dependent inhibition of cell proliferation, protein production, glucose consumption and lactate production. Combined treatment with aphidicolin and irradiation caused an augmentation of the respective single effects. The inhibitory effects were more pronounced under serum-free than serum-containing culture conditions. Influence of aphidicolin and irradiation did not result in an immediate cell death, but in a state of unbalanced growth with enlarged cells (in part with an increased number of nuclei) and an increased cellular protein content. Conclusions: The combination of aphidicolin with X-ray irradiation caused a stronger effect than the respective single treatments. (orig.)

Eriocalyxin B Inhibits STAT3 Signaling by Covalently Targeting STAT3 and Blocking Phosphorylation and Activation of STAT3.

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Xiaokui Yu

Full Text Available Activated STAT3 plays an important role in oncogenesis by stimulating cell proliferation and resisting apoptosis. STAT3 therefore is an attractive target for cancer therapy. We have screened a traditional Chinese herb medicine compound library and found Eriocalyxin B (EB, a diterpenoid from Isodon eriocalyx, as a specific inhibitor of STAT3. EB selectively inhibited constitutive as well as IL-6-induced phosphorylation of STAT3 and induced apoptosis of STAT3-dependent tumor cells. EB did not affect the upstream protein tyrosine kinases or the phosphatase (PTPase of STAT3, but rather interacted directly with STAT3. The effects of EB could be abolished by DTT or GSH, suggesting a thiol-mediated covalent linkage between EB and STAT3. Site mutagenesis of cysteine in and near the SH2 domain of STAT3 identified Cys712 to be the critical amino acid for the EB-induced inactivation of STAT3. Furthermore, LC/MS/MS analyses demonstrated that an α, β-unsaturated carbonyl of EB covalently interacted with the Cys712 of STAT3. Computational modeling analyses also supported a direct interaction between EB and the Cys712 of STAT3. These data strongly suggest that EB directly targets STAT3 through a covalent linkage to inhibit the phosphorylation and activation of STAT3 and induces apoptosis of STAT3-dependent tumor cells.

Oridonin effectively reverses the drug resistance of cisplatin involving induction of cell apoptosis and inhibition of MMP expression in human acute myeloid leukemia cells

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Yuan Zhang

2017-03-01

Full Text Available Cisplatin is the first generation platinum-based chemotherapy agent. However, the extensive application of cisplatin inevitably causes drug resistance, which is a major obstacle to cancer chemotherapy. Oridonin is a diterpenoid isolated from Rabdosia rubescens with potent anticancer activity. The aim of our study is to investigate the role of oridonin to reverse the cisplatin-resistance in human acute myeloid leukemia (AML cells. The effect of oridonin on human AML cell proliferation was evaluated by MTT assay, cell migration and invasion were evaluated by transwell migration and invasion assays in cisplatin-resistant human AML cells. Furthermore, cell apoptosis was examined by flow cytometry. The inhibitive effect of oridonin in vivo was determined using xenografted nude mice. In addition, the expressions of MMP2 and MMP9 were detected by Western blot. There was a synergistic antitumor effect between cisplatin and oridonin on cisplatin-resistant human AML cells in vitro and in vivo. In addition, the combination of cisplatin and oridonin synergistically induced cell apoptosis. Furthermore, the combination treatment not only inhibited AML cell migration and invasion, but more significantly, decreased the expressions of MMP2 and MMP9 proteins. Our results suggest that the synergistic effect between both agents is likely to be driven by the inhibition of MMP expression and the resulting increased apoptosis.

Oridonin Targets Multiple Drug-Resistant Tumor Cells as Determined by in Silico and in Vitro Analyses

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Onat Kadioglu

2018-04-01

Full Text Available Drug resistance is one of the main reasons of chemotherapy failure. Therefore, overcoming drug resistance is an invaluable approach to identify novel anticancer drugs that have the potential to bypass or overcome resistance to established drugs and to substantially increase life span of cancer patients for effective chemotherapy. Oridonin is a cytotoxic diterpenoid isolated from Rabdosia rubescens with in vivo anticancer activity. In the present study, we evaluated the cytotoxicity of oridonin toward a panel of drug-resistant cancer cells overexpressing ABCB1, ABCG2, or ΔEGFR or with a knockout deletion of TP53. Interestingly, oridonin revealed lower degree of resistance than the control drug, doxorubicin. Molecular docking analyses pointed out that oridonin can interact with Akt/EGFR pathway proteins with comparable binding energies and similar docking poses as the known inhibitors. Molecular dynamics results validated the stable conformation of oridonin docking pose on Akt kinase domain. Western blot experiments clearly revealed dose-dependent downregulation of Akt and STAT3. Pharmacogenomics analyses pointed to a mRNA signature that predicted sensitivity and resistance to oridonin. In conclusion, oridonin bypasses major drug resistance mechanisms and targets Akt pathway and might be effective toward drug refractory tumors. The identification of oridonin-specific gene expressions may be useful for the development of personalized treatment approaches.

Intracellular Glutathione Depletion by Oridonin Leads to Apoptosis in Hepatic Stellate Cells

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Liang-Mou Kuo

2014-03-01

Full Text Available Proliferation of hepatic stellate cells (HSCs plays a key role in the pathogenesis of liver fibrosis. Induction of HSC apoptosis by natural products is considered an effective strategy for treating liver fibrosis. Herein, the apoptotic effects of 7,20-epoxy-ent-kaurane (oridonin, a diterpenoid isolated from Rabdosia rubescens, and its underlying mechanisms were investigated in rat HSC cell line, HSC-T6. We found that oridonin inhibited cell viability of HSC-T6 in a concentration-dependent manner. Oridonin induced a reduction in mitochondrial membrane potential and increases in caspase 3 activation, subG1 phase, and DNA fragmentation. These apoptotic effects of oridonin were completely reversed by thiol antioxidants, N-acetylcysteine (NAC and glutathione monoethyl ester. Moreover, oridonin increased production of reactive oxygen species (ROS, which was also inhibited by NAC. Significantly, oridonin reduced intracellular glutathione (GSH level in a concentration- and time-dependent fashion. Additionally, oridonin induced phosphorylations of extracellular signal-regulated kinase (ERK, c-Jun N-terminal kinase (JNK, and p38 mitogen-activated protein kinase (MAPK. NAC prevented the activation of MAPKs in oridonin-induced cells. However, selective inhibitors of MAPKs failed to alter oridonin-induced cell death. In summary, these results demonstrate that induction of apoptosis in HSC-T6 by oridonin is associated with a decrease in cellular GSH level and increase in ROS production.

Preparation, Characterization, and In Vitro and Vivo Antitumor Activity of Oridonin-Conjugated Multiwalled Carbon Nanotubes Functionalized with Carboxylic Group

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Chuanjin Wang

2016-01-01

Full Text Available Carbon nanotubes have shown great potential in tumor therapy. Oridonin (ORI is a poorly water-soluble diterpenoid compound (C20H28O6 used in the treatment of esophageal and hepatic carcinoma for decades. For the purpose of enhancing the antitumor potency and reducing cytotoxicity of ORI, multiwalled carbon nanotubes functionalized with carboxylic group (MWCNTs-COOH were used as ORI carrier. ORI was noncovalently encapsulated into (or onto the functionalized carbon nanotubes (MWCNTs-ORI. The obtained MWCNTs-ORI has been characterized. The ORI loading efficiency in MWCNTs-COOH carrier was studied to be about 82.6% (w/w. In vitro cytotoxicity assay on MWCNTs-ORI gave IC50 of 7.29±0.5 μg/mL and ORI-F gave IC50 of 14.5±1.4 μg/mL. The antitumor effect studies in vivo showed that MWCNTs-ORI improved antitumor activity of ORI in comparison with ORI-F. The tumor inhibition ratio for MWCNTs-ORI (1.68×10-2 g·Kg−1·d−1 was 86.4%, higher than that of ORI-F (1.68×10-2 g·Kg−1·d−1 which was 39.2%. This can greatly improve the pharmaceutical efficiency and reduce potential side effects.

Oridonin Loaded Solid Lipid Nanoparticles Enhanced Antitumor Activity in MCF-7 Cells

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Lu Wang

2014-01-01

Full Text Available Oridonin (ORI, a famous diterpenoid from Chinese herbal medicine, has drawn rising attention for its remarkable apoptosis and autophagy-inducing activity in human cancer therapy, while clinical application of ORI is limited by its strong hydrophobicity and rapid plasma clearance. The purpose of this study was to evaluate whether the antitumor activity of ORI could be enhanced by loading into solid lipid nanoparticles (SLNs. ORI-loaded SLNs were prepared by hot high pressure homogenization with narrow size distribution and good entrapment efficacy. MTT assay indicated that ORI-loaded SLNs enhanced the inhibition of proliferation against several human cancer cell lines including breast cancer MCF-7 cells, hepatocellular carcinoma HepG 2 cells, and lung carcinoma A549 cells compared with free ORI, while no significant enhancement of toxicity to human mammary epithelial MCF-10A cells was shown. Meanwhile, flow cytometric analysis demonstrated that ORI-SLNs induced more significant cell cycle arrest at S and decreased cell cycle arrest at G1/G0 phase in MCF-7 cells than bulk ORI solution. Hoechst 33342 staining and Annexin V/PI assay indicated that apoptotic rates of cells treated with ORI-loaded SLNs were higher compared with free ORI. In summary, our data indicated that SLNs may be a potential carrier for enhancing the antitumor effect of hydrophobic drug ORI.

Metabolomics reveals biotic and abiotic elicitor effects on the soft coral Sarcophyton ehrenbergi terpenoid content.

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Farag, Mohamed A; Al-Mahdy, Dalia A; Meyer, Achim; Westphal, Hildegard; Wessjohann, Ludger A

2017-04-05

The effects of six biotic and abiotic elicitors, i.e. MeJA (methyl jasmonate), SA (salicylic acid), ZnCl 2 , glutathione and β-glucan BG (fungal elicitor), and wounding, on the secondary metabolite accumulation in the soft coral Sarcophyton ehrenbergi were assessed. Upon elicitation, metabolites were extracted and analysed by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Except for MeJA, no differences in photosynthetic efficiency were observed after treatments, suggesting the absence of a remarkable stress on primary production. Chemometric analyses of UPLC-MS data showed clear segregation of SA and ZnCl 2 elicited samples at 24 and 48 h post elicitation. Levels of acetylated diterpene and sterol viz., sarcophytonolide I and cholesteryl acetate, was increased in ZnCl 2 and SA groups, respectively, suggesting an activation of specific acetyl transferases. Post elicitation, sarcophytonolide I level increased 132 and 17-folds at 48 h in 0.1 mM SA and 1 mM ZnCl 2 groups, respectively. Interestingly, decrease in sarcophine, a major diterpene was observed only in response to ZnCl 2 , whereas no change was observed in sesquiterpene content following treatments. To the best of our knowledge, this study provides the first documentation for elicitation effects on a soft corals secondary metabolome and suggests that SA could be applied to increase diterpenoid levels in corals.

Strong synergistic induction of CYP1A1 expression by andrographolide plus typical CYP1A inducers in mouse hepatocytes

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Jaruchotikamol, Atika [Department of Toxicology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan); Jarukamjorn, Kanokwan [Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002 (Thailand); Sirisangtrakul, Wanna [Department of Toxicology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan); Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002 (Thailand); Sakuma, Tsutomu; Kawasaki, Yuki [Department of Toxicology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan); Nemoto, Nobuo [Department of Toxicology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194 (Japan)

2007-10-15

The effects of andrographolide, the major diterpenoid constituent of Andrographis paniculata, on the expression of cytochrome P450 superfamily 1 members, including CYP1A1, CYP1A2, and CYP1B1, as well as on aryl hydrocarbon receptor (AhR) expression in primary cultures of mouse hepatocytes were investigated in comparison with the effects of typical CYP1A inducers, including benz[a]anthracene, {beta}-naphthoflavone, and 2,3,7,8-tetrachlorodibenzo-p-dioxin. Andrographolide significantly induced the expression of CYP1A1 and CYP1A2 mRNAs in a concentration-dependent manner, as did the typical CYP1A inducers, but did not induce that of CYP1B1 or AhR. Interestingly, andrographolide plus the typical CYP1A inducers synergistically induced CYP1A1 expression, and the synergism was blocked by an AhR antagonist, resveratrol. The CYP1A1 enzyme activity showed a similar pattern of induction. This is the first report that shows that andrographolide has a potency to induce CYP1A1 enzyme and indicates that andrographolide could be a very useful compound for investigating the regulatory mechanism of the CYP1A1 induction pathway. In addition, our findings suggest preparing advice for rational administration of A. paniculata, according to its ability to induce CYP1A1 expression.

Andrographolide Stimulates Neurogenesis in the Adult Hippocampus

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Lorena Varela-Nallar

2015-01-01

Full Text Available Andrographolide (ANDRO is a labdane diterpenoid component of Andrographis paniculata widely used for its anti-inflammatory properties. We have recently determined that ANDRO is a competitive inhibitor of glycogen synthase kinase-3β (GSK-3β, a key enzyme of the Wnt/β-catenin signaling cascade. Since this signaling pathway regulates neurogenesis in the adult hippocampus, we evaluated whether ANDRO stimulates this process. Treatment with ANDRO increased neural progenitor cell proliferation and the number of immature neurons in the hippocampus of 2- and 10-month-old mice compared to age-matched control mice. Moreover, ANDRO stimulated neurogenesis increasing the number of newborn dentate granule neurons. Also, the effect of ANDRO was evaluated in the APPswe/PS1ΔE9 transgenic mouse model of Alzheimer’s disease. In these mice, ANDRO increased cell proliferation and the density of immature neurons in the dentate gyrus. Concomitantly with the increase in neurogenesis, ANDRO induced the activation of the Wnt signaling pathway in the hippocampus of wild-type and APPswe/PS1ΔE9 mice determined by increased levels of β-catenin, the inactive form of GSK-3β, and NeuroD1, a Wnt target gene involved in neurogenesis. Our findings indicate that ANDRO stimulates neurogenesis in the adult hippocampus suggesting that this drug could be used as a therapy in diseases in which neurogenesis is affected.

Nain-e Havandi Andrographis paniculata present yesterday, absent today: a plenary review on underutilized herb of Iran's pharmaceutical plants.

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Valdiani, Alireza; Kadir, Mihdzar Abdul; Tan, Soon Guan; Talei, Daryush; Abdullah, Mohd Puad; Nikzad, Sonia

2012-05-01

Nain-e Havandi (Andrographis paniculata Nees.) (AP) is an annual herbaceous plant belonging to the family Acanthacea. Only a few species of Andrographis genus out of 28 are medicinally concerned of which AP is the most important. Knowledge about the arrival of AP to Iran is extremely lacking but most probably it has been imported from India. However, evidence implies the familiarity of Iran's folkloric medicine with this plant, but it has been disappeared from contemporary medicine for unknown reasons. Presence of active ingredients from diterpenoids group such as andrographolide, neoandrographolide and 14-deoxy-11,12-didehydroandrographolide has given incredible unique medicinal properties to the plant. Traditionally, Nain-e Havandi has been used in the role of a non-farm plant as a remedy for skin problems, flu, respiratory disease, and snakebite in East and Southeast Asia for centuries. Recently, it has been utilized as a treatment for HIV, hepatitis, diabetes, cancer and kidney disorders. Intensive cultivation of the herb started only in the past decade in countries such as China, India, Thailand, Indonesia, West Indies, Mauritius and to some extent, in Malaysia. Availability of different ecological zones in Iran complies with reestablishment of AP in tropical and temperate regions of the country. This is killing two birds with one stone, supporting the conservational and economic aspects.

Strong synergistic induction of CYP1A1 expression by andrographolide plus typical CYP1A inducers in mouse hepatocytes

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Jaruchotikamol, Atika; Jarukamjorn, Kanokwan; Sirisangtrakul, Wanna; Sakuma, Tsutomu; Kawasaki, Yuki; Nemoto, Nobuo

2007-01-01

The effects of andrographolide, the major diterpenoid constituent of Andrographis paniculata, on the expression of cytochrome P450 superfamily 1 members, including CYP1A1, CYP1A2, and CYP1B1, as well as on aryl hydrocarbon receptor (AhR) expression in primary cultures of mouse hepatocytes were investigated in comparison with the effects of typical CYP1A inducers, including benz[a]anthracene, β-naphthoflavone, and 2,3,7,8-tetrachlorodibenzo-p-dioxin. Andrographolide significantly induced the expression of CYP1A1 and CYP1A2 mRNAs in a concentration-dependent manner, as did the typical CYP1A inducers, but did not induce that of CYP1B1 or AhR. Interestingly, andrographolide plus the typical CYP1A inducers synergistically induced CYP1A1 expression, and the synergism was blocked by an AhR antagonist, resveratrol. The CYP1A1 enzyme activity showed a similar pattern of induction. This is the first report that shows that andrographolide has a potency to induce CYP1A1 enzyme and indicates that andrographolide could be a very useful compound for investigating the regulatory mechanism of the CYP1A1 induction pathway. In addition, our findings suggest preparing advice for rational administration of A. paniculata, according to its ability to induce CYP1A1 expression

Engineering Isoprenoid Biosynthesis in Artemisia annua L. for the Production of Taxadiene: A Key Intermediate of Taxol

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Meiya Li

2015-01-01

Full Text Available Taxadiene is the first committed precursor to paclitaxel, marketed as Taxol, arguably the most important anticancer agent against ovarian and breast cancer. In Taxus, taxadiene is directly synthesized from geranylgeranyl diphosphate (GGPP that is the common precursor for diterpenoids and is found in most plants and microbes. In this study, Artemisia annua L., a Chinese medicinal herb that grows fast and is rich in terpenoids, was used as a genetic engineering host to produce taxadiene. The TXS (taxadiene synthase gene, cloned from Taxus and inserted into pCAMBIA1304, was transformed into Artemisia annua L. using the Agrobacterium tumefaciens-mediated method. Thirty independent transgenic plants were obtained, and GC-MS analysis was used to confirm that taxadiene was produced and accumulated up to 129.7 μg/g dry mass. However, the high expression of TXS did not affect plant growth or photosynthesis in transgenic Artemisia annua L. It is notable that artemisinin is produced and stored in leaves and most taxadiene accumulated in the stem of transgenic Artemisia annua L., suggesting a new way to produce two important compounds in one transgenic plant: leaves for artemisinin and stem for taxadiene. Overall, this study demonstrates that genetic engineering of the taxane biosynthetic pathway in Artemisia annua L. for the production of taxadiene is feasible.

Studies on polynuclear furoquinones. Part 1: Synthesis of tri- and tetra-cyclic furoquinones simulating BCD/ABCD ring system of furoquinone diterpenoids

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Faruk H. Shaik

2009-09-01

Full Text Available Synthesis of phenanthro[1,2-b]furan-10,11-dione, the core nucleus present in Tanshinone-I is described in 8–10 steps starting from 2-bromo-3,4-dihydro-1-naphthaldehyde. The bromoaldehyde was converted to methyl 2-(2-bromo-1-naphthylacetate or 2-(2-bromo-1-naphthylacetonitrile following the protocol of functional group transformations. Subsequent Suzuki coupling of this ester/nitrile derivative with furan-2-boronic acid produced [2-(2-furyl-1-naphthyl]acetic ester/nitrile which on hydrolysis furnished the corresponding acid derivative. Cyclization of the acid followed by oxidation of the phenol, with Fremy’s salt, produced the tetra-cyclic furoquinone, phenanthro[1,2-b]furan-10,11-dione. This method has also been extended for the synthesis of the tricyclic furoquinone, naphtho[1,2-b]furan-4,5-dione.

Analgesic, anti-inflammatory, antipyretic and haematological effects of aethiopinone, an o-naphthoquinone diterpenoid from Salvia aethiopis roots and two hemisynthetic derivatives.

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Hernández-Pérez, M; Rabanal, R M; de la Torre, M C; Rodríguez, B

1995-12-01

Aethiopinone (1), an o-naphthoquinone diterpene from Salvia aethiopis L. roots and two hemisynthetic derivatives 2 and 3 have been evaluated for toxicity, anti-inflammatory, analgesic, antipyretic, and haemostatic activities. The compounds tested showed low toxicity and a pharmacological profile similar to other NSAI substances on reducing the edema induced by carrageenan and contractions induced by phenyl-p-quinone; the most active compounds were 1 and 2. In the same way and as expected with these types of substances, the bleeding time increased. In the TPA-induced ear inflammation model, the three compounds showed a moderate reduction of edema, and 1 produced a significant increase in the reaction time against thermal painful stimuli in the tail immersion test. The results demonstrated strong anti-inflammatory, peripheral and central analgesic properties for 1, as well as antiedematose topical action and peripheral analgesic properties for 2 and 3.

Identification of some diterpenoids and hydroxy fatty acids from carrot root cell walls that stimulate the presymbiotic hyphal growth of AM fungi

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Arbuscular mycorrhizal (AM) fungi infect about 80% of all land plants (Smith and Read 1997). They are soil borne and establish a mutually beneficial symbiotic association with a host root after colonization. The fungal hyphae from a colonized root can more thoroughly explore the soil than the root...

Analyzing the Interaction of Andrographolide and Neoandrographolide, Diterpenoid Compounds From Andrographis Paniculata (Burm.F Nees, to Cyclooxygenase-2 Enzyme by Docking Simulation

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Jutti Levita

2009-09-01

Full Text Available Cyclooxygenase (COX, an enzyme involved in the conversion of arachidonic acid to prostaglandins, exists in two isoforms, which are COX-1 and COX-2. Despite the similarities of COX-1 and COX-2, the two isoforms show subtle differences in amino acid composition at the active sites. Since COX-1 has isoleucine, a bulkier amino acid at position 523 than COX-2’s valine, it allows COX-2 to have a larger space in its active site. Andrographolide reduces COX-2 expression induced by PAF and fMLP in HL60/neutrophils. Neoandrographolide inhibits COX-2 expression at the translational level. The purpose of this study is to examine the binding modes of andrographolide and neoandrographolide against COX-1 and COX-2 in terms of hydrogen bonds and docking energy, to understand their antiinflammatory property. The docking study indicates that both andrographolide and neoandrographolide are able to be located in the COX-2’s binding pocket but not in the COX-1’s. It confirms that COX-1’s binding pocket is smaller than COX-2’s. Based on this study, both andrographolide and neoandrographolide show selective inhibitory property to COX-2. Their selectivity are due to their specific interaction with Arg 513 in the binding pocket of COX-2, which is also shown by SC-558, a COX-2 selective inhibitor.

Total asymmetric synthesis of the putative structure of the cytotoxic diterpenoid (-)-sclerophytin a and of the authentic natural sclerophytins A and B.

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Bernardelli, P; Moradei, O M; Friedrich, D; Yang, J; Gallou, F; Dyck, B P; Doskotch, R W; Lange, T; Paquette, L A

2001-09-19

An enantioselective synthetic route to the thermodynamically most stable diastereomer of the structure assigned to sclerophytin A (5) has been realized. The required tricyclic ketone 33 was prepared by sequential Tebbe-Claisen rearrangement of lactones 29 and 30, which originated from the Diels-Alder cycloaddition of Danishefsky's diene to (5S)-5-(d-menthyloxy)-2(5H)-furanone (14). An allyl and a cyano group were introduced into the resulting adduct by means of stereocontrolled allylindation under aqueous Barbier-like conditions and by way of cyanotrimethylsilane, respectively. Following stereocontrolled nucleophilic addition of a methyl group to 33, ring A was elaborated by formation of the silyl enol ether, ytterbium triflate-catalyzed condensation with formaldehyde, O-silylation, and Cu(I)-promoted 1,4-addition of isopropylmagnesium chloride. The superfluous ketone carbonyl was subsequently removed and the second ether bridge introduced by means of oxymercuration chemistry. Only then was the exocyclic methylene group unmasked via elimination. An alternative approach to the alpha-carbinol diastereomer proceeds by initial alpha-oxygenation of 37 and ensuing 1,2-carbonyl transposition. Neither this series of steps nor the Wittig olefination to follow induced epimerization at C10. Through deployment of oxymercuration chemistry, it was again possible to elaborate the dual oxygen-bridge network of the target ring system. Oxidation of the organomercurial products with O(2) in the presence of sodium borohydride furnished 72, which was readily separated from its isomer 73 after oxidation to 61. Hydride attack on this ketone proceeded with high selectivity from the beta-direction to deliver (-)-60. Comparison of the high-field (1)H and (13)C NMR properties and polarity of synthetic 5 with natural material required that structural revision be made. Following a complete spectral reassessment of the structural assignments to many sclerophytin diterpenes, a general approach to sclerophytin A, three diastereomers thereof, and of sclerophytin B was devised. The presence of two oxygen bridges as originally formulated was thereby ruled out, and absolute configurations were properly determined. Key elements of the strategy include dihydroxylation of a medium-ring double bond, oxidation of the secondary hydroxyl in the two resulting diols, unmasking of an exocyclic methylene group at C-11, and stereocontrolled 1,2-reduction of the alpha-hydroxy ketone functionality made available earlier.

Comparison of Polyphenol Profile and Antimutagenic and Antioxidant Activities in Two Species Used as Source of Solidaginis herba - Goldenrod.

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Woźniak, Dorota; Ślusarczyk, Sylwester; Domaradzki, Krzysztof; Dryś, Andrzej; Matkowski, Adam

2018-04-01

European Pharmacopoeia accepts two equivalent species Solidago canadensis L. and S. gigantea Aiton as goldenrod (Solidaginis herba). We compared phytochemical profile of both species from invasive populations in Poland. Further, we compared in vitro antimutagenic and antioxidant activities of solvent extracts from aerial (AP) and underground parts (UP). In S. gigantea, flavonoid profile was dominated by quercetin glycosides, with quercitrin as the major compound. In S. canadensis, quercetin and kaempferol rutinosides were two major constituents. Caffeoylquinic acids (CQAs) were less diverse with 5-CQA as a main compound. In UP, over 20 putative diterpenoids were detected, mostly unidentified. Several CQAs were present in higher amounts than in AP. Antioxidant and antimutagenic activities were different between species and organs, with the strongest inhibition of lipid peroxidation by Et 2 O and AcOEt fractions from AP of both species (IC 50 13.33 - 16.89 μg/mL) and BuOH fraction from S. gigantea UP (IC 50  = 13.32 μg/mL). Chemical mutagenesis was completely inhibited by non-polar fractions, but oxidative mutagenesis was inhibited up to 35% only by S. canadensis. No clear relationship was found between chemical profiles and antimutagenic activity. In conclusion, both species have diverse activity and their phytochemical profiles should be considered in quality evaluation. UP of these weeds can also provide potential chemopreventive substances for further studies. © 2018 Wiley-VHCA AG, Zurich, Switzerland.

Transcriptome mining, functional characterization, and phylogeny of a large terpene synthase gene family in spruce (Picea spp.

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Dullat Harpreet K

2011-03-01

Full Text Available Abstract Background In conifers, terpene synthases (TPSs of the gymnosperm-specific TPS-d subfamily form a diverse array of mono-, sesqui-, and diterpenoid compounds, which are components of the oleoresin secretions and volatile emissions. These compounds contribute to defence against herbivores and pathogens and perhaps also protect against abiotic stress. Results The availability of extensive transcriptome resources in the form of expressed sequence tags (ESTs and full-length cDNAs in several spruce (Picea species allowed us to estimate that a conifer genome contains at least 69 unique and transcriptionally active TPS genes. This number is comparable to the number of TPSs found in any of the sequenced and well-annotated angiosperm genomes. We functionally characterized a total of 21 spruce TPSs: 12 from Sitka spruce (P. sitchensis, 5 from white spruce (P. glauca, and 4 from hybrid white spruce (P. glauca × P. engelmannii, which included 15 monoterpene synthases, 4 sesquiterpene synthases, and 2 diterpene synthases. Conclusions The functional diversity of these characterized TPSs parallels the diversity of terpenoids found in the oleoresin and volatile emissions of Sitka spruce and provides a context for understanding this chemical diversity at the molecular and mechanistic levels. The comparative characterization of Sitka spruce and Norway spruce diterpene synthases revealed the natural occurrence of TPS sequence variants between closely related spruce species, confirming a previous prediction from site-directed mutagenesis and modelling.

Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats.

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Chen, Haw-Wen; Huang, Chin-Shiu; Li, Chien-Chun; Lin, Ai-Hsuan; Huang, Yu-Ju; Wang, Tsu-Shing; Yao, Hsien-Tsung; Lii, Chong-Kuei

2014-10-01

Andrographolide, a bioactive diterpenoid, is identified in Andrographis paniculata. In this study, we investigated the pharmacokinetics and bioavailability of andrographolide in rats and studied whether andrographolide enhances antioxidant defense in a variety of tissues and protects against carbon tetrachloride-induced oxidative damage. After a single 50-mg/kg administration, the maximum plasma concentration of andrographolide was 1μM which peaked at 30min. The bioavailability of andrographolide was 1.19%. In a hepatoprotection study, rats were intragastrically dosed with 30 or 50mg/kg andrographolide for 5 consecutive days. The results showed that andrographolide up-regulated glutamate cysteine ligase (GCL) catalytic and modifier subunits, superoxide dismutase (SOD)-1, heme oxygenase (HO)-1, and glutathione (GSH) S-transferase (GST) Ya/Yb protein and mRNA expression in the liver, heart, and kidneys. The activity of SOD, GST, and GSH reductase was also increased in rats dosed with andrographolide (pandrographolide increased nuclear Nrf2 contents and Nrf2 binding to DNA, respectively. After the 5-day andrographolide treatment, one group of animals was intraperitoneally injected with carbon tetrachloride (CCl4) at day 6. Andrographolide pretreatment suppressed CCl4-induced plasma aminotransferase activity and hepatic lipid peroxidation (pandrographolide is quickly absorbed in the intestinal tract in rats with a bioavailability of 1.19%. Andrographolide protects against chemical-induced oxidative damage by up-regulating the gene transcription and activity of antioxidant enzymes in various tissues. Copyright © 2014 Elsevier Inc. All rights reserved.

Andrographolide downregulates the v-Src and Bcr-Abl oncoproteins and induces Hsp90 cleavage in the ROS-dependent suppression of cancer malignancy.

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Liu, Sheng-Hung; Lin, Chao-Hsiung; Liang, Fong-Ping; Chen, Pei-Fen; Kuo, Cheng-Deng; Alam, Mohd Mujahid; Maiti, Barnali; Hung, Shih-Kai; Chi, Chin-Wen; Sun, Chung-Ming; Fu, Shu-Ling

2014-01-15

Andrographolide is a diterpenoid compound isolated from Andrographis paniculata that exhibits anticancer activity. We previously reported that andrographolide suppressed v-Src-mediated cellular transformation by promoting the degradation of Src. In the present study, we demonstrated the involvement of Hsp90 in the andrographolide-mediated inhibition of Src oncogenic activity. Using a proteomics approach, a cleavage fragment of Hsp90α was identified in andrographolide-treated cells. The concentration- and time-dependent induction of Hsp90 cleavage that accompanied the reduction in Src was validated in RK3E cells transformed with either v-Src or a human truncated c-Src variant and treated with andrographolide. In cancer cells, the induction of Hsp90 cleavage by andrographolide and its structural derivatives correlated well with decreased Src levels, the suppression of transformation, and the induction of apoptosis. Moreover, the andrographolide-induced Hsp90 cleavage, Src degradation, inhibition of transformation, and induction of apoptosis were abolished by a ROS inhibitor, N-acetyl-cysteine. Notably, Hsp90 cleavage, decreased levels of Bcr-Abl (another known Hsp90 client protein), and the induction of apoptosis were also observed in human K562 leukemia cells treated with andrographolide or its active derivatives. Together, we demonstrated a novel mechanism by which andrographolide suppressed cancer malignancy that involved inhibiting Hsp90 function and reducing the levels of Hsp90 client proteins. Our results broaden the molecular basis of andrographolide-mediated anticancer activity. Copyright © 2013 Elsevier Inc. All rights reserved.

Evaluating Andrographolide as a Potent Inhibitor of NS3-4A Protease and Its Drug-Resistant Mutants Using In Silico Approaches

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Vivek Chandramohan

2015-01-01

Full Text Available Current combination therapy of PEG-INF and ribavirin against the Hepatitis C Virus (HCV genotype-1 infections is ineffective in maintaining sustained viral response in 50% of the infection cases. New compounds in the form of protease inhibitors can complement the combination therapy. Asunaprevir is new to the drug regiment as the NS3-4A protease inhibitor, but it is susceptible to two mutations, namely, R155K and D168A in the protein. Thus, in our study, we sought to evaluate Andrographolide, a labdane-diterpenoid from the Andrographis paniculata plant as an effective compound for inhibiting the NS3-4A protease as well as its concomitant drug-resistant mutants by using molecular docking and dynamic simulations. Our study shows that Andrographolide has best docking scores of −15.0862, −15.2322, and −13.9072 compared to those of Asunaprevir −3.7159, −2.6431, and −5.4149 with wild-type R155K and D168A mutants, respectively. Also, as shown in the MD simulations, the compound was good in binding the target proteins and maintains strong bonds causing very less to negligible perturbation in the protein backbone structures. Our results validate the susceptibility of Asunaprevir to protein variants as seen from our docking studies and trajectory period analysis. Therefore, from our study, we hope to add one more option in the drug regiment to tackle drug resistance in HCV infections.

Development of a Bifunctional Andrographolide-Based Chemical Probe for Pharmacological Study.

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Hsu, Ya-Hsin; Hsu, Yu-Ling; Liu, Sheng-Hung; Liao, Hsin-Chia; Lee, Po-Xuan; Lin, Chao-Hsiung; Lo, Lee-Chiang; Fu, Shu-Ling

2016-01-01

Andrographolide (ANDRO) is a lactone diterpenoid compound present in the medicinal plant Andrographis paniculata which is clinically applied for multiple human diseases in Asia and Europe. The pharmacological activities of andrographolide have been widely demonstrated, including anti-inflammation, anti-cancer and hepatoprotection. However, the pharmacological mechanism of andrographolide remains unclear. Therefore, further characterization on the kinetics and molecular targets of andrographolide is essential. In this study, we described the synthesis and characterization of a novel fluorescent andrographolide derivative (ANDRO-NBD). ANDRO-NBD exhibited a comparable anti-cancer spectrum to andrographolide: ANDRO-NBD was cytotoxic to various types of cancer cells and suppressed the migration activity of melanoma cells; ANDRO-NBD treatment induced the cleavage of heat shock protein 90 (Hsp90) and the downregulation of its client oncoproteins, v-Src and Bcr-abl. Notably, ANDRO-NBD showed superior inhibitory effects to andrographolide in all anticancer assays we have performed. In addition, ANDRO-NBD was further used as a fluorescent probe to investigate the uptake kinetics, cellular distribution and molecular targets of andrographolide. Our data revealed that ANDRO-NBD entered cells rapidly and its fluorescent signal could be detected in nucleus, cytoplasm, mitochondria, and lysosome. Moreover, we demonstrated that ANDRO-NBD was covalently bound to several putative target proteins of andrographolide, including NF-κB and hnRNPK. In summary, we developed a fluorescent andrographolide probe with comparable bioactivity to andrographolide, which serves as a powerful tool to explore the pharmacological mechanism of andrographolide.

Andrographolide reversed 5-FU resistance in human colorectal cancer by elevating BAX expression.

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Wang, Weicheng; Guo, Wenjie; Li, Lele; Fu, Zan; Liu, Wen; Gao, Jian; Shu, Yongqian; Xu, Qiang; Sun, Yang; Gu, Yanhong

2016-12-01

5-FU is the first line therapy for colorectal cancer, however, treatment effect is often hampered by the development of drug resistance or toxicity at high doses. Andrographolide is a natural diterpenoid from Andrographis paniculata which has anti-bacterial, anti-antiviral and anti-inflammation activities. In the current study, we test the hypothesis that Andrographolide reverses 5-FU resistance in colorectal cancer and examine the underlying mechanism. In vitro and vivo studies indicated that Andrographolide treatment significantly re-sensitizes HCT116/5-FUR cells (HCT116 cells which are 5-FU resistant) to cytotoxicity of 5-FU. Mechanism analysis showed that Andrographolide/5-FU co-treatment elevated apoptosis level of HCT116/5-FUR cells with highly increased level of BAX. By using biotin-Andrographolide pull down and cellular thermal shift assay, we found out that Andrographolide can directly target to BAX. Andrographolide-BAX interaction prevented BAX degradation, enhancing mitochondria-mediated apoptosis thus reversed 5-FU resistance while BAX silence diminished this effect. Further, by analyzing patient samples who received 5-FU involved chemotherapy, we found that expression level of BAX is correlated with PFS. Our results here provide a novel combination treatment strategy, especially for patients with 5-FU-resistant tumors expressing low level of BAX. Meanwhile, we also proposed that BAX expression may be a predicted and prognosis marker of 5-FU involved chemotherapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Development of a Bifunctional Andrographolide-Based Chemical Probe for Pharmacological Study.

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Ya-Hsin Hsu

Full Text Available Andrographolide (ANDRO is a lactone diterpenoid compound present in the medicinal plant Andrographis paniculata which is clinically applied for multiple human diseases in Asia and Europe. The pharmacological activities of andrographolide have been widely demonstrated, including anti-inflammation, anti-cancer and hepatoprotection. However, the pharmacological mechanism of andrographolide remains unclear. Therefore, further characterization on the kinetics and molecular targets of andrographolide is essential. In this study, we described the synthesis and characterization of a novel fluorescent andrographolide derivative (ANDRO-NBD. ANDRO-NBD exhibited a comparable anti-cancer spectrum to andrographolide: ANDRO-NBD was cytotoxic to various types of cancer cells and suppressed the migration activity of melanoma cells; ANDRO-NBD treatment induced the cleavage of heat shock protein 90 (Hsp90 and the downregulation of its client oncoproteins, v-Src and Bcr-abl. Notably, ANDRO-NBD showed superior inhibitory effects to andrographolide in all anticancer assays we have performed. In addition, ANDRO-NBD was further used as a fluorescent probe to investigate the uptake kinetics, cellular distribution and molecular targets of andrographolide. Our data revealed that ANDRO-NBD entered cells rapidly and its fluorescent signal could be detected in nucleus, cytoplasm, mitochondria, and lysosome. Moreover, we demonstrated that ANDRO-NBD was covalently bound to several putative target proteins of andrographolide, including NF-κB and hnRNPK. In summary, we developed a fluorescent andrographolide probe with comparable bioactivity to andrographolide, which serves as a powerful tool to explore the pharmacological mechanism of andrographolide.

Pachydictyols B and C: New Diterpenes from Dictyota dichotoma Hudson

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Hartmut Laatsch

2013-08-01

Full Text Available Two new diterpenoids, pachydictyol B (1a/1b and C (2, were isolated from the dichloromethane extract of the marine brown alga, Dictyota dichotoma, collected from the Red Sea coast of Egypt, along with the known metabolites, pachydictyol A (3a, dictyol E (4, cis-africanan-1α-ol (5a, fucosterol (6, tetrahydrothiophen-1,1-dioxide and poly-β-hydroxybutyric acid. GC-MS analysis of the nonpolar fractions also indicated the presence of β-bourbonene and nonanal, along with three hydrocarbons and five fatty acids or their simple derivatives, respectively. GC-MS analysis of the unsaponifiable algal petroleum ether extract revealed the presence of a further eight compounds, among them 2,2,6,7-tetramethyl-10-oxatricyclo[4.3.0.1(1,7]decan-5-one (7, N-(4-bromo-n-butyl-pipe ridin-2-one (8 and tert-hexadecanethiol. Structures 1–6 were assigned by 1D and 2D NMR, mass spectra (EI, CI, HREI and HRESI and by comparison with data from related structures. The crude algal extract was potently active against the breast carcinoma tumor cell line, MCF7 (IC50 = 0.6 µg mL−1; pachydictyol B (1a and dictyol E (4 showed weak antimicrobial properties, and the other compounds were inactive. Pachydictyols B (1a and C (2 demonstrated a weak and unselective cytotoxicity against twelve human tumor cell lines with a mean IC50 of >30.0 µM.

[Chemical composition of essential oils from leaves of Helicteres guazumifolia (Sterculiaceae), Piper tuberculatum (Piperaceae), Scoparia dulcis (Arecaceae) and Solanum subinerme (Solanaceae) from Sucre, Venezuela].

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Ordaz, Gabriel; D'Armas, Haydelba; Yáñez, Dayanis; Moreno, Shailili

2011-06-01

Essential oils, biosynthesized and accumulated in aromatic plants, have a wide range of applications in the pharmaceutical health, cosmetics, food and agricultural industry. This study aimed to analyze the secondary metabolites in some plant species in order to contribute to their chemotaxonomy. Leaves from Helicteres guazumifolia, Piper tuberculatum, Scoparia dulcis and Solanum subinerme were collected and their essential oils were obtained by means of hydro-distillation. The oil fraction was analyzed and identified by GC/MS. The extraction yields were of 0.004, 0.032, 0.016 and 0.005%, and the oil constituents of 88.00, 89.80, 87.50 and 89.47%, respectively. The principal oils found were: non-terpenoids volatile secondary metabolites (30.28%) in H. guazumifolia; sesquiterpenoids (20.82 and 26.09%) and oxigen derivated (52.19 and 25.18%) in P. tuberculatum and S. dulcis; and oxigen diterpenoids (39.67%) in S. subinerme. The diisobuthylphtalate (13.11%) in H. guazumifolia, (-)-spathulenol (11.37%) in P. tuberculatum and trans-phytol (8.29 and 36.00%) in S. dulcis and S. subinerme, were the principal constituents in their respective essential oils. The diisooctylphtalate were the essential oil common to all species, but the volatile compounds such as trans-pinane, L-linalool, beta-ionone, isophytol, neophytadiene, trans-phytol, dibutylphtalate and methyl hexadecanoate, were only detected in three of these essences. This suggests that these plants may require similar secondary metabolites for their ecological interactions, possibly due to common environmental factors.

Isolation, Purification, and Identification of Taxol and Related Taxanes from Taxol-Producing Fungus Aspergillus niger subsp. taxi.

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Li, Dan; Fu, Dongwei; Zhang, Yue; Ma, Xueling; Gao, Liguo; Wang, Xioahua; Zhou, Dongpo; Zhao, Kai

2017-08-28

The content of taxol in the bark of yews is very low, and this is not affordable from the environmental point of view. Thus, it is a necessity to look for alternative sources of taxol production to solve its supply. Currently, a large portion of the taxol in the market comes from chemical semi-synthesis, but the semi-synthetic precursors such as baccatin III and 10-deacetyl-baccatin III are extracted from needles and twigs of yew trees. Taxol-producing fungi as a renewable resource is a very promising way to increase the scale of taxol production. Our group has obtained a taxol-producing endophytic fungus, Aspergillus niger subsp. taxi HD86-9, to examine if A. niger can produce the taxanes. Six compounds from the fermentation broth of strain HD86-9 were isolated and identified by 1 H NMR, 13 C NMR, and ESI-MS. The results showed that the six compounds included four taxane diterpenoids (taxol, cephalomannine, baccatin III, and 10-deacetyl-baccatin III) and two non-taxane compounds (β-sitosterol and flavonoid isovitexin). The study verified that the taxanes can be produced by the A. niger , which is very important to taxol production via chemical semi-synthesis. Additionally, the finding is potentially very significant to solve the taxol semi-synthetic precursors extracted from needles and twigs of yew trees, and the precursor production can be easily increased through the culture condition optimization, genetic breeding, and metabolic engineering of the A. niger .

Seed oil composition of Acacia nilotica (L. Delile from Iran / Skład oleju z nasion Acacia nilotica (L. Delile rosnącej w Iranie

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Abbasian Karim

2016-03-01

Full Text Available Wstęp: Acacia nilotica (L. Delile należy do rodziny Fabaceae, podrodziny Mimosoideae; otrzymuje się z niej gumę arabską. W południowym Iranie są spożywane pieczone młode strąki i nasiona tej rośliny Cel: Badano skład oleju z dojrzałych nasion A. nilotica zebranych z naturalnych stanowisk na południu Iranu w celu określenia jego przydatności do spożycia przez ludzi i zwierzęta. Metody: Wyekstrahowany olej analizowano metodą chromatografii gazowej sprzężonej ze spektrometrią mas (GC/MS. Wyniki: Zawartość oleju w jadalnych nasionach wynosiła 3.4% (v/w świeżej masy. Olej zawierał rzadko spotykany fitosterol, sześć kwasów tłuszczowych, dziewięć węgolwodorów i jeden diterpenoid; związki te stanowiły łącznie około 83.5% oleju. Głównymi składnikami oleju były: fitosterol, 26-ethylcholesta-5,25(Z-dien-3.β-ol (20.8% oraz nasycone i nienasycone kwasy tłuszczowe. Zawartość pozostałych składników nie przekroczyła 5%. Wniosek: Olej z nasion omawianego gatunku może być nowym naturalnym środkiem odżywczym dla ludzi.

GC/MS Analysis of Oil Extractives from Wood and Bark of Pinus sylvestris, Abies alba, Picea abies, and Larix decidua

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Mohamed Zidan Mohamed Salem

2015-09-01

Full Text Available Wood and bark oil extractives components (OECs of Pinus sylvestris, Abies alba, Picea abies, and Larix decidua grown in the Czech Republic were analyzed using gas chromatography/ mass spectrometry (GC/MS. The analysis showed the presence of monoterpene, sesquiterpene, diterpenoids, and resin acids. The highest percentages of OECs in the wood of P. sylvestris were α-fenchyl alcohol (26.04%, D-fenchyl alcohol (12.39%, and L-borneol (8.81%; the OECs in the bark included α-methyl-γ-butyrolactone (31.88% and isodecyl octyl phthalate (15.85%. The most frequently occurring OEC in A. alba wood were 4-hydroxy-4-methyl-2-pentanone (73.36%, α-cedrol (10.08%, and 2,6-dimethyl-1,3,6-heptatriene (7.35%; the most OECs in the bark were di(2-ethylhexylphthalate (59.83%, methyl cyclopentane (16.63%, and 13-epimanool (6.31%. P. abies wood OECs included 4-hydroxy-4-methyl-2-pentanone (29.42%, α-cedrol (26.98%, ∆3-carene (6.08%, and terpinen-4-ol (5.42%; the most OECs in the bark were di(2-ethylhexylphthalate (30.91%, cyclohexane (12.89%, caryophyllene oxide (8.90%, and α-pinene (4.59%. OECs of L. decidua wood were α-terpineol (26.06%, isoborneol (14.12%, camphene (11.78%, D-fenchyl alcohol (10.39%, and larixol (4.85%; OECs in the bark were larixol (33.29%, phthalic acid mono-2-ethylhexyl ester (16.96%, 13-epimanool (15.40%, and cyclohexane (8.44%.

Lasiodin inhibits proliferation of human nasopharyngeal carcinoma cells by simultaneous modulation of the Apaf-1/caspase, AKT/MAPK and COX-2/NF-κB signaling pathways.

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Lianzhu Lin

Full Text Available Rabdosia serra has been widely used for the treatment of the various human diseases. However, the antiproliferative effects and underlying mechanisms of the compounds in this herb remain largely unknown. In this study, an antiproliferative compound against human nasopharyngeal carcinoma (NPC cells from Rabdosia serra was purified and identified as lasiodin (a diterpenoid. The treatment with lasiodin inhibited cell viability and migration. Lasiodin also mediated the cell morphology change and induced apoptosis in NPC cells. The treatment with lasiodin induced the Apaf-1 expression, triggered the cytochrome-C release, and stimulated the PARP, caspase-3 and caspase-9 cleavages, thereby activating the apoptotic pathways. The treatment with lasiodin also significantly inhibited the phosphorylations of the AKT, ERK1/2, p38 and JNK proteins. The pretreatment with the AKT or MAPK-selective inhibitors considerably blocked the lasiodin-mediated inhibition of cell proliferation. Moreover, the treatment with lasiodin inhibited the COX-2 expression, abrogated NF-κB binding to the COX-2 promoter, and promoted the NF-κB translocation from cell nuclei to cytosol. The pretreatment with a COX-2-selective inhibitor abrogated the lasiodin-induced inhibition of cell proliferation. These results indicated that lasiodin simultaneously activated the Apaf-1/caspase-dependent apoptotic pathways and suppressed the AKT/MAPK and COX-2/NF-κB signaling pathways. This study also suggested that lasiodin could be a promising natural compound for the prevention and treatment of NPC.

Engineered andrographolide nanosystems for smart recovery in hepatotoxic conditions

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Roy P

2014-10-01

Full Text Available Partha Roy,1,2 Suvadra Das,1 Runa Ghosh Auddy,1,3 Arup Mukherjee1,3 1Division of Pharmaceutical and Fine Chemicals Technology, Department of Chemical Technology, University of Calcutta, Kolkata, India; 2Faculty of Technology (Pharmaceutical, Universiti Malaysia, Pahang, Malaysia; 3Centre for Research in Nanoscience and Nanotechnology, University of Calcutta, Kolkata, India Abstract: Andrographolide (AG is one of the most potent labdane diterpenoid-type free radical scavengers available from plant sources. The compound is the principal bioactive component in Andrographis paniculata leaf extracts, and is responsible for anti-inflammatory, anticancer, and immunomodulatory activity. The application of AG in therapeutics, however, is severely constrained, due to its low aqueous solubility, short biological half-life, and poor cellular permeability. Engineered nanoparticles in biodegradable polymer systems were therefore conceived as one solution to aid in further drug-like applications of AG. In this study, a cationic modified poly(lactic-co-glycolic acid nanosystem was applied for evaluation against experimental mouse hepatotoxic conditions. Biopolymeric nanoparticles of hydrodynamic size of 229.7±17.17 nm and ζ-potential +34.4±1.87 mV facilitated marked restoration in liver functions and oxidative stress markers. Superior dissolution for bioactive AG, hepatic residence, and favorable cytokine regulation in the liver tissues are some of the factors responsible for the newer nanosystem-assisted rapid recovery. Keywords: andrographolide, engineered nanosystems, poly(lactic-co-glycolic acid, cytokine regulation, hepatotoxicity

Antimicrobial and Antioxidant Activities of Resins and Essential Oil From Pine (Pinus merkusii, Pinuso ocarpa, Pinus insularis and Agathis (Agathis loranthifolia

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Mardho Tillah

2017-04-01

Full Text Available The most common human pathogen that colonizes in a third of healthy people around the world are Staphylococcus aureus, and one of the materials allegedly able to overcome the pathogen is resin. Resin has been used in folk medicine for thousands of years to treat diseases. The antimicrobial activity of natural resins can be associated with a variety of organic compounds contained in them such as diterpenoids and triterpenoids. This research aimed to explore the antibacterial and antioxidant activities of Pinus merkusii, P. oocarpa, P. insularis, Agathis loranthifolia resins and essential oil. Resin was separated by distillation process to get essential oil and the residue was extracted using n-hexane, ethyl acetate (EtOAc, and methanol (MeOH. Antioxidant activity was performed by DPPH (1,1diphenyl-2-picryl hydrazyl radical scavenging method. The antibacterial activity of resins and essential oil of the samples determined using the disc diffusion method against Staphylococcus aureus and Escherichia coli. The results showed that the yield of resin extract was ranging from 8.44 % to 95.56%. All extracts and essential oil could not inhibit E coli growth but inhibit the S. aureus growth. This experiment concluded that resin n-hexane extract from P.oocarpa was the most potent as antibacterial activity against S. aureus. All of the samples used had less potential antioxidant activity compared to positive control ascorbic acid. Result of this study show that pine resin from Indonesia has potential as an antibacterial agent. 

Plectranthus amboinicus (Lour. Spreng: Botanical, Phytochemical, Pharmacological and Nutritional Significance

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Greetha Arumugam

2016-03-01

Full Text Available Plectranthus amboinicus (Lour. Spreng. is a perennial herb belonging to the family Lamiaceae which occurs naturally throughout the tropics and warm regions of Africa, Asia and Australia. This herb has therapeutic and nutritional properties attributed to its natural phytochemical compounds which are highly valued in the pharmaceutical industry. Besides, it has horticultural properties due to its aromatic nature and essential oil producing capability. It is widely used in folk medicine to treat conditions like cold, asthma, constipation, headache, cough, fever and skin diseases. The leaves of the plant are often eaten raw or used as flavoring agents, or incorporated as ingredients in the preparation of traditional food. The literature survey revealed the occurrence 76 volatiles and 30 non-volatile compounds belonging to different classes of phytochemicals such as monoterpenoids, diterpenoids, triterpenoids, sesquiterpenoids, phenolics, flavonoids, esters, alcohols and aldehydes. Studies have cited numerous pharmacological properties including antimicrobial, antiinflammatory, antitumor, wound healing, anti-epileptic, larvicidal, antioxidant and analgesic activities. Also, it has been found to be effective against respiratory, cardiovascular, oral, skin, digestive and urinary diseases. Yet, scientific validation of many other traditional uses would be appreciated, mainly to discover and authenticate novel bioactive compounds from this herb. This review article provides comprehensive information on the botany, phytochemistry, pharmacology and nutritional importance of P. amboinicus essential oil and its various solvent extracts. This article allows researchers to further explore the further potential of this multi-utility herb for various biomedical applications.

Plectranthus amboinicus (Lour.) Spreng: Botanical, Phytochemical, Pharmacological and Nutritional Significance.

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Arumugam, Greetha; Swamy, Mallappa Kumara; Sinniah, Uma Rani

2016-03-30

Plectranthus amboinicus (Lour.) Spreng. is a perennial herb belonging to the family Lamiaceae which occurs naturally throughout the tropics and warm regions of Africa, Asia and Australia. This herb has therapeutic and nutritional properties attributed to its natural phytochemical compounds which are highly valued in the pharmaceutical industry. Besides, it has horticultural properties due to its aromatic nature and essential oil producing capability. It is widely used in folk medicine to treat conditions like cold, asthma, constipation, headache, cough, fever and skin diseases. The leaves of the plant are often eaten raw or used as flavoring agents, or incorporated as ingredients in the preparation of traditional food. The literature survey revealed the occurrence 76 volatiles and 30 non-volatile compounds belonging to different classes of phytochemicals such as monoterpenoids, diterpenoids, triterpenoids, sesquiterpenoids, phenolics, flavonoids, esters, alcohols and aldehydes. Studies have cited numerous pharmacological properties including antimicrobial, antiinflammatory, antitumor, wound healing, anti-epileptic, larvicidal, antioxidant and analgesic activities. Also, it has been found to be effective against respiratory, cardiovascular, oral, skin, digestive and urinary diseases. Yet, scientific validation of many other traditional uses would be appreciated, mainly to discover and authenticate novel bioactive compounds from this herb. This review article provides comprehensive information on the botany, phytochemistry, pharmacology and nutritional importance of P. amboinicus essential oil and its various solvent extracts. This article allows researchers to further explore the further potential of this multi-utility herb for various biomedical applications.

Preventive effects of andrographolide on the development of diabetes in autoimmune diabetic NOD mice by inducing immune tolerance.

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Zhang, Chengliang; Gui, Ling; Xu, Yanjiao; Wu, Tao; Liu, Dong

2013-08-01

Andrographolide, an active component in traditional anti-diabetic herbal plants, is a diterpenoid lactone isolated from Andrographis paniculata because of its potent anti-inflammatory and hypoglycemic effects. However, the effect of andrographolide on the development of diabetes in autoimmune non-obese diabetic (NOD) mice remains unknown. This study aimed to investigate the protective effects of andrographolide on the development of autoimmune diabetes and clarify the underlying mechanism. NOD mice were randomly divided into four groups and administered with water and andrographolide at 50, 100, and 150mg/kg body weight for four weeks. ICR mice were also selected as the control group. Oral glucose tolerance and histopathological insulitis were examined. Th1/Th2/Th17 cytokine secretion was determined by ELISA. The transcriptional profiles of T-bet, GATA3, and RORγt in the pancreatic lymphatic node samples derived from the NOD mice were detected by RT-PCR. After four weeks of oral supplementation, andrographolide significantly inhibited insulitis, delayed the onset, and suppressed the development of diabetes in 30-week-old NOD mice in a dose dependent manner. This protective status was correlated with a substantially decreased production of interferon (IFN)-γ and interleukin (IL)-2, increased IL-10 and transforming growth factor (TGF)-β, and a reduced IL-17. Andrographolide also increased GATA3 mRNA expression but decreased T-bet and RORγt mRNA expressions. Our results suggested that andrographolide prevented type 1 diabetes by maintaining Th1/Th2/Th17 homeostasis. Copyright © 2013 Elsevier B.V. All rights reserved.

Single-crystal neutron diffraction studies of hydrogen-bonded systems: Two recent examples from IPNS

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Koetzle, Thomas F. [IPNS Division, Argonne National Laboratory, Argonne, IL 60439 (United States)], E-mail: tkoetzle@anl.gov; Piccoli, Paula M.B.; Schultz, Arthur J. [IPNS Division, Argonne National Laboratory, Argonne, IL 60439 (United States)

2009-02-21

Beginning with work in the 1950s at the first generation of research reactors, studies of hydrogen-bonded systems have been a prime application for single-crystal neutron diffraction. The range of systems studied was extended in the 1960s and 1970s, with the advent of high flux reactor sources, and beginning around 1980 studies at pulsed neutron sources have made increasingly important contributions. Recently at the Argonne Intense Pulsed Neutron Source (IPNS), working with collaborators, we completed two studies of hydrogen-bonded systems that will serve to illustrate topics of current interest. In the first study, on andrographolide, an active diterpenoid natural product, our neutron diffraction results definitively characterize the hydrogen-bonding interactions. The second IPNS study is on tetraacetylethane (TAE), a {beta}-diketone enol system with a very short, strong intramolecular O-H...O hydrogen bond. At IPNS, we have determined the neutron crystal structure of TAE at five temperatures between 20 and 298 K to investigate changes in the structure with temperature and to probe for disorder. Despite the successes illustrated by the two examples presented here and by many other studies, at present applications of single-crystal neutron diffraction continue to be extremely flux limited and constrained by the requirement for mm-size crystals for many problems. These limitations are being addressed through the realization of powerful instruments at a new generation of pulsed neutron sources, including in the USA the TOPAZ and MaNDi single-crystal diffractometers that are under development at the Spallation Neutron Source (SNS)

Single-crystal neutron diffraction studies of hydrogen-bonded systems: Two recent examples from IPNS

Science.gov (United States)

Koetzle, Thomas F.; Piccoli, Paula M. B.; Schultz, Arthur J.

2009-02-01

Beginning with work in the 1950s at the first generation of research reactors, studies of hydrogen-bonded systems have been a prime application for single-crystal neutron diffraction. The range of systems studied was extended in the 1960s and 1970s, with the advent of high flux reactor sources, and beginning around 1980 studies at pulsed neutron sources have made increasingly important contributions. Recently at the Argonne Intense Pulsed Neutron Source (IPNS), working with collaborators, we completed two studies of hydrogen-bonded systems that will serve to illustrate topics of current interest. In the first study, on andrographolide, an active diterpenoid natural product, our neutron diffraction results definitively characterize the hydrogen-bonding interactions. The second IPNS study is on tetraacetylethane (TAE), a β-diketone enol system with a very short, strong intramolecular O-H⋯O hydrogen bond. At IPNS, we have determined the neutron crystal structure of TAE at five temperatures between 20 and 298 K to investigate changes in the structure with temperature and to probe for disorder. Despite the successes illustrated by the two examples presented here and by many other studies, at present applications of single-crystal neutron diffraction continue to be extremely flux limited and constrained by the requirement for mm-size crystals for many problems. These limitations are being addressed through the realization of powerful instruments at a new generation of pulsed neutron sources, including in the USA the TOPAZ and MaNDi single-crystal diffractometers that are under development at the Spallation Neutron Source (SNS).

Single-crystal neutron diffraction studies of hydrogen-bonded systems: Two recent examples from IPNS

International Nuclear Information System (INIS)

Koetzle, Thomas F.; Piccoli, Paula M.B.; Schultz, Arthur J.

2009-01-01

Beginning with work in the 1950s at the first generation of research reactors, studies of hydrogen-bonded systems have been a prime application for single-crystal neutron diffraction. The range of systems studied was extended in the 1960s and 1970s, with the advent of high flux reactor sources, and beginning around 1980 studies at pulsed neutron sources have made increasingly important contributions. Recently at the Argonne Intense Pulsed Neutron Source (IPNS), working with collaborators, we completed two studies of hydrogen-bonded systems that will serve to illustrate topics of current interest. In the first study, on andrographolide, an active diterpenoid natural product, our neutron diffraction results definitively characterize the hydrogen-bonding interactions. The second IPNS study is on tetraacetylethane (TAE), a β-diketone enol system with a very short, strong intramolecular O-H...O hydrogen bond. At IPNS, we have determined the neutron crystal structure of TAE at five temperatures between 20 and 298 K to investigate changes in the structure with temperature and to probe for disorder. Despite the successes illustrated by the two examples presented here and by many other studies, at present applications of single-crystal neutron diffraction continue to be extremely flux limited and constrained by the requirement for mm-size crystals for many problems. These limitations are being addressed through the realization of powerful instruments at a new generation of pulsed neutron sources, including in the USA the TOPAZ and MaNDi single-crystal diffractometers that are under development at the Spallation Neutron Source (SNS).

Genome-Wide Analysis of the Biosynthesis and Deactivation of Gibberellin-Dioxygenases Gene Family in Camellia sinensis (L. O. Kuntze

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Cheng Pan

2017-09-01

Full Text Available Gibberellins (GAs, a class of diterpenoid phytohormones, play a key role in regulating diverse processes throughout the life cycle of plants. Bioactive GA levels are rapidly regulated by Gibberellin-dioxygenases (GAox, which are involved in the biosynthesis and deactivation of gibberellin. In this manuscript, a comprehensive genome-wide analysis was carried out to find all GAox in Camellia sinensis. For the first time in a tea plant, 14 CsGAox genes, containing two domains, DIOX_N (PF14226 and 2OG-FeII_Oxy, were identified (PF03171. These genes all belong to 2-oxoglutarate-dependent dioxygenases (2-ODD, including four CsGA20ox (EC: 1.14.11.12, three CsGA3ox (EC: 1.14.11.15, and seven CsGA2ox (EC: 1.14.11.13. According to the phylogenetic classification as in Arabidopsis, the CsGAox genes spanned five subgroups. Each CsGAox shows tissue-specific expression patterns, although these vary greatly. Some candidate genes, which may play an important role in response to external abiotic stresses, have been identified with regards to patterns, such as CsGA20ox2, CsGA3ox2, CsGA3ox3, CsGA2ox1, CsGA2ox2, and CsGA2ox4. The bioactive GA levels may be closely related to the GA20ox, GA3ox and GA2ox genes. In addition, the candidate genes could be used as marker genes for abiotic stress resistance breeding in tea plants.

Self-assembly of gibberellic amide assemblies and their applications in the growth and fabrication of ordered gold nanoparticles

International Nuclear Information System (INIS)

Smoak, Evan M; Carlo, Andrew D; Fowles, Catherine C; Banerjee, Ipsita A

2010-01-01

Gibberellins are a group of naturally occurring diterpenoid based phytohormones that play a vital role in plant growth and development. In this work, we have studied the self-assembly of gibberellic acid, a phytohormone, which belongs to the family of gibberellins, and designed amide derivatives of gibberellic acid (GA 3 ) for the facile, green synthesis of gold nanoparticles. It was found that the derivatives self-assembled into nanofibers and nanoribbons in aqueous solutions at varying pH. Further, upon incubation with tetrachloroaurate, the self-assembled GA 3 -amide derivatives efficiently nucleated and formed gold nanoparticles when heated to 60 deg. C. Energy dispersive x-ray spectroscopy, transmission electron microscopy and scanning electron microscopy analyses revealed that uniform coatings of gold nanoparticles in the 10-20 nm range were obtained at low pH on the nanowire surfaces without the assistance of additional reducing agents. This simple method for the development of morphology controlled gold nanoparticles using a plant hormone derivative opens doors for a new class of plant biomaterials which can efficiently yield gold nanoparticles in an environmentally friendly manner. The gold encrusted nanowires formed using biomimetic methods may lead on to the formation of conductive nanowires, which may be useful for a wide range of applications such as in optoelectronics and sensors. Further, the spontaneous formation of highly organized nanostructures obtained from plant phytohormone derivatives such as gibberellic acid is of particular interest as it might help in further understanding the supramolecular assembly mechanism of more highly organized biological structures.

Hydroalcoholic extract of Stevia rebaudiana bert. leaves and stevioside ameliorates lipopolysaccharide induced acute liver injury in rats.

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S, Latha; Chaudhary, Sheetal; R S, Ray

2017-11-01

Oxidative stress and hepatic inflammatory response is primarily implicated in the pathogenesis of LPS induced acute liver injury. Stevioside, a diterpenoidal glycoside isolated from the Stevia rebaudiana leaves, exerts potent anti-oxidant, anti-inflammatory and immunomodulatory activities. The present study was aimed to investigate the hepatoprotective effect of hydroalcoholic extract of Stevia rebaudiana leaves (STE EXT) and its major phytochemical constituent, stevioside (STE) in LPS induced acute liver injury. The hepatoprotective activity of STE EXT (500mg/kg p.o) and STE (250mg/kg p.o) was investigated in lipopolysaccharide (LPS 5mg/kg i.p.) induced acute liver injury in male wistar rats. Our results revealed that both STE EXT and STE treatment ameliorated LPS induced hepatic oxidative stress, evident from altered levels of reduced SOD, Catalase, GSH, MDA, NO. Histopathological observations revealed that both STE EXT and STE attenuated LPS induced structural changes and hepatocellular apoptosis providing additional evidence for its hepatoprotective effect. Further, STE EXT and STE significantly restored the elevated serum and tissue levels of AST and ALT in LPS treated rats. Furthermore, both STE EXT and STE rescued hepatocellular dysfunctions to normal by altering the level of proinflammatory cytokines such as TNF-α, IL-1β and IL-6 exhibiting its anti-inflammatory potential. In conclusion, both STE EXT and STE demonstrated excellent hepatoprotective effects against endotoxemia induced acute liver injury possibly through suppression of hepatic inflammatory response and oxidative stress, attributing to its medicinal importance in treating various liver ailments. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

An integrative in-silico approach for therapeutic target identification in the human pathogen Corynebacterium diphtheriae.

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Syed Babar Jamal

Full Text Available Corynebacterium diphtheriae (Cd is a Gram-positive human pathogen responsible for diphtheria infection and once regarded for high mortalities worldwide. The fatality gradually decreased with improved living standards and further alleviated when many immunization programs were introduced. However, numerous drug-resistant strains emerged recently that consequently decreased the efficacy of current therapeutics and vaccines, thereby obliging the scientific community to start investigating new therapeutic targets in pathogenic microorganisms. In this study, our contributions include the prediction of modelome of 13 C. diphtheriae strains, using the MHOLline workflow. A set of 463 conserved proteins were identified by combining the results of pangenomics based core-genome and core-modelome analyses. Further, using subtractive proteomics and modelomics approaches for target identification, a set of 23 proteins was selected as essential for the bacteria. Considering human as a host, eight of these proteins (glpX, nusB, rpsH, hisE, smpB, bioB, DIP1084, and DIP0983 were considered as essential and non-host homologs, and have been subjected to virtual screening using four different compound libraries (extracted from the ZINC database, plant-derived natural compounds and Di-terpenoid Iso-steviol derivatives. The proposed ligand molecules showed favorable interactions, lowered energy values and high complementarity with the predicted targets. Our proposed approach expedites the selection of C. diphtheriae putative proteins for broad-spectrum development of novel drugs and vaccines, owing to the fact that some of these targets have already been identified and validated in other organisms.

Analysis by high-performance liquid chromatography of teucrin A in beverages flavoured with an extract of Teucrium chamaedrys L.

Science.gov (United States)

Bosisio, E; Giavarini, F; Dell'Agli, M; Galli, G; Galli, C L

2004-05-01

Due to its liver toxicity, the medicinal use of germander (Teucrium chamaedrys L.) was banned in some countries. Nevertheless, alcoholic extracts are still permitted as flavour ingredients since they are fundamental in providing a bitter aromatic taste. Teucrin A represents the substance of major concern regarding the potential toxicity of germander. Hence, teucrin A represents the best analytical and toxicological marker of alcoholic extracts of T. chamaedrys. A sensitive high-performance liquid chromatography method to detect teucrin A in beverages is reported. Teucrin A was prepared by isolation from the plant extract using column chromatography and crystallization. The identity and purity (99%) were established by melting point, nuclear magnetic resonance and liquid chromatography-mass spectrometry. The high-performance liquid chromatography procedure was validated and its intra- and interday performance was established (relative standard deviation beverages not containing T. chamaedrys spiked with a range of concentrations of teucrin A. The limit of detection was 0.1 ppm and the limit of quantification was 0.3 ppm. Teucrin A accounted for about 70% of the neo-clerodane diterpenoids found in the total extract of a specimen of T. chamaedrys. The content (+/- standard deviation) in 18 batches of different geographical origin was 2338 +/- 740 ppm, per cent coefficient of variation = 32, minimum-maximum = 999 - 3445 ppm. The mean level of teucrin A in 10 bottles of the same brand was 6.1 +/- 0.8 ppm, per cent coefficient of variation = 12. In 10 different brands found on the Italian market, the content of teucrin A ranged from not detectable to 10 ppm.

Effusanin E suppresses nasopharyngeal carcinoma cell growth by inhibiting NF-κB and COX-2 signaling.

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Mingzhu Zhuang

Full Text Available Rabdosia serra is well known for its antibacterial, anti-inflammatory and antitumor activities, but no information has been available for the active compounds derived from this plant in inhibiting human nasopharyngeal carcinoma (NPC cell growth. In this study, we isolated and purified a natural diterpenoid from Rabdosia serra and identified its chemical structure as effusanin E and elucidated its underlying mechanism of action in inhibiting NPC cell growth. Effusanin E significantly inhibited cell proliferation and induced apoptosis in NPC cells. Effusanin E also induced the cleavage of PARP, caspase-3 and -9 proteins and inhibited the nuclear translocation of p65 NF-κB proteins. Moreover, effusanin E abrogated the binding of NF-κB to the COX-2 promoter, thereby inhibiting the expression and promoter activity of COX-2. Pretreatment with a COX-2 or NF-κB-selective inhibitor (celecoxib or ammonium pyrrolidinedithiocarbamate had an additive effect on the effusanin E-mediated inhibition of proliferation, while pretreatment with an activator of NF-κB/COX-2 (lipopolysaccharides abrogated the effusanin E-mediated inhibition of proliferation. Effusanin E also significantly suppressed tumor growth in a xenograft mouse model without obvious toxicity, furthermore, the expression of p50 NF-κB and COX-2 were down-regulated in the tumors of nude mice. These data suggest that effusanin E suppresses p50/p65 proteins to down-regulate COX-2 expression, thereby inhibiting NPC cell growth. Our findings provide new insights into exploring effusanin E as a potential therapeutic compound for the treatment of human nasopharyngeal carcinoma.

Kirenol inhibits adipogenesis through activation of the Wnt/β-catenin signaling pathway in 3T3-L1 adipocytes

Energy Technology Data Exchange (ETDEWEB)

Kim, Mi-Bo [Department of Biomaterials Science and Engineering, Yonsei University, Seoul 120-749 (Korea, Republic of); Song, Youngwoo; Kim, Changhee [Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of); Hwang, Jae-Kwan, E-mail: jkhwang@yonsei.ac.kr [Department of Biomaterials Science and Engineering, Yonsei University, Seoul 120-749 (Korea, Republic of); Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749 (Korea, Republic of)

2014-03-07

Highlights: • Kirenol inhibits the adipogenic transcription factors and lipogenic enzymes. • Kirenol stimulates the Wnt/β-catenin signaling pathway components. • Kirenol inhibits adipogenesis through activation of the Wnt/β-catenin signaling pathway. - Abstract: Kirenol, a natural diterpenoid compound, has been reported to possess anti-oxidant, anti-inflammatory, anti-allergic, and anti-arthritic activities; however, its anti-adipogenic effect remains to be studied. The present study evaluated the effect of kirenol on anti-adipogenesis through the activation of the Wnt/β-catenin signaling pathway. Kirenol prevented intracellular lipid accumulation by down-regulating key adipogenesis transcription factors [peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding proteins α (C/EBPα), and sterol regulatory element binding protein-1c (SREBP-1c)] and lipid biosynthesis-related enzymes [fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC)], as well as adipocytokines (adiponectin and leptin). Kirenol effectively activated the Wnt/β-catenin signaling pathway, in which kirenol up-regulated the expression of low density lipoprotein receptor related protein 6 (LRP6), disheveled 2 (DVL2), β-catenin, and cyclin D1 (CCND1), while it inactivated glycogen synthase kinase 3β (GSK3β) by increasing its phosphorylation. Kirenol down-regulated the expression levels of PPARγ and C/EBPα, which were up-regulated by siRNA knockdown of β-catenin. Overall, kirenol is capable of inhibiting the differentiation and lipogenesis of 3T3-L1 adipocytes through the activation of the Wnt/β-catenin signaling pathway, suggesting its potential as natural anti-obesity agent.

Taxadiene Synthase Structure and Evolution of Modular Architecture in Terpene Biosynthesis

Energy Technology Data Exchange (ETDEWEB)

M Köksal; Y Jin; R Coates; R Croteau; D Christianson

2011-12-31

With more than 55,000 members identified so far in all forms of life, the family of terpene or terpenoid natural products represents the epitome of molecular biodiversity. A well-known and important member of this family is the polycyclic diterpenoid Taxol (paclitaxel), which promotes tubulin polymerization and shows remarkable efficacy in cancer chemotherapy. The first committed step of Taxol biosynthesis in the Pacific yew (Taxus brevifolia) is the cyclization of the linear isoprenoid substrate geranylgeranyl diphosphate (GGPP) to form taxa-4(5),11(12)diene, which is catalysed by taxadiene synthase. The full-length form of this diterpene cyclase contains 862 residues, but a roughly 80-residue amino-terminal transit sequence is cleaved on maturation in plastids. We now report the X-ray crystal structure of a truncation variant lacking the transit sequence and an additional 27 residues at the N terminus, hereafter designated TXS. Specifically, we have determined structures of TXS complexed with 13-aza-13,14-dihydrocopalyl diphosphate (1.82 {angstrom} resolution) and 2-fluorogeranylgeranyl diphosphate (2.25 {angstrom} resolution). The TXS structure reveals a modular assembly of three {alpha}-helical domains. The carboxy-terminal catalytic domain is a class I terpenoid cyclase, which binds and activates substrate GGPP with a three-metal ion cluster. The N-terminal domain and a third 'insertion' domain together adopt the fold of a vestigial class II terpenoid cyclase. A class II cyclase activates the isoprenoid substrate by protonation instead of ionization, and the TXS structure reveals a definitive connection between the two distinct cyclase classes in the evolution of terpenoid biosynthesis.

Mechanisms of herb-induced nephrotoxicity.

Science.gov (United States)

Allard, T; Wenner, T; Greten, H J; Efferth, T

2013-01-01

Herbal therapies gained much popularity among the general public, but compared to therapies approved by official authorities, toxicological studies are frequently not available for them. Hence, there may be inherent risks and the kidneys may be especially vulnerable to toxic effects. Herbs may induce nephrotoxicity by induction of apoptosis. High oxalate contents in Star fruit (Averrhoa carambola L.) may induce acute nephropathy. Triptolide from Thunder God Vine (Triperygium wilfordii Hook) is a diterpenoid epoxide with induces reactive oxygen species and nephrotubular apoptosis. Cranberry juice is discussed as promoter of kidney stone formation (nephrolithiasis). Abuse of guaifenesin from Roughbark (Guaicum officinale L.) increases stone formation. Aristolochia acids from Aristolochia fangchi Y.C.Wu ex L.D. Chow & S.M. Hwang causes the well-known aristolochic acid nephropathy and carcinogenesis by DNA adduct formation. Carboxyatractyloside from Impila (Callilepsis laureola DC.) inhibits mitochondrial ATP synthesis. Acute allergic interstitial nephritis was diagnosed after intake of Peruvian Cat's claw (Uncaria tomentosa Willd. DC.). Whether or not Willow Bark (Salix alba L.) induces analgesic nephropathwy is a matter of discussion. Other herbal therapies are considered to affect the rennin-angiotensisn-aldosterone (RAA) system Ephedra sinica Stapf with its ingredient ephedrine. Devil's Claw (Harpagophytum procumbens DC. Ex Meisn.) and licorice (Glycyrrhiza glabra L.) may inhibit major renal transport processes needed for filtration, secretion, and absorption. Strategies to minimize nephrotoxicity include (1) quality control and standardization of herbal products, (2) research on the molecular modes of action to better understand pathophysiological mechanisms of herbal products as well as (3) clinical trials to demonstrate efficacy and safety.

Mutational, Phylogeny and Evolution Analyses of Salvia Copalyl Diphosphate Synthase

International Nuclear Information System (INIS)

Hao, D. C.; Thimmappa, R. B.; Xiao, P. G.

2016-01-01

The cyclization of geranylgeranyl diphosphate (GGPP) is catalyzed by copalyl diphosphate synthase (CPS), a class II diterpene synthase (diTPS), to form copalyl diphosphate (CPP), which is an essential substrate of a variety of diterpenes in secondary metabolism of angiosperm including Salvia medicinal plants. The protein environment of the N-terminal class II active site stabilizes the carbocation intermediates and maintains the catalytic activity of angiosperm class II diTPS. The virtual modeling and mutagenesis of the class II diTPS of Salvia miltiorrhiza (SmCPS) were accomplished to illuminate the catalytic activity of SmCPS. Terminal truncations and point mutations established the role of the Beta-Gamma domain and Alpha domain, i.e., they facilitate the flexible conformational change of the class II active site after substrate binding. E203 and K238 in the N-ter Gamma domain of SmCPS1 are functional in the substrate binding and conformational transition and might be essential in catalysis. Similar to other CPSs, the ensuing protonation of the GGPP substrate and coordination of the diphosphate group are governed by highly conserved residues in the DxDD motif of SmCPS, e.g., D372 of CPS1. Moreover, F256 and Y505 stabilize the carbocation and control the enzymatic activity during CPP formation. The amino acids of the predicted active sites, despite under purifying selection, vary greatly, corresponding to the functional flexibility of angiosperm CPSs. Molecular phylogeny and evolution analyses suggest early and ongoing evolution of labdane-related diterpenoid metabolism in angiosperm. (author)

Andrographolide attenuates skeletal muscle dystrophy in mdx mice and increases efficiency of cell therapy by reducing fibrosis.

Science.gov (United States)

Cabrera, Daniel; Gutiérrez, Jaime; Cabello-Verrugio, Claudio; Morales, Maria Gabriela; Mezzano, Sergio; Fadic, Ricardo; Casar, Juan Carlos; Hancke, Juan L; Brandan, Enrique

2014-01-01

Duchenne muscular dystrophy (DMD) is characterized by the absence of the cytoskeletal protein dystrophin, muscle wasting, increased transforming growth factor type beta (TGF-β) signaling, and fibrosis. At the present time, the only clinically validated treatments for DMD are glucocorticoids. These drugs prolong muscle strength and ambulation of patients for a short term only and have severe adverse effects. Andrographolide, a bicyclic diterpenoid lactone, has traditionally been used for the treatment of colds, fever, laryngitis, and other infections with no or minimal side effects. We determined whether andrographolide treatment of mdx mice, an animal model for DMD, affects muscle damage, physiology, fibrosis, and efficiency of cell therapy. mdx mice were treated with andrographolide for three months and skeletal muscle histology, creatine kinase activity, and permeability of muscle fibers were evaluated. Fibrosis and TGF-β signaling were evaluated by indirect immunofluorescence and Western blot analyses. Muscle strength was determined in isolated skeletal muscles and by a running test. Efficiency of cell therapy was determined by grafting isolated skeletal muscle satellite cells onto the tibialis anterior of mdx mice. mdx mice treated with andrographolide exhibited less severe muscular dystrophy than untreated dystrophic mice. They performed better in an exercise endurance test and had improved muscle strength in isolated muscles, reduced skeletal muscle impairment, diminished fibrosis and a significant reduction in TGF-β signaling. Moreover, andrographolide treatment of mdx mice improved grafting efficiency upon intramuscular injection of dystrophin-positive satellite cells. These results suggest that andrographolide could be used to improve quality of life in individuals with DMD.

Jolkinolide B induces apoptosis of colorectal carcinoma through ROS-ER stress-Ca2+-mitochondria dependent pathway.

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Zhang, Jing; Wang, Yang; Zhou, Ye; He, Qing-Yu

2017-10-31

Colorectal carcinoma (CRC) remains one of the leading causes of death in cancer-related diseases. In this study, we aimed to investigate the anticancer effect of Jolkinolide B (JB), a bioactive diterpenoid component isolated from the dried roots of Euphorbia fischeriana Steud, on CRC cells and its underlying mechanisms. We found that JB suppressed the cell viability and colony formation of CRC cells, HT29 and SW620. Annexin V/PI assay revealed that JB induced apoptosis in CRC cells, which was further confirmed by the increased expression of cleaved-caspase3 and cleaved-PARP. iTRAQ-based quantitative proteomics was performed to identify JB-regulated proteins in CRC cells. Gene Ontology (GO) analysis revealed that these JB-regulated proteins were mainly involved in ER stress response, which was evidenced by the expression of ER stress marker proteins, HSP90, Bip and PDI. Moreover, we found that JB provoked the generation of reactive oxygen species (ROS), and that inhibition of the ROS generation with N-acetyl L-cysteine could reverse the JB-induced apoptosis. Confocal microscopy and flow cytometry showed that JB treatment enhanced intracellular and mitochondrial Ca 2+ level and JC-1 assay revealed a loss of mitochondrial membrane potential in CRC after JB treatment. The mitochondrial Ca 2+ uptake and depolarization can be blocked by Ruthenium Red (RuRed), an inhibitor of mitochondrial Ca 2+ uniporter. Taken together, we demonstrated that JB exerts its anticancer effect by ER stress-Ca 2+ -mitochondria signaling, suggesting the promising chemotherapeutic potential of JB for the treatment of CRC.

Scopadulcic acid B, a new tetracyclic diterpenoid from Scoparia dulcis L. Its structure, H+, K(+)-adenosine triphosphatase inhibitory activity and pharmacokinetic behaviour in rats.

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Hayashi, T; Okamura, K; Kakemi, M; Asano, S; Mizutani, M; Takeguchi, N; Kawasaki, M; Tezuka, Y; Kikuchi, T; Morita, N

1990-10-01

The structure of scopadulcic acid B (2, SDB), a major ingredient of the Paraguayan herb "Typychá kuratũ" (Scoparia dulcis L.), was elucidated mainly by comparison of its spectral data with that of scopadulcic acid A (1). SDB inhibited both the K(+)-dependent adenosine triphosphatase (ATPase) activity of a hog gastric proton pump (H+, K(+)-ATPase) with a value of 20-30 microM for IC50 and proton transport into gastric vesicles. Pharmacokinetic studies of SDB in rats indicated that plasma SDB concentrations after i.v. injection of the sodium salt of SDB (SDB-Na) were described reasonably well by a two-compartment open model with Michaelis-Menten elimination kinetics. Plasma concentrations after oral administration of SDB-Na or SDB showed a much slower decline than what was expected following the i. v. study. It was suggested that the sustained plasma level of SDB after oral administration of SDB-Na or SDB was accounted for by relatively slow but efficient gastro-intestinal absorption in rats.

Pharmacokinetics difference of multiple active constituents from decoction and maceration of Fuzi Xiexin Tang after oral administration in rat by UPLC-MS/MS.

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Zhang, Qian; Ma, Yue-ming; Wang, Zheng-tao; Wang, Chang-hong

2014-04-01

Fuzi Xiexin Tang (FXT) is a classic traditional Chinese medicine formula which has been employed in clinical for more than 1800 years. The distinctive preparation method (maceration) recorded in ancient time is different from one in modern clinical practice (decoction). Aim of this study is to investigate the pharmacokinetic difference of alkaloids, flavones and anthraquinones in rats after oral administration of decoction of FXT (DFXT, 30gkg(-1)), maceration of FXT (MFXT, 30gkg(-1)) and decoction of Aconiti Lateralis Radix Preparata (DAR, 6gkg(-1)) by a validated UPLC-MS/MS method. Plasma concentrations and pharmacokinetic parameters of 16 active constituents (aconitine, hypaconitine, mesaconitine, benzoylaconine, benzoylhypaconine, benzoylmesaconine, berberine, palmatine, jatrorrhizine, coptisine, baicalin, wogonin, wogonoside, emodin, aloe-emodin, rhein) in rat were quantified and compared. Different preparative methods resulted in significant difference on exposure and pharmacokinetic characteristics of alkaloids, flavones and anthraquinones from FXT, especially protoberberine alkaloids. Concentrations of monoester-diterpenoid alkaloids were below the LOD in rat plasma after administration of DFXT and MFXT because of the existence of other three herbs from FXT. Maceration could decrease the absorption of flavones while increased the absorption of anthraquinones. Cmax of emodin and rhein were 3.1 and 10.3 times increased, while eliminations of these two constituents were 8.0 and 19.0 times slower after administration of MFXT. Bioavailability of both flavones and anthraquinones increased after administration of MFXT, especially emodin and rhein increasing as much as 13.5 and 20.7 times. Herb-herb interaction between DAR and other three herbs from FXT significantly influenced the exposure of aconitum alkaloids. Copyright © 2014 Elsevier B.V. All rights reserved.

Croton schiedeanus Schltd prevents experimental hypertension in rats induced by nitric oxide deficit

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María Teresa Páez

2013-12-01

Full Text Available Croton schiedeanus Schltd (N.V.: "almizclillo" is a plant used in traditional medicine as an antihypertensive in Colombia. It contains flavonoid, diterpenoid and fenilbutanoid metabolites that have vasodilatation effects linked to the NO/cGMP pathway. This work aimed to assess the capacity of a 96% EtOH extract to prevent the hypertension induced by nitric oxide (NO deficiency in rats. The NO synthase inhibitor L-NAME (10 mg/kg/d, i.p was administered during five weeks to three groups of rats (6-7 animals: C. Schiedeanus (200 mg/kg/d, p.o, enalapril (reference, 10 mg/kg/d, p.o and vehicle (control: olive oil 1 ml/kg/d, p.o. In addition, the blank group received only vehicle. The arterial blood pressure (BP and heart rate (HR were measured daily for six weeks. After sacrificing the animals, the aortic rings were isolated, contraction was triggered with phenylephrine (PE 10-6 M and relaxant responses were achieved with cumulative concentrations of acetylcholine (ACh, 10-10 - 10-4 M. L-NAME increased the systolic arterial pressure in the control group, attaining mean values of 131 mm Hg at week 5, whereas the C. schiedeanus, enalapril and blank groups maintained blood pressure under 100 mm Hg. The capacity of PE to contract aortic rings was greater in the C. schiedeanus, enalapril and blank groups than in the control group (2157, 2005, 1910 and 1646 mg, respectively. The pEC50 values for ACh were as follows: C. Schiedeanus (6.89 >enalapril (6.39 > blank (5.68 > control (5.09. These results give support to C. Schiedeanus as a natural antihypertensive source.

Eriocalyxin B induces apoptosis and cell cycle arrest in pancreatic adenocarcinoma cells through caspase- and p53-dependent pathways

International Nuclear Information System (INIS)

Li, Lin; Yue, Grace G.L.; Lau, Clara B.S.; Sun, Handong; Fung, Kwok Pui; Leung, Ping Chung; Han, Quanbin; Leung, Po Sing

2012-01-01

Pancreatic cancer is difficult to detect early and responds poorly to chemotherapy. A breakthrough in the development of new therapeutic agents is urgently needed. Eriocalyxin B (EriB), isolated from the Isodon eriocalyx plant, is an ent-kaurane diterpenoid with promise as a broad-spectrum anti-cancer agent. The anti-leukemic activity of EriB, including the underlying mechanisms involved, has been particularly well documented. In this study, we demonstrated for the first time EriB's potent cytotoxicity against four pancreatic adenocarcinoma cell lines, namely PANC-1, SW1990, CAPAN-1, and CAPAN-2. The effects were comparable to that of the chemotherapeutic camptothecin (CAM), but with much lower toxicity against normal human liver WRL68 cells. EriB's cytoxicity against CAPAN-2 cells was found to involve caspase-dependent apoptosis and cell cycle arrest at the G2/M phase. Moreover, the p53 pathway was found to be activated by EriB in these cells. Furthermore, in vivo studies showed that EriB inhibited the growth of human pancreatic tumor xenografts in BALB/c nude mice without significant secondary adverse effects. These results suggest that EriB should be considered a candidate for pancreatic cancer treatment. -- Highlights: ► We study Eriocalyxin B (EriB)'s cytotoxic effects on pancreatic cancer cell lines. ► EriB inhibits cell proliferation via mediation of apoptosis and cell cycle arrest. ► The effects are involved in caspase-dependent apoptosis and p53 pathway. ► In vivo study also shows EriB inhibits the growth of human pancreatic tumor. ► EriB can be a good candidate for chemotherapy in pancreatic cancer.

Andrographolide exerts anti-hepatitis C virus activity by up-regulating haeme oxygenase-1 via the p38 MAPK/Nrf2 pathway in human hepatoma cells.

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Lee, Jin-Ching; Tseng, Chin-Kai; Young, Kung-Chia; Sun, Hung-Yu; Wang, Shainn-Wei; Chen, Wei-Chun; Lin, Chun-Kuang; Wu, Yu-Hsuan

2014-01-01

This study aimed to evaluate the anti-hepatitis C virus (HCV) activity of andrographolide, a diterpenoid lactone extracted from Andrographis paniculata, and to identify the signalling pathway involved in its antiviral action. Using HCV replicon and HCVcc infectious systems, we identified anti-HCV activity of andrographolide by measuring protein and RNA levels. A reporter activity assay was used to determine transcriptional regulation of anti-HCV agents. A specific inhibitor and short hairpin RNAs were used to investigate the mechanism responsible for the effect of andrographolide on HCV replication. In HCV replicon and HCVcc infectious systems, andrographolide time- and dose-dependently suppressed HCV replication. When combined with IFN-α, an inhibitor targeting HCV NS3/4A protease (telaprevir), or NS5B polymerase (PSI-7977), andrographolide exhibited a significant synergistic effect. Andrographolide up-regulated the expression of haeme oxygenase-1 (HO-1), leading to increased amounts of its metabolite biliverdin, which was found to suppress HCV replication by promoting the antiviral IFN responses and inhibiting NS3/4A protease activity. Significantly, these antiviral effects were attenuated by an HO-1-specific inhibitor or HO-1 gene knockdown, indicating that HO-1 contributed to the anti-HCV activity of andrographolide. Andrographolide activated p38 MAPK phosphorylation, which stimulated nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated HO-1 expression, and this was found to be associated with its anti-HCV activity. Our results demonstrate that andrographolide has the potential to control HCV replication and suggest that targeting the Nrf2-HO-1 signalling pathway might be a promising strategy for drug development. © 2013 The British Pharmacological Society.

Neuroprotective effects of andrographolide in a rat model of permanent cerebral ischaemia

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Chan, Su Jing; Wong, WS Fred; Wong, Peter TH; Bian, Jin-Song

2010-01-01

BACKGROUND AND PURPOSE Andrographolide is a diterpenoid lactone isolated from a traditional medicinal herb, Andrographis paniculata. It possesses potent anti-inflammatory activity. The present study examined potential therapeutic effects of andrographolide on cerebral ischaemia using a rat model with permanent middle cerebral artery occlusion (pMCAO). EXPERIMENTAL APPROACH The MCA in rats was permanently occluded (by cautery), and 24 h later neurological effects were assessed with behavioural scores. Infarct volume and microglial activation were determined histologically. The p65 form of the transcription factor, nuclear factor-κB (NF-κB), was measured by Western blot, and cytokines by immunoassay of brain extracts. KEY RESULTS Andrographolide, given i.p. 1 h after pMCAO, reduced infarct volume with a maximum reduction of approximately 50% obtained at 0.1 mg·kg−1. Neurological deficits were also reduced by andrographolide, reflecting a correlation between infarct volume and neurological deficits. pMCAO was found to induce activation of microglia and elevate tumour necrosis factor (TNF)-α, interleukin (IL)-1β and prostaglandin (PG)E2 in the ischaemic brain areas. Andrographolide (0.1 mg·kg−1) significantly attenuated or abolished these effects. In addition, andrographolide suppressed the translocation of p65 from cytosol to nucleus, indicating reduced NF-κB activation. CONCLUSIONS AND IMPLICATIONS Andrographolide exhibited neuroprotective effects, with accompanying suppression of NF-κB and microglial activation, and reduction in the production of cytokines including TNF-α and IL-1β, and pro-inflammatory factors such as PGE2. Our findings suggest that andrographolide may have therapeutic value in the treatment of stroke. PMID:20880404

Jaridonin-induced G2/M phase arrest in human esophageal cancer cells is caused by reactive oxygen species-dependent Cdc2-tyr15 phosphorylation via ATM–Chk1/2–Cdc25C pathway

Energy Technology Data Exchange (ETDEWEB)

Ma, Yong-Cheng [Clinical Pharmacology Laboratory, Henan Province People' s Hospital, No. 7, Wei Wu Road, Zhengzhou, Henan (China); Su, Nan [Department of Quality Detection and Management, Henan University of Animal Husbandry and Economy, Zhengzhou, Henan (China); Shi, Xiao-Jing; Zhao, Wen; Ke, Yu [School of Pharmaceutical Sciences, Zhengzhou University, No. 100, Science Avenue, Zhengzhou, Henan (China); Zi, Xiaolin [Department of Urology, University of California, Irvine, Orange, CA (United States); Department of Pharmacology, University of California, Irvine, Orange, CA (United States); Department of Pharmaceutical Sciences, University of California, Irvine, Orange, CA (United States); Zhao, Ning-Min; Qin, Yu-Hua; Zhao, Hong-Wei [Clinical Pharmacology Laboratory, Henan Province People' s Hospital, No. 7, Wei Wu Road, Zhengzhou, Henan (China); Liu, Hong-Min, E-mail: liuhm@zzu.edu.cn [School of Pharmaceutical Sciences, Zhengzhou University, No. 100, Science Avenue, Zhengzhou, Henan (China)

2015-01-15

Jaridonin, a novel diterpenoid from Isodon rubescens, has been shown previously to inhibit proliferation of esophageal squamous cancer cells (ESCC) through G2/M phase cell cycle arrest. However, the involved mechanism is not fully understood. In this study, we found that the cell cycle arrest by Jaridonin was associated with the increased expression of phosphorylation of ATM at Ser1981 and Cdc2 at Tyr15. Jaridonin also resulted in enhanced phosphorylation of Cdc25C via the activation of checkpoint kinases Chk1 and Chk2, as well as in increased phospho-H2A.X (Ser139), which is known to be phosphorylated by ATM in response to DNA damage. Furthermore, Jaridonin-mediated alterations in cell cycle arrest were significantly attenuated in the presence of NAC, implicating the involvement of ROS in Jaridonin's effects. On the other hand, addition of ATM inhibitors reversed Jaridonin-related activation of ATM and Chk1/2 as well as phosphorylation of Cdc25C, Cdc2 and H2A.X and G2/M phase arrest. In conclusion, these findings identified that Jaridonin-induced cell cycle arrest in human esophageal cancer cells is associated with ROS-mediated activation of ATM–Chk1/2–Cdc25C pathway. - Highlights: • Jaridonin induced G2/M phase arrest through induction of redox imbalance. • Jaridonin increased the level of ROS through depleting glutathione in cell. • ATM–Chk1/2–Cdc25C were involved in Jaridonin-induced cell cycle arrest. • Jaridonin selectively inhibited cancer cell viability and cell cycle progression.

Identification and Functional Characterization of Monofunctional ent-Copalyl Diphosphate and ent-Kaurene Synthases in White Spruce Reveal Different Patterns for Diterpene Synthase Evolution for Primary and Secondary Metabolism in Gymnosperms1[W][OA

Science.gov (United States)

Keeling, Christopher I.; Dullat, Harpreet K.; Yuen, Mack; Ralph, Steven G.; Jancsik, Sharon; Bohlmann, Jörg

2010-01-01

The biosynthesis of the tetracyclic diterpene ent-kaurene is a critical step in the general (primary) metabolism of gibberellin hormones. ent-Kaurene is formed by a two-step cyclization of geranylgeranyl diphosphate via the intermediate ent-copalyl diphosphate. In a lower land plant, the moss Physcomitrella patens, a single bifunctional diterpene synthase (diTPS) catalyzes both steps. In contrast, in angiosperms, the two consecutive cyclizations are catalyzed by two distinct monofunctional enzymes, ent-copalyl diphosphate synthase (CPS) and ent-kaurene synthase (KS). The enzyme, or enzymes, responsible for ent-kaurene biosynthesis in gymnosperms has been elusive. However, several bifunctional diTPS of specialized (secondary) metabolism have previously been characterized in gymnosperms, and all known diTPSs for resin acid biosynthesis in conifers are bifunctional. To further understand the evolution of ent-kaurene biosynthesis as well as the evolution of general and specialized diterpenoid metabolisms in gymnosperms, we set out to determine whether conifers use a single bifunctional diTPS or two monofunctional diTPSs in the ent-kaurene pathway. Using a combination of expressed sequence tag, full-length cDNA, genomic DNA, and targeted bacterial artificial chromosome sequencing, we identified two candidate CPS and KS genes from white spruce (Picea glauca) and their orthologs in Sitka spruce (Picea sitchensis). Functional characterization of the recombinant enzymes established that ent-kaurene biosynthesis in white spruce is catalyzed by two monofunctional diTPSs, PgCPS and PgKS. Comparative analysis of gene structures and enzyme functions highlights the molecular evolution of these diTPSs as conserved between gymnosperms and angiosperms. In contrast, diTPSs for specialized metabolism have evolved differently in angiosperms and gymnosperms. PMID:20044448

Light induced degradation of phorbol esters.

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Yunping, Bu; Ha, Bui Thi Ngoc; Eunice, Yeo; Chueng, Lo Loong; Yan, Hong

2012-10-01

Jatropha curcas (Jatropha) is a tropical shrub that is gaining popularity as a biofuel feedstock plant. Phorbol esters (PEs) are tetracyclic tiglian diterpenoids that are present in Jatropha seeds and other parts of plant. Epidermal cell irritating and cancer promoting PEs not only reduce commercial values of Jatropha seed cake but also cause some safety and environment concerns on PE leaching to soil. A simple bioassay of PE toxicity was conducted by incubating 48 h old brine shrimp (Artemia salina) nauplii with Jatropha oil for 24 h. 1-4% of Jatropha oil (corresponding to PE concentration of 25-100 mg L(-1)) had mortality rate of 5-95%, with LC50 estimated to be 2.7% of oil or 67 mg L(-1) of PE. Jatropha oil was incubated with clay or black soil (autoclaved or non-autoclaved) in the darkness or under sunlight for different periods of time before oil was re-extracted and tested for PE content by HPLC and for remaining toxicity with the brine shrimp bioassay. Under sunlight, PE decreased to non-detectable level within six days. Toxicity reduced to less than 5% mortality rate that is comparable to rapeseed oil control within the same period. In contrast, PE level and toxicity remained little changed when Jatropha oil was incubated in the darkness. Such PE degradation/detoxification was also found independent of the presence of soil or soil microorganisms. We conclude that sunlight directly degrades and detoxifies PEs and this finding should alleviate the concern on long term environmental impact of PE leaching. Copyright © 2012 Elsevier Inc. All rights reserved.

Eriocalyxin B induces apoptosis and cell cycle arrest in pancreatic adenocarcinoma cells through caspase- and p53-dependent pathways

Energy Technology Data Exchange (ETDEWEB)

Li, Lin [School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong (China); Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong (China); Yue, Grace G.L. [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong (China); Lau, Clara B.S. [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); Sun, Handong [State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, CAS, Yunnan (China); Fung, Kwok Pui [School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong (China); Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong (China); Leung, Ping Chung [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong (China); Han, Quanbin, E-mail: simonhan@hkbu.edu.hk [Institute of Chinese Medicine, The Chinese University of Hong Kong, Hong Kong (China); State Key Laboratory of Phytochemistry and Plant Resources in West China, The Chinese University of Hong Kong, Hong Kong (China); School of Chinese Medicine, The Hong Kong Baptist University, Hong Kong (China); Leung, Po Sing, E-mail: psleung@cuhk.edu.hk [School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong (China)

2012-07-01

Pancreatic cancer is difficult to detect early and responds poorly to chemotherapy. A breakthrough in the development of new therapeutic agents is urgently needed. Eriocalyxin B (EriB), isolated from the Isodon eriocalyx plant, is an ent-kaurane diterpenoid with promise as a broad-spectrum anti-cancer agent. The anti-leukemic activity of EriB, including the underlying mechanisms involved, has been particularly well documented. In this study, we demonstrated for the first time EriB's potent cytotoxicity against four pancreatic adenocarcinoma cell lines, namely PANC-1, SW1990, CAPAN-1, and CAPAN-2. The effects were comparable to that of the chemotherapeutic camptothecin (CAM), but with much lower toxicity against normal human liver WRL68 cells. EriB's cytoxicity against CAPAN-2 cells was found to involve caspase-dependent apoptosis and cell cycle arrest at the G2/M phase. Moreover, the p53 pathway was found to be activated by EriB in these cells. Furthermore, in vivo studies showed that EriB inhibited the growth of human pancreatic tumor xenografts in BALB/c nude mice without significant secondary adverse effects. These results suggest that EriB should be considered a candidate for pancreatic cancer treatment. -- Highlights: ► We study Eriocalyxin B (EriB)'s cytotoxic effects on pancreatic cancer cell lines. ► EriB inhibits cell proliferation via mediation of apoptosis and cell cycle arrest. ► The effects are involved in caspase-dependent apoptosis and p53 pathway. ► In vivo study also shows EriB inhibits the growth of human pancreatic tumor. ► EriB can be a good candidate for chemotherapy in pancreatic cancer.

Andrographolide down-regulates hypoxia-inducible factor-1{alpha} in human non-small cell lung cancer A549 cells

Energy Technology Data Exchange (ETDEWEB)

Lin, Hui-Hsuan [School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China); Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Tsai, Chia-Wen [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Chou, Fen-Pi [Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China); Wang, Chau-Jong [Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan (China); Hsuan, Shu-Wen [Department of Medical Laboratory Science and Biotechnology, College of Medicine and Life Science, Chung Hwa University of Medical Technology, No.89, Wen Hwa 1st St., Rende Shiang, Tainan County 717, Taiwan (China); Wang, Cheng-Kun [E-Chyun Dermatology Clinic, No.70, Sec. 3, Jhonghua E. Rd., East District, Tainan, Taiwan (China); Chen, Jing-Hsien [Department of Medical Laboratory Science and Biotechnology, College of Medicine and Life Science, Chung Hwa University of Medical Technology, No.89, Wen Hwa 1st St., Rende Shiang, Tainan County 717, Taiwan (China)

2011-02-01

Andrographolide (Andro), a diterpenoid lactone isolated from a traditional herbal medicine Andrographis paniculata, is known to possess multiple pharmacological activities. In our previous study, Andro had been shown to inhibit non-small cell lung cancer (NSCLC) A549 cell migration and invasion via down-regulation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Here we demonstrated that Andro inhibited the expression of hypoxia-inducible factor-1{alpha} (HIF-1{alpha}) in A549 cells. HIF-1{alpha} plays an important role in tumor growth, angiogenesis and lymph node metastasis of NSCLC. The Andro-induced decrease of cellular protein level of HIF-1{alpha} was correlated with a rapid ubiquitin-dependent degradation of HIF-1{alpha}, and was accompanied by increased expressions of hydroxyl-HIF-1{alpha} and prolyl hydroxylase (PHD2), and a later decrease of vascular endothelial growth factor (VEGF) upon the treatment of Andro. The Andro-inhibited VEGF expression appeared to be a consequence of HIF-1{alpha} inactivation, because its DNA binding activity was suppressed by Andro. Molecular data showed that all these effects of Andro might be mediated via TGF{beta}1/PHD2/HIF-1{alpha} pathway, as demonstrated by the transfection of TGF{beta}1 overexpression vector and PHD2 siRNA, and the usage of a pharmacological MG132 inhibitor. Furthermore, we elucidated the involvement of Andro in HIF-1{alpha} transduced VEGF expression in A549 cells and other NSCLC cell lines. In conclusion, these results highlighted the potential effects of Andro, which may be developed as a chemotherapeutic or an anti-angiogenesis agent for NSCLC in the future.

14-Deoxy-11,12-didehydroandrographolide induces DDIT3-dependent endoplasmic reticulum stress-mediated autophagy in T-47D breast carcinoma cells

International Nuclear Information System (INIS)

Tan, Heng Kean; Muhammad, Tengku Sifzizul Tengku; Tan, Mei Lan

2016-01-01

14-Deoxy-11,12-didehydroandrographolide (14-DDA), a major diterpenoid isolated from Andrographis paniculata (Burm.f.) Nees, is known to be cytotoxic and elicits a non-apoptotic cell death in T-47D breast carcinoma cells. In this study, the mechanistic toxicology properties of 14-DDA in T-47D cells were further investigated. 14-DDA is found to induce the formation of endoplasmic reticulum (ER) vacuoles and autophagosomes, with concurrent upregulation of LC3-II in the breast carcinoma cells. It stimulated an increase in cytosolic calcium concentration and caused a collapse in mitochondrial membrane potential in these cells. In addition, both DDIT3 and GADD45A, molecules implicated in ER stress pathway, were significantly upregulated. DDIT3 knockdown suppressed the formation of both ER vacuoles and autophagosomes, indicating that 14-DDA-induced ER stress and autophagy is dependent on this transcription factor. Collectively, it is possible that GADD45A/p38 MAPK/DDIT3 pathway is involved in the 14-DDA-induced ER-stress-mediated autophagy in T-47D cells. - Highlights: • The mechanistic toxicology properties of 14-DDA in T-47D breast carcinoma cells were investigated. • 14-DDA induces the formation of ER vacuoles and autophagosomes, with concurrent upregulation of LC3-II. • It stimulates an increase in cytosolic calcium concentration and causing collapse in the mitochondrial membrane potential. • Both DDIT3 and GADD45A, molecules implicated in ER stress pathway, were significantly upregulated. • 4-DDA induces ER stress-mediated autophagy in T-47D cells possibly via GADD45A/p38 MAPK/DDIT3 pathway.

Andrographolide down-regulates hypoxia-inducible factor-1α in human non-small cell lung cancer A549 cells

International Nuclear Information System (INIS)

Lin, Hui-Hsuan; Tsai, Chia-Wen; Chou, Fen-Pi; Wang, Chau-Jong; Hsuan, Shu-Wen; Wang, Cheng-Kun; Chen, Jing-Hsien

2011-01-01

Andrographolide (Andro), a diterpenoid lactone isolated from a traditional herbal medicine Andrographis paniculata, is known to possess multiple pharmacological activities. In our previous study, Andro had been shown to inhibit non-small cell lung cancer (NSCLC) A549 cell migration and invasion via down-regulation of phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Here we demonstrated that Andro inhibited the expression of hypoxia-inducible factor-1α (HIF-1α) in A549 cells. HIF-1α plays an important role in tumor growth, angiogenesis and lymph node metastasis of NSCLC. The Andro-induced decrease of cellular protein level of HIF-1α was correlated with a rapid ubiquitin-dependent degradation of HIF-1α, and was accompanied by increased expressions of hydroxyl-HIF-1α and prolyl hydroxylase (PHD2), and a later decrease of vascular endothelial growth factor (VEGF) upon the treatment of Andro. The Andro-inhibited VEGF expression appeared to be a consequence of HIF-1α inactivation, because its DNA binding activity was suppressed by Andro. Molecular data showed that all these effects of Andro might be mediated via TGFβ1/PHD2/HIF-1α pathway, as demonstrated by the transfection of TGFβ1 overexpression vector and PHD2 siRNA, and the usage of a pharmacological MG132 inhibitor. Furthermore, we elucidated the involvement of Andro in HIF-1α transduced VEGF expression in A549 cells and other NSCLC cell lines. In conclusion, these results highlighted the potential effects of Andro, which may be developed as a chemotherapeutic or an anti-angiogenesis agent for NSCLC in the future.

Comparison of total phenolic content, scavenging activity and HPLC-ESI-MS/MS profiles of both young and mature leaves and stems of Andrographis paniculata.

Science.gov (United States)

Chua, Lee Suan; Yap, Ken Choy; Jaganath, Indu Bala

2013-12-01

The total phenolic content and radical scavenging activity of Andrographis paniculata has been investigated to estimate the amount of phenolic compounds and diterpene lactones, respectively in the plant extracts. The stem extracts exhibited higher total phenolic content and scavenging activity than those of the leaf extracts from both young and mature plants. A range of 19.6-47.8 mg extract of A. paniculata from different parts of the plant is equivalent to the scavenging activity exhibited by one mg of standard Trolox. HPLC-ESI-MS/MS was also used to identify simultaneously the phytochemicals from the leaves and stems of both young and mature plant samples. Of the identified compounds, seven of the sixteen diterpene lactones, three of the six flavonoids, five of the six phenolic acids and two cyclic acids are reported here for the first time for this species. Multivariate statistical approaches such as Hierarchiral Component Analysis (HCA) and Principle Component Analysis (PCA) have clustered the plant extracts into the leaf and stem groups, regardless of plant age. Further classification based on the phytochemical profiles revealed that mostly phenolic acids and flavonoids were from the young leaf extracts, and diterpenoids and their glycosides from the mature leaf extracts. However, the phytochemical profiles for the stems of both young and mature plants were not significantly different as presented in the dendrogram of HCA and the score plot of PCA. The marker for mature plants might be the m/z 557 ion (dihydroxyl dimethyl 19-[(beta-D-glucopyranosyl)oxy]-19-oxo-ent-labda-8(17),13-dien-16,15-olide), whereas the m/z 521 ion (propyl neoandrographolide) could be the marker for leaf extracts.

Larkspur (Delphinium spp.) poisoning in livestock.

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Pfister, J A; Gardner, D R; Panter, K E; Manners, G D; Ralphs, M H; Stegelmeier, B L; Schoch, T K

1999-02-01

Larkspurs (Delphinium spp.) are toxic plants that contain numerous diterpenoid alkaloids which occur as one of two structural types: (1) lycotonine, and (2) 7,8-methylenedioxylycoctonine (MDL-type). Among the lycoctonine type alkaloids are three N-(methylsuccinimido) anthranoyllycoctonine (MSAL-type) alkaloids which appear to be most toxic: methyllycaconitine (MLA), 14-deacetylnudicauline (DAN), and nudicauline. An ester function at C-18 is an important structural requirement for toxicity. Intoxication results from neuromuscular paralysis, as nicotinic acetylcholine receptors in the muscle and brain are blocked by toxic alkaloids. Clinical signs include labored breathing, rapid and irregular heartbeat, muscular weakness, and collapse. Toxic alkaloid concentration generally declines in tall larkspurs with maturation, but alkaloid concentration varies over years and from plant to plant, and is of little use for predicting consumption by cattle. Knowledge of toxic alkaloid concentration is valuable for management purposes when cattle begin to eat larkspur. Cattle generally begin consuming tall larkspur after flowering racemes are elongated, and consumption increases as larkspur matures. Weather is also a major factor in cattle consumption, as cattle tend to eat more larkspur during or just after summer storms. Management options that may be useful for livestock producers include conditioning cattle to avoid larkspur (food aversion learning), grazing tall larkspur ranges before flowering (early grazing) and after seed shatter (late grazing), grazing sheep before cattle, herbicidal control of larkspur plants, and drug therapy for intoxicated animals. Some potentially fruitful research avenues include examining alkaloid chemistry in low and plains larkspurs, developing immunologic methods for analyzing larkspur alkaloids, developing drug therapy, and devising grazing regimes specifically for low and plains larkspur.

Hericium erinaceus mycelium and its isolated erinacine A protection from MPTP-induced neurotoxicity through the ER stress, triggering an apoptosis cascade.

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Kuo, Hsing-Chun; Lu, Chien-Chang; Shen, Chien-Heng; Tung, Shui-Yi; Hsieh, Meng Chiao; Lee, Ko-Chao; Lee, Li-Ya; Chen, Chin-Chu; Teng, Chih-Chuan; Huang, Wen-Shih; Chen, Te-Chuan; Lee, Kam-Fai

2016-03-18

Hericium erinaceus is an edible mushroom; its various pharmacological effects which have been investigated. This study aimed to demonstrate whether efficacy of oral administration of H. erinaceus mycelium (HEM) and its isolated diterpenoid derivative, erinacine A, can act as an anti-neuroinflammatory agent to bring about neuroprotection using an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson's disease, which results in motor disturbances, in addition to elucidating the mechanisms involved. Mice were treated with and without HEM or erinacine A, after MPTP injection for brain injuries by the degeneration of dopaminergic nigrostriatal neurons. The efficacy of oral administration of HEM improved MPTP-induced loss of tyrosine hydroxylase positive neurons and brain impairment in the substantia nigra pars compacta as measured by brain histological examination. Treatment with HEM reduced MPTP-induced dopaminergic cell loss, apoptotic cell death induced by oxidative stress, as well as the level of glutathione, nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE). Furthermore, HEM reversed MPTP-associated motor deficits, as revealed by the analysis of rotarod assessment. Our results demonstrated that erinacine A decreases the impairment of MPP-induced neuronal cell cytotoxicity and apoptosis, which were accompanied by ER stress-sustained activation of the IRE1α/TRAF2, JNK1/2 and p38 MAPK pathways, the expression of C/EBP homologous protein (CHOP), IKB-β and NF-κB, as well as Fas and Bax. These physiological and brain histological changes provide HEM neuron-protective insights into the progression of Parkinson's disease, and this protective effect seems to exist both in vivo and in vitro.

Protective effects of Hericium erinaceus mycelium and its isolated erinacine A against ischemia-injury-induced neuronal cell death via the inhibition of iNOS/p38 MAPK and nitrotyrosine.

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Lee, Kam-Fai; Chen, Jiann-Hwa; Teng, Chih-Chuan; Shen, Chien-Heng; Hsieh, Meng-Chiao; Lu, Chien-Chang; Lee, Ko-Chao; Lee, Li-Ya; Chen, Wan-Ping; Chen, Chin-Chu; Huang, Wen-Shih; Kuo, Hsing-Chun

2014-08-27

Hericium erinaceus, an edible mushroom, has been demonstrated to potentiate the effects of numerous biological activities. The aim of this study was to investigate whether H. erinaceus mycelium could act as an anti-inflammatory agent to bring about neuroprotection using a model of global ischemic stroke and the mechanisms involved. Rats were treated with H. erinaceus mycelium and its isolated diterpenoid derivative, erinacine A, after ischemia reperfusion brain injuries caused by the occlusion of the two common carotid arteries. The production of inflammatory cytokines in serum and the infracted volume of the brain were measured. The proteins from the stroke animal model (SAM) were evaluated to determine the effect of H. erinaceus mycelium. H. erinaceus mycelium reduced the total infarcted volumes by 22% and 44% at a concentration of 50 and 300 mg/kg, respectively, compared to the SAM group. The levels of acute inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor á, were all reduced by erinacine A. Levels of nitrotyrosine-containing proteins, phosphorylation of p38 MAPK and CCAAT enhancer-binding protein (C/EBP) and homologous protein (CHOP) expression were attenuated by erinacine A. Moreover, the modulation of ischemia injury factors present in the SAM model by erinacine A seemed to result in the suppression of reactive nitrogen species and the downregulation of inducible NO synthase (iNOS), p38 MAPK and CHOP. These findings confirm the nerve-growth properties of Hericium erinaceus mycelium, which include the prevention of ischemic injury to neurons; this protective effect seems to be involved in the in vivo activity of iNOS, p38 MAPK and CHOP.

Protective Effects of Hericium erinaceus Mycelium and Its Isolated Erinacine A against Ischemia-Injury-Induced Neuronal Cell Death via the Inhibition of iNOS/p38 MAPK and Nitrotyrosine

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Kam-Fai Lee

2014-08-01

Full Text Available Hericium erinaceus, an edible mushroom, has been demonstrated to potentiate the effects of numerous biological activities. The aim of this study was to investigate whether H. erinaceus mycelium could act as an anti-inflammatory agent to bring about neuroprotection using a model of global ischemic stroke and the mechanisms involved. Rats were treated with H. erinaceus mycelium and its isolated diterpenoid derivative, erinacine A, after ischemia reperfusion brain injuries caused by the occlusion of the two common carotid arteries. The production of inflammatory cytokines in serum and the infracted volume of the brain were measured. The proteins from the stroke animal model (SAM were evaluated to determine the effect of H. erinaceus mycelium. H. erinaceus mycelium reduced the total infarcted volumes by 22% and 44% at a concentration of 50 and 300 mg/kg, respectively, compared to the SAM group. The levels of acute inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor á, were all reduced by erinacine A. Levels of nitrotyrosine-containing proteins, phosphorylation of p38 MAPK and CCAAT enhancer-binding protein (C/EBP and homologous protein (CHOP expression were attenuated by erinacine A. Moreover, the modulation of ischemia injury factors present in the SAM model by erinacine A seemed to result in the suppression of reactive nitrogen species and the downregulation of inducible NO synthase (iNOS, p38 MAPK and CHOP. These findings confirm the nerve-growth properties of Hericium erinaceus mycelium, which include the prevention of ischemic injury to neurons; this protective effect seems to be involved in the in vivo activity of iNOS, p38 MAPK and CHOP.

Magnaporthe oryzae Glycine-Rich Secretion Protein, Rbf1 Critically Participates in Pathogenicity through the Focal Formation of the Biotrophic Interfacial Complex.

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Takeshi Nishimura

2016-10-01

Full Text Available Magnaporthe oryzae, the fungus causing rice blast disease, should contend with host innate immunity to develop invasive hyphae (IH within living host cells. However, molecular strategies to establish the biotrophic interactions are largely unknown. Here, we report the biological function of a M. oryzae-specific gene, Required-for-Focal-BIC-Formation 1 (RBF1. RBF1 expression was induced in appressoria and IH only when the fungus was inoculated to living plant tissues. Long-term successive imaging of live cell fluorescence revealed that the expression of RBF1 was upregulated each time the fungus crossed a host cell wall. Like other symplastic effector proteins of the rice blast fungus, Rbf1 accumulated in the biotrophic interfacial complex (BIC and was translocated into the rice cytoplasm. RBF1-knockout mutants (Δrbf1 were severely deficient in their virulence to rice leaves, but were capable of proliferating in abscisic acid-treated or salicylic acid-deficient rice plants. In rice leaves, Δrbf1 inoculation caused necrosis and induced defense-related gene expression, which led to a higher level of diterpenoid phytoalexin accumulation than the wild-type fungus did. Δrbf1 showed unusual differentiation of IH and dispersal of the normally BIC-focused effectors around the short primary hypha and the first bulbous cell. In the Δrbf1-invaded cells, symplastic effectors were still translocated into rice cells but with a lower efficiency. These data indicate that RBF1 is a virulence gene essential for the focal BIC formation, which is critical for the rice blast fungus to suppress host immune responses.

Pharmacokinetics and Metabolism of 4R-Cembranoid.

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Wanda Vélez-Carrasco

Full Text Available 4R-cembranoid (4R is a natural cyclic diterpenoid found in tobacco leaves that displays neuroprotective activity. 4R protects against NMDA, paraoxon (POX, and diisopropylfluorophosphate (DFP damage in rat hippocampal slices and against DFP in rats in vivo. The purpose of this study was to examine the metabolism and pharmacokinetics of 4R as part of its preclinical development as a neuroprotective drug. 10 µM 4R was found to be very stable in plasma for up to 1 hr incubation. 4R metabolism in human microsomes was faster than in the rat. Ten metabolites of 4R were detected in the microsomal samples; 6 dihydroxy and 4 monohydroxy forms of 4R. Male rats received a single dose of 4R at 6 mg/kg i.v., i.m., or s.c. The i.v. group had the highest plasma concentration of 1017 ng/mL. The t1/2 was 36 min and reached the brain within 10 min. The brain peak concentration was 6516 ng/g. The peak plasma concentration in the i.m. group was 163 ng/mL compared to 138 ng/mL in the s.c. group. The t1/2 of 4R after i.m. and s.c. administration was approximately 1.5 hr. The brain peak concentration was 329 ng/g in the i.m. group and 323 ng/g for the s.c. group. The brain to plasma ratio in the i.v. group was 6.4, reached 10 min after dose, whereas in the i.m. and s.c. groups was 2.49 and 2.48, respectively, at 90 min after dose. Our data show that 4R crosses the BBB and concentrates in the brain where it exerts its neuroprotective effect.

Pharmacokinetics and Metabolism of 4R-Cembranoid.

Science.gov (United States)

Vélez-Carrasco, Wanda; Green, Carol E; Catz, Paul; Furimsky, Anna; O'Loughlin, Kathleen; Eterović, Vesna A; Ferchmin, P A

2015-01-01

4R-cembranoid (4R) is a natural cyclic diterpenoid found in tobacco leaves that displays neuroprotective activity. 4R protects against NMDA, paraoxon (POX), and diisopropylfluorophosphate (DFP) damage in rat hippocampal slices and against DFP in rats in vivo. The purpose of this study was to examine the metabolism and pharmacokinetics of 4R as part of its preclinical development as a neuroprotective drug. 10 µM 4R was found to be very stable in plasma for up to 1 hr incubation. 4R metabolism in human microsomes was faster than in the rat. Ten metabolites of 4R were detected in the microsomal samples; 6 dihydroxy and 4 monohydroxy forms of 4R. Male rats received a single dose of 4R at 6 mg/kg i.v., i.m., or s.c. The i.v. group had the highest plasma concentration of 1017 ng/mL. The t1/2 was 36 min and reached the brain within 10 min. The brain peak concentration was 6516 ng/g. The peak plasma concentration in the i.m. group was 163 ng/mL compared to 138 ng/mL in the s.c. group. The t1/2 of 4R after i.m. and s.c. administration was approximately 1.5 hr. The brain peak concentration was 329 ng/g in the i.m. group and 323 ng/g for the s.c. group. The brain to plasma ratio in the i.v. group was 6.4, reached 10 min after dose, whereas in the i.m. and s.c. groups was 2.49 and 2.48, respectively, at 90 min after dose. Our data show that 4R crosses the BBB and concentrates in the brain where it exerts its neuroprotective effect.

Oridonin induces apoptosis and senescence in colorectal cancer cells by increasing histone hyperacetylation and regulation of p16, p21, p27 and c-myc

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Gao, Feng-Hou; Liu, Feng; Zhao, Ying-Zheng; Fang, Yong; Chen, Fang-Yuan; Wu, Ying-Li; Hu, Xiao-Hui; Li, Wei; Liu, Hua; Zhang, Yan-Jie; Guo, Zhu-Ying; Xu, Mang-Hua; Wang, Shi-Ting; Jiang, Bin

2010-01-01

Oridonin, a tetracycline diterpenoid compound, has the potential antitumor activities. Here, we evaluate the antitumor activity and action mechanisms of oridonin in colorectal cancer. Effects of oridonin on cell proliferation were determined by using a CCK-8 Kit. Cell cycle distribution was determined by flow cytometry. Apoptosis was examined by analyzing subdiploid population and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Senescent cells were determined by senescence-associated β-galactosidase activity analysis. Semi-quantitative RT-PCR was used to examine the changes of mRNA of p16, p21, p27 and c-myc. The concomitant changes of protein expression were analyzed with Western blot. Expression of AcH3 and AcH4 were examined by immunofluorescence staining and Western blots. Effects of oridonin on colony formation of SW1116 were examined by Soft Agar assay. The in vivo efficacy of oridonin was detected using a xenograft colorectal cancer model in nude mice. Oridonin induced potent growth inhibition, cell cycle arrest, apoptosis, senescence and colony-forming inhibition in three colorectal cancer cell lines in a dose-dependent manner in vitro. Daily i.p. injection of oridonin (6.25, 12.5 or 25 mg/kg) for 28 days significantly inhibited the growth of SW1116 s.c. xenografts in BABL/C nude mice. With western blot and reverse transcription-PCR, we further showed that the antitumor activities of oridonin correlated with induction of histone (H3 and H4) hyperacetylation, activation of p21, p27 and p16, and suppression of c-myc expression. Oridonin possesses potent in vitro and in vivo anti-colorectal cancer activities that correlated with induction of histone hyperacetylation and regulation of pathways critical for maintaining growth inhibition and cell cycle arrest. Therefore, oridonin may represent a novel therapeutic option in colorectal cancer treatment

Andrographolide inhibits adipogenesis of 3T3-L1 cells by suppressing C/EBPβ expression and activation.

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Chen, Ching-Chu; Chuang, Wei-Ting; Lin, Ai-Hsuan; Tsai, Chia-Wen; Huang, Chin-Shiu; Chen, Yun-Ting; Chen, Haw-Wen; Lii, Chong-Kuei

2016-09-15

Andrographolide, a diterpenoid, is the most abundant terpenoid in Andrographis paniculata, a popular Chinese herbal medicine. Andrographolide displays diverse biological activities including hypoglycemia, hypolipidemia, anti-inflammation, and anti-tumorigenesis. Recent evidence indicates that andrographolide displays anti-obesity property by inhibiting lipogenic gene expression, however, the underlying mechanisms remain to be elucidated. In this study, the effects of andrographolide on transcription factor cascade and mitotic clonal expansion in 3T3-L1 preadipocyte differentiation into adipocyte were determined. Andrographolide dose-dependently (0-15μM) inhibited CCAAT/enhancer-binding protein α (C/EBPα) and C/EBPβ mRNA and protein expression as well as peroxisome proliferator-activated receptor γ (PPARγ) protein level during the adipogenesis of 3T3-L1 cells. Concomitantly, fatty acid synthase and stearoyl-CoA desaturase expression and lipid accumulation were attenuated by andrographolide. Oil-red O staining further showed that the first 48h after the initiation of differentiation was critical for andrographolide inhibition of adipocyte formation. Andrographolide inhibited the phosphorylation of PKA and the activation of cAMP response element-binding protein (CREB) in response to a differentiation cocktail, which led to attenuated C/EBPβ expression. In addition, ERK and GSK3β-dependent C/EBPβ phosphorylation was attenuated by andrographolide. Moreover, andrographolide suppressed cyclin A, cyclin E, and CDK2 expression and impaired the progression of mitotic clonal expansion (MCE) by arresting the cell cycle at the Go/G1 phase. Taken together, these results indicate that andrographolide has a potent anti-obesity action by inhibiting PKA-CREB-mediated C/EBPβ expression as well as C/EBPβ transcriptional activity, which halts MCE progression and attenuates C/EBPα and PPARγ expression. Copyright © 2016 Elsevier Inc. All rights reserved.

Andrographolide antagonizes cigarette smoke extract-induced inflammatory response and oxidative stress in human alveolar epithelial A549 cells through induction of microRNA-218.

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Li, Ying-jie; Yu, Chang-hai; Li, Jing-bo; Wu, Xi-ya

2013-12-01

Andrographolide is a major bioactive labdane diterpenoid isolated from Andrographis paniculata and has protective effects against cigarette smoke (CS)-induced lung injury. This study was done to determine whether such protective effects were mediated through modulation of microRNA (miR)-218 expression. Therefore, we exposed human alveolar epithelial A549 cells to cigarette smoke extract (CSE) with or without andrographolide pretreatment and measured the level of glutathione, nuclear factor-kappaB (NF-κB) activation, proinflammatory cytokine production, and miR-218 expression. We found that andrographolide pretreatment significantly restored the glutathione level in CSE-exposed A549 cells, coupled with reduced inhibitor κB (IκB)-α phosphorylation and p65 nuclear translocation and interleukin (IL)-8 and IL-6 secretion. The miR-218 expression was significantly upregulated by andrographolide pretreatment. To determine the biological role of miR-218, we overexpressed and downregulated its expression using miR-218 mimic and anti-miR-218 inhibitor, respectively. We observed that miR-218 overexpression led to a marked reduction in IκB-α phosphorylation, p65 nuclear accumulation, and NF-κB-dependent transcriptional activity in CSE-treated A549 cells. In contrast, miR-218 silencing enhanced IκB-α phosphorylation and p65 nuclear accumulation in cells with andrographolide pretreatment and reversed andrographolide-mediated reduction of IL-6 and IL-8 production. In addition, depletion of miR-218 significantly reversed the upregulation of glutathione levels in A549 cells by andrographolide. Taken together, our results demonstrate that andrographolide mitigates CSE-induced inflammatory response in A549 cells, largely through inhibition of NF-κB activation via upregulation of miR-218, and thus has preventive benefits in CS-induced inflammatory lung diseases.

Holy smoke in medieval funerary rites: chemical fingerprints of frankincense in southern Belgian incense burners.

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Baeten, Jan; Deforce, Koen; Challe, Sophie; De Vos, Dirk; Degryse, Patrick

2014-01-01

Frankincense, the oleogum resin from Boswellia sp., has been an early luxury good in both Western and Eastern societies and is particularly used in Christian funerary and liturgical rites. The scant grave goods in late medieval burials comprise laterally perforated pottery vessels which are usually filled with charcoal. They occur in most regions of western Europe and are interpreted as incense burners but have never been investigated with advanced analytical techniques. We herein present chemical and anthracological results on perforated funerary pots from 4 Wallonian sites dating to the 12-14th century AD. Chromatographic and mass spectrometric analysis of lipid extracts of the ancient residues and comparison with extracts from four Boswellia species clearly evidence the presence of degraded frankincense in the former, based on characteristic triterpenoids, viz. boswellic and tirucallic acids, and their myriad dehydrated and oxygenated derivatives. Cembrane-type diterpenoids indicate B. sacra (southern Arabia) and B. serrata (India) as possible botanical origins. Furthermore, traces of juniper and possibly pine tar demonstrate that small amounts of locally available fragrances were mixed with frankincense, most likely to reduce its cost. Additionally, markers of ruminant fats in one sample from a domestic context indicate that this vessel was used for food preparation. Anthracological analysis demonstrates that the charcoal was used as fuel only and that no fragrant wood species were burned. The chars derived from local woody plants and were most likely recovered from domestic fires. Furthermore, vessel recycling is indicated by both contextual and biomarker evidence. The results shed a new light on funerary practices in the Middle Ages and at the same time reveal useful insights into the chemistry of burned frankincense. The discovery of novel biomarkers, namely Δ2-boswellic acids and a series of polyunsaturated and aromatic hydrocarbons, demonstrates the high

Engineering low phorbol ester Jatropha curcas seed by intercepting casbene biosynthesis.

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Li, Chunhong; Ng, Ailing; Xie, Lifen; Mao, Huizhu; Qiu, Chengxiang; Srinivasan, Ramachandran; Yin, Zhongchao; Hong, Yan

2016-01-01

Casbene is a precursor to phorbol esters and down-regulating casbene synthase effectively reduces phorbol ester biosynthesis. Seed-specific reduction of phorbol ester (PE) helps develop Jatropha seed cake for animal nutrition. Phorbol esters (PEs) are diterpenoids present in some Euphorbiaceae family members like Jatropha curcas L. (Jatropha), a tropical shrub yielding high-quality oil suitable as feedstock for biodiesel and bio jet fuel. Jatropha seed contains up to 40 % of oil and can produce oil together with cake containing high-quality proteins. However, skin-irritating and cancer-promoting PEs make Jatropha cake meal unsuitable for animal nutrition and also raise some safety and environmental concerns on its planting and processing. Two casbene synthase gene (JcCASA163 and JcCASD168) homologues were cloned from Jatropha genome and both genes were highly expressed during seed development. In vitro functional analysis proved casbene synthase activity of JcCASA163 in converting geranylgeranyl diphosphate into casbene which has been speculated to be the precursor to PEs. A seed-specific promoter driving inverted repeats for RNAi interference targeting at either JcCASA163 or both genes could effectively down-regulate casbene synthase gene expression with concurrent marked reduction of PE level (by as much as 85 %) in seeds with no pleiotropic effects observed. Such engineered low PE in seed was heritable and co-segregated with the transgene. Our work implicated casbene synthase in Jatropha PE biosynthesis and provided evidence for casbene being the precursor for PEs. The success in reducing seed PE content through down-regulation of casbene synthase demonstrates the feasibility of intercepting PE biosynthesis in Jatropha seed to help address safety concerns on Jatropha plantation and seed processing and facilitate use of its seed protein for animal nutrition.

Prediction of operon-like gene clusters in the Arabidopsis thaliana genome based on co-expression analysis of neighboring genes.

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Wada, Masayoshi; Takahashi, Hiroki; Altaf-Ul-Amin, Md; Nakamura, Kensuke; Hirai, Masami Y; Ohta, Daisaku; Kanaya, Shigehiko

2012-07-15

Operon-like arrangements of genes occur in eukaryotes ranging from yeasts and filamentous fungi to nematodes, plants, and mammals. In plants, several examples of operon-like gene clusters involved in metabolic pathways have recently been characterized, e.g. the cyclic hydroxamic acid pathways in maize, the avenacin biosynthesis gene clusters in oat, the thalianol pathway in Arabidopsis thaliana, and the diterpenoid momilactone cluster in rice. Such operon-like gene clusters are defined by their co-regulation or neighboring positions within immediate vicinity of chromosomal regions. A comprehensive analysis of the expression of neighboring genes therefore accounts a crucial step to reveal the complete set of operon-like gene clusters within a genome. Genome-wide prediction of operon-like gene clusters should contribute to functional annotation efforts and provide novel insight into evolutionary aspects acquiring certain biological functions as well. We predicted co-expressed gene clusters by comparing the Pearson correlation coefficient of neighboring genes and randomly selected gene pairs, based on a statistical method that takes false discovery rate (FDR) into consideration for 1469 microarray gene expression datasets of A. thaliana. We estimated that A. thaliana contains 100 operon-like gene clusters in total. We predicted 34 statistically significant gene clusters consisting of 3 to 22 genes each, based on a stringent FDR threshold of 0.1. Functional relationships among genes in individual clusters were estimated by sequence similarity and functional annotation of genes. Duplicated gene pairs (determined based on BLAST with a cutoff of EOperon-like clusters tend to include genes encoding bio-machinery associated with ribosomes, the ubiquitin/proteasome system, secondary metabolic pathways, lipid and fatty-acid metabolism, and the lipid transfer system. Copyright © 2012 Elsevier B.V. All rights reserved.

New biomarkers of coffee consumption identified by the non-targeted metabolomic profiling of cohort study subjects.

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Joseph A Rothwell

Full Text Available Coffee contains various bioactives implicated with human health and disease risk. To accurately assess the effects of overall consumption upon health and disease, individual intake must be measured in large epidemiological studies. Metabolomics has emerged as a powerful approach to discover biomarkers of intake for a large range of foods. Here we report the profiling of the urinary metabolome of cohort study subjects to search for new biomarkers of coffee intake. Using repeated 24-hour dietary records and a food frequency questionnaire, 20 high coffee consumers (183-540 mL/d and 19 low consumers were selected from the French SU.VI.MAX2 cohort. Morning spot urine samples from each subject were profiled by high-resolution mass spectrometry. Partial least-square discriminant analysis of multidimensional liquid chromatography-mass spectrometry data clearly distinguished high consumers from low via 132 significant (p-value<0.05 discriminating features. Ion clusters whose intensities were most elevated in the high consumers were annotated using online and in-house databases and their identities checked using commercial standards and MS-MS fragmentation. The best discriminants, and thus potential markers of coffee consumption, were the glucuronide of the diterpenoid atractyligenin, the diketopiperazine cyclo(isoleucyl-prolyl, and the alkaloid trigonelline. Some caffeine metabolites, such as 1-methylxanthine, were also among the discriminants, however caffeine may be consumed from other sources and its metabolism is subject to inter-individual variation. Receiver operating characteristics curve analysis showed that the biomarkers identified could be used effectively in combination for increased sensitivity and specificity. Once validated in other cohorts or intervention studies, these specific single or combined biomarkers will become a valuable alternative to assessment of coffee intake by dietary survey and finally lead to a better understanding of

RNA-Seq for gene identification and transcript profiling of three Stevia rebaudiana genotypes.

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Chen, Junwen; Hou, Kai; Qin, Peng; Liu, Hongchang; Yi, Bin; Yang, Wenting; Wu, Wei

2014-07-07

Stevia (Stevia rebaudiana) is an important medicinal plant that yields diterpenoid steviol glycosides (SGs). SGs are currently used in the preparation of medicines, food products and neutraceuticals because of its sweetening property (zero calories and about 300 times sweeter than sugar). Recently, some progress has been made in understanding the biosynthesis of SGs in Stevia, but little is known about the molecular mechanisms underlying this process. Additionally, the genomics of Stevia, a non-model species, remains uncharacterized. The recent advent of RNA-Seq, a next generation sequencing technology, provides an opportunity to expand the identification of Stevia genes through in-depth transcript profiling. We present a comprehensive landscape of the transcriptome profiles of three genotypes of Stevia with divergent SG compositions characterized using RNA-seq. 191,590,282 high-quality reads were generated and then assembled into 171,837 transcripts with an average sequence length of 969 base pairs. A total of 80,160 unigenes were annotated, and 14,211 of the unique sequences were assigned to specific metabolic pathways by the Kyoto Encyclopedia of Genes and Genomes. Gene sequences of all enzymes known to be involved in SG synthesis were examined. A total of 143 UDP-glucosyltransferase (UGT) unigenes were identified, some of which might be involved in SG biosynthesis. The expression patterns of eight of these genes were further confirmed by RT-QPCR. RNA-seq analysis identified candidate genes encoding enzymes responsible for the biosynthesis of SGs in Stevia, a non-model plant without a reference genome. The transcriptome data from this study yielded new insights into the process of SG accumulation in Stevia. Our results demonstrate that RNA-Seq can be successfully used for gene identification and transcript profiling in a non-model species.

Oridonin nanosuspension was more effective than free oridonin on G2/M cell cycle arrest and apoptosis in the human pancreatic cancer PANC-1 cell line

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Qi XL

2012-04-01

Full Text Available Xiaoli Qi1, Dianrui Zhang2, Xia Xu1, Feifei Feng2, Guijie Ren1, Qianqian Chu1, Qiang Zhang3, Keli Tian11Department of Biochemistry and Molecular Biology, Shandong University School of Medicine, Jinan, 2Department of Pharmaceutics, College of Pharmacy, Shandong University, Jinan, 3State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of ChinaAbstract: Oridonin, a diterpenoid isolated from Rabdosia rubescencs, has been reported to have antitumor effects. However, low solubility has limited its clinical applications. Preparation of drugs in the form of nanosuspensions is an extensively utilized protocol. In this study, we investigated the anticancer activity of oridonin and oridonin nanosuspension on human pancreatic carcinoma PANC-1 cells. 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay was performed to investigate the effect of oridonin on cell growth. Propidium iodide and Hoechst 33342 staining were used to detect morphologic changes. The percentage of apoptosis and cell cycle progression was determined by flow cytometric method staining with propidium iodide. Annexin V-fluorescein isothiocyanate (FITC/PI staining was used to evaluate cell apoptosis by flow cytometry. Caspase-3 activity was measured by spectrophotometry. The apoptotic and cell cycle protein expression were determined by Western blot analysis. Both oridonin and oridonin nanosuspension induced apoptosis and G2/M phase cell cycle arrest, and the latter had a more significant cytotoxic effect. The ratio of Bcl-2/Bax protein expression was decreased and caspase-3 activity was stimulated. The expression of cyclin B1 and p-cdc2 (T161 was suppressed. Our results showed that oridonin nanosuspension was more effective than free oridonin on G2/M cell cycle arrest and apoptosis in the human pancreatic cancer PANC-1 cell line.Keywords: cyclin B1, cdc2, caspase-3, Bcl-2, Bax

Andrographolide suppresses thymic stromal lymphopoietin in phorbol myristate acetate/calcium ionophore A23187-activated mast cells and 2,4-dinitrofluorobenzene-induced atopic dermatitis-like mice model

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Li CX

2016-02-01

Full Text Available Chun-xiao Li,* Hua-guo Li,* Hui Zhang,* Ru-hong Cheng, Ming Li, Jian-ying Liang, Yan Gu, Bo Ling, Zhi-rong Yao, Hong Yu Department of Dermatology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China *These authors contributed equally to this work Background: Atopic dermatitis (AD is one of the most common inflammatory cutaneous diseases. Thymic stromal lymphopoietin (TSLP has been demonstrated to be an important immunologic factor in the pathogenesis of AD. The production of TSLP can be induced by a high level of intracellular calcium concentration and activation of the receptor-interacting protein 2/caspase-1/NF-κB pathway. Andrographolide (ANDRO, a natural bicyclic diterpenoid lactone, has been found to exert anti-inflammatory effects in gastrointestinal inflammatory disorders through suppressing the NF-κB pathway. Objective: To explore the effect of ANDRO on the production of TSLP in human mast cells and AD mice model. Methods: We utilized enzyme-linked immunosorbent assay, real-time reverse transcription polymerase chain reaction analysis, Western blot analysis, and immunofluorescence staining assay to investigate the effects of ANDRO on AD. Results: ANDRO ameliorated the increase in the intracellular calcium, protein, and messenger RNA levels of TSLP induced by phorbol myristate acetate/calcium ionophore A23187, through the blocking of the receptor-interacting protein 2/caspase-1/NF-κB pathway in human mast cell line 1 cells. ANDRO, via oral or local administration, also attenuated clinical symptoms in 2,4-dinitrofluorobenzene-induced AD mice model and suppressed the levels of TSLP in lesional skin. Conclusion: Taken together, ANDRO may be a potential therapeutic agent for AD through suppressing the expression of TSLP. Keywords: atopic dermatitis, thymic stromal lymphopoietin, andrographolide, human mast cell

Cytogenetic Studies on Sativa Rebounded Produced by Tissue Culture and Affected by GAMMA Rays and Drought

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Awad, A.S.A.

2009-01-01

Stevia rebaudiana Bertoni is a plant which produces a variety of high-potency, low-calorie sweetener in its leaf tissue (Jarma et al ., 2006). The leaves of this plant contain sweet diterpene glucosides; rebaudioside A, rebaudioside C, stevioside and dulcoside. Stevioside is about 110 to 270 times sweeter than sucrose, while rebaudioside A is 150 to 320 times sweeter than sucrose (Yao et al., 1999). The leaves also produce biologically active substances, e.g. flavonoids, coumarins, cinnamic acids and essential oil (Dzyuba, 1998). (Lobov and Yurtaeva, 2002) showed that diterpenoid glycosides from leaves of S. rebaudiana were the most promising non-sugar sweeteners of plant origin for food and pharmaceutical industries to overcome the problem of human diseases related to disorders of carbon metabolism. The sweetener from leaves has a good taste and is suitable for use in food products as chocolates, marmalades, biscuits, ice-cream, sweets, juices, beverages and candy. The dried leaves could be mixed within the tea packages to reduce the consumption of sugar. The stevioside does not induce tooth decay could safely by used by diabetic patients and could be used in the low caloric diets to reduce human body weight without side effects for these reasons many countries are now using this plant to produce a larger portion of their sugar consumption (El-Zifzafi, 2003). Stevia, Stevia rebaudiana Bertoni is a small herbaceous plant (2 n = 22). It is a member of compositae family (Yao et al., 1999). Estimates of total number of species in this genus ranges from 150 to 300 . Stevia rebaudiana is one of the species of the genus stevia, which includes S.eupatoria, S.purpurea and S .serrata (Lisitsin and kovalev, 2000).

Insecticidal effect of plant extracts on Phlebotomus argentipes (Diptera: Psychodidae) in Bihar, India.

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Dinesh, Diwakar Singh; Kumari, Seema; Pandit, Vibhishan; Kumar, Jainendra; Kumari, Nisha; Kumar, Prahlad; Hassan, Faizan; Kumar, Vijay; Das, Pradeep

2015-12-01

Phlebotomus argentipes (Diptera: Psychodidae), the established vector for kala-azar is presently being controlled by indoor residual spray of DDT in kala-azar endemic areas in India. Search for non-hazardous and non-toxic biodegradable active molecules from botanicals may provide cost-effective and eco-friendly alternatives to synthetic insecticides. The present study was aimed at evaluating various plant extracts from endemic and non-endemic areas of Bihar for their insecticidal activity against sandfly to identify the most effective plant extract. Bio-assay test was conducted with larvae and adult of P. argentipes with different plant extracts collected in distilled water, hexane, ethyl acetate, acetone and methanol. Thin layer chromatography (TLC), column chromatography and high performance liquid chromatography (HPLC) were conducted for detection of active molecules. Adults and larvae of sandflies exposed to the aqueous extract of Nicotiana tabacum resulted in 100 per cent mortality. The hexane extract of Clerodendrum infortunatum was found to kill 77 per cent adults but was ineffective against larvae. Bio-assay test of the ninth fraction (hexane extract-methanol phase) separated by column chromatography was found to be 63 per cent effective. The purple spot on the TLC of this fraction indicated the presence of a diterpenoid. HPLC of this fraction detected nine compounds with two peaks covering 20.44 and 56.52 per cent areas with retention time of 2.439 and 5.182 min, respectively supporting the TLC results. The column separated 9 [th] fraction of C. infortunatum extract was found to be effective in killing 63 per cent of adult P. argentipes. Compounds of this fraction need to be evaluated further for identification and characterization of the active molecule by conducting individual bio-assay tests followed by further fractionation and HPLC. Once the structure of the active molecule is identified and validated, it may be synthesized and formulated as a product.

Bio-crude transcriptomics: Gene discovery and metabolic network reconstruction for the biosynthesis of the terpenome of the hydrocarbon oil-producing green alga, Botryococcus braunii race B (Showa*

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Molnár István

2012-10-01

Full Text Available Abstract Background Microalgae hold promise for yielding a biofuel feedstock that is sustainable, carbon-neutral, distributed, and only minimally disruptive for the production of food and feed by traditional agriculture. Amongst oleaginous eukaryotic algae, the B race of Botryococcus braunii is unique in that it produces large amounts of liquid hydrocarbons of terpenoid origin. These are comparable to fossil crude oil, and are sequestered outside the cells in a communal extracellular polymeric matrix material. Biosynthetic engineering of terpenoid bio-crude production requires identification of genes and reconstruction of metabolic pathways responsible for production of both hydrocarbons and other metabolites of the alga that compete for photosynthetic carbon and energy. Results A de novo assembly of 1,334,609 next-generation pyrosequencing reads form the Showa strain of the B race of B. braunii yielded a transcriptomic database of 46,422 contigs with an average length of 756 bp. Contigs were annotated with pathway, ontology, and protein domain identifiers. Manual curation allowed the reconstruction of pathways that produce terpenoid liquid hydrocarbons from primary metabolites, and pathways that divert photosynthetic carbon into tetraterpenoid carotenoids, diterpenoids, and the prenyl chains of meroterpenoid quinones and chlorophyll. Inventories of machine-assembled contigs are also presented for reconstructed pathways for the biosynthesis of competing storage compounds including triacylglycerol and starch. Regeneration of S-adenosylmethionine, and the extracellular localization of the hydrocarbon oils by active transport and possibly autophagy are also investigated. Conclusions The construction of an annotated transcriptomic database, publicly available in a web-based data depository and annotation tool, provides a foundation for metabolic pathway and network reconstruction, and facilitates further omics studies in the absence of a genome

Glaucocalyxin B Alleviates Lipopolysaccharide-Induced Parkinson’s Disease by Inhibiting TLR/NF-κB and Activating Nrf2/HO-1 Pathway

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Wei Xu

2017-12-01

Full Text Available Background/Aims: Parkinson’s disease (PD is a common neurodegenerative disease in the old population, characterized by dopaminergic neuron loss, inflammation and oxidative stress injury in the substantia nigra. Glaucocalyxin B (GLB, an ent-kauranoid diterpenoid isolated from Rabdosia japonica, has anti-inflammation and anti-tumor effects. However, its effects on PD remain unclear. Methods: PD was introduced in rats via injection of lipopolysaccharide (LPS into cerebral corpus striatum, and GLB was given intracerebroventricularly to these rats. Their walking, climbing and sensory states were detected by Stepping, Whisker and Cylinder Tests. The expression of tyrosine hydroxylase (TH, glial fibrillary acidic protein (GFAP, CD11b and ionized calcium binding adaptor molecule (IBA-1 were detected by immunohischemical staining. The levels of a series of inflammatory factors, oxidative stress-related factors and apoptosis-related factors were measured by real-time PCR, immunoblotting and ELISA. In addition, Toll-like receptor (TLR/nuclear factor kappa B (NF-κB and nuclear factor erythroid 2-related factor 2 (Nrf2/heme oxygenase (HO-1 pathways were investigated to illustrate the underlying mechanism. In vitro, microglial cells exposed to LPS were treated with GLB. Results: The injection of LPS caused walking, climbing and sensory disturbances in rats, induced inflammation, oxidative stress response and apoptosis, and activated TLR/NF-κB and Nrf2/ HO-1 pathways in the cerebral tissue. GLB administration attenuated LPS-induced alterations. The TLR/NF-κB pathway was deactivated and Nrf2/HO-1 was activated after application of GLB. In vitro, cytotoxic effects induced by the conditioned medium derived from microglial cells exposed to LPS in PC12 cells were attenuated by GLB. Conclusion: GLB suppresses LPS-induced PD symptoms by modification of TLR/NF-κB and Nrf2/HO-1 pathways in vivo and in vitro.

Glaucocalyxin A inhibits platelet activation and thrombus formation preferentially via GPVI signaling pathway.

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Wei Li

Full Text Available Platelets play a pivotal role in atherothrombosis and the antiplatelet agents have been proved to be useful in preventing onset of acute clinical events including myocardial infarction and stroke. Increasing number of natural compounds has been identified to be potential antiplatelet agents. Here we report the antiplatelet effect of glaucocalyxin A (GLA, an ent-diterpenoid that we isolated and purified from the aerial parts of Rabdosia japonica (Burm. f. var. glaucocalyx (Maxim. Hara, and investigate the molecular mechanisms by which GLA inhibits platelet activation and thrombus formation. The effect of GLA on platelet activation was measured using platelets freshly isolated from peripheral blood of healthy donors. Results showed that pretreatment of human platelets with lower concentrations of GLA (0.01 μg/ml, 0.1 μg/ml significantly inhibited platelet aggregation induced by collagen (P<0.001 and CRP (P<0.01, a synthetic GPVI ligand, but not by ADP and U46619. Accordingly, GLA inhibited collagen-stimulated tyrosine phosphorylation of Syk, LAT, and phospholipase Cγ2, the signaling events in collagen receptor GPⅥ pathway. GLA also inhibited platelet p-selectin secretion and integrin activation by convulxin, a GPVI selective ligand. Additionally, GLA was found to inhibit low-dose thrombin-induced platelet activation. Using a flow chamber device, GLA was found to attenuate platelet adhesion on collagen surfaces in high shear condition. In vivo studies showed that GLA administration increased the time for complete occlusion upon vascular injury in mice, but did not extend tail-bleeding time when mice were administered with relatively lower doses of GLA. Therefore, the present results provide the molecular basis for the inhibition effect of GLA on platelet activation and its in vivo effect on thrombus formation, suggesting that GLA could potentially be developed as an antiplatelet and antithrombotic agent.

Oridonin induces apoptosis and senescence in colorectal cancer cells by increasing histone hyperacetylation and regulation of p16, p21, p27 and c-myc

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Zhao Ying-Zheng

2010-11-01

Full Text Available Abstract Background Oridonin, a tetracycline diterpenoid compound, has the potential antitumor activities. Here, we evaluate the antitumor activity and action mechanisms of oridonin in colorectal cancer. Methods Effects of oridonin on cell proliferation were determined by using a CCK-8 Kit. Cell cycle distribution was determined by flow cytometry. Apoptosis was examined by analyzing subdiploid population and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling assay. Senescent cells were determined by senescence-associated β-galactosidase activity analysis. Semi-quantitative RT-PCR was used to examine the changes of mRNA of p16, p21, p27 and c-myc. The concomitant changes of protein expression were analyzed with Western blot. Expression of AcH3 and AcH4 were examined by immunofluorescence staining and Western blots. Effects of oridonin on colony formation of SW1116 were examined by Soft Agar assay. The in vivo efficacy of oridonin was detected using a xenograft colorectal cancer model in nude mice. Results Oridonin induced potent growth inhibition, cell cycle arrest, apoptosis, senescence and colony-forming inhibition in three colorectal cancer cell lines in a dose-dependent manner in vitro. Daily i.p. injection of oridonin (6.25, 12.5 or 25 mg/kg for 28 days significantly inhibited the growth of SW1116 s.c. xenografts in BABL/C nude mice. With western blot and reverse transcription-PCR, we further showed that the antitumor activities of oridonin correlated with induction of histone (H3 and H4 hyperacetylation, activation of p21, p27 and p16, and suppression of c-myc expression. Conclusion Oridonin possesses potent in vitro and in vivo anti-colorectal cancer activities that correlated with induction of histone hyperacetylation and regulation of pathways critical for maintaining growth inhibition and cell cycle arrest. Therefore, oridonin may represent a novel therapeutic option in colorectal cancer treatment.

Ecosystem, location, and climate effects on foliar secondary metabolites of lodgepole pine populations from central British Columbia.

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Wallis, Christopher M; Huber, Dezene P W; Lewis, Kathy J

2011-06-01

Lodgepole pines, Pinus contorta Douglas ex Louden var. latifolia Engelm. ex S. Watson, are encountering increased abiotic stress and pest activity due to recent increases in temperature and changes in precipitation throughout their range. This tree species counters these threats by producing secondary metabolites, including phenolics and terpenoids. We examined foliar levels of lignin, soluble phenolics, monoterpenoids, sesquiterpenoids, and diterpenoids in 12 stands in British Columbia, Canada. We used these data to assess associations among foliar secondary metabolite levels and ecosystem, geographic, and climatic variables. Regressions were also performed to observe which combinations of variables best explained secondary metabolite variance. Stands of P. c. latifolia in the Coastal Western Hemlock and Interior Cedar/Hemlock biogeoclimatic zones had consistently greater foliar levels of almost all measured secondary metabolites than did other stands. Lignin was present in greater amounts in Boreal White/Black Spruce ecosystem (i.e., northern) stands than in southern stands, suggesting a role for this metabolite in pine survival in the boreal forest. Attempts to develop regression models with geographic and climatic variables to explain foliar secondary metabolite levels resulted in multiple models with similar predictive capability. Since foliar secondary metabolite levels appeared to vary most between stand ecosystem types and not as much due to geographic and climatic variables, metabolic profiles appeared best matched to the stress levels within local environments. It is unknown if differences in secondary metabolite levels are the result of genetic adaptation or phenotypic plasticity, but results from this and other studies suggest that both are important. These results are interpreted in light of ongoing efforts to assist in the migration of certain populations of P. c. latifolia northward in an effort to counter predicted effects of climate change.

Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats

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Chen, Haw-Wen [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Huang, Chin-Shiu [Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China); Li, Chien-Chun [School of Nutrition, Chung Shan Medical University, Taichung, Taiwan (China); Department of Nutrition, Chung Shan Medical University Hospital, Taichung, Taiwan (China); Lin, Ai-Hsuan; Huang, Yu-Ju [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Wang, Tsu-Shing [Department of Biomedical Science, Chung Shan Medical University, Taichung, Taiwan (China); Yao, Hsien-Tsung [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Lii, Chong-Kuei [Department of Nutrition, China Medical University, Taichung, Taiwan (China); Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan (China)

2014-10-01

Andrographolide, a bioactive diterpenoid, is identified in Andrographis paniculata. In this study, we investigated the pharmacokinetics and bioavailability of andrographolide in rats and studied whether andrographolide enhances antioxidant defense in a variety of tissues and protects against carbon tetrachloride-induced oxidative damage. After a single 50-mg/kg administration, the maximum plasma concentration of andrographolide was 1 μM which peaked at 30 min. The bioavailability of andrographolide was 1.19%. In a hepatoprotection study, rats were intragastrically dosed with 30 or 50 mg/kg andrographolide for 5 consecutive days. The results showed that andrographolide up-regulated glutamate cysteine ligase (GCL) catalytic and modifier subunits, superoxide dismutase (SOD)-1, heme oxygenase (HO)-1, and glutathione (GSH) S-transferase (GST) Ya/Yb protein and mRNA expression in the liver, heart, and kidneys. The activity of SOD, GST, and GSH reductase was also increased in rats dosed with andrographolide (p < 0.05). Immunoblot analysis and EMSA revealed that andrographolide increased nuclear Nrf2 contents and Nrf2 binding to DNA, respectively. After the 5-day andrographolide treatment, one group of animals was intraperitoneally injected with carbon tetrachloride (CCl{sub 4}) at day 6. Andrographolide pretreatment suppressed CCl{sub 4}-induced plasma aminotransferase activity and hepatic lipid peroxidation (p < 0.05). These results suggest that andrographolide is quickly absorbed in the intestinal tract in rats with a bioavailability of 1.19%. Andrographolide protects against chemical-induced oxidative damage by up-regulating the gene transcription and activity of antioxidant enzymes in various tissues. - Highlights: • The bioavailability of andrographolide is 1.19% in rats. • Plasma concentration reaches 1 μM after giving 50 mg/kg andrographolide. • Andrographolide up-regulates Nrf2-dependent antioxidant genes. • Andrographolide increases antioxidant defense

Bioavailability of andrographolide and protection against carbon tetrachloride-induced oxidative damage in rats

International Nuclear Information System (INIS)

Chen, Haw-Wen; Huang, Chin-Shiu; Li, Chien-Chun; Lin, Ai-Hsuan; Huang, Yu-Ju; Wang, Tsu-Shing; Yao, Hsien-Tsung; Lii, Chong-Kuei

2014-01-01

Andrographolide, a bioactive diterpenoid, is identified in Andrographis paniculata. In this study, we investigated the pharmacokinetics and bioavailability of andrographolide in rats and studied whether andrographolide enhances antioxidant defense in a variety of tissues and protects against carbon tetrachloride-induced oxidative damage. After a single 50-mg/kg administration, the maximum plasma concentration of andrographolide was 1 μM which peaked at 30 min. The bioavailability of andrographolide was 1.19%. In a hepatoprotection study, rats were intragastrically dosed with 30 or 50 mg/kg andrographolide for 5 consecutive days. The results showed that andrographolide up-regulated glutamate cysteine ligase (GCL) catalytic and modifier subunits, superoxide dismutase (SOD)-1, heme oxygenase (HO)-1, and glutathione (GSH) S-transferase (GST) Ya/Yb protein and mRNA expression in the liver, heart, and kidneys. The activity of SOD, GST, and GSH reductase was also increased in rats dosed with andrographolide (p < 0.05). Immunoblot analysis and EMSA revealed that andrographolide increased nuclear Nrf2 contents and Nrf2 binding to DNA, respectively. After the 5-day andrographolide treatment, one group of animals was intraperitoneally injected with carbon tetrachloride (CCl 4 ) at day 6. Andrographolide pretreatment suppressed CCl 4 -induced plasma aminotransferase activity and hepatic lipid peroxidation (p < 0.05). These results suggest that andrographolide is quickly absorbed in the intestinal tract in rats with a bioavailability of 1.19%. Andrographolide protects against chemical-induced oxidative damage by up-regulating the gene transcription and activity of antioxidant enzymes in various tissues. - Highlights: • The bioavailability of andrographolide is 1.19% in rats. • Plasma concentration reaches 1 μM after giving 50 mg/kg andrographolide. • Andrographolide up-regulates Nrf2-dependent antioxidant genes. • Andrographolide increases antioxidant defense in

Compositions, sources and depositional environments of organic matter from the Middle Jurassic clays of Poland

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Marynowski, Leszek; Zaton, Michal; Simoneit, Bernd R.T.; Otto, Angelika; Jedrysek, Mariusz O.; Grelowski, Cezary; Kurkiewicz, Slawomir

2007-01-01

The comprehensive biomarker characteristics from previously undescribed Middle Jurassic clays of Poland are presented. The molecular composition of the organic matter (OM) derived from clays of Aalenian to Callovian age has not changed significantly through time. High relative concentrations of many biomarkers typical for terrestrial material suggest a distinct dominance of OM derived from land plants. Increasing concentrations of C 29 -diaster-13(17)-enes towards the northern part of the basin indicate an increase in terrestrial input. This terrestrial material would have originated from the enhanced transport of organic matter from land situated at the northern bank of the basin, i.e., the Fennoscandian Shield. The organic matter was deposited in an oxic to suboxic environment, as indicated by relatively low concentrations of C 33 -C 35 homohopanes, moderate to high Pr/Ph ratio values, an absence of compounds characteristic for anoxia and water column stratification, such as isorenieratane, aryl isoprenoids and gammacerane, as well as common benthic fauna and burrows. δ 18 O measurements from calcitic rostra of belemnites suggest that the mean value of the Middle Jurassic sea-water temperature of the Polish Basin was 13.1 deg. C. It is suggested that this mirrored the temperature of the lower water column because belemnites are considered here to be necto-benthic. The organic matter from the Middle Jurassic basin of Poland is immature. This is clearly indicated by a large concentration of biomarkers with the biogenic configurations, such as ββ-hopanes, hop-13(18)-enes, hop-17(21)-enes, diasterenes and sterenes. The identification of preserved, unaltered biomolecules like ferruginol, 6,7-dehydroferruginol and sugiol in Protopodocarpoxylon wood samples from these sediments present particularly strong evidence for the presence of immature OM in the Middle Jurassic sediments. Moreover, the occurrence of these polar diterpenoids is important due to the fact that

Intensified Separation of Steviol Glycosides from a Crude Aqueous Extract of Stevia rebaudiana Leaves Using Centrifugal Partition Chromatography.

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Hubert, Jane; Borie, Nicolas; Chollet, Sébastien; Perret, Joël; Barbet-Massin, Claire; Berger, Monique; Daydé, Jean; Renault, Jean-Hugues

2015-11-01

Aqueous extracts of Stevia rebaudiana leaves have been approved since 2008 by the Joint Expert Committee for Food Additives as sugar substitutes in many food and beverages in Western and Far East Asian countries. The compounds responsible for the natural sweetness of Stevia leaves include a diversity of diterpenoid glycosides derived from a steviol skeleton. These steviol glycosides also exhibit a low calorific value as well as promising therapeutic applications, particularly for the treatment of sugar metabolism disturbances. In this work, centrifugal partition chromatography is proposed as an efficient technical alternative to purify steviol glycosides from crude aqueous extracts of Stevia leaves on a multigram scale. Two different commercial instruments, including an ASCPC250® and a FCPE300® made of columns containing 1890 and 231 twin-cells, respectively, were evaluated and compared. All experiments were performed with a polar biphasic solvent system composed of ethyl acetate, n-butanol, and water in a gradient elution mode. When using the 1890 partition cell centrifugal partition chromatography column of 250 mL, 42 mg of stevioside, 68 mg of dulcoside A, and 172 mg of rebaudioside A, three major constituents of the initial extract were obtained from 1 g of the initial mixture at purities of 81%, 83%, and 99%, respectively. The productivity was further improved by intensifying the procedure on the 231 partition cell centrifugal partition chromatography column of 303 mL with the sample mass loading increased up to 5 g, resulting in the recovery of 1.2 g of stevioside, 100 mg of dulcoside A, and 1.1 g of rebaudioside A at purities of 79%, 62%, and 98%, respectively. The structures of the isolated compounds were validated by HPLC-UV, ESI-MS, (1)H, and (13)C NMR analyses. Altogether, the results demonstrate that the column design (i.e., the partition cell number) is an important aspect to be considered for a larger scale centrifugal partition chromatography

Anti-angiogenic effect of triptolide in rheumatoid arthritis by targeting angiogenic cascade.

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Xiangying Kong

Full Text Available Rheumatoid arthritis (RA is characterized by a pre-vascular seriously inflammatory phase, followed by a vascular phase with high increase in vessel growth. Since angiogenesis has been considered as an essential event in perpetuating inflammatory and immune responses, as well as supporting pannus growth and development of RA, inhibition of angiogenesis has been proposed as a novel therapeutic strategy for RA. Triptolide, a diterpenoid triepoxide from Tripterygium wilfordii Hook F, has been extensively used in treatment of RA patients. It also acts as a small molecule inhibitor of tumor angiogenesis in several cancer types. However, it is unclear whether triptolide possesses an anti-angiogenic effect in RA. To address this problem, we constructed collagen-induced arthritis (CIA model using DA rats by the injection of bovine type II collagen. Then, CIA rats were treated with triptolide (11-45 µg/kg/day starting on the day 1 after first immunization. The arthritis scores (P<0.05 and the arthritis incidence (P<0.05 of inflamed joints were both significantly decreased in triptolide-treated CIA rats compared to vehicle CIA rats. More interestingly, doses of 11~45 µg/kg triptolide could markedly reduce the capillaries, small, medium and large vessel density in synovial membrane tissues of inflamed joints (all P<0.05. Moreover, triptolide inhibited matrigel-induced cell adhesion of HFLS-RA and HUVEC. It also disrupted tube formation of HUVEC on matrigel and suppressed the VEGF-induced chemotactic migration of HFLS-RA and HUVEC, respectively. Furthermore, triptolide significantly reduced the expression of angiogenic activators including TNF-α, IL-17, VEGF, VEGFR, Ang-1, Ang-2 and Tie2, as well as suppressed the IL1-β-induced phosphorylated of ERK, p38 and JNK at protein levels. In conclusion, our data suggest for the first time that triptolide may possess anti-angiogenic effect in RA both in vivo and in vitro assay systems by downregulating the

Aconitine-induced Ca2+ overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats

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Sun, Gui-bo; Sun, Hong; Meng, Xiang-bao; Hu, Jin; Zhang, Qiang; Liu, Bo; Wang, Min; Xu, Hui-bo; Sun, Xiao-bo

2014-01-01

Aconitine is a major bioactive diterpenoid alkaloid with high content derived from herbal aconitum plants. Emerging evidence indicates that voltage-dependent Na + channels have pivotal roles in the cardiotoxicity of aconitine. However, no reports are available on the role of Ca 2+ in aconitine poisoning. In this study, we explored the importance of pathological Ca 2+ signaling in aconitine poisoning in vitro and in vivo. We found that Ca 2+ overload lead to accelerated beating rhythm in adult rat ventricular myocytes and caused arrhythmia in conscious freely moving rats. To investigate effects of aconitine on myocardial injury, we performed cytotoxicity assay in neonatal rat ventricular myocytes (NRVMs), as well as measured lactate dehydrogenase level in the culture medium of NRVMs and activities of serum cardiac enzymes in rats. The results showed that aconitine resulted in myocardial injury and reduced NRVMs viability dose-dependently. To confirm the pro-apoptotic effects, we performed flow cytometric detection, cardiac histology, transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. The results showed that aconitine stimulated apoptosis time-dependently. The expression analysis of Ca 2+ handling proteins demonstrated that aconitine promoted Ca 2+ overload through the expression regulation of Ca 2+ handling proteins. The expression analysis of apoptosis-related proteins revealed that pro-apoptotic protein expression was upregulated, and anti-apoptotic protein BCL-2 expression was downregulated. Furthermore, increased phosphorylation of MAPK family members, especially the P-P38/P38 ratio was found in cardiac tissues. Hence, our results suggest that aconitine significantly aggravates Ca 2+ overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38 mitogen-activated protein kinase. - Highlights: • Aconitine-induced Ca 2+ overload causes arrhythmia in rats

Aqueous extract of Rabdosia rubescens leaves: forming nanoparticles, targeting P-selectin, and inhibiting thrombosis

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Wang Y

2015-11-01

Full Text Available Yuji Wang,1 Jingcheng Tang,1 Haimei Zhu,1 Xueyun Jiang,1 Jiawang Liu,1 Wenyun Xu,1 Haiping Ma,1 Qiqi Feng,1 Jianhui Wu,1 Ming Zhao,1,2 Shiqi Peng1 1Beijing Area Major Laboratory of Peptide and Small Molecular Drugs, Engineering Research Center of Endogenous Prophylactic of Ministry of Education of China, Beijing Laboratory of Biomedical Materials, College of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 2Faculty of Biomedical Science and Environmental Biology, Kaohsiung Medical University, Kaohsiung, Taiwan Abstract: The hot water extract of Rabdosia rubescens was traditionally used as an antithrombotic medicine. To explore its antithrombotic utility and mechanism, we carried out a series of in vitro and in vivo assays in this study. In vitro platelet aggregation assay showed that the half maximal inhibitory concentration values of aqueous extract of R. rubescens leaves (AERL inhibiting platelet aggregation induced by thrombin, arachidonic acid, adenosine diphosphate, and platelet-activating factor ranged from 0.12 mg/mL to 1.43 mg/mL. The minimal effective oral dose of AERL inhibiting the rats from forming thrombus was 25 mg/kg. Both in vitro and in vivo actions were correlated with AERL concentration-dependently inhibiting sP-selectin release. In water, AERL formed nanoparticles, and their size depended on the concentration. Docking the five nucleotides, 21 phenolic acids, and four diterpenoids identified by high-performance liquid chromatography–photodiode array detector/(-electrospray ionization-tandem mass spectrometry analysis into the active site of P-selectin, rosmarinic acid was predicted to be the antithrombotic ingredient of AERL. In flow cytometry analysis, 1 µM of rosmarinic acid effectively inhibited sP-selectin release in arachidonic acid-activated platelets. In a rat model, 5 mg/kg of oral rosmarinic acid effectively inhibited thrombosis. Keywords: R. rubescens, s

Aconitine-induced Ca{sup 2+} overload causes arrhythmia and triggers apoptosis through p38 MAPK signaling pathway in rats

Energy Technology Data Exchange (ETDEWEB)

Sun, Gui-bo; Sun, Hong; Meng, Xiang-bao [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China); Hu, Jin; Zhang, Qiang; Liu, Bo [Academy of Chinese Medical Sciences of Jilin Province, Changchun, Jilin 130021 (China); Wang, Min [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China); Xu, Hui-bo, E-mail: xhb_6505@163.com [Academy of Chinese Medical Sciences of Jilin Province, Changchun, Jilin 130021 (China); Sun, Xiao-bo, E-mail: sun_xiaobo163@163.com [Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100193 (China)

2014-08-15

Aconitine is a major bioactive diterpenoid alkaloid with high content derived from herbal aconitum plants. Emerging evidence indicates that voltage-dependent Na{sup +} channels have pivotal roles in the cardiotoxicity of aconitine. However, no reports are available on the role of Ca{sup 2+} in aconitine poisoning. In this study, we explored the importance of pathological Ca{sup 2+} signaling in aconitine poisoning in vitro and in vivo. We found that Ca{sup 2+} overload lead to accelerated beating rhythm in adult rat ventricular myocytes and caused arrhythmia in conscious freely moving rats. To investigate effects of aconitine on myocardial injury, we performed cytotoxicity assay in neonatal rat ventricular myocytes (NRVMs), as well as measured lactate dehydrogenase level in the culture medium of NRVMs and activities of serum cardiac enzymes in rats. The results showed that aconitine resulted in myocardial injury and reduced NRVMs viability dose-dependently. To confirm the pro-apoptotic effects, we performed flow cytometric detection, cardiac histology, transmission electron microscopy and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. The results showed that aconitine stimulated apoptosis time-dependently. The expression analysis of Ca{sup 2+} handling proteins demonstrated that aconitine promoted Ca{sup 2+} overload through the expression regulation of Ca{sup 2+} handling proteins. The expression analysis of apoptosis-related proteins revealed that pro-apoptotic protein expression was upregulated, and anti-apoptotic protein BCL-2 expression was downregulated. Furthermore, increased phosphorylation of MAPK family members, especially the P-P38/P38 ratio was found in cardiac tissues. Hence, our results suggest that aconitine significantly aggravates Ca{sup 2+} overload and causes arrhythmia and finally promotes apoptotic development via phosphorylation of P38 mitogen-activated protein kinase. - Highlights: • Aconitine-induced Ca

A multiscale active structural model of the arterial wall accounting for smooth muscle dynamics.

Science.gov (United States)

Coccarelli, Alberto; Edwards, David Hughes; Aggarwal, Ankush; Nithiarasu, Perumal; Parthimos, Dimitris

2018-02-01

Arterial wall dynamics arise from the synergy of passive mechano-elastic properties of the vascular tissue and the active contractile behaviour of smooth muscle cells (SMCs) that form the media layer of vessels. We have developed a computational framework that incorporates both these components to account for vascular responses to mechanical and pharmacological stimuli. To validate the proposed framework and demonstrate its potential for testing hypotheses on the pathogenesis of vascular disease, we have employed a number of pharmacological probes that modulate the arterial wall contractile machinery by selectively inhibiting a range of intracellular signalling pathways. Experimental probes used on ring segments from the rabbit central ear artery are: phenylephrine, a selective α 1-adrenergic receptor agonist that induces vasoconstriction; cyclopiazonic acid (CPA), a specific inhibitor of sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase; and ryanodine, a diterpenoid that modulates Ca 2+ release from the sarcoplasmic reticulum. These interventions were able to delineate the role of membrane versus intracellular signalling, previously identified as main factors in smooth muscle contraction and the generation of vessel tone. Each SMC was modelled by a system of nonlinear differential equations that account for intracellular ionic signalling, and in particular Ca 2+ dynamics. Cytosolic Ca 2+ concentrations formed the catalytic input to a cross-bridge kinetics model. Contractile output from these cellular components forms the input to the finite-element model of the arterial rings under isometric conditions that reproduces the experimental conditions. The model does not account for the role of the endothelium, as the nitric oxide production was suppressed by the action of L-NAME, and also due to the absence of shear stress on the arterial ring, as the experimental set-up did not involve flow. Simulations generated by the integrated model closely matched experimental

Involvement of P-glycoprotein and multidrug resistance associated protein 1 in the transport of tanshinone IIB, a primary active diterpenoid quinone from the roots of Salvia miltiorrhiza, across the blood-brain barrier.

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Zhou, Zhi-Wei; Chen, Xiao; Liang, Jun; Yu, Xi-Yong; Wen, Jing-Yuan; Zhou, Shu-Feng

2007-08-01

Tanshinone IIB (TSB) is a major constituent of Salvia miltiorrhiza, which is widely used in treatment of cardiovascular and central nervous system (CNS) diseases such as coronary heart disease and stroke. This study aimed to investigate the role of various drug transporters in the brain penetration of TSB using several in vitro and in vivo mouse and rat models. The uptake and efflux of TSB in rat primary microvascular endothelial cells (RBMVECs) were ATP-dependent and significantly altered in the presence of a P-glycoprotein (P-gp) or multidrug resistance associated protein (Mrp1/2) inhibitor. A polarized transport of TSB was found in RBMVEC monolayers with facilitated efflux from the abluminal to luminal side. Addition of a P-gp inhibitor (e.g. verapamil) in both abluminal and luminal sides attenuated the polarized transport. In an in situ rat brain perfusion model, TSB crossed the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier at a greater rate than that for sucrose, and the brain penetration was increased in the presence of a P-gp or Mrp1/2 inhibitor. The brain levels of TSB were only about 30% of that in the plasma and it could be increased to up to 72% of plasma levels when verapamil, quinidine, or probenecid was co-administered in rats. The entry of TSB to CNS increased by 67-97% in rats subjected to middle cerebral artery occlusion or treatment with the neurotoxin, quinolinic acid, compared to normal rats. Furthermore, The brain levels of TSB in mdr1a(-/-) and mrp1(-/-) mice were 28- to 2.6-fold higher than those in the wild-type mice. TSB has limited brain penetration through the BBB due to the contribution of P-gp and to a lesser extent of Mrp1 in rodents. Further studies are needed to confirm whether these corresponding transporters in humans are involved in limiting the penetration of TSB across the BBB and the clinical relevance.

Formulation and pharmacokinetic evaluation of a paclitaxel nanosuspension for intravenous delivery

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Wang YL

2011-07-01

Full Text Available Yonglu Wang1,4, Xueming Li1,2*, Liyao Wang3, Yuanlong Xu1, Xiaodan Cheng1, Ping Wei41College of Pharmacy, Nanjing University of Technology, Nanjing; 2State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing University of Technology, Nanjing; 3College of Life Science, Anhui Agricultural University, Hefei; 4College of Biotechnology and Pharmaceutical Engineering, Nanjing University of Technology, Nanjing, People’s Republic of China *These authors contributed equally to this work.Abstract: Paclitaxel is a diterpenoid isolated from Taxus brevifolia. It is effective for various cancers, especially ovarian and breast cancer. Due to its aqueous insolubility, it is administered dissolved in ethanol and Cremophor® EL (BASF, Ludwigshafen, Germany, which can cause serious allergic reactions. In order to eliminate Cremophor EL, paclitaxel was formulated as a nanosuspension by high-pressure homogenization. The nanosuspension was lyophilized to obtain the dry paclitaxel nanoparticles (average size, 214.4 ± 15.03 nm, which enhanced both the physical and chemical stability of paclitaxel nanoparticles. Paclitaxel dissolution was also enhanced by the nanosuspension. Differential scanning calorimetry showed that the crystallinity of paclitaxel was preserved during the high-pressure homogenization process. The pharmacokinetics and tissue distribution of paclitaxel were compared after intravenous administration of paclitaxel nanosuspension and paclitaxel injection. In rat plasma, paclitaxel nanosuspension exhibited a significantly (P < 0.01 reduced area under the concentration curve (AUC0–∞ (20.343 ± 9.119 µg · h · mL−1 vs 5.196 ± 1.426 µg · h · mL−1, greater clearance (2.050 ± 0.616 L · kg−1 · h−1 vs 0.556 ± 0.190 L · kg−1 · h−1, and shorter elimination half-life (5.646 ± 2.941 vs 3.774 ± 1.352 hours compared with the paclitaxel solution. In contrast, the paclitaxel nanosuspension resulted in a

Fabrication and in vitro/in vivo evaluation of amorphous andrographolide nanosuspensions stabilized by d-α-tocopheryl polyethylene glycol 1000 succinate/sodium lauryl sulfate.

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Qiao, Hongzhi; Chen, Lihua; Rui, Tianqi; Wang, Jingxian; Chen, Ting; Fu, Tingming; Li, Junsong; Di, Liuqing

2017-01-01

Andrographolide (ADG) is a diterpenoid isolated from Andrographis paniculata with a wide spectrum of biological activities, including anti-inflammatory, anticancer and hepatoprotective effects. However, its poor water solubility and efflux by P-glycoprotein have resulted in lower bioavailability. In this study, ADG nanosuspensions (ADG-NS) were prepared using a wet media milling technique followed by freeze drying. d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS), a surfactant that inhibits P-glycoprotein function, and sodium lauryl sulfate were used as surface stabilizers. A Box-Behnken design was used to optimize the nanosuspension preparation. The products of these optimal preparation conditions were amorphous and possessed much faster dissolution in vitro than a coarse powder of ADG. The particle size and redispersibility index of the freeze-dried ADG-NS were 244.6±3.0 nm and 113%±1.14% (n=3), respectively. A short-term stability study indicated that the freeze-dried ADG-NS could remain highly stable as nanosuspensions during the testing period. A test of transport across a Caco-2 cell monolayer revealed that the membrane permeability ( P app ) of ADG-NS was significantly higher than the permeability of the ADG coarse powder or ADG-NS without TPGS ( P <0.01). Compared to the ADG coarse powder, a physical mixture, commercial dripping pills and ADG-NS without TPGS, ADG-NS exhibited significantly higher plasma exposure with significant enhancements in C max and area under the curve of plasma concentration versus time from zero to the last sampling time (AUC 0- t ) ( P <0.01). An evaluation of the anti-inflammatory effect on Carr-induced paw edema demonstrated that the ADG-NS were more effective in reducing the rate of paw swelling, producing a greater increase in the serum levels of nitric oxide (NO), Interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) ( P <0.01) and an increase in superoxide dismutase activity ( P <0.05) compared to the ADG

Fabrication and in vitro/in vivo evaluation of amorphous andrographolide nanosuspensions stabilized by d-α-tocopheryl polyethylene glycol 1000 succinate/sodium lauryl sulfate

Science.gov (United States)

Qiao, Hongzhi; Chen, Lihua; Rui, Tianqi; Wang, Jingxian; Chen, Ting; Fu, Tingming; Li, Junsong; Di, Liuqing

2017-01-01

Andrographolide (ADG) is a diterpenoid isolated from Andrographis paniculata with a wide spectrum of biological activities, including anti-inflammatory, anticancer and hepatoprotective effects. However, its poor water solubility and efflux by P-glycoprotein have resulted in lower bioavailability. In this study, ADG nanosuspensions (ADG-NS) were prepared using a wet media milling technique followed by freeze drying. d-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS), a surfactant that inhibits P-glycoprotein function, and sodium lauryl sulfate were used as surface stabilizers. A Box–Behnken design was used to optimize the nanosuspension preparation. The products of these optimal preparation conditions were amorphous and possessed much faster dissolution in vitro than a coarse powder of ADG. The particle size and redispersibility index of the freeze-dried ADG-NS were 244.6±3.0 nm and 113%±1.14% (n=3), respectively. A short-term stability study indicated that the freeze-dried ADG-NS could remain highly stable as nanosuspensions during the testing period. A test of transport across a Caco-2 cell monolayer revealed that the membrane permeability (Papp) of ADG-NS was significantly higher than the permeability of the ADG coarse powder or ADG-NS without TPGS (P<0.01). Compared to the ADG coarse powder, a physical mixture, commercial dripping pills and ADG-NS without TPGS, ADG-NS exhibited significantly higher plasma exposure with significant enhancements in Cmax and area under the curve of plasma concentration versus time from zero to the last sampling time (AUC0−t) (P<0.01). An evaluation of the anti-inflammatory effect on Carr-induced paw edema demonstrated that the ADG-NS were more effective in reducing the rate of paw swelling, producing a greater increase in the serum levels of nitric oxide (NO), Interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α) (P<0.01) and an increase in superoxide dismutase activity (P<0.05) compared to the ADG coarse powder

The in vitro and in vivo anti-cancer activities of a standardized quassinoids composition from Eurycoma longifolia on LNCaP human prostate cancer cells.

Directory of Open Access Journals (Sweden)

Kind Leng Tong

Full Text Available Quassinoids are a group of diterpenoids found in plants from the Simaroubaceae family. They are also the major bioactive compounds found in Eurycoma longifolia which is commonly used as traditional medicine in South East Asia to treat various ailments including sexual dysfunction and infertility. These uses are attributed to its ability to improve testosterone level in men. Chronic consumption of E. longifolia extracts has been reported to increase testosterone level in men and animal model but its effect on prostate growth remains unknown. Therefore, the present study investigates the effects of a standardized total quassinoids composition (SQ40 containing 40% of the total quassinoids found in E. longifolia on LNCaP human prostate cancer cell line. SQ40 inhibited LNCaP cell growth at IC50 value of 5.97 μg/mL while the IC50 on RWPE-1 human prostate normal cells was 59.26 μg/mL. SQ40 also inhibited 5α-dihydrotestosterone-stimulated growth in LNCaP cells dose-dependently. The inhibitory effect of SQ40 in anchorage-independent growth of LNCaP cells was also demonstrated using soft agar assay. SQ40 suppressed LNCaP cell growth via G0/G1 phase arrest which was accompanied by the down-regulation of CDK4, CDK2, Cyclin D1 and Cyclin D3 and up-regulation of p21Waf1/Cip1 protein levels. SQ40 at higher concentrations or longer treatment duration can cause G2M growth arrest leading to apoptotic cell death as demonstrated by the detection of poly(ADP-ribose polymerase cleavage in LNCaP cells. Moreover, SQ40 also inhibited androgen receptor translocation to nucleus which is important for the transactivation of its target gene, prostate-specific antigen (PSA and resulted in a significant reduction of PSA secretion after the treatment. In addition, intraperitoneal injection of 5 and 10 mg/kg of SQ40 also significantly suppressed the LNCaP tumor growth on mouse xenograft model. Results from the present study suggest that the standardized total quassinoids

Oridonin stabilizes retinoic acid receptor alpha through ROS-activated NF-κB signaling.

Science.gov (United States)

Cao, Yang; Wei, Wei; Zhang, Nan; Yu, Qing; Xu, Wen-Bin; Yu, Wen-Jun; Chen, Guo-Qiang; Wu, Ying-Li; Yan, Hua

2015-04-10

Retinoic acid receptor alpha (RARα) plays an essential role in the regulation of many biological processes, such as hematopoietic cell differentiation, while abnormal RARα function contributes to the pathogenesis of certain diseases including cancers, especially acute promyelocytic leukemia (APL). Recently, oridonin, a natural diterpenoid isolated from Rabdosia rubescens, was demonstrated to regulate RARα by increasing its protein level. However, the underlying molecular mechanism for this action has not been fully elucidated. In the APL cell line, NB4, the effect of oridonin on RARα protein was analyzed by western blot and real-time quantitative RT-PCR analyses. Flow cytometry was performed to detect intracellular levels of reactive oxygen species (ROS). The association between nuclear factor-kappa B (NF-κB) signaling and the effect of oridonin was assessed using specific inhibitors, shRNA gene knockdown, and immunofluorescence assays. In addition, primary leukemia cells were treated with oridonin and analyzed by western blot in this study. RARα possesses transcriptional activity in the presence of its ligand, all-trans retinoic acid (ATRA). Oridonin remarkably stabilized the RARα protein, which retained transcriptional activity. Oridonin also moderately increased intracellular ROS levels, while pretreatment with the ROS scavenger, N-acetyl-l-cysteine (NAC), dramatically abrogated RARα stabilization by oridonin. More intriguingly, direct exposure to low concentrations of H2O2 also increased RARα protein but not mRNA levels, suggesting a role for ROS in oridonin stabilization of RARα protein. Further investigations showed that NAC antagonized oridonin-induced activation of NF-κB signaling, while the NF-κB signaling inhibitor, Bay 11-7082, effectively blocked the oridonin increase in RARα protein levels. In line with this, over-expression of IκΒα (A32/36), a super-repressor form of IκΒα, or NF-κB-p65 knockdown inhibited oridonin or H2O2-induced

Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction

Energy Technology Data Exchange (ETDEWEB)

Gao, Yuanxue; Xu, Xiaojun; Chang, Sai; Wang, Yunjie; Xu, Yazhou; Ran, Siqi [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Huang, Zhangjian [Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, China Pharmaceutical University, Nanjing 210009 (China); Li, Ping [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Li, Jia [National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guo Shoujing Road, Shanghai 201203 (China); Zhang, Luyong [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Saavedra, Juan M. [Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057 (United States); Liao, Hong, E-mail: liaohong56@hotmail.com [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Pang, Tao, E-mail: tpang@cpu.edu.cn [Jiangsu Key Laboratory of Drug Screening, State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Department of Pharmacology and Physiology, Georgetown University Medical Center, Washington, DC 20057 (United States)

2015-12-01

The natural product totarol, a phenolic diterpenoid and a major constituent isolated from the sap of Podocarpus totara, has been reported to have a potent antimicrobial activity. In this study, we determined whether totarol possessed an additional neuroprotective activity in vitro and in vivo. We found that totarol prevented glutamate- and oxygen and glucose deprivation-induced neuronal death in primary rat cerebellar granule neuronal cells and cerebral cortical neurons. Totarol increased Akt and GSK-3β phosphorylation, Nrf2 and heme oxygenase-1 (HO-1) protein expressions and suppressed oxidative stress by increasing GSH and SOD activities. The PI3K/Akt inhibitor LY294002 prevented totarol neuroprotective effect by suppressing the totarol-induced changes in HO-1 expression and the activities of GSH and SOD. The HO-1 inhibitor ZnPPIX also prevented totarol-increased GSH and SOD activities. In a model of acute cerebral ischemic injury in Sprague–Dawley rats, produced by occlusion of the middle cerebral artery for 2 h followed by 22 h or 46 h of reperfusion, totarol significantly reduced infarct volume and improved the neurological deficit. In this model, totarol increased HO-1 expression and the activities of GSH and SOD. These observations suggest that totarol may be a novel activator of the Akt/HO-1 pathway protecting against ischemic stroke through reduction of oxidative stress. - Graphical abstract: It is unknown whether the natural product totarol has neuroprotective effects in vitro and in vivo. This study underscores that totarol prevents neuronal injury in vitro, not only by activating PI3K/Akt pathway, but also via induction of Nrf2, HO-1, GSH and SOD expressions. Totarol also ameliorated acute cerebral ischemic injury in a rat ischemic stroke model. The findings highlight that totarol may be exploited for protecting against ischemic stroke through Akt/HO-1 pathway. - Highlights: • Totarol protects glutamate- and OGD-induced neuronal injury in vitro. �

Exploring the Q-marker of "sweat soaking method" processed radix Wikstroemia indica: Based on the "effect-toxicity-chemicals" study.

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Feng, Guo; Chen, Yun-Long; Li, Wei; Li, Lai-Lai; Wu, Zeng-Guang; Wu, Zi-Jun; Hai, Yue; Zhang, Si-Chao; Zheng, Chuan-Qi; Liu, Chang-Xiao; He, Xin

2018-06-01

Radix Wikstroemia indica (RWI), named "Liao Ge Wang" in Chinese, is a kind of toxic Chinese herbal medicine (CHM) commonly used in Miao nationality of South China. "Sweat soaking method" processed RWI could effectively decrease its toxicity and preserve therapeutic effect. However, the underlying mechanism of processing is still not clear, and the Q-markers database for processed RWI has not been established. Our study is to investigate and establish the quality evaluation system and potential Q-markers based on "effect-toxicity-chemicals" relationship of RWI for quality/safety assessment of "sweat soaking method" processing. The variation of RWI in efficacy and toxicity before and after processing was investigated by pharmacological and toxicological studies. Cytotoxicity test was used to screen the cytotoxicity of components in RWI. The material basis in ethanol extract of raw and processed RWI was studied by UPLC-Q-TOF/MS. And the potential Q-markers were analyzed and predicted according to "effect-toxicity-chemical" relationship. RWI was processed by "sweat soaking method", which could preserve efficacy and reduce toxicity. Raw RWI and processed RWI did not show significant difference on the antinociceptive and anti-inflammatory effect, however, the injury of liver and kidney by processed RWI was much weaker than that by raw RWI. The 20 compounds were identified from the ethanol extract of raw product and processed product of RWI using UPLC-Q-TOF/MS, including daphnoretin, emodin, triumbelletin, dibutyl phthalate, Methyl Paraben, YH-10 + OH and matairesinol, arctigenin, kaempferol and physcion. Furthermore, 3 diterpenoids (YH-10, YH-12 and YH-15) were proved to possess the high toxicity and decreased by 48%, 44% and 65%, respectively, which could be regarded as the potential Q-markers for quality/safety assessment of "sweat soaking method" processed RWI. A Q-marker database of processed RWI by "sweat soaking method" was established according to the results

Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction

International Nuclear Information System (INIS)

Gao, Yuanxue; Xu, Xiaojun; Chang, Sai; Wang, Yunjie; Xu, Yazhou; Ran, Siqi; Huang, Zhangjian; Li, Ping; Li, Jia; Zhang, Luyong; Saavedra, Juan M.; Liao, Hong; Pang, Tao

2015-01-01

The natural product totarol, a phenolic diterpenoid and a major constituent isolated from the sap of Podocarpus totara, has been reported to have a potent antimicrobial activity. In this study, we determined whether totarol possessed an additional neuroprotective activity in vitro and in vivo. We found that totarol prevented glutamate- and oxygen and glucose deprivation-induced neuronal death in primary rat cerebellar granule neuronal cells and cerebral cortical neurons. Totarol increased Akt and GSK-3β phosphorylation, Nrf2 and heme oxygenase-1 (HO-1) protein expressions and suppressed oxidative stress by increasing GSH and SOD activities. The PI3K/Akt inhibitor LY294002 prevented totarol neuroprotective effect by suppressing the totarol-induced changes in HO-1 expression and the activities of GSH and SOD. The HO-1 inhibitor ZnPPIX also prevented totarol-increased GSH and SOD activities. In a model of acute cerebral ischemic injury in Sprague–Dawley rats, produced by occlusion of the middle cerebral artery for 2 h followed by 22 h or 46 h of reperfusion, totarol significantly reduced infarct volume and improved the neurological deficit. In this model, totarol increased HO-1 expression and the activities of GSH and SOD. These observations suggest that totarol may be a novel activator of the Akt/HO-1 pathway protecting against ischemic stroke through reduction of oxidative stress. - Graphical abstract: It is unknown whether the natural product totarol has neuroprotective effects in vitro and in vivo. This study underscores that totarol prevents neuronal injury in vitro, not only by activating PI3K/Akt pathway, but also via induction of Nrf2, HO-1, GSH and SOD expressions. Totarol also ameliorated acute cerebral ischemic injury in a rat ischemic stroke model. The findings highlight that totarol may be exploited for protecting against ischemic stroke through Akt/HO-1 pathway. - Highlights: • Totarol protects glutamate- and OGD-induced neuronal injury in vitro. �

Silicon Utilizing Microbial Bioactivities in the Biosphere

Science.gov (United States)

Sen, M. M.; Das, S.

2012-12-01

potential as a source of biomass for the production of biofuels, due to their high growth rates and high cellular lipid content. Petroleum pollutant degradation can also be done by these organisms-Achanthes minutissima has degradable effects involving petroleum hydocarbons. Stephanopyxis turris a silicon utilizing organism releases a blend of chlorinated C8 hydrocarbons. This adds a fundamentally new pathway to the limited set of halogenating enzymatic activities known from nature. Many silicon utilizing organisms can produce PUFA from saturated fatty acids which ultimately produce many important bioactive chemicals like hormosirene, finaverrene, heptadienal, dietyopterene, cystophorene, decadienal. Trienoic acid, octadiene and many other important agents. Similarly terpenoid biosynthetic pathway is activated by them with formation of diterpenoids, sesterpenoids, triterpenoids and sterols.

Cytotoxicity and cell cycle arrest induced by andrographolide lead to programmed cell death of MDA-MB-231 breast cancer cell line.

Science.gov (United States)

Banerjee, Malabika; Chattopadhyay, Subrata; Choudhuri, Tathagata; Bera, Rammohan; Kumar, Sanjay; Chakraborty, Biswajit; Mukherjee, Samir Kumar

2016-04-16

Breast cancer is considered as an increasing major life-threatening concern among the malignancies encountered globally in females. Traditional therapy is far from satisfactory due to drug resistance and various side effects, thus a search for complementary/alternative medicines from natural sources with lesser side effects is being emphasized. Andrographis paniculata, an oriental, traditional medicinal herb commonly available in Asian countries, has a long history of treating a variety of diseases, such as respiratory infection, fever, bacterial dysentery, diarrhea, inflammation etc. Extracts of this plant showed a wide spectrum of therapeutic effects, such as anti-bacterial, anti-malarial, anti-viral and anti-carcinogenic properties. Andrographolide, a diterpenoid lactone, is the major active component of this plant. This study reports on andrographolide induced apoptosis and its possible mechanism in highly proliferative, invasive breast cancer cells, MDA-MB-231 lacking a functional p53 and estrogen receptor (ER). Furthermore, the pharmacokinetic properties of andrographolide have also been studied in mice following intravenous and oral administration. Andrographolide showed a time- and concentration- dependent inhibitory effect on MDA-MB-231 breast cancer cell proliferation, but the treatment did not affect normal breast epithelial cells, MCF-10A (>80 %). The number of cells in S as well as G2/M phase was increased after 36 h of treatment. Elevated reactive oxygen species (ROS) production with concomitant decrease in Mitochondrial Membrane Potential (MMP) and externalization of phosphatidyl serine were observed. Flow cytometry with Annexin V revealed that the population of apoptotic cells increased with prolonged exposure to andrographolide. Activation of caspase-3 and caspase-9 were also noted. Bax and Apaf-1 expression were notably increased with decreased Bcl-2 and Bcl-xL expression in andrographolide-treated cells. Pharmacokinetic study with andrographolide

Potential treatments to reduce phorbol esters levels in jatropha seed cake for improving the value added product.

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Sadubthummarak, Umapron; Parkpian, Preeda; Ruchirawat, Mathuros; Kongchum, Manoch; Delaune, R D

2013-01-01

Jatropha seed cake contains high amounts of protein and other nutrients, however it has a drawback due to toxic compounds. The aim of this study was to investigate the methods applied to detoxify the main toxin, phorbol esters in jatropha seed cake, to a safe and acceptable level by maintaining the nutritional values. Phorbol esters are tetracyclic diterpenoids-polycyclic compounds that are known as tumor promoters and hence exhibited the toxicity within a broad range of species. Mismanagement of the jatropha waste from jatropha oil industries would lead to contamination of the environment, affecting living organisms and human health through the food chain, so several methods were tested for reducing the toxicity of the seed cake. The results from this investigation showed that heat treatments at either 120°C or 220°C for 1 hour and then mixing with adsorbing bentonite (10%), nanoparticles of zinc oxide (100 μg/g) plus NaHCO3 at 4%, followed by a 4-week incubation period yielded the best final product. The remaining phorbol esters concentration (0.05-0.04 mg/g) from this treatment was less than that reported for the nontoxic jatropha varieties (0.11-0.27 mg/g). Nutritional values of the seed cake after treatment remained at the same levels found in the control group and these values were crude protein (20.47-21.40 + 0.17-0.25%), crude lipid (14.27-14.68 + 0.13-0.14%) and crude fiber (27.33-29.67 + 0.58%). A cytotoxicity test conducted using L929 and normal human dermal fibroblast cell lines confirmed that most of the toxic compounds, especially phorbol esters, were shown as completely eliminated. The results suggested that the detoxification of phorbol esters residues in the jatropha seed cake was possible while it also retained nutritional values. Therefore, the methods to detoxify phorbol esters are necessary to minimize the toxicity of jatropha seed cake. Further, it is essential to reduce the possible environmental impacts that may be generated

Discovery and functional characterization of two diterpene synthases for sclareol biosynthesis in Salvia sclarea (L. and their relevance for perfume manufacture

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Caniard Anne

2012-07-01

Full Text Available Abstract Background Sclareol is a diterpene natural product of high value for the fragrance industry. Its labdane carbon skeleton and its two hydroxyl groups also make it a valued starting material for semisynthesis of numerous commercial substances, including production of Ambrox® and related ambergris substitutes used in the formulation of high end perfumes. Most of the commercially-produced sclareol is derived from cultivated clary sage (Salvia sclarea and extraction of the plant material. In clary sage, sclareol mainly accumulates in essential oil-producing trichomes that densely cover flower calices. Manool also is a minor diterpene of this species and the main diterpene of related Salvia species. Results Based on previous general knowledge of diterpene biosynthesis in angiosperms, and based on mining of our recently published transcriptome database obtained by deep 454-sequencing of cDNA from clary sage calices, we cloned and functionally characterized two new diterpene synthase (diTPS enzymes for the complete biosynthesis of sclareol in clary sage. A class II diTPS (SsLPPS produced labda-13-en-8-ol diphosphate as major product from geranylgeranyl diphosphate (GGPP with some minor quantities of its non-hydroxylated analogue, (9 S, 10 S-copalyl diphosphate. A class I diTPS (SsSS then transformed these intermediates into sclareol and manool, respectively. The production of sclareol was reconstructed in vitro by combining the two recombinant diTPS enzymes with the GGPP starting substrate and in vivo by co-expression of the two proteins in yeast (Saccharomyces cerevisiae. Tobacco-based transient expression assays of green fluorescent protein-fusion constructs revealed that both enzymes possess an N-terminal signal sequence that actively targets SsLPPS and SsSS to the chloroplast, a major site of GGPP and diterpene production in plants. Conclusions SsLPPS and SsSS are two monofunctional diTPSs which, together, produce the diterpenoid

Discovery and functional characterization of two diterpene synthases for sclareol biosynthesis in Salvia sclarea (L.) and their relevance for perfume manufacture.

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Caniard, Anne; Zerbe, Philipp; Legrand, Sylvain; Cohade, Allison; Valot, Nadine; Magnard, Jean-Louis; Bohlmann, Jörg; Legendre, Laurent

2012-07-26

Sclareol is a diterpene natural product of high value for the fragrance industry. Its labdane carbon skeleton and its two hydroxyl groups also make it a valued starting material for semisynthesis of numerous commercial substances, including production of Ambrox® and related ambergris substitutes used in the formulation of high end perfumes. Most of the commercially-produced sclareol is derived from cultivated clary sage (Salvia sclarea) and extraction of the plant material. In clary sage, sclareol mainly accumulates in essential oil-producing trichomes that densely cover flower calices. Manool also is a minor diterpene of this species and the main diterpene of related Salvia species. Based on previous general knowledge of diterpene biosynthesis in angiosperms, and based on mining of our recently published transcriptome database obtained by deep 454-sequencing of cDNA from clary sage calices, we cloned and functionally characterized two new diterpene synthase (diTPS) enzymes for the complete biosynthesis of sclareol in clary sage. A class II diTPS (SsLPPS) produced labda-13-en-8-ol diphosphate as major product from geranylgeranyl diphosphate (GGPP) with some minor quantities of its non-hydroxylated analogue, (9 S, 10 S)-copalyl diphosphate. A class I diTPS (SsSS) then transformed these intermediates into sclareol and manool, respectively. The production of sclareol was reconstructed in vitro by combining the two recombinant diTPS enzymes with the GGPP starting substrate and in vivo by co-expression of the two proteins in yeast (Saccharomyces cerevisiae). Tobacco-based transient expression assays of green fluorescent protein-fusion constructs revealed that both enzymes possess an N-terminal signal sequence that actively targets SsLPPS and SsSS to the chloroplast, a major site of GGPP and diterpene production in plants. SsLPPS and SsSS are two monofunctional diTPSs which, together, produce the diterpenoid specialized metabolite sclareol in a two-step process. They

Comparação de diferentes metodologias para obtenção de cultura de calos de Stevia rebaudiana (Bertoni Bertoni - DOI: 10.4025/actascihealthsci.1090 Comparison of different methodologies for obtaining callus cultures from Stevia rebaudiana (Bertoni Bertoni - DOI: 10.4025/actascihealthsci.1090

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Regina Aparecida Correia Gonçalves

2008-03-01

Full Text Available As folhas de Stevia rebaudiana (Bertoni Bertoni (Asteraceae contêm glicosídeos diterpenóides (GDS, que são cerca de 300 vezes mais doce que a sacarose a 4%. O objetivo deste estudo foi avaliar a formação de calos, a partir de folhas obtidas in vivo e in vitro de S. rebaudiana em dois meios já descritos na literatura: Murashige e Skoog (MS, suplementado com 3 mg L-1 de ácido 2,4-diclorofenóxiacético (2,4-D, e o MS suplementado com 1 mg L-1 de ácido naftalenoacético (ANA e 0,5 mg L-1 de 6-benzilaminopurina 6-BAP e um desenvolvido em nosso laboratório o Woody Plant Medium (WPM, suplementado com 6 mg L-1 de ANA e 4 mg L-1 de cinetina (CIN. Os explantes obtidos in vitro iniciaram a formação de calos um pouco mais rapidamente que os das folhas de plantas advindas da natureza. A utilização dos nutrientes do meio WPM, associada a uma combinação de fitorreguladores adequada, proporcionou velocidade de indução e multiplicação de calos bem maiores que as apresentadas nos meios que empregaram os nutrientes do MS. Novos experimentos serão realizados, depois de alcançada a estabilidade genética dos calos, visando avaliar a capacidade destes em biossintetizar os GDSThe leaves from Stevia rebaudiana (Bertoni Bertoni (Asteraceae contain diterpenoid glycosides (GDS, which are almost 300 times sweeter than sucrose at 4%. The subject of this study was to evaluate the callus-formation from in vivo and in vitro leaves of Stevia rebaudiana in two already described in literature: Murashige and Skoog (MS supplemented with 3 mg L-1 of 2,4-dichlorophenoxyacetic acid (2,4-D; MS supplemented with 1 mg L-1 of naphthaleneacetic acid (NAA and 0.5 mg L-1 of 6-benzylaminopurine (6-BAP and other developed in our laboratory the Woody Plant Medium (WPM with 6 mg L-1 of NAA and 4 mg L-1 of Kinetin (KIN. The explants obtained in vitro initiated callus formation faster than leaves from natural plants. The utilization of WPM nutrients, associated with an

Comparação de diferentes metodologias para obtenção de cultura de calos de Stevia rebaudiana (Bertoni Bertoni = Comparison of different methodologies for obtaining callus cultures from Stevia rebaudiana (Bertoni Bertoni

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Ana Paula Patrão

2007-07-01

Full Text Available As folhas de Stevia rebaudiana (Bertoni Bertoni (Asteraceae contêm glicosídeos diterpenóides (GDS, que são cerca de 300 vezes mais doce que a sacarose a 4%. O objetivo deste estudo foi avaliar a formação de calos, a partir de folhas obtidas in vivo e in vitro de S. rebaudiana em dois meios já descritos na literatura: Murashige e Skoog (MS, suplementado com 3 mg L-1 de ácido 2,4-diclorofenóxiacético (2,4-D, e o MS suplementado com 1 mg L-1 de ácido naftalenoacético (ANA e 0,5 mg L-1 de 6-benzilaminopurina 6-BAP e um desenvolvido em nosso laboratório o Woody Plant Medium (WPM, suplementado com 6 mg L-1 de ANA e 4 mg L-1 de cinetina (CIN. Os explantes obtidos in vitro iniciaram a formação de calos um pouco mais rapidamente que os das folhas de plantas advindas da natureza. A utilização dos nutrientes do meio WPM, associada a uma combinação de fitorreguladores adequada, proporcionou velocidade de indução e multiplicação de calos bem maiores que as apresentadas nos meios que empregaram os nutrientes do MS. Novos experimentos serão realizados, depois de alcançada a estabilidade genética dos calos, visando avaliar a capacidade destes em biossintetizar os GDS.The leaves from Stevia rebaudiana (Bertoni Bertoni (Asteraceae contain diterpenoid glycosides (GDS, which are almost 300 times sweeter than sucrose at 4%. The subject of this study was to evaluate the callus-formation from in vivo and in vitro leaves of Stevia rebaudiana in two already described in literature: Murashige and Skoog (MS supplemented with 3 mg L-1 of 2,4-dichlorophenoxyacetic acid (2,4-D; MS supplemented with 1 mg L-1 of naphthaleneacetic acid (NAA and 0.5 mg L-1 of 6-benzylaminopurine (6-BAP and other developed in our laboratory the Woody Plant Medium (WPM with 6 mg L-1 of NAA and 4 mg L-1 of Kinetin (KIN. The explants obtained in vitro initiated callus formation faster than leaves from natural plants. The utilization of WPM nutrients, associated with an

Fabrication and in vitro/in vivo evaluation of amorphous andrographolide nanosuspensions stabilized by D-α-tocopheryl polyethylene glycol 1000 succinate/sodium lauryl sulfate

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Qiao H

2017-02-01

Full Text Available Hongzhi Qiao,1,2,* Lihua Chen,3,* Tianqi Rui,1,2 Jingxian Wang,1,2 Ting Chen,1,2 Tingming Fu,1,2 Junsong Li,1,2 Liuqing Di1,2 1College of Pharmacy, Nanjing University of Chinese Medicine, 2Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing, 3Key Laboratory of Modern Preparation of Traditional Chinese Medicine, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang, China *These authors contributed equally to this work Abstract: Andrographolide (ADG is a diterpenoid isolated from Andrographis paniculata with a wide spectrum of biological activities, including anti-inflammatory, anticancer and hepatoprotective effects. However, its poor water solubility and efflux by P-glycoprotein have resulted in lower bioavailability. In this study, ADG nanosuspensions (ADG-NS were prepared using a wet media milling technique followed by freeze drying. D-α-Tocopheryl polyethylene glycol 1000 succinate (TPGS, a surfactant that inhibits P-glycoprotein function, and sodium lauryl sulfate were used as surface stabilizers. A Box–Behnken design was used to optimize the nanosuspension preparation. The products of these optimal preparation conditions were amorphous and possessed much faster dissolution in vitro than a coarse powder of ADG. The particle size and redispersibility index of the freeze-dried ADG-NS were 244.6±3.0 nm and 113%±1.14% (n=3, respectively. A short-term stability study indicated that the freeze-dried ADG-NS could remain highly stable as nanosuspensions during the testing period. A test of transport across a Caco-2 cell monolayer revealed that the membrane permeability (Papp of ADG-NS was significantly higher than the permeability of the ADG coarse powder or ADG-NS without TPGS (P<0.01. Compared to the ADG coarse powder, a physical mixture, commercial dripping pills and ADG-NS without TPGS, ADG-NS exhibited significantly higher plasma exposure with significant enhancements in Cmax

(1S*,2S*,5R*,8S*,11S*,14R*,17S*,20R*-14-Methyl-6-methylene-10,16,18-trioxahexacyclo[12.5.1.15,8.01,11.02,8.017,20]henicosane-7,9-dione: natural diterpenoid macrocalyxoformin B

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Hao Shi

2008-01-01

Full Text Available The title compound, C20H24O5, isolated from Rabdosia var. lophanthoides Hara, is built up from six fused rings. Cyclohexane ring A adopts a chair conformation, ring B exists in a screw-boat conformation and ring C adopts a boat conformation; the three five-membered rings D, E and F adopt envelope conformations.

Organic geochemistry and petrology of subsurface Paleocene-Eocene Wilcox and Claiborne Group coal beds, Zavala County, Maverick Basin, Texas, USA

Science.gov (United States)

Hackley, Paul C.; Warwick, Peter D.; Hook, Robert W.; Alimi, Hossein; Mastalerz, Maria; Swanson, Sharon M.

2012-01-01

degradation at the beginning and end of Indio mire development. Fluorescence spectra of sporinite and resinite are consistent and distinctly different from each other, attributed to the presence of a greater proportion of complex asphaltene and polar molecules in resinite. Gas chromatography of resinite-rich coal shows sesquiterpenoid and diterpenoid peaks in the C14–17 range, which are not present in resinite-poor coal. Quantities of extracts suggest bitumen concentration below the threshold for effective source rocks [30–50 mg hydrocarbon/g total organic carbon (HC/g TOC)]. Saturate/aromatic and pristane/phytane (Pr/Ph) ratios are different from values for nearby Tertiary-reservoired crude oil, suggesting that the Indio coals are too immature to source liquid hydrocarbons in the area. However, moderately high HI values (200–400 mg HC/g rock) may suggest some potential for naphthenic–paraffinic oil generation where buried more deeply down stratigraphic/structural dip. Extractable phenols and C20+ alkanes are suggested as possible intermediates for acetate fermentation in microbial methanogenesis which may, however, be limited by poor nutrient supply related to low rainfall and meteoric recharge rate or high local sulfate concentration.

Métodos de secagem e rendimento dos extratos de folhas de Plectranthus barbatus (boldo-da-terra e P. ornatus (boldo-miúdo Methods estimated drying and percentage of extracts in leaves of Plectranthus barbatus (Brazilian bold and P. ornatus (false bold

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T.S. Rodrigues

2011-01-01

Full Text Available Plectranthus sp. pertence à família Lamiaceae e inclui cerca de 300 espécies. Duas delas, P. barbatus (PB e P. ornatus (PO destacam-se pelo interesse medicinal. As principais substâncias encontradas em Plectranthus sp. são os diterpenóides, óleos essenciais e compostos fenólicos. A melhor forma de utilizar as folhas de PB e PO é a fresco; porém, na comercialização há necessidade de recorrer a processos de secagem. Entretanto, isto pode interferir no princípio ativo, desta forma, estudos para determinar o melhor método gravimétrico são importantes. O objetivo deste estudo foi avaliar qual o melhor método de secagem, onde haja maior perda de água possível, e calcular os rendimentos dos extratos visando avaliar se o método gravimétrico interfere na quantidade de extrato produzido. Desta forma, utilizou-se quatro métodos de secagem e após evaporação do solvente, fez-se o cálculo do rendimento dos extratos secos. O percentual de água foi superior em PB e PO (média geral de 90,12±8,22%. Dentre as secagens, em estufa de ventilação forçada (EVF foi mais eficiente em PB (88,87% e em estufa convencional (ECO foi melhor em PO (95,13%. O maior rendimento do extrato seco em PB foi na secagem em camada delgada (CD (20,96%, enquanto que em PO foi ECO (41,34%. Não houve correlação entre o método de secagem e o rendimento de extrato obtido.Plectranthus sp. belongs to the family Lamiaceae and includes about 300 species. Two of them, P. barbatus (PB and P. ornatus (PO, have medicinal interest. The main substances found in Plectranthus sp. are the diterpenoids, essential oils and phenolic compounds. The best way to use the leaves of PB and PO is cool; but for marketing there is a need of resort to drying processes. However, this may interfere on the values of active principle; thus, studies to determine the best gravimetric methods are important. The objective of this study was to evaluate the best method of drying, where there

Composición química de los aceites esenciales de las hojas de Helicteres guazumifolia (Sterculiaceae, Piper tuberculatum (Piperaceae, Scoparia dulcis (Arecaceae y Solanum subinerme (Solanaceae, recolectadas en Sucre, Venezuela

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Gabriel Ordaz

2011-06-01

metabolites in some plant species in order to contribute to their chemotaxonomy. Leaves from Helicteres guazumifolia, Piper tuberculatum, Scoparia dulcis and Solanum subinerme were collected and their essential oils were obtained by means of hydro-distillation. The oil fraction was analyzed and identified by GC/MS. The extraction yields were of 0.004, 0.032, 0.016 and 0.005%, and the oil constituents of 88.00, 89.80, 87.50 and 89.47%, respectively. The principal oils found were: non-terpenoids volatile secondary metabolites (30.28% in H. guazumifolia; sesquiterpenoids (20.82 and 26.09% and oxigen derivated (52.19 and 25.18% in P. tuberculatum and S. dulcis; and oxigen diterpenoids (39.67% in S. subinerme. The diisobuthylphtalate (13.11 % in H. guazumifolia, (--spathulenol (11.37% in P. tuberculatum and trans-phytol (8.29 and 36.00% in S. dulcis and S. subinerme, were the principal constituents in their respective essential oils. The diisooctylphtalate were the essential oil common to all species, but the volatile compounds such as trans-pinane, L-linalool, β-ionone, isophytol, neophytadiene, trans-phytol, dibutylphtalate and methyl hexadecanoate, were only detected in three of these essences. This suggests that these plants may require similar secondary metabolites for their ecological interactions, possibly due to common environmental factors. Rev. Biol. Trop. 59 (2: 585-595. Epub 2011 June 01.

Poisonous Properties of Larkspur (Delphinium spp.

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Olsen, John D.

1990-12-01

Full Text Available Some members of the tribe DelphineaeWarming are useful as forage for grazing cattle or as a source of medicaments for man. However, under certain circumstances their consumption results in poisoning, apparently because of norditerpenoid alkaloids. At least 150 diterpenoid alkaloids have been identified in Delphinium. In this report, factors influencing the alkaloid content and the toxicity of the plant are discussed. Relative change in content of eight alkaloids at four stages of growth of Delphinium occidentale (Watson Watson is reported . The most dominant alkaloids in nine species of Delphinium are listed. Toxicity of eight species was compared al the flower stage of growth using a mouse assay with D. barbeyi; (Huth Huth being about four times more toxic than D. glaucescens Rydb. or D. geyeri Greene and about ten times more toxic than Consolida CV., D. accidentale, or Aconitum columbianum var. columbianum Nutt. (vegetative stage. Stress by aphid infestation or relatively low water availability had little if any effect on toxicity of D. barbeyi and D. occidentale, respectively. From chemical analysis of D. barbeyi tested previously in cattle. the LD₅₀ for a s ingle intraruminal dose of methyllycaconitine was estimated to be less than 6.3 mg/kg body wt.

[ca] Alguns membres de la tribu Delphineae Warming són emprats com a farratge per a bestiar de pastura o com a font de medicaments per a l'home. Tanmateix, sota determinades circumstàncies, el seu consum esdevé intoxicació. aparentment per causa d'alcaloides norditerpènics. Al menys 150 alcaloides diterpènics han estat identificats en Delphinium. En aquest treball es discuteixen els factors que influeixen en el contingut alcalòidic, i, per tant, en la toxicitat de la planla. Es reporten els canvis relatius en el contingut de vuit alcaloides en Quatre estadis de

Avaliação biológica de Foeniculum vulgare (Mill. (Umbelliferae/Apiaceae Biological evaluation of Foeniculum vulgare (Mill. (Umbelliferae/Apiaceae

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O. Araujo R

2013-01-01

territory. It is commonly known as fennel or "erva-doce" and has been used in medicine as analgesic, digestive, carminative, diuretic, expectorant, lactigenous, anti-inflammatory, and antispasmodic agent. Crude ethanolic extract for the verification of biological activities was prepared from seeds bought in the market. For the phytochemical profile, analytical thin-layer chromatography was used; the antimicrobial activity was determined by the paper disc diffusion test and minimum inhibitory concentration (MIC; the antinociceptive activity was verified by the method of abdominal writhings in the animals. The tested microorganisms were multiresistant clinical isolates obtained from the Bacteriology Sector of the Clinical Hospital of Pernambuco. The phytochemical study identified the majority of secondary compounds present in the methanolic fraction of seeds, as follows: triterpenes, flavanoid glycosides, smaller terpenes (monoterpenoids, sesquiterpenoids and diterpenoids and reducing sugars. The obtained results showed that the ethanolic extract had greater activity against Micrococcus spp. (MIC=250µg/mL. Results of the evaluation of the antinociceptive activity demonstrated that only the dosage of 298 mg/Kg, compared to the indomethacin pattern, led to a significant reduction in the number of abdominal writhings in the animals. Further studies will be carried out for the identification and isolation of some secondary compounds, as well as other analgesic protocols.