PI-103 and Quercetin Attenuate PI3K-AKT Signaling Pathway in T- Cell Lymphoma Exposed to Hydrogen Peroxide.

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Akhilendra Kumar Maurya

Full Text Available Phosphatidylinositol 3 kinase-protein kinase B (PI3K-AKT pathway has been considered as major drug target site due to its frequent activation in cancer. AKT regulates the activity of various targets to promote tumorigenesis and metastasis. Accumulation of reactive oxygen species (ROS has been linked to oxidative stress and regulation of signaling pathways for metabolic adaptation of tumor microenvironment. Hydrogen peroxide (H2O2 in this context is used as ROS source for oxidative stress preconditioning. Antioxidants are commonly considered to be beneficial to reduce detrimental effects of ROS and are recommended as dietary supplements. Quercetin, a ubiquitous bioactive flavonoid is a dietary component which has attracted much of interest due to its potential health-promoting effects. Present study is aimed to analyze PI3K-AKT signaling pathway in H2O2 exposed Dalton's lymphoma ascite (DLA cells. Further, regulation of PI3K-AKT pathway by quercetin as well as PI-103, an inhibitor of PI3K was analyzed. Exposure of H2O2 (1mM H2O2 for 30min to DLA cells caused ROS accumulation and resulted in increased phosphorylation of PI3K and downstream proteins PDK1 and AKT (Ser-473 and Thr-308, cell survival factors BAD and ERK1/2, as well as TNFR1. However, level of tumor suppressor PTEN was declined. Both PI-103 & quercetin suppressed the enhanced level of ROS and significantly down-regulated phosphorylation of AKT, PDK1, BAD and level of TNFR1 as well as increased the level of PTEN in H2O2 induced lymphoma cells. The overall result suggests that quercetin and PI3K inhibitor PI-103 attenuate PI3K-AKT pathway in a similar mechanism.

Effect of quercetin on paracetamole-induced liver disjunction in irradiated rats

International Nuclear Information System (INIS)

Hedayat, I.S.

2005-01-01

Nowadays, increasing attention has been given to the role of free radicals generated through oxidation stress. Persons subjected to radiation, such as radiotherapy, consuming analgesic drugs such as paracetamole which accumulates at relatively high concentration in liver, are in need to be investigated to explore the synergetic effects of these stresses. Many radical scavengers, interestingly naturally occurring antioxidants, have been found to be effective in inhibiting the oxidative damage Quercetin, the well known phenolic compound widely present in the plant kingdom, has been investigated for its possible protection effect against gamma irradiation and paracetamole-induced hepatic damage. Data revealed serious effects of oral administration of sublethal dose of paracetamole (500 mg/kg) and/or exposure to 6 Gy whole body gamma irradiation on liver. This damage is reflected by increased hepatic levels of MDA, carbonyl content and ALT activity, associated by decrease in hepatic SOD, catalase and GSH when compared with respective control values. The combination of quercetin with paracetamole and/or gamma irradiation have clearly reduced liver damage. It was noticed that the restoration of peroxides and carbonyls rates has occurred. Quercetin seems to act by activation of the turnover of SOD, catalase and GSH and permitting the capitation of reactive metabolites of paracetamole as well as its ability in quenching free radicals induced by exposure of rats to gamma irradiation, thus improving regeneration in the biological tissues

X-ray attenuation of the liver and kidney in cats considered at varying risk of hepatic lipidosis.

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Lam, Richard; Niessen, Stijn J; Lamb, Christopher R

2014-01-01

X-ray attenuation of the liver has been measured using computed tomography (CT) and reported to decrease in cats with experimentally induced hepatic lipidosis. To assess the clinical utility of this technique, medical records and noncontrast CT scans of a series of cats were retrospectively reviewed. A total of 112 cats met inclusion criteria and were stratified into three hepatic lipidosis risk groups. Group 1 cats were considered low-risk based on no history of inappetence or weight loss, and normal serum chemistry values; Group 2 cats were considered intermediate risk based on weight loss, serum hepatic enzymes above normal limits, or reasonably controlled diabetes mellitus; and Group 3 cats were considered high risk based on poorly controlled diabetes mellitus due to hypersomatotropism. Mean CT attenuation values (Hounsfield units, HU) were measured using regions of interest placed within the liver and cranial pole of the right kidney. Hepatic and renal attenuation were weakly positively correlated with each other (r = 0.2, P = 0.03) and weakly negatively correlated with body weight (r = -0.21, P = 0.05, and r = -0.34, P = 0.001, respectively). Mean (SD) hepatic and renal cortical attenuation values were 70.7 (8.7) HU and 49.6 (9.2) HU for Group 1 cats, 71.4 (7.9) HU and 48.6 (9.1) HU for Group 2, and 68.9 (7.6) HU and 47.6 (7.2) HU for Group 3. There were no significant differences in hepatic or renal attenuation among groups. Findings indicated that CT measures of X-ray attenuation in the liver and kidney may not be accurate predictors of naturally occurring hepatic lipidosis in cats. © 2013 American College of Veterinary Radiology.

Wu-Chia-Pi Solution Attenuates Carbon Tetrachloride-Induced Hepatic Injury through the Antioxidative Abilities of Its Components Acteoside and Quercetin

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Ching-Chiung Wang

2012-12-01

Full Text Available Wu-Chia-Pi medicated wine, composed nine Chinese medicines soaked in 35% alcohol, is widely used in Asia for its health-promoting functions. However, long-term consumption of alcohol could result in liver dysfunction. In this study, Wu-Chia-Pi solution (WCPS and extract (WCPE were prepared by modification of the principals given by the Committee on Chinese Medicine and Pharmacy in Taiwan. The aim of this study was to explore the protective effect of WCPS against carbon tetrachloride (CCl4-induced liver injury and to clarify its active component(s. Antioxidative effects of the test samples were evaluated via MDA inhibition, catalase activity and DPPH-scavenging assays. HPLC was used to analysis the active components. Results showed that WCPS (1 and 5 mL/kg significantly prevented CCl4-induced liver injury without chronic liver toxicity. Referring to the antioxidative activities, WCPE displayed significant MDA inhibitory and DPPH-scavenging activities with IC50 values of 0.91 ± 0.03 and 0.60 ± 0.04 mg/mL, respectively. Catalase activity was also enhanced by treatment of WCPE, acteoside and quercetin. Therefore, we suggest that acteoside and quercetin are the major contributors to the antioxidative and hepatoprotective activities of WCPS, and a possible mechanism could be mediated through reduction of oxidative stress.

Ibuprofen administration attenuates serum TNF-α levels, hepatic glutathione depletion, hepatic apoptosis and mouse mortality after Fas stimulation

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Cazanave, Sophie; Vadrot, Nathalie; Tinel, Marina; Berson, Alain; Letteron, Philippe; Larosche, Isabelle; Descatoire, Veronique; Feldmann, Gerard; Robin, Marie-Anne; Pessayre, Dominique

2008-01-01

Fas stimulation recruits neutrophils and activates macrophages that secrete tumor necrosis factor-α (TNF-α), which aggravates Fas-mediated liver injury. To determine whether nonsteroidal anti-inflammatory drugs modify these processes, we challenged 24-hour-fasted mice with the agonistic Jo2 anti-Fas antibody (4 μg/mouse), and treated the animals 1 h later with saline or ibuprofen (250 mg/kg), a dual cyclooxygenase (COX)-1 and COX-2 inhibitor. Ibuprofen attenuated the Jo2-mediated recruitment/activation of myeloperoxidase-secreting neutrophils/macrophages in the liver, and attenuated the surge in serum TNF-α. Ibuprofen also minimized hepatic glutathione depletion, Bid truncation, caspase activation, outer mitochondrial membrane rupture, hepatocyte apoptosis and the increase in serum alanine aminotransferase (ALT) activity 5 h after Jo2 administration, to finally decrease mouse mortality at later times. The concomitant administration of pentoxifylline (decreasing TNF-α secretion) and infliximab (trapping TNF-α) likewise attenuated the Jo2-mediated increase in TNF-α, the decrease in hepatic glutathione, and the increase in serum ALT activity 5 h after Jo2 administration. The concomitant administration of the COX-1 inhibitor, SC-560 (10 mg/kg) and the COX-2 inhibitor, celecoxib (40 mg/kg) 1 h after Jo2 administration, also decreased liver injury 5 h after Jo2 administration. In contrast, SC-560 (10 mg/kg) or celecoxib (40 or 160 mg/kg) given alone had no significant protective effects. In conclusion, secondary TNF-α secretion plays an important role in Jo2-mediated glutathione depletion and liver injury. The combined inhibition of COX-1 and COX-2 by ibuprofen attenuates TNF-α secretion, glutathione depletion, mitochondrial alterations, hepatic apoptosis and mortality in Jo2-treated fasted mice

Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats.

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Chang, Xue-Ying; Cui, Lei; Wang, Xing-Zhi; Zhang, Lei; Zhu, Dan; Zhou, Xiao-Rong; Hao, Li-Rong

2017-01-01

This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism. Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta ( P chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway.

Quercetin Attenuates Vascular Calcification through Suppressed Oxidative Stress in Adenine-Induced Chronic Renal Failure Rats

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Chang, Xue-ying; Cui, Lei; Wang, Xing-zhi; Zhang, Lei; Zhu, Dan

2017-01-01

Background This study investigated whether quercetin could alleviate vascular calcification in experimental chronic renal failure rats induced by adenine. Methods 32 adult male Wistar rats were randomly divided into 4 groups fed normal diet, normal diet with quercetin supplementation (25 mg/kg·BW/d), 0.75% adenine diet, or adenine diet with quercetin supplementation. All rats were sacrificed after 6 weeks of intervention. Serum renal functions biomarkers and oxidative stress biomarkers were measured and status of vascular calcification in aorta was assessed. Furthermore, the induced nitric oxide synthase (iNOS)/p38 mitogen activated protein kinase (p38MAPK) pathway was determined to explore the potential mechanism. Results Adenine successfully induced renal failure and vascular calcification in rat model. Quercetin supplementation reversed unfavorable changes of phosphorous, uric acid (UA) and creatinine levels, malonaldehyde (MDA) content, and superoxide dismutase (SOD) activity in serum and the increases of calcium and alkaline phosphatase (ALP) activity in the aorta (P chronic renal failure rats, possibly through the modulation of oxidative stress and iNOs/p38MAPK pathway. PMID:28691026

Quercetin suppresses cyclooxygenase-2 expression and angiogenesis through inactivation of P300 signaling.

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Xiangsheng Xiao

Full Text Available Quercetin, a polyphenolic bioflavonoid, possesses multiple pharmacological actions including anti-inflammatory and antitumor properties. However, the precise action mechanisms of quercetin remain unclear. Here, we reported the regulatory actions of quercetin on cyclooxygenase-2 (COX-2, an important mediator in inflammation and tumor promotion, and revealed the underlying mechanisms. Quercetin significantly suppressed COX-2 mRNA and protein expression and prostaglandin (PG E(2 production, as well as COX-2 promoter activation in breast cancer cells. Quercetin also significantly inhibited COX-2-mediated angiogenesis in human endothelial cells in a dose-dependent manner. The in vitro streptavidin-agarose pulldown assay and in vivo chromatin immunoprecipitation assay showed that quercetin considerably inhibited the binding of the transactivators CREB2, C-Jun, C/EBPβ and NF-κB and blocked the recruitment of the coactivator p300 to COX-2 promoter. Moreover, quercetin effectively inhibited p300 histone acetyltransferase (HAT activity, thereby attenuating the p300-mediated acetylation of NF-κB. Treatment of cells with p300 HAT inhibitor roscovitine was as effective as quercetin at inhibiting p300 HAT activity. Addition of quercetin to roscovitine-treated cells did not change the roscovitine-induced inhibition of p300 HAT activity. Conversely, gene delivery of constitutively active p300 significantly reversed the quercetin-mediated inhibition of endogenous HAT activity. These results indicate that quercetin suppresses COX-2 expression by inhibiting the p300 signaling and blocking the binding of multiple transactivators to COX-2 promoter. Our findings therefore reveal a novel mechanism of action of quercetin and suggest a potential use for quercetin in the treatment of COX-2-mediated diseases such as breast cancers.

Attenuation of CCl4-induced hepatic fibrosis in mice by vaccinating against TGF-β1.

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Xiaobao Fan

Full Text Available Transforming growth factor β1 (TGF-β1 is the pivotal pro-fibrogenic cytokine in hepatic fibrosis. Reducing the over-produced expression of TGF-β1 or blocking its signaling pathways is considered to be a promising therapeutic strategy for hepatic fibrosis. In this study, we evaluated the feasibility of attenuating hepatic fibrosis by vaccination against TGF-β1 with TGF-β1 kinoids. Two TGF-β1 kinoid vaccines were prepared by cross-linking TGF-β1-derived polypeptides (TGF-β1(25-[41-65] and TGF-β1(30-[83-112] to keyhole limpet hemocyanin (KLH. Immunization with the two TGF-β1 kinoids efficiently elicited the production of high-levels of TGF-β1-specific antibodies against in BALB/c mice as tested by enzyme-linked immunosorbent assay (ELISA and Western blotting. The antisera neutralized TGF-β1-induced growth-inhibition on mink lung epithelial cells (Mv1Lu and attenuated TGF-β1-induced Smad2/3 phosphorylation, α-SMA, collagen type 1 alpha 2 (COL1A2, plasminogen activator inhibitor-1 (PAI-1 and tissue inhibitor of metalloproteinase-1 (TIMP-1 expression in the rat hepatic stellate cell (HSC line, HSC-T6. Vaccination against TGF-β1 with the kinoids significantly suppressed CCl4-induced collagen deposition and the expression of α-SMA and desmin, attenuated hepatocyte apoptosis and accelerated hepatocyte proliferation in BALB/c mice. These results demonstrated that immunization with the TGF-β1 kinoids efficiently attenuated CCl4-induced hepatic fibrosis and liver injury. Our study suggests that vaccination against TGF-β1 might be developed into a feasible therapeutic approach for the treatment of chronic fibrotic liver diseases.

The quercetin paradox

International Nuclear Information System (INIS)

Boots, Agnes W.; Li, Hui; Schins, Roel P.F.; Duffin, Rodger; Heemskerk, Johan W.M.; Bast, Aalt; Haenen, Guido R.M.M.

2007-01-01

Free radical scavenging antioxidants, such as quercetin, are chemically converted into oxidation products when they protect against free radicals. The main oxidation product of quercetin, however, displays a high reactivity towards thiols, which can lead to the loss of protein function. The quercetin paradox is that in the process of offering protection, quercetin is converted into a potential toxic product. In the present study, this paradox is evaluated using rat lung epithelial (RLE) cells. It was found that quercetin efficiently protects against H 2 O 2 -induced DNA damage in RLE cells, but this damage is swapped for a reduction in GSH level, an increase in LDH leakage as well as an increase of the cytosolic free calcium concentration. To our knowledge, this is the first study that indicates that the quercetin paradox, i.e. the exchange of damage caused by quercetin and its metabolites, also occurs in living lung cells. Following depletion of GSH in the cells by BSO pre-treatment, this quercetin paradox becomes more pronounced, confirming that the formation of thiol reactive quercetin metabolites is involved in the quercetin paradox. The quercetin paradox in living cells implies that the anti-oxidant directs oxidative damage selectively to thiol arylation. Apparently, the potential toxicity of metabolites formed during the actual antioxidant activity of free radical scavengers should be considered in antioxidant supplementation

Partial Portal Vein Arterialization Attenuates Acute Bile Duct Injury Induced by Hepatic Dearterialization in a Rat Model.

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Jiang, Jun; Wei, Jishu; Wu, Junli; Gao, Wentao; Li, Qiang; Jiang, Kuirong; Miao, Yi

2016-01-01

Hepatic infarcts or abscesses occur after hepatic artery interruption. We explored the mechanisms of hepatic deprivation-induced acute liver injury and determine whether partial portal vein arterialization attenuated this injury in rats. Male Sprague-Dawley rats underwent either complete hepatic arterial deprivation or partial portal vein arterialization, or both. Hepatic ischemia was evaluated using biochemical analysis, light microscopy, and transmission electron microscopy. Hepatic ATP levels, the expression of hypoxia- and inflammation-associated genes and proteins, and the expression of bile transporter genes were assessed. Complete dearterialization of the liver induced acute liver injury, as evidenced by the histological changes, significantly increased serum biochemical markers, decreased ATP content, increased expression of hypoxia- and inflammation-associated genes and proteins, and decreased expression of bile transporter genes. These detrimental changes were extenuated but not fully reversed by partial portal vein arterialization, which also attenuated ductular reaction and fibrosis in completely dearterialized rat livers. Collectively, complete hepatic deprivation causes severe liver injury, including bile infarcts and biloma formation. Partial portal vein arterialization seems to protect against acute ischemia-hypoxia-induced liver injury.

Partial Portal Vein Arterialization Attenuates Acute Bile Duct Injury Induced by Hepatic Dearterialization in a Rat Model

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Jun Jiang

2016-01-01

Full Text Available Hepatic infarcts or abscesses occur after hepatic artery interruption. We explored the mechanisms of hepatic deprivation-induced acute liver injury and determine whether partial portal vein arterialization attenuated this injury in rats. Male Sprague-Dawley rats underwent either complete hepatic arterial deprivation or partial portal vein arterialization, or both. Hepatic ischemia was evaluated using biochemical analysis, light microscopy, and transmission electron microscopy. Hepatic ATP levels, the expression of hypoxia- and inflammation-associated genes and proteins, and the expression of bile transporter genes were assessed. Complete dearterialization of the liver induced acute liver injury, as evidenced by the histological changes, significantly increased serum biochemical markers, decreased ATP content, increased expression of hypoxia- and inflammation-associated genes and proteins, and decreased expression of bile transporter genes. These detrimental changes were extenuated but not fully reversed by partial portal vein arterialization, which also attenuated ductular reaction and fibrosis in completely dearterialized rat livers. Collectively, complete hepatic deprivation causes severe liver injury, including bile infarcts and biloma formation. Partial portal vein arterialization seems to protect against acute ischemia-hypoxia-induced liver injury.

Determination of quercetins in onion (Allium cepa) using infrared spectroscopy.

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Lu, Xiaonan; Ross, Carolyn F; Powers, Joseph R; Rasco, Barbara A

2011-06-22

The rapid quantification of flavonoid compounds in onions by attenuated total reflectance (ATR) Fourier transform infrared (FT-IR) spectroscopy combined with multivariate analysis was evaluated as a possible alternative to high-performance liquid chromatography (HPLC) analysis. Quercetin content in onion varieties (yellow, red, and sweet) was quantified using ATR FT-IR (4000 to 400 cm⁻¹) spectroscopy and HPLC methods. Quercetin-3,4'-O-diglucoside (3,4'-Qdg) and quercetin-4'-O-glucoside (4'-Qmg) comprised >80% of the total flavonol content detected in the studied varieties. The quercetin compounds (3,4'-Qdg and 4'-Qmg) and total flavonol conjugates were quantified by HPLC, and results correlated closely with ATR-IR values (R > 0.95). Cross-validated (leave-one-out) partial least-squares regression (PLSR) models successfully predicted concentrations of these quercetins. The standard errors of cross-validation (SECV) of 3,4'-Qdg and 4'-Qmg, total quercetin, and total flavonol contents of onions were 20.43, 21.18, and 21.02 mg/kg fresh weight, respectively. In addition, supervised and unsupervised segregation analyses (principal component analysis, discriminant function analysis, and soft independent modeling of class analogue) were performed to classify onion varieties on the basis of unique infrared spectral features. There was a high degree of segregation (interclass distances > 3.0) for the different types of onion. This study indicated that the IR technique could predict 3,4'-Qdg, 4'-Qmg, total quercetin, and total flavonol contents and has advantages over the traditional HPLC method in providing a valid, efficient, and cost-effective method requiring less sample preparation for the quantification of quercetins in onion.

Quercetin prevents chronic unpredictable stress induced behavioral dysfunction in mice by alleviating hippocampal oxidative and inflammatory stress.

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Mehta, Vineet; Parashar, Arun; Udayabanu, Malairaman

2017-03-15

It is now evident that chronic stress is associated with anxiety, depression and cognitive dysfunction and very few studies have focused on identifying possible methods to prevent these stress-induced disorders. Previously, we identified abundance of quercetin in Urtica dioica extract, which efficiently attenuated stress related complications. Therefore, current study was designed to investigate the effect of quercetin on chronic unpredicted stress (CUS) induced behavioral dysfunction, oxidative stress and neuroinflammation in the mouse hippocampus. Animals were subjected to unpredicted stress for 21days, during which 30mg/kg quercetin was orally administered to them. Effect of CUS and quercetin treatment on animal behavior was assessed between day 22-26. Afterward, the hippocampus was processed to evaluate neuronal damage, oxidative and inflammatory stress. Results revealed that stressed animals were highly anxious (Elevated Plus Maze and Open Field), showed depressive-like behavior (sucrose preference task), performed poorly in short-term and long-term associative memory task (passive avoidance step-through task) and displayed reduced locomotion (open field). Quercetin alleviated behavioral dysfunction in chronically stressed animals. Compared to CUS, quercetin treatment significantly reduced anxiety, attenuated depression, improved cognitive dysfunction and normalized locomotor activity. Further, CUS elevated the levels of oxidative stress markers (TBARS, nitric oxide), lowered antioxidants (total thiol, catalase), enhanced expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β and COX-2) in the hippocampus and damaged hippocampal neurons. Quercetin treatment significantly lowered oxidative and inflammatory stress and prevented neural damage. In conclusion, quercetin can efficiently prevent stress induced neurological complications by rescuing brain from oxidative and inflammatory stress. Copyright © 2017 Elsevier Inc. All rights reserved.

Selective inhibition of iNOS attenuates trauma-hemorrhage/resuscitation-induced hepatic injury.

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Kan, Wen-Hong; Hsu, Jun-Te; Schwacha, Martin G; Choudhry, Mashkoor A; Raju, Raghavan; Bland, Kirby I; Chaudry, Irshad H

2008-10-01

Although trauma-hemorrhage produces tissue hypoxia, systemic inflammatory response and organ dysfunction, the mechanisms responsible for these alterations are not clear. Using a potent selective inducible nitric oxide (NO) synthase inhibitor, N-[3-(aminomethyl) benzyl]acetamidine (1400W), and a nonselective NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), we investigated whether inducible NO synthase plays any role in producing hepatic injury, inflammation, and changes of protein expression following trauma-hemorrhage. To investigate this, male Sprague-Dawley rats were subjected to midline laparotomy and hemorrhagic shock (mean blood pressure 35-40 mmHg for approximately 90 min) followed by fluid resuscitation. Animals were treated with either vehicle (DMSO) or 1400W (10 mg/kg body wt ip), or L-NAME (30 mg/kg iv), 30 min before resuscitation and killed 2 h after resuscitation. Trauma-hemorrhage/resuscitation induced a marked hypotension and increase in markers of hepatic injury (i.e., plasma alpha-glutathione S-transferase, tissue myeloperoxidase activity, and nitrotyrosine formation). Hepatic expression of iNOS, hypoxia-inducible factor-1alpha, ICAM-1, IL-6, TNF-alpha, and neutrophil chemoattractant (cytokine-induced neutrophil chemoattractant-1 and macrophage inflammatory protein-2) protein levels were also markedly increased following trauma-hemorrhage/resuscitation. Administration of the iNOS inhibitor 1400W significantly attenuated hypotension and expression of these mediators of hepatic injury induced by trauma-hemorrhage/resuscitation. However, administration of L-NAME could not attenuate hepatic dysfunction and tissue injury mediated by trauma-hemorrhage, although it improved mean blood pressure as did 1400W. These results indicate that increased expression of iNOS following trauma-hemorrhage plays an important role in the induction of hepatic damage under such conditions.

The beneficial effect of the flavonoid quercetin on behavioral changes in hemi-Parkinsonian rats

OpenAIRE

Mehdi Mehdizadeh; Mohammad Taghi Joghataei; Maliheh Nobakht; Roya Aryanpour

2010-01-01

  Abstract   Introduction: A large body of experimental evidence supports a role for oxidative stress as a mediator of nerve cell death in Parkinson's disease (PD). Flavonoids like quercetin have been reported to prevent neuronal degeneration caused by increased oxidative burden, therefore, this study examined whether quercetin administration at a high dose would attenuate behavioral abnormalities in experimental model of PD in rat.   Methods: For this purpose, unilateral intrastriatal 6-hydr...

Transient hepatic attenuation differences in neonates

International Nuclear Information System (INIS)

Towbin, Alexander J.; Fleck, Robert; Ying, Jun

2009-01-01

A transient hepatic attenuation difference (THAD) is a hepatic perfusion anomaly seen on contrast-enhanced CT scans caused by an alteration in the dual blood supply of the liver. Although THADs have been described in adolescents and adults, they have not previously been described in neonates. We describe the appearance and evaluate the frequency of THADs in neonates ≤1 month of age compared to other infants younger than 2 years. A retrospective study was performed looking at all CT angiograms from 2000 to 2007 in infants <2 years of age. The incidence of THADs was compared among four age groups. Significance was determined using a logistic regression model. The study included 128 CT angiograms. A THAD was seen in 9/26 infants <1 month of age, in 3/50 infants 1 to 6 months of age, in 1/23 infants 6 months to 1 year of age, and in 1/29 infants 1 to 2 years of age. A THAD was found significantly more frequently in infants <1 month of age than in the older age groups (P<0.05). THADs are benign entities that can be seen normally in the neonatal age group. When the characteristic appearance is seen on CT, no further imaging is needed. (orig.)

Systemic Lidocaine Does Not Attenuate Hepatic Dysfunction After Liver Surgery in Rats

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de Graaf, Wilmar; Diepenhorst, Gwen M. P.; Herroeder, Susanne; Erdogan, Deha; Hollmann, Markus W.; van Gulik, Thomas M.

2012-01-01

BACKGROUND: Lidocaine has been shown to attenuate ischemia-reperfusion (I/R) injury in the heart, lung, and brain, potentially due to modulation of inflammatory responses and apoptotic signaling pathways. Because hepatic I/R injury after liver surgery still poses a significant risk for postoperative

New Approaches to Attenuated Hepatitis a Vaccine Development: Cloning and Sequencing of Cell-Culture Adapted Viral cDNA.

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1987-10-13

after multiple passages in vivo and in vitro. J. Gen. Virol. 67, 1741- 1744. Sabin , A.B. (1985). Oral poliovirus vaccine : history of its development...IN (N NEW APPROACHES TO ATTENUATED HEPATITIS A VACCINE DEVELOPMENT: Q) CLONING AND SEQUENCING OF CELL-CULTURE ADAPTED VIRAL cDNA I ANNUAL REPORT...6ll02Bsl0 A 055 11. TITLE (Include Security Classification) New Approaches to Attenuated Hepatitis A Vaccine Development: Cloning and Sequencing of Cell

Acetonic and Methanolic Extracts of Heterotheca inuloides, and Quercetin, Decrease CCl4-Oxidative Stress in Several Rat Tissues

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Coballase-Urrutia, Elvia; Pedraza-Chaverri, José; Cárdenas-Rodríguez, Noemí; Huerta-Gertrudis, Bernardino; García-Cruz, Mercedes Edna; Montesinos-Correa, Hortencia; Sánchez-González, Dolores Javier; Camacho-Carranza, Rafael; Espinosa-Aguirre, Jesús Javier

2013-01-01

The present study was designed to test the hypothesis that the acetonic and methanolic extracts of H. inuloides prevent carbon tetrachloride-(CCl4) induced oxidative stress in vital tissues. Pretreatment with both H. inuloides extracts or quercetin attenuated the increase in serum activity of alkaline phosphatase (ALP), total bilirubin (BB), creatinine (CRE), and creatine kinase (CK), and impeded the decrease of γ-globulin (γ-GLOB) and albumin (ALB) observed in CCl4-induced tissue injury. The protective effect was confirmed by histological analysis with hematoxylin-eosin and periodic acid/Schiff's reagent. Level of lipid peroxidation was higher in the organs of rats exposed to CCl4 than in those of the animals treated with Heterohteca extracts or quercetin, and these showed levels similar to the untreated group. Pretreatment of animals with either of the extracts or quercetin also prevented the increase of 4-hydroxynonenal and 3-nitrotyrosine. Pretreatment with the plant extracts or quercetin attenuated CCl4 toxic effects on the activity of several antioxidant enzymes. The present results strongly suggest that the chemopreventive effect of the extracts used and quercetin, against CCl4 toxicity, is associated with their antioxidant properties and corroborated previous results obtained in liver tissue. PMID:23365610

A review of immunogenicity and tolerability of live attenuated Hepatitis A vaccine in children

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Rao, Sameer; Mao, J. S.; Motlekar, Salman; Fangcheng, Zhuang; Kadhe, Ganesh

2016-01-01

ABSTRACT Changing epidemiology of Hepatitis A virus (HAV) has led to an increased susceptibility of adolescents and adults to the infection. Vaccination can remarkably reduce the incidence and associated morbidity of HAV infection. This review is focused on the safety and efficacy of H2 strain derived live attenuated Hepatitis A vaccine. We found the vaccine to be highly immunogenic with minimal or negligible safety issues. Moreover, a single dose of live attenuated vaccine persists a long term immune response and can be a preferred option for developing countries. In 2014, Indian Academy of Paediatrics (IAP) also updated their recommendations for H2 vaccine as a single dose as against the previous 2 dose schedule. A focused approach to include the vaccine in national immunization program should be explored. PMID:27532370

Quercetin- A Flavanoid

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Aarti Sharma

2010-01-01

Full Text Available Quercetin is the most abundant form of the flavonoids. It gain attention when quercetin was found to cause DNA mutations which can then contribute to cancer treatment. Quercitrin is present in the bark of Quercus tinctoria (American Oak. It is generally available in natural sources. In this article we have tried to simplify the basic un-derstanding of quercetin, its synthesis, structure activity relationship, chemical reaction etc. It will help students to understand basic concept and chemistry of quercetin.

Transient hepatic attenuation difference of lobar or segmental distribution detected by dynamic computed tomography

International Nuclear Information System (INIS)

Itai, Y.; Moss, A.A.; Goldberg, H.I.

1982-01-01

Dynamic computed tomography of hepatic tumors revealed a transient attenuation difference of the liver in a lobar or segmental distribution in three cases. The difference was most prominent during the hepatogram phase. It was attributed to siphonage of arterial blood by hepatic tumors in two cases, while an increase of arterial flow induced by portal vein occlusion was inferred in the other case. Results indicate dynamic computed tomography will be usful in analysis of geometrical hemodynamics

Effect of different exposed lights on quercetin and quercetin glucoside content in onion (Allium cepa L.)

OpenAIRE

Ko, Eun Young; Nile, Shivraj Hariram; Sharma, Kavita; Li, Guan Hao; Park, Se Won

2014-01-01

Quercetin and quercetin glucosides are the major flavonols present in onion (Allium cepa L.) and are predominantly present as quercetin, quercetin-3,4′-diglucoside and quercetin-4′-glucoside. Effect of different light wavelengths on onion after harvest and storage, with fluorescent, blue, red and ultra violet light influenced the quercetin and quercetin glucosides profile. In a peeled onion, all the light treatments elevated quercetin content in bulb. Among them, particularly fluorescent ligh...

Quercetin-6-C-β-D-glucopyranoside, natural analog of quercetin exhibits anti-prostate cancer activity by inhibiting Akt-mTOR pathway via aryl hydrocarbon receptor.

Science.gov (United States)

Hamidullah; Kumar, Rajeev; Saini, Karan Singh; Kumar, Amit; Kumar, Sudhir; Ramakrishna, E; Maurya, Rakesh; Konwar, Rituraj; Chattopadhyay, Naibedya

2015-12-01

Pre-clinical studies suggest mitigating effect of dietary flavonoid quercetin against cancer and other diseases. However, quercetin suffers from poor metabolic stability, which appears to offset its pharmacological efficacy. Recently, we isolated quercetin-6-C-β-D-glucopyranoside (QCG) from Ulmus wallichiana planchon that has greater stability profile over quercetin. In the present study, the cytotoxic and apoptotic effects of QCG on prostate cancer cells were assessed. QCG inhibited prostate cancer cell proliferation by arresting cells at G0/G1 phase of cell cycle and induces apoptosis as evident from cytochrome c release, cleavage of caspase 3 and poly (ADP-ribose) polymerase. Mechanistic studies revealed that QCG inhibited reactive oxygen species (ROS) generation and Akt/mTOR cell survival pathways. Aryl hydrocarbon receptor (AhR) was a critical mediator of QCG action as knockdown of AhR attenuated QCG-induced cell cycle arrest, apoptosis and inhibition of Akt/mTOR pathway in prostate cancer cells. Taken together, our results suggest that QCG exhibits anti-cancer activity against prostate cancer cells via AhR-mediated down regulation of Akt/mTOR pathway in PC-3 cells. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Intracellular ROS protection efficiency and free radical-scavenging activity of quercetin and quercetin-encapsulated liposomes.

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Rezaei-Sadabady, Rogaie; Eidi, Akram; Zarghami, Nosratollah; Barzegar, Abolfazl

2016-01-01

Quercetin (3,5,7,3',4'-pentahydroxyflavone) is a natural bio-flavonoid originating from fruits, vegetables, seeds, berries, and tea. The antioxidant activity of quercetin and its protective effects against cardiovascular disorders, anti-cancer, anti-inflammatory, and anti-viral activities have been extensively documented; however, the clinical request of quercetin in cancer treatment is significantly limited due to its very poor delivery features. In order to increase the hydrophilicity and drug delivery capability, we encapsulated quercetin into liposomes. Our data indicated that liposomal quercetin can significantly improve the solubility and bioavailability of quercetin and can be used as an effective antioxidant for ROS protection within the polar cytoplasm, and the nano-sized quercetin encapsulated by liposomes enhanced the cellular uptake (cancer cell human MCF_7). Quercetin has many pharmaceutical applications, many of which arise from its potent antioxidant properties. The present research examined the antioxidant activities of quercetin in polar solvents by a comparative study using reduction of ferric iron in aqueous medium, intracellular ROS/toxicity assays, and reducing DPPH assays. Cell viability and ROS assays demonstrated that quercetin was able to penetrate into the polar medium inside the cells and to protect them against the highly toxic and deadly belongings of cumene hydroperoxide. The purpose of this study was to determine whether a liposomal formulation of quercetin can suggestively improve its solubility and bioavailability and can be a possible request in the treatment of tumor. The authors encapsulated quercetin in a liposomal delivery system. They studied the in vitro effects of this compound on proliferation using human MCF-7 carcinoma cells. The activity of liposomal quercetin was equal to or better than that of free quercetin at equimolar concentrations. Our data indicated that liposomal quercetin can significantly improve the

CTRP3 attenuates diet-induced hepatic steatosis by regulating triglyceride metabolism.

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Peterson, Jonathan M; Seldin, Marcus M; Wei, Zhikui; Aja, Susan; Wong, G William

2013-08-01

CTRP3 is a secreted plasma protein of the C1q family that helps regulate hepatic gluconeogenesis and is downregulated in a diet-induced obese state. However, the role of CTRP3 in regulating lipid metabolism has not been established. Here, we used a transgenic mouse model to address the potential function of CTRP3 in ameliorating high-fat diet-induced metabolic stress. Both transgenic and wild-type mice fed a high-fat diet showed similar body weight gain, food intake, and energy expenditure. Despite similar adiposity to wild-type mice upon diet-induced obesity (DIO), CTRP3 transgenic mice were strikingly resistant to the development of hepatic steatosis, had reduced serum TNF-α levels, and demonstrated a modest improvement in systemic insulin sensitivity. Additionally, reduced hepatic triglyceride levels were due to decreased expression of enzymes (GPAT, AGPAT, and DGAT) involved in triglyceride synthesis. Importantly, short-term daily administration of recombinant CTRP3 to DIO mice for 5 days was sufficient to improve the fatty liver phenotype, evident as reduced hepatic triglyceride content and expression of triglyceride synthesis genes. Consistent with a direct effect on liver cells, recombinant CTRP3 treatment reduced fatty acid synthesis and neutral lipid accumulation in cultured rat H4IIE hepatocytes. Together, these results establish a novel role for CTRP3 hormone in regulating hepatic lipid metabolism and highlight its protective function and therapeutic potential in attenuating hepatic steatosis.

Comparison of immune persistence among inactivated and live attenuated hepatitis a vaccines 2 years after a single dose

Science.gov (United States)

Zhang, Xiaoshu; An, Jing; Tu, Aixia; Liang, Xuefeng; Cui, Fuqiang; Zheng, Hui; Tang, Yu; Liu, Jianfeng; Wang, Xuxia; Zhang, Ningjing; Li, Hui

2016-01-01

ABSTRACT Objective: Compare immune persistence from one dose of each of 3 different hepatitis A vaccines when given to school-age children: a domestic, live attenuated hepatitis A vaccine (H2 vaccine); a domestic inactivated hepatitis A vaccine (Healive®); and an imported, inactivated hepatitis A vaccine (Havrix®),.Methods: School-age children were randomized into 1 of 4 groups to receive a single dose of a vaccine: H2 vaccine, Healive®, Havrix®, or hepatitis B vaccine [control]. Serum samples were collected 12 and 24 months after vaccination for measurement of anti-HAV IgG using microparticle enzyme immunoassay. Seropositivity was defined as ≥ 20 mUI/ml. We compared groups on seropositivity and geometric mean concentration (GMC). Results: Seropositive rates for the H2, Healive®, Havrix®, and control groups were 64%, 94.4%, 73%, and 1.0%, respectively, 12-months post-vaccination; and 63%, 95.6%, 72%, and 1.0%, respectively 24-months post-vaccination. Seropositivity was greater for Healive® than for H2 and Havrix® at 12 months (p-values a single dose of inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine. PMID:27494260

Opuntia ficus indica (nopal) attenuates hepatic steatosis and oxidative stress in obese Zucker (fa/fa) rats.

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Morán-Ramos, Sofía; Avila-Nava, Azalia; Tovar, Armando R; Pedraza-Chaverri, José; López-Romero, Patricia; Torres, Nimbe

2012-11-01

Nonalcoholic fatty liver disease (NAFLD) is associated with multiple factors such as obesity, insulin resistance, and oxidative stress. Nopal, a cactus plant widely consumed in the Mexican diet, is considered a functional food because of its antioxidant activity and ability to improve biomarkers of metabolic syndrome. The aim of this study was to assess the effect of nopal consumption on the development of hepatic steatosis and hepatic oxidative stress and on the regulation of genes involved in hepatic lipid metabolism. Obese Zucker (fa/fa) rats were fed a control diet or a diet containing 4% nopal for 7 wk. Rats fed the nopal-containing diet had ∼50% lower hepatic TG than the control group as well as a reduction in hepatomegaly and biomarkers of hepatocyte injury such as alanine and aspartate aminotransferases. Attenuation of hepatic steatosis by nopal consumption was accompanied by a higher serum concentration of adiponectin and a greater abundance of mRNA for genes involved in lipid oxidation and lipid export and production of carnitine palmitoyltransferase-1 and microsomal TG transfer proteins in liver. Hepatic reactive oxygen species and lipid peroxidation biomarkers were significantly lower in rats fed nopal compared with the control rats. Furthermore, rats fed the nopal diet had a lower postprandial serum insulin concentration and a greater liver phosphorylated protein kinase B (pAKT):AKT ratio in the postprandial state. This study suggests that nopal consumption attenuates hepatic steatosis by increasing fatty acid oxidation and VLDL synthesis, decreasing oxidative stress, and improving liver insulin signaling in obese Zucker (fa/fa) rats.

Effect of different exposed lights on quercetin and quercetin glucoside content in onion (Allium cepa L.).

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Ko, Eun Young; Nile, Shivraj Hariram; Sharma, Kavita; Li, Guan Hao; Park, Se Won

2015-07-01

Quercetin and quercetin glucosides are the major flavonols present in onion (Allium cepa L.) and are predominantly present as quercetin, quercetin-3,4'-diglucoside and quercetin-4'-glucoside. Effect of different light wavelengths on onion after harvest and storage, with fluorescent, blue, red and ultra violet light influenced the quercetin and quercetin glucosides profile. In a peeled onion, all the light treatments elevated quercetin content in bulb. Among them, particularly fluorescent light effect was more eminent which stimulates the maximum synthesis of quercetin in onion. In case of whole onion bulb, skin and pulp showed different responses to light treatment, respectively. The pulp had the highest quercetin glucosides under blue light, whereas the lowest under fluorescent light. Onion skin showed nearly opposite pattern as compared to the pulp. In particular, light treatment proved to be a better way to increase the level of quercetin content in onions which might be utilized for industrial production of bioactive compounds from onion and onion waste products.

Opuntia ficus-indica seed attenuates hepatic steatosis and promotes M2 macrophage polarization in high-fat diet-fed mice.

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Kang, Jung-Woo; Shin, Jun-Kyu; Koh, Eun-Ji; Ryu, Hyojeong; Kim, Hyoung Ja; Lee, Sun-Mee

2016-04-01

Opuntia ficus-indica (L.) is a popular edible plant that possesses considerable nutritional value and exhibits diverse biological actions including anti-inflammatory and antidiabetic activities. In this study, we hypothesized that DWJ504, an extract of O ficus-indica seed, would ameliorate hepatic steatosis and inflammation by regulating hepatic de novo lipogenesis and macrophage polarization against experimental nonalcoholic steatohepatitis. Mice were fed a normal diet or a high-fat diet (HFD) for 10 weeks. DWJ504 (250, 500, and 1000 mg/kg) or vehicle (0.5% carboxymethyl cellulose) were orally administered for the last 4 weeks of the 10-week HFD feeding period. DWJ504 treatment remarkably attenuated HFD-induced increases in hepatic lipid content and hepatocellular damage. DWJ504 attenuated increases in sterol regulatory element-binding protein 1 and carbohydrate-responsive element-binding protein expression and a decrease in carnitine palmitoyltransferase 1A. Although DWJ504 augmented peroxisome proliferator-activated receptor α protein expression, it attenuated peroxisome proliferator-activated receptor γ expression. Moreover, DWJ504 promoted hepatic M2 macrophage polarization as indicated by attenuation of the M1 marker genes and enhancement of M2 marker genes. Finally, DWJ504 attenuated expression of toll-like receptor 4, nuclear factor κB, tumor necrosis factor α, interleukin 6, TIR-domain-containing adapter-inducing interferon β, and interferon β levels. Our results demonstrate that DWJ504 prevented intrahepatic lipid accumulation, induced M2 macrophage polarization, and suppressed the toll-like receptor 4-mediated inflammatory signaling pathway. Thus, DWJ504 has therapeutic potential in the prevention of nonalcoholic fatty liver disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Osthole attenuates hepatic injury in a rodent model of trauma-hemorrhage.

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Yu, Huang-Ping; Liu, Fu-Chao; Tsai, Yung-Fong; Hwang, Tsong-Long

2013-01-01

Recent evidences show that osthole possesses anti-inflammatory properties and protective effects following shock-like states, but the mechanism of these effects remains unknown. The p38 mitogen-activated protein kinase (p38 MAPK) pathway exerts anti-inflammatory effects in injury. The aim of this study was to investigate whether p38 MAPK plays any role in the osthole-mediated attenuation of hepatic injury after trauma-hemorrhage. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35-40 mmHg for 90 minutes), followed by fluid resuscitation. During resuscitation, a single dose of osthole (3 mg/kg, intravenously) with and without a p38 MAPK inhibitor SB-203580 (2 mg/kg, intravenously), SB-203580 or vehicle was administered. Plasma alanine aminotransferase (ALT) with aspartate aminotransferase (AST) concentrations and various hepatic parameters were measured (n = 8 rats/group) at 24 hours after resuscitation. The results showed that trauma-hemorrhage increased hepatic myeloperoxidase activity, intercellular adhesion molecule-1 and interleukin-6 levels, and plasma ALT and AST concentrations. These parameters were significantly improved in the osthole-treated rats subjected to trauma-hemorrhage. Osthole treatment also increased hepatic phospho-p38 MAPK expression compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of SB-203580 with osthole abolished the osthole-induced beneficial effects on the above parameters and hepatic injury. These results suggest that the protective effect of osthole administration on alleviation of hepatic injury after trauma-hemorrhage, which is, at least in part, through p38 MAPK-dependent pathway.

Jiao Tai Wan Attenuates Hepatic Lipid Accumulation in Type 2 Diabetes Mellitus

Directory of Open Access Journals (Sweden)

Zhaoyi Huang

2013-01-01

Full Text Available Jiao Tai Wan (JTW, a Chinese herbal formula containing Rhizoma Coptidis and Cortex Cinnamomi, has been used for diabetic treatment for many years. The aim of this study was to determine the main components in JTW and to investigate the effects of JTW on hepatic lipid accumulation in diabetic rats and humans. JTW extract was prepared and the main components were assayed by HPLC. An animal model of diabetes mellitus was established and JTW was administered intragastrically. In the clinical study, diabetic patients with poor glycemic control were treated with JTW. Blood glucose and lipid parameters, liver histology, hepatic triglyceride content and lipogenic gene expression were examined. Our data demonstrated that JTW significantly improved hyperglycemia, hyperlipidemia and hepatic lipid accumulation in diabetic rats. This was accompanied by the down-regulation of acetyl coenzyme A carboxylase (ACC and fatty acid synthase (FAS protein expressions, and the up-regulation of AMP-activated protein kinase (AMPK and phosphorylated-ACC (pACC protein expressions in the liver tissues. Diabetic patients also exhibited decreases in their hepatic triglyceride content. The results suggest that JTW attenuates hepatic lipid accumulation in diabetic rats and humans. These beneficial effects are possibly associated with the inhibition of lipogenic gene expression in the liver.

Quercetin enhances hypoxia-mediated apoptosis via direct inhibition of AMPK activity in HCT116 colon cancer.

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Kim, Hak-Su; Wannatung, Tirawat; Lee, Sooho; Yang, Woo Kyeom; Chung, Sung Hyun; Lim, Jong-Seok; Choe, Wonchae; Kang, Insug; Kim, Sung-Soo; Ha, Joohun

2012-09-01

Tumor hypoxia is considered the best validated target in clinical oncology because of its significant contribution to chemotherapy failure and drug resistance. As an approach to target hypoxia, we assessed the potential of quercetin, a flavonoid widely distributed in plants, as a anticancer agent under hypoxic conditions and examined its pharmacological mechanisms by primarily focusing on the role of AMP-activated protein kinase (AMPK). Quercetin significantly attenuated tumor growth in an HCT116 cancer xenograft in vivo model with a substantial reduction of AMPK activity. In a cell culture system, quercetin more dramatically induced apoptosis of HCT116 cancer cells under hypoxic conditions than normoxic conditions, and this was tightly associated with inhibition of hypoxia-induced AMPK activity. An in vitro kinase assay demonstrated that quercetin directly inhibits AMPK activity. Inhibition of AMPK by expressing a dominant-negative form resulted in an increase of apoptosis under hypoxia, and a constitutively active form of AMPK effectively blocked quercetin-induced apoptosis under hypoxia. Collectively, our data suggest that quercetin directly inhibits hypoxia-induced AMPK, which plays a protective role against hypoxia. Quercetin also reduced the activity of hypoxia-inducible factor-1 (HIF-1), a major transcription factor for adaptive cellular response to hypoxia. Moreover, quercetin sensitized HCT116 cancer cells to the anticancer drugs cisplatin and etoposide under hypoxic conditions. Our findings suggest that AMPK may serve as a novel target for overcoming tumor hypoxia-associated negative aspects.

Perfluorooctane Sulfonate-Induced Hepatic Steatosis in Male Sprague Dawley Rats Is Not Attenuated by Dietary Choline Supplementation.

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Bagley, Bradford D; Chang, Shu-Ching; Ehresman, David J; Eveland, Alan; Zitzow, Jeremiah D; Parker, George A; Peters, Jeffrey M; Wallace, Kendall B; Butenhoff, John L

2017-12-01

Perfluorooctane sulfonate (PFOS) is an environmentally persistent chemical. Dietary 100 ppm PFOS fed to male mice and rats for 4 weeks caused hepatic steatosis through an unknown mechanism. Choline deficient diets can cause hepatic steatosis. A hepatic choline:PFOS ion complex was hypothesized to cause this effect in mice. This study tested whether dietary choline supplementation attenuates PFOS-induced hepatic steatosis in rats. Sprague Dawley rats (12/sex/group) were fed control, choline supplemented (CS), 100 ppm PFOS, or 100 ppm PFOS + CS diets for 3 weeks. Male rats fed both PFOS-containing diets had decreased serum cholesterol and triglycerides (TGs) on days 9, 16, and/or 23 and increased hepatic free fatty acids and TG (ie, steatosis). Female rats fed both PFOS diets had decreased serum cholesterol on days 9 and 16 and decreased hepatic free fatty acid and TG at termination (ie, no steatosis). Liver PFOS concentrations were similar for both sexes. Liver choline concentrations were increased in male rats fed PFOS (±CS), but the increase was lower in the PFOS + CS group. Female liver choline concentrations were not altered by any diet. These findings demonstrate a clear sex-related difference in PFOS-induced hepatic steatosis in the rat. Additional evaluated mechanisms (ie, nuclear receptor activation, mRNA upregulation, and choline kinase activity inhibition) did not appear to be involved in the hepatic steatosis. Dietary PFOS (100 ppm) induced hepatic steatosis in male, but not female, rats that was not attenuated by choline supplementation. The mechanism of lipid accumulation and the sex-related differences warrant further investigation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Acute Ethanol Gavage Attenuates Hemorrhage/Resuscitation-Induced Hepatic Oxidative Stress in Rats

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B. Relja

2012-01-01

Full Text Available Acute ethanol intoxication increases the production of reactive oxygen species (ROS. Hemorrhagic shock with subsequent resuscitation (H/R also induces ROS resulting in cellular and hepatic damage in vivo. We examined the role of acute ethanol intoxication upon oxidative stress and subsequent hepatic cell death after H/R. 14 h before H/R, rats were gavaged with single dose of ethanol or saline (5 g/kg, EtOH and ctrl; H/R_EtOH or H/R_ctrl, resp.. Then, rats were hemorrhaged to a mean arterial blood pressure of 30±2 mmHg for 60 min and resuscitated. Two control groups underwent surgical procedures without H/R (sham_ctrl and sham_EtOH, resp.. Liver tissues were harvested at 2, 24, and 72 h after resuscitation. EtOH-gavage induced histological picture of acute fatty liver. Hepatic oxidative (4-hydroxynonenal, 4-HNE and nitrosative (3-nitrotyrosine, 3-NT stress were significantly reduced in EtOH-gavaged rats compared to controls after H/R. Proapoptotic caspase-8 and Bax expressions were markedly diminished in EtOH-gavaged animals compared with controls 2 h after resuscitation. EtOH-gavage increased antiapoptotic Bcl-2 gene expression compared with controls 2 h after resuscitation. iNOS protein expression increased following H/R but was attenuated in EtOH-gavaged animals after H/R. Taken together, the data suggest that acute EtOH-gavage may attenuate H/R-induced oxidative stress thereby reducing cellular injury in rat liver.

Quercetin protects liver injury induced by bile duct ligation via attenuation of Rac1 and NADPH oxidase1 expression in rats.

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Kabirifar, Razieh; Ghoreshi, Zohreh-Al-Sadat; Safari, Fatemeh; Karimollah, Alireza; Moradi, Ali; Eskandari-Nasab, Ebrahim

2017-02-01

Bile duct ligation (BDL) and subsequent cholestasis are correlated with oxidative stress, hepatocellular injury and fibrosis. Quercetin is a flavonoid with antifibrotic, and hepatoprotective properties. However, the molecular mechanism underlying quercetin-mediated hepatoprotection is not fully understood. The current study was to evaluate mechanisms of hepatoprotective effect of quercetin in BDL rat model. We divided male Wistar rats into 4 groups (n=8 for each): sham, sham+quercetin (30 mg/kg per day), BDL, and BDL+quercetin (30 mg/kg per day). Four weeks later, the rats were sacrificed, the blood was collected for liver enzyme measurements and liver for the measurement of Rac1, Rac1-GTP and NOX1 mRNA and protein levels by quantitative PCR and Western blotting, respectively. Quercetin significantly alleviated liver injury in BDL rats as evidenced by histology and reduced liver enzymes. Furthermore, the mRNA and protein expression of Rac1, Rac1-GTP and NOX1 were significantly increased in BDL rats compared with those in the sham group (Pliver injury through increasing antioxidant capacity of the liver tissue, while preventing the production of Rac1, Rac1-GTP and NOX1 proteins.

Quercetin, not caffeine, is a major neuroprotective component in coffee.

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Lee, Moonhee; McGeer, Edith G; McGeer, Patrick L

2016-10-01

Epidemiologic studies indicate that coffee consumption reduces the risk of Parkinson's disease and Alzheimer's disease. To determine the factors involved, we examined the protective effects of coffee components. The test involved prevention of neurotoxicity to SH-SY5Y cells that was induced by lipopolysaccharide plus interferon-γ or interferon-γ released from activated microglia and astrocytes. We found that quercetin, flavones, chlorogenic acid, and caffeine protected SH-SY5Y cells from these toxins. They also reduced the release of tumor necrosis factor-α and interleukin-6 from the activated microglia and astrocytes and attenuated the activation of proteins from P38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa light chain enhancer of activated B cells (NFκB). After exposure to toxin containing glial-stimulated conditioned medium, we also found that quercetin reduced oxidative/nitrative damage to DNA, as well as to the lipids and proteins of SH-SY5Y cells. There was a resultant increase in [GSH]i in SH-SY5Y cells. The data indicate that quercetin is the major neuroprotective component in coffee against Parkinson's disease and Alzheimer's disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Hepatic gene expression and plasma albumin concentration related to outcome after attenuation of a congenital portosystemic shunt in dogs

NARCIS (Netherlands)

Kummeling, A.; Penning, L.C.; Rothuizen, J.; Brinkhof, B.; Weber, M.F.; van Sluijs, F.J.

2012-01-01

Abstract In dogs with a congenital portosystemic shunt (CPSS), the outcome after CPSS attenuation is difficult to predict but is most likely related to hepatic and vascular proliferation that follows the attenuation. The aim of this study was to evaluate the prognostic value of shunt localization

Genetic ablation or chemical inhibition of phosphatidylcholine transfer protein attenuates diet-induced hepatic glucose production.

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Shishova, Ekaterina Y; Stoll, Janis M; Ersoy, Baran A; Shrestha, Sudeep; Scapa, Erez F; Li, Yingxia; Niepel, Michele W; Su, Ya; Jelicks, Linda A; Stahl, Gregory L; Glicksman, Marcie A; Gutierrez-Juarez, Roger; Cuny, Gregory D; Cohen, David E

2011-08-01

Phosphatidylcholine transfer protein (PC-TP, synonym StARD2) is a highly specific intracellular lipid binding protein that is enriched in liver. Coding region polymorphisms in both humans and mice appear to confer protection against measures of insulin resistance. The current study was designed to test the hypotheses that Pctp-/- mice are protected against diet-induced increases in hepatic glucose production and that small molecule inhibition of PC-TP recapitulates this phenotype. Pctp-/- and wildtype mice were subjected to high-fat feeding and rates of hepatic glucose production and glucose clearance were quantified by hyperinsulinemic euglycemic clamp studies and pyruvate tolerance tests. These studies revealed that high-fat diet-induced increases in hepatic glucose production were markedly attenuated in Pctp-/- mice. Small molecule inhibitors of PC-TP were synthesized and their potencies, as well as mechanism of inhibition, were characterized in vitro. An optimized inhibitor was administered to high-fat-fed mice and used to explore effects on insulin signaling in cell culture systems. Small molecule inhibitors bound PC-TP, displaced phosphatidylcholines from the lipid binding site, and increased the thermal stability of the protein. Administration of the optimized inhibitor to wildtype mice attenuated hepatic glucose production associated with high-fat feeding, but had no activity in Pctp-/- mice. Indicative of a mechanism for reducing glucose intolerance that is distinct from commonly utilized insulin-sensitizing agents, the inhibitor promoted insulin-independent phosphorylation of key insulin signaling molecules. These findings suggest PC-TP inhibition as a novel therapeutic strategy in the management of hepatic insulin resistance. Copyright © 2011 American Association for the Study of Liver Diseases.

Forkhead Box O6 (FoxO6) Depletion Attenuates Hepatic Gluconeogenesis and Protects against Fat-induced Glucose Disorder in Mice*

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Calabuig-Navarro, Virtu; Yamauchi, Jun; Lee, Sojin; Zhang, Ting; Liu, Yun-Zi; Sadlek, Kelsey; Coudriet, Gina M.; Piganelli, Jon D.; Jiang, Chun-Lei; Miller, Rita; Lowe, Mark; Harashima, Hideyoshi; Dong, H. Henry

2015-01-01

Excessive endogenous glucose production contributes to fasting hyperglycemia in diabetes. FoxO6 is a distinct member of the FoxO subfamily. To elucidate the role of FoxO6 in hepatic gluconeogenesis and assess its contribution to the pathogenesis of fasting hyperglycemia in diabetes, we generated FoxO6 knock-out (FoxO6-KO) mice followed by determining the effect of FoxO6 loss-of-function on hepatic gluconeogenesis under physiological and pathological conditions. FoxO6 depletion attenuated hepatic gluconeogenesis and lowered fasting glycemia in FoxO6-KO mice. FoxO6-deficient primary hepatocytes were associated with reduced capacities to produce glucose in response to glucagon. When fed a high fat diet, FoxO6-KO mice exhibited significantly enhanced glucose tolerance and reduced blood glucose levels accompanied by improved insulin sensitivity. These effects correlated with attenuated hepatic gluconeogenesis in FoxO6-KO mice. In contrast, wild-type littermates developed fat-induced glucose intolerance with a concomitant induction of fasting hyperinsulinemia and hyperglycemia. Furthermore, FoxO6-KO mice displayed significantly diminished macrophage infiltration into liver and adipose tissues, correlating with the reduction of macrophage expression of C-C chemokine receptor 2 (CCR2), a factor that is critical for regulating macrophage recruitment in peripheral tissues. Our data indicate that FoxO6 depletion protected against diet-induced glucose intolerance and insulin resistance by attenuating hepatic gluconeogenesis and curbing macrophage infiltration in liver and adipose tissues in mice. PMID:25944898

Comparison of the nucleotide sequence of wild-type hepatitis - A virus and its attenuated candidate vaccine derivative

International Nuclear Information System (INIS)

Cohen, J.I.; Rosenblum, B.; Ticehurst, J.R.; Daemer, R.; Feinstone, S.; Purcell, R.H.

1987-01-01

Development of attenuated mutants for use as vaccines is in progress for other viruses, including influenza, rotavirus, varicella-zoster, cytomegalovirus, and hepatitis-A virus (HAV). Attenuated viruses may be derived from naturally occurring mutants that infect human or nonhuman hosts. Alternatively, attenuated mutants may be generated by passage of wild-type virus in cell culture. Production of attenuated viruses in cell culture is a laborious and empiric process. Despite previous empiric successes, understanding the molecular basis for attenuation of vaccine viruses could facilitate future development and use of live-virus vaccines. Comparison of the complete nucleotide sequences of wild-type (virulent) and vaccine (attenuated) viruses has been reported for polioviruses and yellow fever virus. Here, the authors compare the nucleotide sequence of wild-type HAV HM-175 with that of a candidate vaccine derivative

Aloe vera attenuated liver injury in mice with acetaminophen-induced hepatitis.

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Werawatganon, Duangporn; Linlawan, Sittikorn; Thanapirom, Kessarin; Somanawat, Kanjana; Klaikeaw, Naruemon; Rerknimitr, Rungsun; Siriviriyakul, Prasong

2014-07-08

An overdose of the acetaminophen causes liver injury. This study aims to examine the anti-oxidative, anti-inflammatory effects of Aloe vera in mice with acetaminophen induced hepatitis. Male mice were randomly divided into three groups (n = 8 each). Control group were given orally distilled water (DW). APAP group were given orally N-acetyl-P-aminophenol (APAP) 400 mg/kg suspended in DW. Aloe vera-treated group were given orally APAP and Aloe vera (150 mg/kg) suspended in DW. Twenty-four hours later, the liver was removed to determine hepatic malondialdehyde (MDA), hepatic glutathione (GSH), the number of interleukin (IL)-12 and IL-18 positive stained cells (%) by immunohistochemistry method, and histopathological examination. Then, the serum was collected to determine transaminase (ALT). In APAP group, ALT, hepatic MDA and the number of IL-12 and IL-18 positive stained cells were significantly increased when compared to control group (1210.50 ± 533.86 vs 85.28 ± 28.27 U/L, 3.60 ± 1.50 vs 1.38 ± 0.15 nmol/mg protein, 12.18 ± 1.10 vs 1.84 ± 1.29%, and 13.26 ± 0.90 vs 2.54 ± 1.29%, P = 0.000, respectively), whereas hepatic GSH was significantly decreased when compared to control group (5.98 ± 0.30 vs 11.65 ± 0.43 nmol/mg protein, P = 0.000). The mean level of ALT, hepatic MDA, the number of IL-12 and IL-18 positive stained cells, and hepatic GSH in Aloe vera-treated group were improved as compared with APAP group (606.38 ± 495.45 vs 1210.50 ± 533.86 U/L, P = 0.024; 1.49 ± 0.64 vs 3.60 ± 1.50 nmol/mg protein, P = 0.001; 5.56 ± 1.25 vs 12.18 ± 1.10%, P = 0.000; 6.23 ± 0.94 vs 13.26 ± 0.90%, P = 0.000; and 10.02 ± 0.20 vs 5.98 ± 0.30 nmol/mg protein, P = 0.000, respectively). Moreover, in the APAP group, the liver showed extensive hemorrhagic hepatic necrosis at all zones while in Aloe vera-treated group, the liver architecture was improved histopathology. APAP overdose can cause liver injury. Our result indicate that Aloe vera attenuate APAP

Bicyclol attenuates tetracycline-induced fatty liver associated with inhibition of hepatic ER stress and apoptosis in mice.

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Yao, Xiao-Min; Li, Yue; Li, Hong-Wei; Cheng, Xiao-Yan; Lin, Ai-Bin; Qu, Jun-Ge

2016-01-01

Endoplasmic reticulum (ER) stress is known to be involved in the development of several metabolic disorders, including non-alcoholic fatty liver disease (NAFLD). Tetracycline can cause hepatic steatosis, and ER stress may be involved in tetracycline-induced fatty liver. Our previous study showed that bicyclol has been proven to protect against tetracycline-induced fatty liver in mice, and ER stress may also be involved in bicyclol's hepatoprotective effect. Therefore, this study was performed to investigate the underlying mechanisms associated with ER stress and apoptosis, by which bicyclol attenuated tetracycline-induced fatty liver in mice. Bicyclol (300 mg/kg) was given to mice by gavage 3 times. Tetracycline (200 mg/kg, intraperitoneally) was injected at 1 h after the last dose of bicyclol. At 6 h and 24 h after single dose of tetracycline injection, serum ALT, AST, TG, CHO and hepatic histopathological examinations were performed to evaluate liver injuries. Hepatic steatosis was assessed by the accumulation of hepatic TG and CHO. Moreover, hepatic apoptosis and ER stress related markers were determined by TUNEL, real-time PCR, and western blot. As a result, bicyclol significantly protected against tetracycline-induced fatty liver as evidenced by the decrease of elevated serum transaminases and hepatic triglyceride, and the attenuation of histopathological changes in mice. In addition, bicyclol remarkably alleviated hepatic apoptosis and the gene expression of caspase-3, and increased the gene expression of XIAP. The gene expressions of ER stress-related markers, including CHOP, GRP78, IRE-1α, and ATF6, which were downregulated by bicyclol pretreatment in tetracycline-injected mice. These results suggested that bicyclol protected tetracycline-induced fatty liver partly due to its ability of anti-apoptosis associated with ER stress.

Forkhead Box O6 (FoxO6) Depletion Attenuates Hepatic Gluconeogenesis and Protects against Fat-induced Glucose Disorder in Mice.

Science.gov (United States)

Calabuig-Navarro, Virtu; Yamauchi, Jun; Lee, Sojin; Zhang, Ting; Liu, Yun-Zi; Sadlek, Kelsey; Coudriet, Gina M; Piganelli, Jon D; Jiang, Chun-Lei; Miller, Rita; Lowe, Mark; Harashima, Hideyoshi; Dong, H Henry

2015-06-19

Excessive endogenous glucose production contributes to fasting hyperglycemia in diabetes. FoxO6 is a distinct member of the FoxO subfamily. To elucidate the role of FoxO6 in hepatic gluconeogenesis and assess its contribution to the pathogenesis of fasting hyperglycemia in diabetes, we generated FoxO6 knock-out (FoxO6-KO) mice followed by determining the effect of FoxO6 loss-of-function on hepatic gluconeogenesis under physiological and pathological conditions. FoxO6 depletion attenuated hepatic gluconeogenesis and lowered fasting glycemia in FoxO6-KO mice. FoxO6-deficient primary hepatocytes were associated with reduced capacities to produce glucose in response to glucagon. When fed a high fat diet, FoxO6-KO mice exhibited significantly enhanced glucose tolerance and reduced blood glucose levels accompanied by improved insulin sensitivity. These effects correlated with attenuated hepatic gluconeogenesis in FoxO6-KO mice. In contrast, wild-type littermates developed fat-induced glucose intolerance with a concomitant induction of fasting hyperinsulinemia and hyperglycemia. Furthermore, FoxO6-KO mice displayed significantly diminished macrophage infiltration into liver and adipose tissues, correlating with the reduction of macrophage expression of C-C chemokine receptor 2 (CCR2), a factor that is critical for regulating macrophage recruitment in peripheral tissues. Our data indicate that FoxO6 depletion protected against diet-induced glucose intolerance and insulin resistance by attenuating hepatic gluconeogenesis and curbing macrophage infiltration in liver and adipose tissues in mice. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Mechanism of estrogen-mediated attenuation of hepatic injury following trauma-hemorrhage: Akt-dependent HO-1 up-regulation.

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Hsu, Jun-Te; Kan, Wen-Hong; Hsieh, Chi-Hsun; Choudhry, Mashkoor A; Schwacha, Martin G; Bland, Kirby I; Chaudry, Irshad H

2007-10-01

Protein kinase B (Akt) is known to be involved in proinflammatory and chemotactic events in response to injury. Akt activation also leads to the induction of heme oxygenase (HO)-1. Up-regulation of HO-1 mediates potent, anti-inflammatory effects and attenuates organ injury. Although studies have shown that 17beta-estradiol (E2) prevents organ damage following trauma-hemorrhage, it remains unknown whether Akt/HO-1 plays any role in E2-mediated attenuation of hepatic injury following trauma-hemorrhage. To study this, male rats underwent trauma-hemorrhage (mean blood pressure, approximately 40 mmHg for 90 min), followed by fluid resuscitation. At the onset of resuscitation, rats were treated with vehicle, E2 (1 mg/kg body weight), E2 plus the PI-3K inhibitor (Wortmannin), or the estrogen receptor (ER) antagonist (ICI 182,780). At 2 h after sham operation or trauma-hemorrhage, plasma alpha-GST and hepatic tissue myeloperoxidase (MPO) activity, IL-6, TNF-alpha, ICAM-1, cytokine-induced neutrophil chemoattractant-1, and MIP-2 levels were measured. Hepatic Akt and HO-1 protein levels were also determined. Trauma-hemorrhage increased hepatic injury markers (alpha-GST and MPO activity), cytokines, ICAM-1, and chemokine levels. These parameters were markedly improved in the E2-treated rats following trauma-hemorrhage. E2 treatment also increased hepatic Akt activation and HO-1 expression compared with vehicle-treated, trauma-hemorrhage rats, which were abolished by coadministration of Wortmannin or ICI 182,780. These results suggest that the salutary effects of E2 on hepatic injury following trauma-hemorrhage are in part mediated via an ER-related, Akt-dependent up-regulation of HO-1.

Divergent antiviral effects of bioflavonoids on the hepatitis C virus life cycle

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Khachatoorian, Ronik, E-mail: RnKhch@ucla.edu [Molecular Biology Interdepartmental Ph.D. Program (MBIDP), Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles, California, CA (United States); Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles, California, CA (United States); Arumugaswami, Vaithilingaraja, E-mail: VArumugaswami@mednet.ucla.edu [Department of Molecular and Medical Pharmacology, David Geffen School of Medicine at University of California, Los Angeles, California, CA (United States); Department of Surgery, Regenerative Medicine Institute at Cedars-Sinai Medical Center, Los Angeles, California, CA (United States); Raychaudhuri, Santanu, E-mail: SRaychau@ucla.edu [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, California, CA (United States); Yeh, George K., E-mail: GgYeh@ucla.edu [Molecular Biology Interdepartmental Ph.D. Program (MBIDP), Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles, California, CA (United States); Molecular Biology Institute, David Geffen School of Medicine at University of California, Los Angeles, California, CA (United States); Maloney, Eden M., E-mail: EMaloney@ucla.edu [Department of Molecular, Cell, and Developmental Biology, University of California, Los Angeles, California, CA (United States); Wang, Julie, E-mail: JulieW1521@ucla.edu [Department of Microbiology, Immunology, and Molecular Genetics, David Geffen School of Medicine at University of California, Los Angeles, California, CA (United States); and others

2012-11-25

We have previously demonstrated that quercetin, a bioflavonoid, blocks hepatitis C virus (HCV) proliferation by inhibiting NS5A-driven internal ribosomal entry site (IRES)-mediated translation of the viral genome. Here, we investigate the mechanisms of antiviral activity of quercetin and six additional bioflavonoids. We demonstrate that catechin, naringenin, and quercetin possess significant antiviral activity, with no associated cytotoxicity. Infectious virion secretion was not significantly altered by these bioflavonoids. Catechin and naringenin demonstrated stronger inhibition of infectious virion assembly compared to quercetin. Quercetin markedly blocked viral translation whereas catechin and naringenin demonstrated mild activity. Similarly quercetin completely blocked NS5A-augmented IRES-mediated translation in an IRES reporter assay, whereas catechin and naringenin had only a mild effect. Moreover, quercetin differentially inhibited HSP70 induction compared to catechin and naringenin. Thus, the antiviral activity of these bioflavonoids is mediated through different mechanisms. Therefore combination of these bioflavonoids may act synergistically against HCV.

Metabolic interactions between acetaminophen (paracetamol) and two flavonoids, luteolin and quercetin, through in-vitro inhibition studies.

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Cao, Lei; Kwara, Awewura; Greenblatt, David J

2017-12-01

Excessive exposure to acetaminophen (APAP, paracetamol) can cause liver injury through formation of a reactive metabolite that depletes hepatic glutathione and causes hepatocellular oxidative stress and damage. Generation of this metabolite is mediated by Cytochrome-P450 (CYP) isoforms, mainly CYP2E1. A number of naturally occurring flavonoids can mitigate APAP-induced hepatotoxicity in experimental animal models. Our objective was to determine the mechanism of these protective effects and to evaluate possible human applicability. Two flavonoids, luteolin and quercetin, were evaluated as potential inhibitors of eight human CYP isoforms, of six UDP-glucuronosyltransferase (UGT) isoforms and of APAP glucuronidation and sulfation. The experimental model was based on in-vitro metabolism by human liver microsomes, using isoform-specific substrates. Luteolin and quercetin inhibited human CYP isoforms to varying degrees, with greatest potency towards CYP1A2 and CYP2C8. However, 50% inhibitory concentrations (IC 50 values) were generally in the micromolar range. UGT isoforms were minimally inhibited. Both luteolin and quercetin inhibited APAP sulfation but not glucuronidation. Inhibition of human CYP activity by luteolin and quercetin occurred with IC 50 values exceeding customary in-vivo human exposure with tolerable supplemental doses of these compounds. The findings indicate that luteolin and quercetin are not likely to be of clinical value for preventing or treating APAP-induced hepatotoxicity. © 2017 Royal Pharmaceutical Society.

Modulation of gut microbiota contributes to curcumin-mediated attenuation of hepatic steatosis in rats.

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Feng, Wenhuan; Wang, Hongdong; Zhang, Pengzi; Gao, Caixia; Tao, Junxian; Ge, Zhijuan; Zhu, Dalong; Bi, Yan

2017-07-01

Structural disruption of gut microbiota contributes to the development of non-alcoholic fatty liver disease (NAFLD) and modulating the gut microbiota represents a novel strategy for NAFLD prevention. Although previous studies have demonstrated that curcumin alleviates hepatic steatosis, its effect on the gut microbiota modulation has not been investigated. Next generation sequencing and multivariate analysis were utilized to evaluate the structural changes of gut microbiota in a NAFLD rat model induced by high fat-diet (HFD) feeding. We found that curcumin attenuated hepatic ectopic fat deposition, improved intestinal barrier integrity, and alleviated metabolic endotoxemia in HFD-fed rats. More importantly, curcumin dramatically shifted the overall structure of the HFD-disrupted gut microbiota toward that of lean rats fed a normal diet and altered the gut microbial composition. The abundances of 110 operational taxonomic units (OTUs) were altered by curcumin. Seventy-six altered OTUs were significantly correlated with one or more hepatic steatosis associated parameters and designated 'functionally relevant phylotypes'. Thirty-six of the 47 functionally relevant OTUs that were positively correlated with hepatic steatosis associated parameters were reduced by curcumin. These results indicate that curcumin alleviates hepatic steatosis in part through stain-specific impacts on hepatic steatosis associated phylotypes of gut microbiota in rats. Compounds with antimicrobial activities should be further investigated as novel adjunctive therapies for NAFLD. Copyright © 2017 Elsevier B.V. All rights reserved.

Huperzine A attenuates hepatic ischemia reperfusion injury via anti-oxidative and anti-apoptotic pathways.

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Xu, Zhe; Wang, Yang

2014-08-01

Hepatic ischemia reperfusion (HI/R) injury may occur during liver transplantation and remains a serious concern in clinical practice. Huperzine A (HupA), an alkaloid isolated from the Chinese traditional medicine Huperzia serrata, has been demonstrated to possess anti‑oxidative and anti‑apoptotic properties. In the present study, a rat model of HI/R was established by clamping the hepatic artery, the hepatoportal vein and the bile duct with a vascular clamp for 30 min followed by reperfusion for 6 h under anesthesia. HupA was injected into the tail vein 5 min prior to the induction of HI/R at doses of 167 and 500 µg/kg. The histopathological assessment of the liver was performed using hematoxylin and eosin staining. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were assayed in the serum samples. The tissue levels of superoxide dismutase (SOD), catalase (CAT), malondiadehyde (MDA) and glutathione (GSH) were also measured spectrophotometrically. Furthermore, the protein expression of caspase‑3, Bcl‑2 and Bax in hepatic tissues was detected via western blot analysis. Treatment of Wistar rats with HupA at doses of 167 and 500 µg/kg markedly attenuated HI/R injury as observed histologically. In addition, the significant reductions of serum ALT and AST were observed in HupA‑treated ischemic rats. Furthermore, HupA treatment enhanced the activity of hepatic tissue SOD, CAT and GSH, but decreased the MDA tissue content. Western blot analysis revealed elevated levels of Bcl‑2 expression but decreased Bax and caspase‑3 tissue expression at the protein level in the HupA‑treated group. The present data suggest that HupA attenuates the HI/R injury of rats through its anti‑oxidative and anti‑apoptotic signaling pathways.

Quercetin: a versatile flavonoid

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Dr. Deepak Kumar Rai

2007-07-01

Full Text Available Associative evidence from observational and intervention studies in human subjects shows that a diet including plant foods (particularly fruit and vegetables rich in antioxidants conveys health benefits. There is no evidence that any particular nutrient or class of bioactive substances makes a special contribution to these benefits. Flavonoids occur naturally in fruits, vegetables and beverages such as tea and wine. Quercetin is the major flavonoid which belongs to the class called flavonols. Quercetin is found in many common foods including apples, tea, onions, nuts, berries, cauliflower, cabbage and many other foods. Quercetin provides many health promoting benefits, including improvement of cardiovascular health, eye diseases, allergic disorders, arthritis, reducing risk for cancers and many more. The main aim of this review is to obtain a further understanding of the reported beneficial health effects of Quercetin, its pharmacological effects, clinical application and also to evaluate its safety.

Endogenous n-3 polyunsaturated fatty acids attenuate T cell-mediated hepatitis via autophagy activation

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Yanli Li

2016-09-01

Full Text Available Omega-3 polyunsaturated fatty acids (n-3 PUFAs exert anti-inflammatory effects in several liver disorders, including cirrhosis, acute liver failure, and fatty liver disease. To date, little is known about their role in immune-mediated liver diseases. In this study, we used fat-1 transgenic mice rich in endogenous n-3 PUFAs to examine the role of n-3 PUFAs in immune-mediated liver injury. Concanavalin A (Con A was administered intravenously to wild-type (WT and fat-1 transgenic mice to induce T cell-mediated hepatitis. Reduced liver damage was shown in Con A-administrated fat-1 transgenic mice, as evidenced by decreased mortality, attenuated hepatic necrosis, lessened serum alanine aminotransferase (ALT activity, and inhibited production of pro-inflammatory cytokines (e.g. TNF-α, IL-6, IL-17A and IFN-γ. In vivo and in vitro studies demonstrated that n-3 PUFAs significantly inhibited the activation of hepatic T cells and the differentiation of Th1 cells after Con A challenge. Further studies showed that n-3 PUFAs markedly increased autophagy level in Con A-treated fat-1 T cells compared with the WT counterparts. Blocking hepatic autophagy activity with chloroquine diminished the differences in T cell activation and liver injury between Con A-injected WT and fat-1 transgenic mice. We conclude that n-3 PUFAs limit Con A-induced hepatitis via an autophagy-dependent mechanism, and could be exploited as a new therapeutic approach for autoimmune hepatitis.

Pharmacokinetic comparison between quercetin and quercetin 3-O-β-glucuronide in rats by UHPLC-MS/MS

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Yang, Le-Le; Xiao, Na; Li, Xiao-Wei; Fan, Yong; Alolga, Raphael N.; Sun, Xiao-Yue; Wang, Shi-Lei; Li, Ping; Qi, Lian-Wen

2016-10-01

Quercetin is a natural flavonoid widely distributed in human diet and functional foods. Quercetin 3-O-β-glucuronide (Q3G) is present in wine and some medicinal plants. Quercetin and Q3G may be metabolized from each other in vivo. While quercetin has been the subject of many studies, the pharmacokinetic profiles of quercetin and Q3G (in animals) have not yet been compared. Herein, we prepared a column-based method for rapid isolation of Q3G from Nelumbo nucifera. Then, we developed an UHPLC-MS/MS method to compare the pharmacokinetics of quercetin and Q3G. Our results showed that the plasma concentration-time curves of quercetin and Q3G show two maxima (Tmax1 ≈ 0.75 h, Tmax2 ≈ 5 h). After oral administration of 100 mg/kg quercetin or 100 mg/kg Q3G in rats, predominantly Q3G was detected in plasma with AUC at 39529.2 ± 6108.2 mg·h·L-1 or 24625.1 ± 1563.8 mg·h·L-1, 18-fold higher than quercetin with AUC at 1583.9 ± 583.3 mg·h·L-1 or 1394.6 ± 868.1 mg·h·L-1, respectively. After intravenous injection of 10 mg/kg in rats, Q3G showed extensive tissue uptake in kidney (409.2 ± 118.4 ng/g), liver (166.1 ± 52.9 ng/g), heart (97.7 ± 22.6 ng/g), and brain (5.8 ± 1.2 ng/g). In conclusion, we have shown that Q3G is a major active component in plasma and tissue for oral administration of quercetin or Q3G.

Effect of quercetin on the production of nitric oxide in murine macrophages stimulated with lipopolysaccharide from Prevotella intermedia.

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Cho, Yun-Jung; Kim, Sung-Jo

2013-08-01

Nitric oxide (NO) is a short-lived bioactive molecule that is known to play an important role in the pathogenesis of periodontal disease. In the current study, we investigated the effect of the flavonoid quercetin on the production of NO in murine macrophages activated with lipopolysaccharide (LPS) from Prevotella intermedia, a pathogen related to inflammatory periodontal disease, and tried to elucidate the underlying mechanisms of action. LPS was isolated from P. intermedia ATCC 25611 cells by the standard hot phenol-water method. The concentration of NO in cell culture supernatants was determined by measuring the accumulation of nitrite. Inducible NO synthase (iNOS) and heme oxygenase-1 (HO-1) protein expression, phosphorylation of c-Jun N-terminal kinase (JNK) and p38, inhibitory κB (IκB)-α degradation, and signal transducer and activator of transcription 1 (STAT1) phosphorylation were analyzed via immunoblotting. Quercetin significantly attenuated iNOS-derived NO production in RAW246.7 cells activated by P. intermedia LPS. In addition, quercetin induced HO-1 protein expression in cells activated with P. intermedia LPS. Tin protoporphyrin IX (SnPP), a competitive inhibitor of HO-1, abolished the inhibitory effect of quercetin on LPS-induced NO production. Quercetin did not affect the phosphorylation of JNK and p38 induced by P. intermedia LPS. The degradation of IκB-α induced by P. intermedia LPS was inhibited when the cells were treated with quercetin. Quercetin also inhibited LPS-induced STAT1 signaling. Quercetin significantly inhibits iNOS-derived NO production in murine macrophages activated by P. intermedia LPS via anti-inflammatory HO-1 induction and inhibition of the nuclear factor-κB and STAT1 signaling pathways. Our study suggests that quercetin may contribute to the modulation of host-destructive responses mediated by NO and appears to have potential as a novel therapeutic agent for treating inflammatory periodontal disease.

Quercetin Isolated from Toona sinensis Leaves Attenuates Hyperglycemia and Protects Hepatocytes in High-Carbohydrate/High-Fat Diet and Alloxan Induced Experimental Diabetic Mice

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Yali Zhang

2016-01-01

Full Text Available The development of diabetes mellitus is related to oxidant stress induced by a high carbohydrate/high-fat diet (HFD. Quercetin, as a major bioactive component in Toona sinensis leaves (QTL, is a natural antioxidant. However, the exact mechanism by which QTL ameliorate diabetes mellitus is still unknown. In this study, we investigated the hypoglycemic effects and hepatocytes protection of QTL on HFD and alloxan induced diabetic mice. Intragastric administration of QTL significantly reduced body weight gain, serum glucose, insulin, total cholesterol, triglyceride, low density lipoprotein-cholesterol, alanine aminotransferase, and aspartate aminotransferase serum levels compared to those of diabetic mice. Furthermore, it significantly attenuated oxidative stress, as determined by lipid peroxidation, nitric oxide content, and inducible nitric oxide synthase activity and as a result attenuated liver injury. QTL also significantly suppressed the diabetes-induced activation of the p65/NF-κB and ERK1/2/MAPK pathways, as well as caspase-9 and caspase-3 levels in liver tissues of diabetic mice. Finally, micrograph analysis of liver samples showed decreased cellular organelle injury in hepatocytes of QTL treated mice. Taken together, QTL can be viewed as a promising dietary agent that can be used to reduce the risk of diabetes mellitus and its secondary complications by ameliorating oxidative stress in the liver.

Dapper1 attenuates hepatic gluconeogenesis and lipogenesis by activating PI3K/Akt signaling.

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Kuang, Jian-Ren; Zhang, Zhi-Hui; Leng, Wei-Ling; Lei, Xiao-Tian; Liang, Zi-Wen

2017-05-15

Studies have shown that hepatic insulin resistance, a disorder of glucose and lipid metabolism, plays a vital role in type 2 diabetes (T2D). To clarify the function of Dapper1 in glucose and lipid metabolism in the liver, we investigated the relationships between Dapper1 and adenosine triphosphate (ATP)- and Ca 2+ -mediated activation of PI3K/Akt. We observed a reduction in hepatic Dapper1 in db/db (mice that are homozygous for a spontaneous diabetes mutation) and HFD-induced diabetic mice with T2D. Hepatic overexpression of Dapper1 improved hyperglycemia, insulin resistance, and fatty liver. It also increased Akt (pAkt) signaling and repressed both gluconeogenesis and lipogenesis. Conversely, Ad-shDapper1-induced knockdown of hepatic Dapper1 promoted gluconeogenesis and lipogenesis. Furthermore, Dapper1 activated PI3K p110α/Akt in an insulin-independent manner by inducing ATP production and secretion in vitro. Blockade of P2 ATP receptors, the downstream phospholipase C (PLC), or the inositol triphosphate receptor (IP3R all reduced the Dapper1-induced increase in cytosolic free calcium and Dapper1-mediated PI3K/Akt activation, as did removal of calcium in the medium. In conclusion, Dapper1 attenuates hepatic gluconeogenesis and lipogenesis in T2D. Copyright © 2017 Elsevier B.V. All rights reserved.

A comparison of hepatic steatosis index, controlled attenuation parameter and ultrasound as noninvasive diagnostic tools for steatosis in chronic hepatitis B.

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Xu, Liang; Lu, Wei; Li, Ping; Shen, Feng; Mi, Yu-Qiang; Fan, Jian-Gao

2017-08-01

To evaluate the value of noninvasive tools for diagnosis of hepatic steatosis in patients with chronic hepatitis B (CHB). Consecutive treatment-naïve patients with CHB with body mass index less than 30kg/m 2 who underwent liver biopsy, ultrasound and FibroScan ® were enrolled. The diagnostic performance of controlled attenuation parameter (CAP), hepatic steatosis index (HSI) and ultrasound for hepatic steatosis compared with liver biopsy was assessed. The areas under receiver operating characteristics curves (AUROCs) were calculated to determine the diagnostic efficacy, with comparisons using the DeLong test. CAP and HSI accuracies were significantly higher than that of ultrasound to detect patients with biopsy-proven mild steatosis (S1, 65.3%, 56.5%, respectively, vs. 17.7%, χ 2 =46.305, 31.736, both Psteatosis (92.3%, 100%, respectively, vs. 53.8%, χ 2 =4.887, 7.800, P=0.037, 0.007, respectively). Both CAP and HSI had lower underestimation rates of steatosis grade than ultrasound (12%, 14.8%, respectively, vs. 29.5%, χ 2 =9.765, 6.452; Phepatic steatosis than HSI and ultrasound in patients with CHB, but further studies are needed to reduce the overestimation rates. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Quercetin loaded biopolymeric colloidal particles prepared by simultaneous precipitation of quercetin with hydrophobic protein in aqueous medium.

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Patel, Ashok R; Heussen, Patricia C M; Hazekamp, Johan; Drost, Ellen; Velikov, Krassimir P

2012-07-15

Quercetin loaded biopolymeric colloidal particles were prepared by precipitating quercetin (water insoluble polyphenol) and zein (hydrophobic protein), simultaneously, by adding their hydro-alcoholic solution to aqueous solution in presence of sodium caseinate as an electrosteric stabiliser. The presence of protein resulted in altering the shape of quercetin precipitates from needle-like to spherical shape at higher zein proportions, as confirmed by transmission electron microscopy. The average particle size of zein:quercetin composite particles was below 200 nm (130-161 nm) with negative surface charge (-30 to -41 mV), as confirmed by dynamic light scattering and electrophoretic mobility data. Solid state characterisation (X-ray diffraction) and spectroscopic measurements (UV-Vis and IR spectroscopy) confirmed characteristic changes in quercetin due to the entrapment in the biopolymeric matrix of colloidal particles. Results from anti-oxidant study demonstrated the advantage of entrapping quercetin in the colloidal particles in terms of the chemical stability in the alkaline pH and against photodegradation under UV-light irradiation. Copyright © 2012 Elsevier Ltd. All rights reserved.

The flavonoid quercetin reverses pulmonary hypertension in rats.

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Daniel Morales-Cano

Full Text Available Quercetin is a dietary flavonoid which exerts vasodilator, antiplatelet and antiproliferative effects and reduces blood pressure, oxidative status and end-organ damage in humans and animal models of systemic hypertension. We hypothesized that oral quercetin treatment might be protective in a rat model of pulmonary arterial hypertension. Three weeks after injection of monocrotaline, quercetin (10 mg/kg/d per os or vehicle was administered for 10 days to adult Wistar rats. Quercetin significantly reduced mortality. In surviving animals, quercetin decreased pulmonary arterial pressure, right ventricular hypertrophy and muscularization of small pulmonary arteries. Classic biomarkers of pulmonary arterial hypertension such as the downregulated expression of lung BMPR2, Kv1.5, Kv2.1, upregulated survivin, endothelial dysfunction and hyperresponsiveness to 5-HT were unaffected by quercetin. Quercetin significantly restored the decrease in Kv currents, the upregulation of 5-HT2A receptors and reduced the Akt and S6 phosphorylation. In vitro, quercetin induced pulmonary artery vasodilator effects, inhibited pulmonary artery smooth muscle cell proliferation and induced apoptosis. In conclusion, quercetin is partially protective in this rat model of PAH. It delayed mortality by lowering PAP, RVH and vascular remodeling. Quercetin exerted effective vasodilator effects in isolated PA, inhibited cell proliferation and induced apoptosis in PASMCs. These effects were associated with decreased 5-HT2A receptor expression and Akt and S6 phosphorylation and partially restored Kv currents. Therefore, quercetin could be useful in the treatment of PAH.

QUERCETIN PHYSICAL-CHEMICAL CHARACTERISTICS’ DEFINITION

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I. V. Kovalevska

2014-04-01

Full Text Available Introduction. The working out of the medicines on the basis of natural bioflavonoids, quercetin in particular, is a perspective direction of broading doctors’ remedy arsenal with polytropic effect. Quercetin has different pharmacological aspects: anti-inflammatory, antioxidant, radioprotective effects and has elements of cardio-, nephro-, gastro- and hondroprotection. Materials and methods. The object of the research is quercetin substance. Microscopic analysis has been held with the help of laboratory microscope «Konus-Akademy» with ocular-camera Scope Tek DCM510. To visualize the pictures software Scope Photo™ has been used, that allowed to measure the line sizes in real time condition and create stative picture. To define the form the roundedness parameter definition has been used, which can be found as ratio of circumference length with the same area as a particle to the factual particle perimeter. The cosine of angle soaking has been researched according to the dynamics of liquid penetration into the substance within 10 minutes. Results and discussions. The results of microscopic analysis indicate that quercetin substance refers to crystalline monoclinical system. The particles have anisodiametrical form with the fragments on the surface. Form factor is 0,2. The roundedness parameter is approaching 0. The particles are able to agglomerate. The definition of not crushed substance fraction composition by means of sieve analysis showed the advantages of 1 mkm particles. The use of microscopic method allowed to establish that the main particle size of not crushed substance vacillates in the interval 1-0,5 mkm, crushed is 0,5-0,25 mkm. The vacillation of the particle size depending on definition method could be explained by the presence of electrostatic power connections between quercetin particles. According to the received dissolvation data quercetin can be referred to the fourth class of biovailability. It allows to affirm the reason of

Effect of Short-term Quercetin, Caloric Restriction and Combined Treatment on Age-related Oxidative Stress Markers in the Rat Cerebral Cortex

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Alugoju, Phaniendra; Swamy, Vkd Krishan; Periyasamy, Latha

2018-03-14

Aging is characterized by gradual accumulation of macromolecular damage leading to progressive loss of physiological function and increased susceptibility to diverse diseases. Effective anti-aging strategies involving caloric restriction or antioxidant supplementation are receiving growing attention to attenuate macromolecular damage in age associated pathology. In the present study, we for the first time investigated the effect of quercetin, caloric restriction and combined treatment (caloric restriction with quercetin) on oxidative stress parameters, acetylcholinesterase and ATPases enzyme activities in the cerebral cortex of aged male Wistar rats. 21 months aged rats were divided into four groups (n=6-8) such as group 1-fed ad libitum (AL); group 2-quercetin supplementation of 50 mg/kg b.w/day for 45 days fed ad libitum (QUER); group 3: caloric restricted (CR) (fed 40% reduced AL for 45 days); group 4-fed 40% CR and 50 mg/kg b.w/day QUER for 45 days (CR + QUER). Group 5-three month age old rats served as young control (YOUNG). Our results demonstrate that combined treatment of caloric restriction and quercetin significantly improved the age associated decline in the activities of endogenous antioxidant enzymes [such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)] and glutathione (GSH) content and attenuated elevated levels of protein carbonyl content (PCC), lipid peroxidation, lipofuscin, reactive oxygen species (ROS), and nitric oxide (NO). Furthermore, it is also observed that combined treatment ameliorated age associated alterations in acetylcholine esterase (AChE) and adenosine triphosphatases (ATPases) such as Na+/K+-ATPase and Ca+2-ATPase (but not Mg+2- ATPase) enzyme activities. Finally, we conclude that combined treatment of caloric restriction and quercetin (but not either treatment alone) in late life is an effective anti-aging therapy to counteract the age related accumulation of oxidative macromolecular damage

The relationship between visceral obesity and hepatic steatosis measured by controlled attenuation parameter

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Jung, Kyu Sik; Chon, Young Eun; Huh, Ji Hye; Park, Kyeong Hye; Chung, Jae Bock; Kim, Chang Oh; Han, Kwang-Hyub

2017-01-01

Background Nonalcoholic fatty liver disease (NAFLD) is closely related with obesity. However, obese subjects, generally represented by high BMI, do not always develop NAFLD. A number of possible causes of NAFLD have been studied, but the exact mechanism has not yet been elucidated. Methods A total of 304 consecutive subjects who underwent general health examinations including abdominal ultrasonography, transient elastography and abdominal fat computed tomography were prospectively enrolled. Significant steatosis was diagnosed by ultrasonography and controlled attenuation parameter (CAP) assessed by transient elastography. Results Visceral fat area (VFA) was significantly related to hepatic steatosis assessed by CAP, whereas body mass index (BMI) was related to CAP only in univariate analysis. In multiple logistic regression analysis, VFA (odds ratio [OR], 1.010; 95% confidence interval [CI], 1.001–1.019; P = 0.028) and triglycerides (TG) (OR, 1.006; 95% CI, 1.001–1.011; P = 0.022) were independent risk factors for significant hepatic steatosis. The risk of significant hepatic steatosis was higher in patients with higher VFA: the OR was 4.838 (P200 cm2, compared to patients with a VFA ≤100 cm2. Conclusions Our data demonstrated that VFA and TG is significantly related to hepatic steatosis assessed by CAP not BMI. This finding suggests that surveillance for subjects with NAFLD should incorporate an indicator of visceral obesity, and not simply rely on BMI. PMID:29077769

Quercetin and quercetin 3-O-glycosides from Bauhinia longifolia (Bong.) Steud. show anti-Mayaro virus activity.

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dos Santos, Alda E; Kuster, Ricardo M; Yamamoto, Kristie A; Salles, Tiago S; Campos, Renata; de Meneses, Marcelo D F; Soares, Márcia R; Ferreira, Davis

2014-03-28

The arthropod-borne Mayaro virus (MAYV) causes 'Mayaro fever', a disease of medical significance, primarily affecting individuals in permanent contact with forested areas in tropical South America. Recently, MAYV has attracted attention due to its likely urbanization. Currently, there are no licensed drugs against most mosquito-transmitted viruses. Here, we investigated the in vitro anti-MAYV activity of the flavonoids quercetin and its derivatives from the Brazilian shrub Bauhinia longifolia (Bong.) Steud. Flavonoids were purified by chromatographic fractionation from leaf extracts of B. longifolia and chemically identified as quercetin and quercetin glycosides using spectroscopic techniques. Cytotoxicity of purified flavonoids and of EtOAc- and n-BuOH-containing flavonoid mixtures was measured by the dye-uptake assay while their antiviral activity was evaluated by a virus yield inhibition assay. The following flavonoids were purified from B. longifolia leaves: non-glycosylated quercetin and its glycosides guaijaverin, quercitrin, isoquercitrin, and hyperin. EtOAc and n-BuOH fractions containing these flavonoids demonstrated the highest antiviral activity of all tested substances, while quercetin had the highest antiviral activity amongst purified flavonoids. Quercetin, EtOAc, or n-BuOH fractions inhibited MAYV production by more than 90% at 25 μg/mL, displaying a stronger antiviral effect than the licensed antiviral ribavirin. A mixture of the isomers isoquercitrin and hyperin had a modest antiviral effect (IC90 = 104.9), while guaijaverin and quercitrin did not show significant antiviral activity. B. longifolia is a good source of flavonoids with anti-Mayaro virus activity. This is the first report of the activity of quercetin and its derivatives against an alphavirus.

Hydrogen sulfide, a potential novel drug, attenuates concanavalin A-induced hepatitis

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Cheng P

2014-09-01

Full Text Available Ping Cheng,* Kan Chen,* Yujing Xia, Weiqi Dai, Fan Wang, Miao Shen, Chengfen Wang, Jing Yang, Rong Zhu, Huawei Zhang, Jingjing Li, Yuanyuan Zheng, Junshan Wang, Yan Zhang, Jie Lu, Yingqun Zhou, Chuanyong GuoDepartment of Gastroenterology, Shanghai Tenth People's Hospital, Tongji University of Medicine, Shanghai, People's Republic of China *These authors contributed equally to this work Background: Hydrogen sulfide (H2S is known to exert anti-inflammatory properties. Apoptosis and autophagy play important roles in concanavalin A (Con A-induced acute hepatitis. The purpose of this study was to explore both the effect and mechanism of H2S on Con A-induced acute hepatitis. Methods: BALB/c mice were randomized into sham group, Con A-injection group, and 14 µmol/kg of sodium hydrosulfide (NaHS, an H2S donor pretreatment group. Results: Aspartate aminotransferase, alanine aminotransferase, and pathological damage were significantly ameliorated by NaHS pretreatment. NaHS pretreatment significantly reduced the levels of interleukin-6 and tumor necrosis factor-α compared with those of the Con A group. The expression of Bcl-2, Bax, Beclin-1, and LC3-2, which play important roles in the apoptosis and autophagy pathways, were also clearly affected by NaHS. Furthermore, NaHS affected the p-mTOR and p-AKT. Conclusion: H2S attenuates Con A-induced acute hepatitis by inhibiting apoptosis and autophagy, in part, through activation of the PtdIns3K-AKT1 signaling pathway. Keywords: NaHS, apoptosis, PtdIns3K-AKT, autophagy

Quercetin Feeding in Newborn Dairy Calves Cannot Compensate Colostrum Deprivation: Study on Metabolic, Antioxidative and Inflammatory Traits

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Gruse, Jeannine; Kanitz, Ellen; Weitzel, Joachim M.; Tuchscherer, Armin; Stefaniak, Tadeusz; Jawor, Paulina; Wolffram, Siegfried; Hammon, Harald M.

2016-01-01

formula- than in colostrum-fed groups. Hepatic mRNA expression of tumor necrosis factor was higher after quercetin feeding and expression of C-reactive protein was higher after formula feeding. Data confirm that colostrum improves neonatal health and indicate that quercetin feeding cannot compensate for insufficient colostrum supply. PMID:26752173

Short-Term Hypocaloric High-Fiber and High-Protein Diet Improves Hepatic Steatosis Assessed by Controlled Attenuation Parameter.

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Arslanow, Anita; Teutsch, Melanie; Walle, Hardy; Grünhage, Frank; Lammert, Frank; Stokes, Caroline S

2016-06-16

Non-alcoholic fatty liver disease is one of the most prevalent liver diseases and increases the risk of fibrosis and cirrhosis. Current standard treatment focuses on lifestyle interventions. The primary aim of this study was to assess the effects of a short-term low-calorie diet on hepatic steatosis, using the controlled attenuation parameter (CAP) as quantitative tool. In this prospective observational study, 60 patients with hepatic steatosis were monitored during a hypocaloric high-fiber, high-protein diet containing 1,000 kcal/day. At baseline and after 14 days, we measured hepatic fat contents using CAP during transient elastography, body composition with bioelectrical impedance analysis, and serum liver function tests and lipid profiles using standard clinical-chemical assays. The median age was 56 years (25-78 years); 51.7% were women and median body mass index was 31.9 kg/m(2) (22.4-44.8 kg/m(2)). After 14 days, a significant CAP reduction (14.0%; Pdiet, together with reductions of body composition parameters, serum lipids, and liver enzymes, pointing to the dynamics of hepatic lipid turnover.

Prophylactic Treatment with Cerium Oxide Nanoparticles Attenuate Hepatic Ischemia Reperfusion Injury in Sprague Dawley Rats

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Nandini D.P.K. Manne

2017-07-01

Full Text Available Background: Hepatic ischemia reperfusion is one the main causes for graft failure following transplantation. Although, the molecular events that lead to hepatic failure following ischemia reperfusion (IR are diverse and complex, previous studies have shown that excessive formation of reactive oxygen species (ROS are responsible for hepatic IR injury. Cerium oxide (CeO2 nanoparticles have been previously shown to act as an anti-oxidant and anti-inflammatory agent. Here, we evaluated the protective effects of CeO2 nanoparticles on hepatic ischemia reperfusion injury. Methods: Male Sprague Dawley rats were randomly assigned to one of the four groups: Control, CeO2 nanoparticle only, hepatic ischemia reperfusion (IR group and hepatic ischemia reperfusion (IR plus CeO2 nanoparticle group (IR+ CeO2. Partial warm hepatic ischemia was induced in left lateral and median lobes for 1h, followed by 6h of reperfusion. Animals were sacrificed after 6h of reperfusion and blood and tissue samples were collected and processed for various biochemical experiments. Results: Prophylactic treatment with CeO2 nanoparticles (0.5mg/kg i.v (IR+CeO2 group 1 hour prior to hepatic ischemia and subsequent reperfusion injury lead to a decrease in serum levels of alanine aminotransaminase and lactate dehydrogenase at 6 hours after reperfusion. These changes were accompanied by significant decrease in hepatocyte necrosis along with reduction in several serum inflammatory markers such as macrophage derived chemokine, macrophage inflammatory protein-2, KC/GRO, myoglobin and plasminogen activator inhibitor-1. However, immunoblotting demonstrated no significant changes in the levels of apoptosis related protein markers such as bax, bcl2 and caspase 3 in IR and IR+ CeO2 groups at 6 hours suggesting necrosis as the main pathway for hepatocyte death. Conclusion: Taken together, these data suggest that CeO2 nanoparticles attenuate IR induced cell death and can be used as a prophylactic

A diet high in α-linolenic acid and monounsaturated fatty acids attenuates hepatic steatosis and alters hepatic phospholipid fatty acid profile in diet-induced obese rats.

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Hanke, Danielle; Zahradka, Peter; Mohankumar, Suresh K; Clark, Jaime L; Taylor, Carla G

2013-01-01

This study investigated the efficacy of the plant-based n-3 fatty acid, α-linolenic acid (ALA), a dietary precursor of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), for modulating hepatic steatosis. Rats were fed high fat (55% energy) diets containing high oleic canola oil, canola oil, a canola/flax oil blend (C/F, 3:1), safflower oil, soybean oil, or lard. After 12 weeks, C/F and weight-matched (WM) groups had 20% less liver lipid. Body mass, liver weight, glucose and lipid metabolism, inflammation and molecular markers of fatty acid oxidation, synthesis, desaturation and elongation did not account for this effect. The C/F group had the highest total n-3 and EPA in hepatic phospholipids (PL), as well as one of the highest DHA and lowest arachidonic acid (n-6) concentrations. In conclusion, the C/F diet with the highest content of the plant-based n-3 ALA attenuated hepatic steatosis and altered the hepatic PL fatty acid profile. © 2013 Published by Elsevier Ltd.

Development of Validated High-performance Thin-layer Chromatography Method for Simultaneous Determination of Quercetin and Kaempferol in Thespesia populnea.

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Panchal, Hiteksha; Amin, Aeshna; Shah, Mamta

2017-01-01

Thespesia populnea L. (Family: Malvaceae) is a well-known medicinal plant distributed in tropical regions of the world and cultivated in South Gujarat and indicated to be useful in cutaneous affections, psoriasis, ringworm, and eczema. Bark and fruits are indicated in the diseases of skin, urethritis, and gonorrhea. The juice of fruits is employed in treating certain hepatic diseases. The plant is reported to contain flavonoids, quercetin, kaempferol, gossypetin, Kaempferol-3-monoglucoside, β-sitosterol, kaempferol-7-glucoside, and gossypol. T. populnea is a common component of many herbal and Ayurvedic formulation such as Kamilari and Liv-52. The present study aimed at developing validated and reliable high-performance thin layer chromatography (HPTLC) method for the analysis of quercetin and kaempferol simultaneously in T. populnea . The method employed thin-layer chromatography aluminum sheets precoated with silica gel as the stationary phase and toluene: ethyl acetate: formic acid (6:4:0.3 v/v/v) as the mobile phase, which gave compact bands of quercetin and kaempferol. Linear regression data for the calibration curves of standard quercetin and kaempferol showed a good linear relationship over a concentration range of 100-600 ng/spot and 500-3000 ng/spot with respect to the area and correlation coefficient (R2) was 0.9955 and 0.9967. The method was evaluated regarding accuracy, precision, selectivity, and robustness. Limits of detection and quantitation were recorded as 32.06 and 85.33 ng/spot and 74.055 and 243.72 ng/spot for quercetin and kaempferol, respectively. We concluded that this method employing HPTLC in the quantitative determination of quercetin and kaempferol is efficient, simple, accurate, and validated.

The supplement-drug interaction of quercetin with tamsulosin on vasorelaxation.

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Vrolijk, Misha F; Haenen, Guido R M M; Opperhuizen, Antoon; Jansen, Eugène H J M; Schiffers, Paul M; Bast, Aalt

2015-01-05

The food supplement quercetin is used as self-medication for prostate disorders and is known to induce vasorelaxation. The drug tamsulosin is used in the treatment of benign prostatic hyperplasia. A major side effect of tamsulosin is orthostatic hypotension, mediated by vasorelaxation resulting from α1-adrenoceptor blockade. The overlapping profile prompted us to investigate the pharmacodynamic interaction of quercetin with tamsulosin. Since quercetin is extensively metabolized in the intestines and the liver, the metabolites quercetin-3-glucuronide and 4'O-methyl-quercetin were also examined. Vasorelaxation induced by the compounds was tested in rat mesenteric arteries (average diameter: 360±μm) constricted by the α1-adrenoceptor agonist phenylephrine. Tamsulosin (0.1nM) decreased phenylephrine sensitivity 17-fold (n=10). Quercetin (5, 10 and 20µM) also caused a decrease (2-, 4- and 6-fold respectively) of phenylephrine sensitivity, while 10µM of quercetin-3-glucuronide and 4'O-methyl-quercetin decreased this sensitivity (1.5- and 2-fold) only slightly (n=6). The combination of tamsulosin with quercetin or quercetin metabolites proved to be far more potent than the compounds in isolation. The combination of quercetin, quercetin-3-glucuronide or 4'O-methyl-quercetin with tamsulosin decreased the phenylephrine sensitivity approximately 200-, 35- and 150-fold (n=6). The strong pharmacodynamic interaction between the food supplement quercetin and tamsulosin underlines the potential of the impact of supplement-drug interactions that warrant more research. Copyright © 2014 Elsevier B.V. All rights reserved.

Silymarin attenuated hepatic steatosis through regulation of lipid metabolism and oxidative stress in a mouse model of nonalcoholic fatty liver disease (NAFLD).

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Ni, Xunjun; Wang, Haiyan

2016-01-01

Silymarin, which derived from the milk thistle plant (silybum marianum), has been used for centuries as a natural remedy for diseases of the liver and biliary tract. Considering the therapeutic potential to liver disease, we tested efficacy of silymarin on hepatic steatosis with a high fat diet (HFD)-induced mouse model of non-alcoholic fatty liver disease (NAFLD), and investigated possible effects on lipid metabolic pathways. In our study, silymarin could attenuate the hepatic steatosis, which was proved by both Oil Red O staining and hepatic triglyceride (TG) level determination. Furthermore, compared with INT-747, a potent and selective FXR agonist, silymarin could preserve plasmatic high-density lipoprotein cholesterol (HDL-C) to a higher level and low-density lipoprotein cholesterol (LDL-C) to a lower level, which benefited more to the circulation system. Through real-time PCR analysis, we clarified a vital protective role of silymarin in mRNA regulation of genes involved in lipid metabolism and oxidative stress. It was also shown that silymarin had no effects on body weight, food intake, and liver transaminase. Taken together, silymarin could attenuate hepatic steatosis in a mouse model of NAFLD through regulation of lipid metabolism and oxidative stress, and benefit to the circulation system. All these findings shed new light on NAFLD treatment.

Tangshen formula attenuates hepatic steatosis by inhibiting hepatic lipogenesis and augmenting fatty acid oxidation in db/db mice.

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Kong, Qin; Zhang, Haojun; Zhao, Tingting; Zhang, Weiku; Yan, Meihua; Dong, Xi; Li, Ping

2016-12-01

Tangshen formula (TSF), a well-prescribed traditional Chinese formula, has been used in the treatment of diabetic nephropathy. However, whether TSF ameliorates dyslipidemia and liver injury associated with diabetes remains unclear. In this study, we examined the effects of TSF on lipid profiles and hepatic steatosis in db/db mice. For this purpose, 8‑week-old db/db mice were treated with TSF or saline for 12 weeks via gavage and db/m mice were used as controls. Body weight and blood glucose levels were monitored weekly and bi-weekly, respectively. Blood samples were obtained for the analysis of lipids and enzymes related to hepatic function, and liver tissues were analyzed by histology, immunohistochemistry and molecular examination. The results revealed that TSF markedly reduced body weight, liver index [liver/body weight (LW/BW)] and improved lipid profiles, hepatic function and steatosis in db/db mice. TSF induced the phosphoralation of AMP-activated protein kinase and inhibited the activity of sterol regulatory element-binding protein 1 together with the inhibition of the expression of genes involved in de novo lipogenesis (DNL) and gluconeogenesis, such as fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), stearoyl CoA desaturase 1 (SCD1), glucose-6-phosphatase (G6pc) and phosphoenolpyruvate carboxykinase 1 (Pck1). Additionally, the silent mating type information regulation 2 homolog 1 (Sirt1)/peroxisome proliferator-activated receptor α (PPARα)/malonyl-CoA decarboxylase (MLYCD) cascade was potently activated by TSF in the liver and skeletal muscle of db/db mice, which led to enhanced fatty acid oxidation. These findings demonstrated that TSF attenuated hepatic fat accumulation and steatosis in db/db mice by inhibiting lipogenesis and augmenting fatty acid oxidation.

Quercetin Efficacy on in vitro Maturation of Porcine Oocytes

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Delia Orlovschi

2014-05-01

Full Text Available The present study proposed to examine the effects of a polyphenol (quercetin on in vitro maturated parameters. Quercetin it has been extensively studied by researchers on animals over the 35 years. It is a plant derived flavonoid from fruits and vegetables that has antioxidant action as a free radical scavenger. Immature porcine oocytes were untreated and treated with 5, 15, 25, 35 µg/ml quercetin during in vitro maturation. After then the mature oocytes were fertilized. It was observed that cumulus cell expansion of COCs cultured in maturation media supplemented with 5 µg/ml quercetin in grad 3 could be very significantly increased (p<0.001. In grad 4 could be significantly between different levels of quercetin (5 vs. 25, 5 vs. 35, p<0.001. The rates of embryos cultured in medium supplemented with different levels of quercetin did not presented significantly statistically different. The presence of 25 µg/ml quercetin in the maturation medium increased the percentage of embryos in the morula stage compared with the control. In the morula stage all the concentrations of quercetin resulted percentages increased to control. This results shows that quercetin added during in vitro maturation has a positive effect on future embryos development.

Electrical characterization of Au/quercetin/n-Si heterojunction diode and optical analysis of quercetin thin film

International Nuclear Information System (INIS)

Tombak, Ahmet; Özaydin, C.; Boğa, M.; Kiliçoğlu, T.

2016-01-01

Quercetin (3,5,7,3’,4’-pentahydroxyflavone, QE), one of the most widely distributed flavonoids in fruits and vegetables, has been reported to possess a wide variety of biological effects, including anti-oxidative, anti-inflammatory, anti-apoptosis, hepatoprotective, renoprotective and neuroprotective effects. In this study organic-inorganic junctions were fabricated by forming quercetin complex thin film using spin coating technique on n-Si and evaporating Au metal on the film. Optical properties of quercetin thin film were studied with the help of spectrophotometer. The current-voltage (I-V) characteristic of Au/quercetin/n-Si heterojunction diode was investigated at room temperature in dark. Some basic parameters of the diode such as ideality factor, rectification ratio, barrier height, series resistance and shunt resistance were calculated using dark current-voltage measurement. It was also seen that the device had good sensitivity to the light under 40-100 mW/cm"2 illumination conditions.

Electrical characterization of Au/quercetin/n-Si heterojunction diode and optical analysis of quercetin thin film

Energy Technology Data Exchange (ETDEWEB)

Tombak, Ahmet, E-mail: tahmet@yahoo.com [Department of Physics, Faculty of Art& Science, Batman University, Batman 72000 (Turkey); Özaydin, C. [Department of Computer Engineering, Faculty of Engineering and Architecture, Batman University, Batman 72000 (Turkey); Boğa, M. [Faculty of Pharmacy, Pharmaceutical Technology Department, Dicle University, Diyarbakir 21280 (Turkey); Kiliçoğlu, T. [Department of Physics, Faculty of Science, Dicle University, Diyarbakir 21280 (Turkey)

2016-03-25

Quercetin (3,5,7,3’,4’-pentahydroxyflavone, QE), one of the most widely distributed flavonoids in fruits and vegetables, has been reported to possess a wide variety of biological effects, including anti-oxidative, anti-inflammatory, anti-apoptosis, hepatoprotective, renoprotective and neuroprotective effects. In this study organic-inorganic junctions were fabricated by forming quercetin complex thin film using spin coating technique on n-Si and evaporating Au metal on the film. Optical properties of quercetin thin film were studied with the help of spectrophotometer. The current-voltage (I-V) characteristic of Au/quercetin/n-Si heterojunction diode was investigated at room temperature in dark. Some basic parameters of the diode such as ideality factor, rectification ratio, barrier height, series resistance and shunt resistance were calculated using dark current-voltage measurement. It was also seen that the device had good sensitivity to the light under 40-100 mW/cm{sup 2} illumination conditions.

Adenoviral overexpression of Lhx2 attenuates cell viability but does not preserve the stem cell like phenotype of hepatic stellate cells

Energy Technology Data Exchange (ETDEWEB)

Genz, Berit [Institute for Experimental Surgery, Rostock University Medical Center, Rostock (Germany); Thomas, Maria [Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart (Germany); Pützer, Brigitte M. [Institute of Experimental Gene Therapy and Cancer Research, Rostock University Medical Center, Rostock (Germany); Siatkowski, Marcin; Fuellen, Georg [Institute for Biostatistics and Informatics in Medicine and Ageing Research, Rostock University Medical Center, Rostock (Germany); Vollmar, Brigitte [Institute for Experimental Surgery, Rostock University Medical Center, Rostock (Germany); Abshagen, Kerstin, E-mail: kerstin.abshagen@uni-rostock.de [Institute for Experimental Surgery, Rostock University Medical Center, Rostock (Germany)

2014-11-01

Hepatic stellate cells (HSC) are well known initiators of hepatic fibrosis. After liver cell damage, HSC transdifferentiate into proliferative myofibroblasts, representing the major source of extracellular matrix in the fibrotic organ. Recent studies also demonstrate a role of HSC as progenitor or stem cell like cells in liver regeneration. Lhx2 is described as stem cell maintaining factor in different organs and as an inhibitory transcription factor in HSC activation. Here we examined whether a continuous expression of Lhx2 in HSC could attenuate their activation and whether Lhx2 could serve as a potential target for antifibrotic gene therapy. Therefore, we evaluated an adenoviral mediated overexpression of Lhx2 in primary HSC and investigated mRNA expression patterns by qRT-PCR as well as the activation status by different in vitro assays. HSC revealed a marked increase in activation markers like smooth muscle actin alpha (αSMA) and collagen 1α independent from adenoviral transduction. Lhx2 overexpression resulted in attenuated cell viability as shown by a slightly hampered migratory and contractile phenotype of HSC. Expression of stem cell factors or signaling components was also unaffected by Lhx2. Summarizing these results, we found no antifibrotic or stem cell maintaining effect of Lhx2 overexpression in primary HSC. - Highlights: • We performed adenoviral overexpression of Lhx2 in primary hepatic stellate cells. • Hepatic stellate cells expressed stem cell markers during cultivation. • Cell migration and contractility was slightly hampered upon Lhx2 overexpression. • Lhx2 overexpression did not affect stem cell character of hepatic stellate cells.

Adenoviral overexpression of Lhx2 attenuates cell viability but does not preserve the stem cell like phenotype of hepatic stellate cells

International Nuclear Information System (INIS)

Genz, Berit; Thomas, Maria; Pützer, Brigitte M.; Siatkowski, Marcin; Fuellen, Georg; Vollmar, Brigitte; Abshagen, Kerstin

2014-01-01

Hepatic stellate cells (HSC) are well known initiators of hepatic fibrosis. After liver cell damage, HSC transdifferentiate into proliferative myofibroblasts, representing the major source of extracellular matrix in the fibrotic organ. Recent studies also demonstrate a role of HSC as progenitor or stem cell like cells in liver regeneration. Lhx2 is described as stem cell maintaining factor in different organs and as an inhibitory transcription factor in HSC activation. Here we examined whether a continuous expression of Lhx2 in HSC could attenuate their activation and whether Lhx2 could serve as a potential target for antifibrotic gene therapy. Therefore, we evaluated an adenoviral mediated overexpression of Lhx2 in primary HSC and investigated mRNA expression patterns by qRT-PCR as well as the activation status by different in vitro assays. HSC revealed a marked increase in activation markers like smooth muscle actin alpha (αSMA) and collagen 1α independent from adenoviral transduction. Lhx2 overexpression resulted in attenuated cell viability as shown by a slightly hampered migratory and contractile phenotype of HSC. Expression of stem cell factors or signaling components was also unaffected by Lhx2. Summarizing these results, we found no antifibrotic or stem cell maintaining effect of Lhx2 overexpression in primary HSC. - Highlights: • We performed adenoviral overexpression of Lhx2 in primary hepatic stellate cells. • Hepatic stellate cells expressed stem cell markers during cultivation. • Cell migration and contractility was slightly hampered upon Lhx2 overexpression. • Lhx2 overexpression did not affect stem cell character of hepatic stellate cells

Dietary supplementation of blueberry juice enhances hepatic expression of metallothionein and attenuates liver fibrosis in rats.

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Yuping Wang

Full Text Available To investigate the effect of blueberry juice intake on rat liver fibrosis and its influence on hepatic antioxidant defense.Rabbiteye blueberry was used to prepare fresh juice to feed rats by daily gastric gavage. Dan-shao-hua-xian capsule (DSHX was used as a positive control for liver fibrosis protection. Liver fibrosis was induced in male Sprague-Dawley rats by subcutaneous injection of CCl4 and feeding a high-lipid/low-protein diet for 8 weeks. Hepatic fibrosis was evaluated by Masson staining. The expression of α-smooth muscle actin (α-SMA and collagen III (Col III were determined by immunohistochemical techniques. The activities of superoxide dismutase (SOD and malondialdehyde (MDA in liver homogenates were determined. Metallothionein (MT expression was detected by real-time RT-PCR and immunohistochemical techniques.Blueberry juice consumption significantly attenuates CCl4-induced rat hepatic fibrosis, which was associated with elevated expression of metallothionein (MT, increased SOD activity, reduced oxidative stress, and decreased levels of α-SMA and Col III in the liver.Our study suggests that dietary supplementation of blueberry juice can augment antioxidative capability of the liver presumably via stimulating MT expression and SOD activity, which in turn promotes HSC inactivation and thus decreases extracellular matrix collagen accumulation in the liver, and thereby alleviating hepatic fibrosis.

Preventive effect of the flavonoid, quercetin, on hepatic cancer in rats via oxidant/antioxidant activity: molecular and histological evidences

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Seufi AlaaEddeen M

2009-06-01

Full Text Available Abstract Background The incidence of hepatocellular carcinoma is increasing in many countries. The estimated number of new cases annually is over 500,000, and the yearly incidence comprises between 2.5 and 7% of patients with liver cirrhosis. The incidence varies between different geographic areas, being higher in developing areas; males are predominantly affected, with a 2:3 male/female ratio Methods Experiments were designed to examine the effect of N-Nitrosodiethylamine (NDEA as cancer-inducer compound and to confirm the preventive effect of the flavonoid quercetin on hepatocellular carcinoma in rats. Briefly, thirty six male albino rats of Wistar strain were divided into 3 groups: the 1st group was administered NDEA alone (NDEA-treated, the 2nd group was treated simultaneously with NDEA and quercetin (NDEA+Q and the 3rd group was used as control (CON. Randomly amplified polymorphic DNA polymerase chain reaction (RAPD-PCR as well as p53-specifi PCR assays were employed to determine genomic difference between treated, and control animals. Histological confirmation as well as oxidant/antioxidant status of the liver tissue was done. Results RAPD analysis of liver samples generated 8 monomorphic bands and 22 polymorphic bands in a total of 30-banded RAPD patterns. Cluster analysis and statistical analyses of RAPD data resulted in grouping control and NDEA+Q samples in the same group with 80% similarity cut-off value. NDEA-treated samples were clustered in a separate group. Specific PCR assay for polymorphism of P53 gene revealed a uniform pattern of allele separation in both control and NDEA+Q samples. Quercetin anticancer effect was exhibited in significant decrease of oxidative stress and significant decrease of antioxidant activity. Histopathological studies showed normal liver histology of the NDEA+Q samples. Meanwhile, several cancer-induced features were clearly observable in NDEA-treated samples. Conclusion This paper demonstrated that

Quercetin - A Flavonoid Compound from Sarcopyramis bodinieri var ...

African Journals Online (AJOL)

DAPI staining and PARP SDS-PAGE tests showed 60 μM quercetin could induce potential apoptotic activity in HepG2 liver cancer cells. Conclusion: Quercetin was the major cytotoxicity constituent in S. bodinieri var. delicate. Keywords: Apoptotic activity, Quercetin, Sarcopyramis bodinieri var. delicate, HepG2 liver cancer ...

Spectrophotometric determination of uranium using quercetin

International Nuclear Information System (INIS)

Barros, A.R.

1972-10-01

A spectrophotometric method for quantitative determination of uranium, using a flavone (quercetin) as complexing agent, is described. The method is based on the reaction between uranyl ion and alcoholic solution of quercetin with a complex formation of intense yellow color. (M.C.L.) [pt

Application of Bioactive Quercetin in Oncotherapy: From Nutrition to Nanomedicine

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Ju-Suk Nam

2016-01-01

Full Text Available Phytochemicals as dietary constituents are being explored for their cancer preventive properties. Quercetin is a major constituent of various dietary products and recently its anti-cancer potential has been extensively explored, revealing its anti-proliferative effect on different cancer cell lines, both in vitro and in vivo. Quercetin is known to have modulatory effects on cell apoptosis, migration and growth via various signaling pathways. Though, quercetin possesses great medicinal value, its applications as a therapeutic drug are limited. Problems like low oral bioavailability and poor aqueous solubility make quercetin an unreliable candidate for therapeutic purposes. Additionally, the rapid gastrointestinal digestion of quercetin is also a major barrier for its clinical translation. Hence, to overcome these disadvantages quercetin-based nanoformulations are being considered in recent times. Nanoformulations of quercetin have shown promising results in its uptake by the epithelial system as well as enhanced delivery to the target site. Herein we have tried to summarize various methods utilized for nanofabrication of quercetin formulations and for stable and sustained delivery of quercetin. We have also highlighted the various desirable measures for its use as a promising onco-therapeutic agent.

Interactions of quercetin-uranium complexes with biomembranes and DNA

Energy Technology Data Exchange (ETDEWEB)

Attia, Enas Mohammed Hassan

2014-07-21

Uranium decontamination gains a great importance with the spread of nuclear waste in both soil and water systems across the planet. All known remediation methods of uranium can be exclusively based either on synthetic materials with high adsorbent power and known physical chemistry or life organisms by which the uranium eventually accumulated inside their tissues. In the present thesis, it was attempted to design a rational approach for uranyl removal primarily from waters using the reducing potential of quercetin, which is a plant-derived small organic molecules, along with its photochemical activities. Such approach, which is neither a fully synthetic nor an organism-based approach, was chosen here to avoid disadvantages with both traditional strategies. Here, complexation experiments were designed to assess the use of uranyl-quercetin complexes for the photoreduction of water-soluble U(VI) to insoluble U(IV) by comparing absorption properties of uranyl-quercetin complexes in acetone, water, and hydrophobic bilayer lipid vesicles. The UV-vis data show that uranyl quercetin complex can form in both hydrophobic and hydrophilic environments. In both cases the B-ring band in quercetin structure becomes reduced, red shifted and a pronounced absorption arises in the 400-500 nm range. Such data suggests that U(VI) binds at the 3-OH and 4-carbonyl of ring C of quercetin. Interestingly, the results of UV-Vis spectroscopy part hint at a crucial role of a stable or transiently ionized hydroxyl for the efficient uranyl-dependent photodegradation of quercetin. FTIR spectroscopy absorption changes further demonstrates that the UV-vis-spectroscopic changes are indeed accompanied by changes in the chemical structure of the complex as expected for a uranyl-dependent photodegradation. IR data thus suggest that U(VI) becomes reduced by the photoreaction, rather than merely changing its coordination shell. The frequency shifts in the C=C and C=O absorption range on the other hand

Interactions of quercetin-uranium complexes with biomembranes and DNA

International Nuclear Information System (INIS)

Attia, Enas Mohammed Hassan

2014-01-01

Uranium decontamination gains a great importance with the spread of nuclear waste in both soil and water systems across the planet. All known remediation methods of uranium can be exclusively based either on synthetic materials with high adsorbent power and known physical chemistry or life organisms by which the uranium eventually accumulated inside their tissues. In the present thesis, it was attempted to design a rational approach for uranyl removal primarily from waters using the reducing potential of quercetin, which is a plant-derived small organic molecules, along with its photochemical activities. Such approach, which is neither a fully synthetic nor an organism-based approach, was chosen here to avoid disadvantages with both traditional strategies. Here, complexation experiments were designed to assess the use of uranyl-quercetin complexes for the photoreduction of water-soluble U(VI) to insoluble U(IV) by comparing absorption properties of uranyl-quercetin complexes in acetone, water, and hydrophobic bilayer lipid vesicles. The UV-vis data show that uranyl quercetin complex can form in both hydrophobic and hydrophilic environments. In both cases the B-ring band in quercetin structure becomes reduced, red shifted and a pronounced absorption arises in the 400-500 nm range. Such data suggests that U(VI) binds at the 3-OH and 4-carbonyl of ring C of quercetin. Interestingly, the results of UV-Vis spectroscopy part hint at a crucial role of a stable or transiently ionized hydroxyl for the efficient uranyl-dependent photodegradation of quercetin. FTIR spectroscopy absorption changes further demonstrates that the UV-vis-spectroscopic changes are indeed accompanied by changes in the chemical structure of the complex as expected for a uranyl-dependent photodegradation. IR data thus suggest that U(VI) becomes reduced by the photoreaction, rather than merely changing its coordination shell. The frequency shifts in the C=C and C=O absorption range on the other hand

Estimated Daily Intake and Seasonal Food Sources of Quercetin in Japan

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Haruno Nishimuro

2015-04-01

Full Text Available Quercetin is a promising food component, which can prevent lifestyle related diseases. To understand the dietary intake of quercetin in the subjects of a population-based cohort study and in the Japanese population, we first determined the quercetin content in foods available in the market during June and July in or near a town in Hokkaido, Japan. Red leaf lettuce, asparagus, and onions contained high amounts of quercetin derivatives. We then estimated the daily quercetin intake by 570 residents aged 20–92 years old in the town using a food frequency questionnaire (FFQ. The average and median quercetin intakes were 16.2 and 15.5 mg day−1, respectively. The quercetin intakes by men were lower than those by women; the quercetin intakes showed a low correlation with age in both men and women. The estimated quercetin intake was similar during summer and winter. Quercetin was mainly ingested from onions and green tea, both in summer and in winter. Vegetables, such as asparagus, green pepper, tomatoes, and red leaf lettuce, were good sources of quercetin in summer. Our results will help to elucidate the association between quercetin intake and risks of lifestyle-related diseases by further prospective cohort study and establish healthy dietary requirements with the consumption of more physiologically useful components from foods.

Protective effect of quercetin on high-fat diet-induced non-alcoholic fatty liver disease in mice is mediated by modulating intestinal microbiota imbalance and related gut-liver axis activation.

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Porras, David; Nistal, Esther; Martínez-Flórez, Susana; Pisonero-Vaquero, Sandra; Olcoz, José Luis; Jover, Ramiro; González-Gallego, Javier; García-Mediavilla, María Victoria; Sánchez-Campos, Sonia

2017-01-01

Gut microbiota is involved in obesity, metabolic syndrome and the progression of nonalcoholic fatty liver disease (NAFLD). It has been recently suggested that the flavonoid quercetin may have the ability to modulate the intestinal microbiota composition, suggesting a prebiotic capacity which highlights a great therapeutic potential in NAFLD. The present study aims to investigate benefits of experimental treatment with quercetin on gut microbial balance and related gut-liver axis activation in a nutritional animal model of NAFLD associated to obesity. C57BL/6J mice were challenged with high fat diet (HFD) supplemented or not with quercetin for 16 weeks. HFD induced obesity, metabolic syndrome and the development of hepatic steatosis as main hepatic histological finding. Increased accumulation of intrahepatic lipids was associated with altered gene expression related to lipid metabolism, as a result of deregulation of their major modulators. Quercetin supplementation decreased insulin resistance and NAFLD activity score, by reducing the intrahepatic lipid accumulation through its ability to modulate lipid metabolism gene expression, cytochrome P450 2E1 (CYP2E1)-dependent lipoperoxidation and related lipotoxicity. Microbiota composition was determined via 16S ribosomal RNA Illumina next-generation sequencing. Metagenomic studies revealed HFD-dependent differences at phylum, class and genus levels leading to dysbiosis, characterized by an increase in Firmicutes/Bacteroidetes ratio and in Gram-negative bacteria, and a dramatically increased detection of Helicobacter genus. Dysbiosis was accompanied by endotoxemia, intestinal barrier dysfunction and gut-liver axis alteration and subsequent inflammatory gene overexpression. Dysbiosis-mediated toll-like receptor 4 (TLR-4)-NF-κB signaling pathway activation was associated with inflammasome initiation response and reticulum stress pathway induction. Quercetin reverted gut microbiota imbalance and related endotoxemia

Production of 3-O-xylosyl quercetin in Escherichia coli

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Pandey, Ramesh Prasad; Malla, Sailesh; Simkhada, Dinesh

2013-01-01

Quercetin, a flavonol aglycone, is one of the most abundant flavonoids with high medicinal value. The bioavailability and pharmacokinetic properties of quercetin are influenced by the type of sugars attached to the molecule. To efficiently diversify the therapeutic uses of quercetin, Escherichia ...

PHYSIOLOGICAL AND MEDICAL EFFECTS OF PLANT FLAVONOID QUERCETIN

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Aneta Štochmaľová

2013-02-01

Full Text Available Flavonoid compounds in vegetable-based diets bring a significant contribution to the role of fruits and vegetables as health-promoting foods. This review summarizes the available data concerning physiological and therapeutical effect of plan flavonoid quercetin. Quercetin has a number of beneficial influence on health because of their antioxidant, anti-inflammatory, anti-proliferative, anti-carcinogenic and anti-diabetes properties. Effects of quercetin have been explained by its interference with cellular enzymes, receptors, transporters and signal transduction systems. Despite the available data reviewed here, the targets, effects, absorption, metabolism and areas of practical application of quercetin are still poorly understood, therefore further studies in this areas are required.

Dietary Supplementation of Blueberry Juice Enhances Hepatic Expression of Metallothionein and Attenuates Liver Fibrosis in Rats

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Wang, Yuping; Cheng, Mingliang; Zhang, Baofang; Nie, Fei; Jiang, Hongmei

2013-01-01

Aim To investigate the effect of blueberry juice intake on rat liver fibrosis and its influence on hepatic antioxidant defense. Methods Rabbiteye blueberry was used to prepare fresh juice to feed rats by daily gastric gavage. Dan-shao-hua-xian capsule (DSHX) was used as a positive control for liver fibrosis protection. Liver fibrosis was induced in male Sprague-Dawley rats by subcutaneous injection of CCl4 and feeding a high-lipid/low-protein diet for 8 weeks. Hepatic fibrosis was evaluated by Masson staining. The expression of α-smooth muscle actin (α-SMA) and collagen III (Col III) were determined by immunohistochemical techniques. The activities of superoxide dismutase (SOD) and malondialdehyde (MDA) in liver homogenates were determined. Metallothionein (MT) expression was detected by real-time RT-PCR and immunohistochemical techniques. Results Blueberry juice consumption significantly attenuates CCl4-induced rat hepatic fibrosis, which was associated with elevated expression of metallothionein (MT), increased SOD activity, reduced oxidative stress, and decreased levels of α-SMA and Col III in the liver. Conclusion Our study suggests that dietary supplementation of blueberry juice can augment antioxidative capability of the liver presumably via stimulating MT expression and SOD activity, which in turn promotes HSC inactivation and thus decreases extracellular matrix collagen accumulation in the liver, and thereby alleviating hepatic fibrosis. PMID:23554912

Quercetin Affects Erythropoiesis and Heart Mitochondrial Function in Mice

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Lina M. Ruiz

2015-01-01

Full Text Available Quercetin, a dietary flavonoid used as a food supplement, showed powerful antioxidant effects in different cellular models. However, recent in vitro and in vivo studies in mammals have suggested a prooxidant effect of quercetin and described an interaction with mitochondria causing an increase in O2∙- production, a decrease in ATP levels, and impairment of respiratory chain in liver tissue. Therefore, because of its dual actions, we studied the effect of quercetin in vivo to analyze heart mitochondrial function and erythropoiesis. Mice were injected with 50 mg/kg of quercetin for 15 days. Treatment with quercetin decreased body weight, serum insulin, and ceruloplasmin levels as compared with untreated mice. Along with an impaired antioxidant capacity in plasma, quercetin-treated mice showed a significant delay on erythropoiesis progression. Heart mitochondrial function was also impaired displaying more protein oxidation and less activity for IV, respectively, than no-treated mice. In addition, a significant reduction in the protein expression levels of Mitofusin 2 and Voltage-Dependent Anion Carrier was observed. All these results suggest that quercetin affects erythropoiesis and mitochondrial function and then its potential use as a dietary supplement should be reexamined.

Relationship between Controlled Attenuation Parameter and Hepatic Steatosis as Assessed by Ultrasound in Alcoholic or Nonalcoholic Fatty Liver Disease.

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Ahn, Jem Ma; Paik, Yong-Han; Min, Sin Yeong; Cho, Ju Yeon; Sohn, Won; Sinn, Dong Hyun; Gwak, Geum-Youn; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul

2016-03-01

The aim of this study was to evaluate the relationship between controlled attenuation parameter (CAP) and hepatic steatosis, as assessed by ultrasound (US) in patients with alcoholic liver disease (ALD) or non-alcoholic fatty liver disease (NAFLD). Patients with either ALD or NAFLD who were diagnosed with fatty liver with US and whose CAP scores were measured, were retrospectively enrolled in this study. The degree of hepatic steatosis assessed by US was categorized into mild (S1), moderate (S2), and severe (S3). A total of 186 patients were included 106 with NAFLD and 80 with ALD. Regarding hepatic steatosis, the CAP score was significantly correlated with US (ρ=0.580, psteatosis were excellent (0.789 and 0.843, respectively). For sensitivity ≥ 90%, CAP cutoffs for the detection of ≥ S2 and ≥ S3 steastosis were separated with a gap of approximately 35 dB/m in all patients and in each of the NAFLD and ALD groups. The CAP score is well correlated with hepatic steatosis, as assessed by US, in both ALD and NAFLD.

Radioprotective effect of flavonoid quercetin on human lymphocytic cells

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Siqueira, Williams N.; Melo, Larissa S.A.; Lima, Maíra V.; Luna Filho, Ricardo L.C.; Melo, Ana M.M.A.; Silva, Edvane B.

2017-01-01

Several substances of synthetic and natural origin have been studied in relation to their ability to protect the body from damage caused by ionizing radiation. Among these substances, quercetin has been shown to be a molecule of natural origin with high radioprotective potential due to its antioxidant properties. The objective of this study was to determine, in vitro, the radioprotective effect of quercetin on human lymphocytes exposed to gamma radiation. Blood was irradiated at the 2.5, 3.5 and 4.5 Gy doses and then lymphocyte culture with quercetin at preselected concentrations of 37.5 and 75 μM. Subsequently, slides were prepared for analysis and quantification of the metaphases present in lymphocyte cells. The results demonstrated that irradiated lymphocytes and later exposed to quercetin presented a lower number of chromosomal alterations compared to the control group which was irradiated and not exposed to quercetin. Therefore, the results suggest a radioprotective effect of flavonoid quercetin on human lymphocytes exposed, in vitro, to ionizing radiation

Ergogenic effects of quercetin supplementation in trained rats

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Casuso Rafael A

2013-01-01

Full Text Available Abstract Background Quercetin is a natural polyphenolic compound currently under study for its ergogenic capacity to improve mitochondrial biogenesis. Sedentary mice have exhibited increased endurance performance, but results are contradictory in human models. Methods We examined the effects of six weeks of endurance training and quercetin supplementation on markers of endurance performance and training in a rodent model. Rats were randomly assigned to one of the following groups: placebo+sedentary (PS, quercetin+sedentary (QS, placebo+endurance training (PT and quercetin+endurance training (QT. Quercetin was administered at a dose of 25 mg/kg on alternate days. During six weeks of treatment volume parameters of training were recorded, and after six weeks all groups performed a maximal graded VO2 max test and a low-intensity endurance run-to-fatigue test. Results No effects were found in VO2 peak (p>0.999, nor in distance run during low-intensity test, although it was 14% greater in QT when compared with PT (P = 0.097. Post-exercise blood lactate was increased in QT when compared with PT (p=0.023 and also in QS compared with PS (p=0.024. Conclusions This study showed no effects in VO2 peak, speed at VO2 peak or endurance time to exhaustion after six weeks of quercetin supplementation compared with placebo in trained rats. Quercetin was show to increase blood lactate production after high-intensity exercise.

HPLC FOR CONTROL STABILITY OF QUERCETIN INJECTABLE DOSAGE FORM

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Martynov AV

2016-12-01

Full Text Available Introduction. Quercetin is a flavone derivatives which known like a substances with vitamin activity, high antioxidant, antimutagenic and anticarcinogenic activity and many other types of biological activity. Wide usage of quercetin prevents their polyphenolic nature structure which does not allow a high bioavailability of pure quercetin when administered orally. This is associated with a wide spectrum variety of chemical reactions for the phenolic groups: from interaction with amino acid residues in proteins to reactions with amine heterocyclic alkaloids and polysaccharides. In our days Corvitin – one from the number of quercetin based drugs with sufficiently low levels all types toxicity, allergenic and has no irritating action on intravenous administration. In the same time quercetin cannot be used in full measure because of the limited number of publications with analysis methods, especially HPLC. Determining the stability over time of concentrate quercetin solution, as well as determining the stability of the concentrate to the original autoclave sterilization conditions is a promising direction in creating new drugs. Materials and methods The objective was to research quercetin soluble formulation samples in different conditions: 1 fresh dilute concentrate (0.9% sodium chloride; 2 the original dilute concentrate, which was stored at room temperature for 14 days in light and 3 similar to the first sample dilute concentrate, which went before breeding in autoclaving at 120 0 C for 20 minutes. The objects used in the studies were industrial drug-substance quercetin (Sinkea manufactured (China, the original pharmaceutical composition as the soluble form of quercetin for injection and aerosol applications, glycerol (Sigma, Polysorbat 80 (Merk, ethanol 96 %. For the HPLC – analysis, chromatograph "Milichrom A-02" (SiChrom, Knauer (Econova, Novosibirsk, Russia was used. Results and discussion Quercetin was identified using information on its

Variation of quercetin glycoside derivatives in three onion (Allium cepa L. varieties

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Jung-Ho Kwak

2017-09-01

Full Text Available The aim of this study was to quantify the contents of individual quercetin glycosides in red, yellow and chartreuse onion by High Performance Liquid Chromatography (HPLC analysis. Acid hydrolysis of individual quercetin glycosides using 6 M hydrochloric acid guided to identify and separate quercetin 7,4′-diglucoside, quercetin 3-glucoside, quercetin 4′-glucoside, and quercetin. The contents of total quercetin glycosides varied extensively among three varieties (ranged from 16.10 to 103.93 mg/g DW. Quercetin was the predominant compound that accounted mean 32.21 mg/g DW in red onion (43.6% of the total and 127.92 mg/g DW in chartreuse onion (78.3% of the total followed by quercetin 3-glucoside (28.83 and 24.16 mg/g DW respectively. Quercetin 3-glucoside levels were much higher in yellow onion (43.85 mg/g DW followed by quercetin 30.08 mg/g DW. Quercetin 4′-glucoside documented the lowest amount that documented mean 2.4% of the total glycosides. The varied contents of glycosides present in the different onion varieties were significant.

Effect of quercetin on apoptosis of PANC-1 cells.

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Lee, Joo Hyun; Lee, Han-Beom; Jung, Gum O; Oh, Jung Taek; Park, Dong Eun; Chae, Kwon Mook

2013-12-01

To investigate the chemotherapeutic effect of quercetin against cancer cells, signaling pathway of apoptosis was explored in human pancreatic cells. Various anticancer drugs including adriamycin, cisplatin, 5-fluorouracil (5-FU) and gemcitabine were used. Cell viability was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphe-nyltetra zolium bromide assay. Apoptosis was determined by 4'-6-diamidino-2-phenylindole nuclei staining and flow cytometry in PANC-1 cells treated with 50 µg/mL quercetin for 24 hours. Expression of endoplas mic reticulum (ER) stress mediators including, Grp78/Bip, p-PERK, PERK, ATF4, ATF6 and GADD153/CHOP proteins were measured by Western blot analysis. Mitochondrial membrane potential was measured by fluorescence staining with JC-1, rhodamine 123. Quercetin induced the apoptosis of PANC-1, which was characterized as nucleic acid and genomic DNA fragmentation, chromatin condensation, and sub-G0/G1 fraction of cell cycle increase. But not adriamycin, cisplatin, gemcitabine, and 5-FU. PANC-1 cells were markedly sensitive to quercetin. Treatment with quercetin resulted in the increased accumulation of intracellular Ca(2+) ion. Treatment with quercetin also increased the expression of Grp78/Bip and GADD153/CHOP protein and induced mitochondrial dysfunction. Quercetin exerted cytotoxicity against human pancreatic cancer cells via ER stress-mediated apoptotic signaling including reactive oxygen species production and mitochondrial dysfunction. These data suggest that quercetin may be an important modulator of chemosensitivity of cancer cells against anticancer chemotherapeutic agents.

Epigallocatechin-3-gallate attenuates apoptosis and autophagy in concanavalin A-induced hepatitis by inhibiting BNIP3

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Li S

2016-02-01

Full Text Available Sainan Li, Yujing Xia, Kan Chen, Jingjing Li, Tong Liu, Fan Wang, Jie Lu, Yingqun Zhou, Chuanyong Guo Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China Background: Epigallocatechin-3-gallate (EGCG is the most effective compound in green tea, and possesses a wide range of beneficial effects, including anti-inflammatory, antioxidant, antiobesity, and anticancer effects. In this study, we investigated the protective effects of EGCG in concanavalin A (ConA-induced hepatitis in mice and explored the possible mechanisms involved in these effects.Methods: Balb/C mice were injected with ConA (25 mg/kg to induce acute autoimmune hepatitis, and EGCG (10 or 30 mg/kg was administered orally twice daily for 10 days before ConA injection. Serum liver enzymes, proinflammatory cytokines, and other marker proteins were determined 2, 8, and 24 hours after the ConA administration.Results: BNIP3 mediated cell apoptosis and autophagy in ConA-induced hepatitis. EGCG decreased the immunoreaction and pathological damage by reducing inflammatory factors, such as TNF-α, IL-6, IFN-γ, and IL-1β. EGCG also exhibited an antiapoptotic and antiautophagic effect by inhibiting BNIP3 via the IL-6/JAKs/STAT3 pathway.Conclusion: EGCG attenuated liver injury in ConA-induced hepatitis by downregulating IL-6/JAKs/STAT3/BNIP3-mediated apoptosis and autophagy. Keywords: concanavalin A, hepatitis, EGCG, autophagy, apoptosis, BNIP3, STAT3, JAKs, IL-6

Antioxidant and hepatoprotective effects of Capparis spinosa L. fractions and Quercetin on tert-butyl hydroperoxide- induced acute liver damage in mice

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Heibatullah Kalantari

2018-01-01

Full Text Available The present study investigates the antioxidant and hepatoprotective effects of Capparis spinosa L. and Quercetin in tert-butyl hydroperoxide (t-BHP induced acute liver damage. Different fractions of C. spinosa were examined for total phenolic content and antioxidant property. Among these fractions, hydroalcoholic extract was used to assess the hepatoprotective effect in tert-butyl hydroperoxide (t-BHP induced hepatotoxicity model by determining serum biochemical markers, sleeping time and antioxidant assay such as reduced glutathione (GSH as well as histopathological examination of liver tissues. The total phenolic and Quercetin contents of hydroalcoholic fraction were significantly higher than other fractions. It also showed high antioxidant activity. Pretreatment with hydroalcoholic fraction at the dose of 400 mg/kg and Quercetin at the dose of 20 mg/kg showed liver protection against t-BHP induced hepatic injury, as it was evident by a significant decrease in serum enzymes marker, sleeping time and MDA and an increase in the GSH, SOD and CAT activities confirmed by pathology tests. The final results ascertained the hepatoprotective and antioxidant effects of C. spinosa and Quercetin in a dose-dependent manner. Moreover, this study suggests that possible mechanism of this protection may be associated with its property of scavenging free radicals which may be due to the presence of phenolic compounds.

Sortilin 1 Loss-of-Function Protects Against Cholestatic Liver Injury by Attenuating Hepatic Bile Acid Accumulation in Bile Duct Ligated Mice.

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Li, Jibiao; Woolbright, Benjamin L; Zhao, Wen; Wang, Yifeng; Matye, David; Hagenbuch, Bruno; Jaeschke, Hartmut; Li, Tiangang

2018-01-01

Sortilin 1 (Sort1) is an intracellular trafficking receptor that mediates protein sorting in the endocytic or secretory pathways. Recent studies revealed a role of Sort1 in the regulation of cholesterol and bile acid (BA) metabolism. This study further investigated the role of Sort1 in modulating BA detoxification and cholestatic liver injury in bile duct ligated mice. We found that Sort1 knockout (KO) mice had attenuated liver injury 24 h after bile duct ligation (BDL), which was mainly attributed to less bile infarct formation. Sham-operated Sort1 KO mice had about 20% larger BA pool size than sham-operated wildtype (WT) mice, but 24 h after BDL Sort1 KO mice had significantly attenuated hepatic BA accumulation and smaller BA pool size. After 14 days BDL, Sort1 KO mice showed significantly lower hepatic BA concentration and reduced expression of inflammatory and fibrotic marker genes, but similar degree of liver fibrosis compared with WT mice. Unbiased quantitative proteomics revealed that Sort1 KO mice had increased hepatic BA sulfotransferase 2A1, but unaltered phase-I BA metabolizing cytochrome P450s or phase-III BA efflux transporters. Consistently, Sort1 KO mice showed elevated plasma sulfated taurocholate after BDL. Finally, we found that liver Sort1 was repressed after BDL, which may be due to BA activation of farnesoid x receptor. In conclusion, we report a role of Sort1 in the regulation of hepatic BA detoxification and cholestatic liver injury in mice. The mechanisms underlying increased hepatic BA elimination in Sort1 KO mice after BDL require further investigation. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Hepatic entropy and uniformity: additional parameters that can potentially increase the effectiveness of contrast enhancement during abdominal CT

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Ganeshan, B.; Miles, K.A.; Young, R.C.D.; Chatwin, C.R.

2007-01-01

Aim: To determine how hepatic entropy and uniformity of computed tomography (CT) images of the liver change after the administration of contrast material and to assess whether these additional parameters are more sensitive to tumour-related changes in the liver than measurements of hepatic attenuation or perfusion. Materials and methods: Hepatic attenuation, entropy, uniformity, and perfusion were measured using multi-phase CT following resection of colorectal cancer. Based on conventional CT and fluorodeoxyglucose positron emission tomography, 12 patients were classified as having no evidence of malignancy, eight with extra-hepatic tumours only, and eight with metastatic liver disease. Results: Hepatic attenuation and entropy increased after CM administration whereas uniformity decreased. Unlike hepatic attenuation, entropy and uniformity changed maximally in the arterial phase. No significant differences in hepatic perfusion or attenuation were found between patient groups, whereas arterial-phase entropy was lower (p = 0.034) and arterial-phase uniformity was higher (p = 0.034) in apparently disease-free areas of liver in patients with hepatic metastases compared with those with no metastases. Conclusion: Temporal changes in hepatic entropy and uniformity differ from those for hepatic attenuation. By reflecting the distribution of hepatic enhancement, these additional parameters are more sensitive to tumour-related changes in the liver than measurements of hepatic attenuation or perfusion

Quercetin Suppresses Twist to Induce Apoptosis in MCF-7 Breast Cancer Cells.

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Santhalakshmi Ranganathan

Full Text Available Quercetin is a dietary flavonoid which exerts anti-oxidant, anti-inflammatory and anti-cancer properties. In this study, we investigated the anti-proliferative effect of quercetin in two breast cancer cell lines (MCF-7 and MDA-MB-231, which differed in hormone receptor. IC50 value (37μM of quercetin showed significant cytotoxicity in MCF-7 cells, which was not observed in MDA-MB-231 cells even at 100μM of quercetin treatment. To study the response of cancer cells to quercetin, with respect to different hormone receptors, both the cell lines were treated with a fixed concentration (40μM of quercetin. MCF-7 cells on quercetin treatment showed more apoptotic cells with G1 phase arrest. In addition, quercetin effectively suppressed the expression of CyclinD1, p21, Twist and phospho p38MAPK, which was not observed in MDA-MB-231 cells. To analyse the molecular mechanism of quercetin in exerting an apoptotic effect in MCF-7 cells, Twist was over-expressed and the molecular changes were observed after quercetin administration. Quercetin effectively regulated the expression of Twist, in turn p16 and p21 which induced apoptosis in MCF-7 cells. In conclusion, quercetin induces apoptosis in breast cancer cells through suppression of Twist via p38MAPK pathway.

Preparation and evaluation of quercetin-loaded lecithin-chitosan nanoparticles for topical delivery

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Tan, Qi; Liu, Weidong; Guo, Chenyu; Zhai, Guangxi

2011-01-01

Background The purpose of this study was to investigate lecithin-chitosan nanoparticles as a topical delivery system for quercetin. Methods Tocopheryl propylene glycol succinate was chosen to be the surfactant for the nanosystem. The mean particle size of the nanoparticles was 95.3 nm, and the entrapment efficiency and drug loading for quercetin were 48.5% and 2.45%, respectively. Topical delivery in vitro and in vivo of the quercetin-loaded nanoparticles was evaluated using quercetin propylene glycol solution as the control. Results Compared with quercetin solution, the quercetin-loaded nanoparticles showed higher permeation ability, and significantly increased accumulation of quercetin in the skin, especially in the epidermis. Microstructure observation of the skin surface after administration indicated that the interaction between ingredients of the nanoparticles and the skin surface markedly changed the morphology of the stratum corneum and disrupted the corneocyte layers, thus facilitating the permeation and accumulation of quercetin in skin. Conclusion Lecithin-chitosan nanoparticles are a promising carrier for topical delivery of quercetin. PMID:21904452

A combination of quercetin and resveratrol reduces obesity in high-fat diet-fed rats by modulation of gut microbiota.

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Zhao, Le; Zhang, Qi; Ma, Weini; Tian, Feng; Shen, Hongyi; Zhou, Mingmei

2017-12-13

Resveratrol and quercetin, widely found in foods and vegetables, are plant polyphenols reported to have a wide range of biological activities. Despite their limited bioavailabilities, both resveratrol and quercetin are known to exhibit anti-inflammation and anti-obesity effects. We hypothesized that gut microbiota may be a potential target for resveratrol and quercetin to prevent the development of obesity. The aim of this research was to confirm whether a combination of quercetin and resveratrol (CQR) could restore the gut microbiota dysbiosis induced by a high-fat diet (HFD). In this study, Wistar rats were divided into three groups: a normal diet (ND) group, a HFD group and a CQR group. The CQR group was treated with a HFD and administered with a combination of quercetin [30 mg per kg body weight (BW) per day] and resveratrol [15 mg per kg body weight (BW) per day] by oral gavage. At the end of 10 weeks, CQR reduced the body weight gain and visceral (epididymal, perirenal) adipose tissue weight. Moreover, CQR also reduced serum lipids, attenuated serum inflammatory markers [interleukin (IL)-6, tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1] and reversed serum biochemical parameters (adiponectin, insulin, leptin, etc.). Importantly, our results demonstrated that CQR could modulate the gut microbiota composition. 16S rRNA gene sequencing revealed that CQR had an impact on gut microbiota, decreasing Firmicutes (P obesity. Moreover, compared with the HFD group, the relative abundance of Bacteroidales_S24-7_group (P obesity, was markedly increased in the CQR group. Overall, these results indicated that administration of CQR may have beneficial effects on ameliorating HFD-induced obesity and reducing HFD-induced gut microbiota dysbiosis.

Effects of a six-week intraduodenal supplementation with quercetin on liver lipid metabolism and oxidative stress in peripartal dairy cows.

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Stoldt, A-K; Mielenz, M; Nürnberg, G; Sauerwein, H; Esatbeyoglu, T; Wagner, A E; Rimbach, G; Starke, A; Wolffram, S; Metges, C C

2016-05-01

The purpose of this study was to evaluate possible effects of quercetin (Q) on liver lipid metabolism and antioxidative status in periparturient dairy cows. The periparturient period is associated with enormous metabolic changes for dairy cows. Energy needs for incipient lactation are too high to be balanced by feed intake, leading to negative energy balance and body fat mobilization. It has been estimated that this leads to the development of fatty liver in about 50% of cows, which are at high risk for disease. Furthermore, the antioxidative status of these cows may be impaired. Quercetin is a plant flavonoid having hepatoprotective and antioxidative potential and the ability to reduce liver lipid accumulation in monogastric animals. Little information is available in regard to these effects in ruminants. To prevent microbial Q degradation in the rumen, Q was administered via a duodenal fistula to improve systemic availability. Five cows of the Q-treated group received, daily, 100 mg of quercetin dehydrate/kg BW in a 0.9% sodium chloride solution from d -20 until d 20 relative to calving, whereas 5 control (CTR) cows received only a sodium chloride solution. Blood samples were taken weekly and liver biopsies were performed in wk -4, -2, and 3 relative to calving. Cows treated with Q showed a tendency ( = 0.082) for lower liver fat content compared with CTR cows. Liver glycogen, glutathione concentrations, and relative mRNA abundance of genes related to hepatic lipid metabolism and antioxidative status as well as parameters of antioxidative status in plasma were not affected ( > 0.1) by Q supplementation. In conclusion, liver fat content in dairy cows tended to be reduced by Q supplementation, but potential underlying mechanisms remain unclear because analyzed parameters related to hepatic lipid metabolism and antioxidative defense were not altered by Q supplementation.

Glucuronidated quercetin lowers blood pressure in spontaneously hypertensive rats via deconjugation.

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Pilar Galindo

Full Text Available BACKGROUND: Chronic oral quercetin reduces blood pressure and restores endothelial dysfunction in hypertensive animals. However, quercetin (aglycone is usually not present in plasma, because it is rapidly metabolized into conjugated, mostly inactive, metabolites. The aim of the study is to analyze whether deconjugation of these metabolites is involved in the blood pressure lowering effect of quercetin. METHODOLOGY/PRINCIPAL FINDINGS: We have analyzed the effects on blood pressure and vascular function in vitro of the conjugated metabolites of quercetin (quercetin-3-glucuronide, Q3GA; isorhamnetin-3-glucuronide, I3GA; and quercetin-3'-sulfate, Q3'S in spontaneously hypertensive rats (SHR. Q3GA and I3GA (1 mg/kg i.v., but not Q3'S, progressively reduced mean blood pressure (MBP, measured in conscious SHR. The hypotensive effect of Q3GA was abolished in SHR treated with the specific inhibitor of β-glucuronidase, saccharic acid 1,4-lactone (SAL, 10 mg/ml. In mesenteric arteries, unlike quercetin, Q3GA had no inhibitory effect in the contractile response to phenylephrine after 30 min of incubation. However, after 1 hour of incubation Q3GA strongly reduced this contractile response and this effect was prevented by SAL. Oral administration of quercetin (10 mg/Kg induced a progressive decrease in MBP, which was also suppressed by SAL. CONCLUSIONS: Conjugated metabolites are involved in the in vivo antihypertensive effect of quercetin, acting as molecules for the plasmatic transport of quercetin to the target tissues. Quercetin released from its glucuronidated metabolites could be responsible for its vasorelaxant and hypotensive effect.

Attenuation of the gamma rays in tissues

International Nuclear Information System (INIS)

Arcos P, A.; Rodriguez N, S.; Pinedo S, A.; Amador V, P.; Chacon R, A.; Vega C, H.R.

2005-01-01

The mass and lineal attenuation coefficient and of hepatic tissue, muscular, osseous and of brain before gamma rays of 10 -3 to 10 5 MeV were calculated. For the case of the osseous tissue the calculation was made for the cartilage, the cortical tissue and the bone marrow. During the calculations the elementary composition of the tissues of human origin was used. The calculations include by separate the Photoelectric effect, the Compton scattering and the Pair production, as well as the total. For to establish a comparison with the attenuation capacities, the coefficients of the water, the aluminum and the lead also were calculated. The study was complemented measuring the attenuation coefficient of hepatic tissue of bovine before gamma rays of 0.662 MeV of a source of 137 Cs. The measurement was made through of an experiment of photons transmission through samples frozen of hepatic tissue and with a Geiger-Mueller detector. (Author)

Enhancement of quercetin water solubility with steviol glucosides and the studies of biological properties

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Thi Thanh Hanh Nguyen

2015-12-01

Full Text Available Background: Quercetin, a flavonol contained in various vegetables and fruits, has various biological activities including anticancer, antiviral, anti-diabetic, and anti-oxidative. However, it has low oral bioavailability due to insolubility in water. Thus, the bioavailability of quercetin administered to human beings in a capsule form, was reported to be less than 1%, with only a small percentage of ingested quercetin getting absorbed in the blood. This leads to certain difficulties in creating highly effective medicines Methods: Quercetin-rubusoside and quercetin-rebaudioside were prepared. The antioxidant activities of quercetin and Q-rubusoside were evaluated by DPPH radical scavenging method. Inhibition activities of quercetin and Quercetin-rubusoside were determined by measuring the remaining activity of 3CLpro with 200 μM inhibitor. The inhibition activity of quercetin, rubusoside and quercetin-rubusoside were determined by measuring the activity of human maltase which remains at 100 μM rubusoside or quercetin-rubusoside. The mushroom tyrosinase inhibition was assayed with the reaction mixture contained 3.3 mM L-DOPA in 50 mM potassium phosphate buffer (pH 6.8, and 10 U mushroom tyrosinase/ml with or without quercetin or quercetin-rubusoside. Results: With 10% rubusoside treatment, quercetin showed solubility of 7.7 mg/ml in water, and its solubility increased as the concentration of rubusoside increased; the quercetin solubility in water increased to 0.83 mg/mlas rubusoside concentration increased to 1 mg/ml. Quercetin solubilized in rubusoside solution showed DPPH radical-scavenging activity and mushroom tyrosinase inhibition activity, similar to that of quercetin solubilized in dimethyl-sulfoxide. Quercetin-rubusoside also showed 1.2 and 1.9 folds higher inhibition activity against 3CLpro of SARS and human intestinal maltase, respectively, than those of quercetin in DMSO. Conclusions: Quercetin can be solubilized in water with

Metformin attenuates olanzapine-induced hepatic, but not peripheral insulin resistance.

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Remington, Gary J; Teo, Celine; Wilson, Virginia; Chintoh, Araba; Guenette, Melanie; Ahsan, Zohra; Giacca, Adria; Hahn, Margaret K

2015-11-01

Antipsychotics (APs) are linked to diabetes, even without weight gain. Whether anti-diabetic drugs are efficacious in reversing the direct effects of APs on glucose pathways is largely undetermined. We tested two metformin (Met) doses to prevent impairments seen following a dose of olanzapine (Ola) (3 mg/kg); glucokinetics were measured using the hyperinsulinemic-euglycemic clamp (HIEC). Met (150 mg/kg; n=13, or 400 mg/kg; n=11) or vehicle (Veh) (n=11) was administered through gavage preceding an overnight fast, followed by a second dose prior to the HIEC. Eleven additional animals were gavaged with Veh and received a Veh injection during the HIEC (Veh/Veh); all others received Ola. Basal glucose was similar across treatment groups. The Met 400 group had significantly greater glucose appearance (Ra) in the basal period (i.e., before Ola, or hyperinsulinemia) vs other groups. During hyperinsulinemia, glucose infusion rate (GINF) to maintain euglycemia (reflective of whole-body insulin sensitivity) was higher in Veh/Veh vs other groups. Met 150/Ola animals demonstrated increased GINF relative to Veh/Ola during early time points of the HIEC. Glucose utilization during hyperinsulinemia, relative to basal conditions, was significantly higher in Veh/Veh vs other groups. The change in hepatic glucose production (HGP) from basal to hyperinsulinemia demonstrated significantly greater decreases in Veh/Veh and Met 150/Ola groups vs Veh/Ola. Given the increase in basal Ra with Met 400, we measured serum lactate (substrate for HGP), finding increased levels in Met 400 vs Veh and Met 150. In conclusion, Met attenuates hepatic insulin resistance observed with acute Ola administration, but fails to improve peripheral insulin resistance. Use of supra-therapeutic doses of Met may mask metabolic benefits by increasing lactate. © 2015 Society for Endocrinology.

Noninvasive detection of hepatic steatosis in patients without ultrasonographic evidence of fatty liver using the controlled attenuation parameter evaluated with transient elastography.

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Yilmaz, Yusuf; Ergelen, Rabia; Akin, Hakan; Imeryuz, Nese

2013-11-01

Although ultrasound is a useful technique for detecting hepatic steatosis, it cannot provide a precise determination of hepatic fat content. A novel attenuation parameter named controlled attenuation parameter (CAP) has been developed to process the raw ultrasonic signals acquired by Fibroscan. The aim of this study was to determine the percentage of hepatic steatosis in apparently healthy Turkish individuals using the proposed diagnostic cut-off points for CAP. In addition, we sought to investigate the association of CAP with the traditional risk factors for nonalcoholic fatty liver disease in a screening setting. In the present study, 102 Turkish individuals without evidence of fatty liver on ultrasound and normal aminotransferase levels underwent CAP measurements by means of Fibroscan. The mean (SD), median (minimum-maximum), and 5th and 95th percentile values of CAP values in this cohort of 102 individuals were 206.99 (48.12), 210.5 (100.0-314.0), 113.4 and 280.2 dB/m, respectively. Using the cut-offs of 222, 238, and 283 dB/m for CAP, there were 39 (38.2%), 23 (22.5%), and five (4.9%) individuals out of 102 who had at least 10% steatosis despite normal liver findings on ultrasound. After allowance for potential confounders, CAP was independently associated with BMI (β=0.39, t=3.5, Phepatic steatosis on the basis of CAP assessment.

Oral quercetin supplementation hampers skeletal muscle adaptations in response to exercise training

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Casuso, R A; Martínez-López, E J; Nordsborg, Nikolai Baastrup

2014-01-01

We aimed to test exercise-induced adaptations on skeletal muscle when quercetin is supplemented. Four groups of rats were tested: quercetin sedentary, quercetin exercised, placebo sedentary, and placebo exercised. Treadmill exercise training took place 5 days a week for 6 weeks. Quercetin groups ...... status was also quantified by measuring muscle antioxidant enzymatic activity and oxidative damage product, such as protein carbonyl content (PCC). Quercetin supplementation increased oxidative damage in both exercised and sedentary rats by inducing higher amounts of PCC (P ...

Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential.

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Caltagirone, S; Rossi, C; Poggi, A; Ranelletti, F O; Natali, P G; Brunetti, M; Aiello, F B; Piantelli, M

2000-08-15

Flavonoids are a class of polyphenolic compounds widely distributed in the plant kingdom, which display a variety of biological activities, including chemoprevention and tumor growth inhibition. Our aim was to investigate the effects of several polyphenols on the growth and metastatic potential of B16-BL6 melanoma cells in vivo. Intraperitoneal administration of quercetin, apigenin, (-)-epigallocathechin-3-gallate (EGCG), resveratrol, and the anti-estrogen tamoxifen, at the time of i.m. injection of B16-BL6 cells into syngeneic mice, resulted in a significant, dose-dependent delay of tumor growth, without toxicity. The relative descending order of potency was EGCG > apigenin = quercetin = tamoxifen > resveratrol > control. Furthermore, polyphenols significantly potentiated the inhibitory effect of a non-toxic dose of cisplatin. When tested for the ability to inhibit lung colonization, quercetin, apigenin, and tamoxifen (but not EGCG or resveratrol) significantly decreased the number of B16-BL6 colonies in the lungs in a dose-dependent manner, with quercetin and apigenin being more effective than tamoxifen. Interestingly, quercetin, apigenin, and tamoxifen (but not EGCG or resveratrol) significantly decreased the invasion of B16-BL6 cells in vitro, with quercetin and apigenin being more effective than tamoxifen. This suggests that anti-invasive activity is one of the mechanisms underlying inhibition of lung colonization by quercetin and apigenin. In conclusion, quercetin and apigenin inhibit melanoma growth and invasive and metastatic potential; therefore, they may constitute a valuable tool in the combination therapy of metastatic melanoma. Copyright 2000 Wiley-Liss, Inc.

Long-Term Quercetin Dietary Enrichment Partially Protects Dystrophic Skeletal Muscle.

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Hannah R Spaulding

Full Text Available Duchenne muscular dystrophy (DMD results from a genetic lesion in the dystrophin gene and leads to progressive muscle damage. PGC-1α pathway activation improves muscle function and decreases histopathological injury. We hypothesized that mild disease found in the limb muscles of mdx mice may be responsive to quercetin-mediated protection of dystrophic muscle via PGC-1α pathway activation. To test this hypothesis muscle function was measured in the soleus and EDL from 14 month old C57, mdx, and mdx mice treated with quercetin (mdxQ; 0.2% dietary enrichment for 12 months. Quercetin reversed 50% of disease-related losses in specific tension and partially preserved fatigue resistance in the soleus. Specific tension and resistance to contraction-induced injury in the EDL were not protected by quercetin. Given some functional gain in the soleus it was probed with histological and biochemical approaches, however, in dystrophic muscle histopathological outcomes were not improved by quercetin and suppressed PGC-1α pathway activation was not increased. Similar to results in the diaphragm from these mice, these data suggest that the benefits conferred to dystrophic muscle following 12 months of quercetin enrichment were underwhelming. Spontaneous activity at the end of the treatment period was greater in mdxQ compared to mdx indicating that quercetin fed mice were more active in addition to engaging in more vigorous activity. Hence, modest preservation of muscle function (specific tension and elevated spontaneous physical activity largely in the absence of tissue damage in mdxQ suggests dietary quercetin may mediate protection.

Protective effect of quercetin on bupivacaine-induced neurotoxicity ...

African Journals Online (AJOL)

... bupivacaine, possibly through inhibition of T-type calcium channel. This finding implies a novel mechanism for neuroprotective effect of quercetin, and its potential for treating toxicity arising from the use of local anesthetic agents. Keywords: Quercetin, Bupivacaine, Local anaesthetic, Neuroprotection, Neurotoxicity, T-type ...

Quercetin enhances adiponectin secretion by a PPAR-gamma independent mechanism

DEFF Research Database (Denmark)

Wein, Silvia; Behm, Norma; Petersen, Rasmus Koefoed

2010-01-01

To study possible insulin sensitizing, anti-inflammatory and anti-oxidative effects of the flavonol quercetin, rats were fed a high-fat diet (19%, w/w) with (HFQ) or without (HF) 0.03% quercetin or a flavonoid-poor low-fat (5%, w/w) maintenance diet (LF) over 4 weeks. Body weight was measured...... and WAT mRNA levels of adiponectin were elevated compared with the HF group, however, PPAR-gamma mRNA concentration in WAT was decreased (HFQ vs. HF). Compared to both other groups quercetin feeding significantly reduced oxidative stress, measured by plasma 8-iso-PGF(2alpha), while body weight gain, body...... composition and plasma leptin levels were not affected. Neither quercetin nor its metabolites induced PPAR-gamma-mediated transactivation in vitro. Adiponectin stimulating effects of quercetin are PPAR-gamma-independent and prevent impairment of insulin sensitivity without affecting body weight...

Quercetin suppresses HeLa cells by blocking PI3K/Akt pathway.

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Xiang, Tao; Fang, Yong; Wang, Shi-Xuan

2014-10-01

To explore the effect of quercetin on the proliferation and apoptosis of HeLa cells, HeLa cells were incubated with quercetin at different concentrations. Cell viability was evaluated by MTT assay, cell apoptosis was detected by Annexin-V/PI double labeled cytometry and DNA ladder assay. Cell cycle was flow cytometrically determined and the morphological changes of the cells were observed under a fluorescence microscope after Hoechst 33258 staining and the apoptosis-related proteins in the HeLa cells were assessed by Western blotting. The results showed that quercetin significantly inhibited the growth of HeLa cells and induced obvious apoptosis in vitro in a time- and dose-dependent manner. Moreover, quercetin induced apoptosis of HeLa cells in cell cycle-dependent manner because quercetin could induce arrest of HeLa cells at G0/G1 phase. Quercetin treatment down-regulated the expression of the PI3K and p-Akt. In addition, quercetin could down-regulate expression of bcl-2, up-regulate Bax, but exerted no effect on the overall expression of Akt. We are led to conclude that quercetin induces apoptosis via PI3k/Akt pathways, and quercetin has potential to be used as an anti-tumor agent against human cervix cancer.

Hot-melt extrusion microencapsulation of quercetin for taste-masking.

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Khor, Chia Miang; Ng, Wai Kiong; Kanaujia, Parijat; Chan, Kok Ping; Dong, Yuancai

2017-02-01

Besides its poor dissolution rate, the bitterness of quercetin also poses a challenge for further development. Using carnauba wax, shellac or zein as the shell-forming excipient, this work aimed to microencapsulate quercetin by hot-melt extrusion for taste-masking. In comparison with non-encapsulated quercetin, the microencapsulated powders exhibited significantly reduced dissolution in the simulated salivary pH 6.8 medium indicative of their potentially good taste-masking efficiency in the order of zein > carnauba wax > shellac. In vitro bitterness analysis by electronic tongue confirmed the good taste-masking efficiency of the microencapsulated powders. In vitro digestion results showed that carnauba wax and shellac-microencapsulated powders presented comparable dissolution rate with the pure quercetin in pH 1.0 (gastric) and 6.8 (intestine) medium; while zein-microencapsulated powders exhibited a remarkably slower dissolution rate. Crystallinity of quercetin was slightly reduced after microencapsulation while its chemical structure remained unchanged. Hot-melt extrusion microencapsulation could thus be an attractive technique to produce taste-masked bioactive powders.

Quercetin inhibits adipogenesis of muscle progenitor cells in vitro

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Tomoko Funakoshi

2018-03-01

Full Text Available Muscle satellite cells are committed myogenic progenitors capable of contributing to myogenesis to maintain adult muscle mass and function. Several experiments have demonstrated that muscle satellite cells can differentiate into adipocytes in vitro, supporting the mesenchymal differentiation potential of these cells. Moreover, muscle satellite cells may be a source of ectopic muscle adipocytes, explaining the lipid accumulation often observed in aged skeletal muscle (sarcopenia and in muscles of patients` with diabetes. Quercetin, a polyphenol, is one of the most abundant flavonoids distributed in edible plants, such as onions and apples, and possesses antioxidant, anticancer, and anti-inflammatory properties. In this study, we examined whether quercetin inhibited the adipogenesis of muscle satellite cells in vitro with primary cells from rat limbs by culture in the presence of quercetin under adipogenic conditions. Morphological observations, Oil Red-O staining results, triglyceride content analysis, and quantitative reverse transcription polymerase chain reaction revealed that quercetin was capable of inhibiting the adipogenic induction of muscle satellite cells into adipocytes in a dose-dependent manner by suppressing the transcript levels of adipogenic markers, such as peroxisome proliferator-activated receptor-γ and fatty acid binding protein 4. Our results suggested that quercetin inhibited the adipogenesis of muscle satellite cells in vitro by suppressing the transcription of adipogenic markers. Keywords: Quercetin, Muscle satellite cell, Differentiation, Intramuscular lipid

Effect of Quercetin on radio-sensitivity of HeLa cells

International Nuclear Information System (INIS)

Wu Xiaofen; Hong Chengjiao; Guo Wenxiu; Pan Yanling; Zhang Baoguo

2011-01-01

In order to investigate the mechanism of Quercetin on radio-sensitivity of human Uterine Cervix Cancer HeLa cells, HeLa cells were cultured in different concentrations of Quercetin and different doses of irradiation. The clonogenic assay was used to observe the cell survival rate. The repair of DNA double-strand breaks and effect of Quercetin combination of radiation on the cell cycle were detected by flow cytometry. The results show that the radio-sensitivity of Quercetin on HeLa cells was obvious and the unrepaired DSBs after irradiation increased, but did not decrease G2/M cell cycle arrest. From this it can be inferred that the effect on HeLa cell radio-sensitivity may be related to the inhibition of the repair of DNA double-strand breaks induced by Quercetin, but it dose not reveal a significant relation with the cell cycle and G2/M arrest. (authors)

Physicochemical properties and thermal stability of quercetin hydrates in the solid state

Energy Technology Data Exchange (ETDEWEB)

Borghetti, G.S., E-mail: greicefarm@yahoo.com.br [Programa de Pos-Graduacao em Ciencias Farmaceuticas, Faculdade de Farmacia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, CEP 90.610-000, Porto Alegre, RS (Brazil); Carini, J.P. [Programa de Pos-Graduacao em Ciencias Farmaceuticas, Faculdade de Farmacia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, CEP 90.610-000, Porto Alegre, RS (Brazil); Honorato, S.B.; Ayala, A.P. [Departamento de Fisica, Universidade Federal do Ceara, Caixa Postal 6030, CEP 60.455-970, Fortaleza, CE (Brazil); Moreira, J.C.F. [Departamento de Bioquimica, Instituto de Ciencias Basicas da Saude, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600, CEP 90035-003, Porto Alegre, RS (Brazil); Bassani, V.L. [Programa de Pos-Graduacao em Ciencias Farmaceuticas, Faculdade de Farmacia, Universidade Federal do Rio Grande do Sul, Av. Ipiranga 2752, CEP 90.610-000, Porto Alegre, RS (Brazil)

2012-07-10

Highlights: Black-Right-Pointing-Pointer Quercetin raw materials may present different degree of hydration. Black-Right-Pointing-Pointer Thermal stability of quercetin in the solid state depends on its degree of hydration. Black-Right-Pointing-Pointer Quercetin dehydrate is thermodynamically more stable than the other crystal forms. - Abstract: In the present work three samples of quercetin raw materials (QCTa, QCTb and QCTc), purchased from different Brazilian suppliers, were characterized employing scanning electron microscopy, Raman spectroscopy, simultaneous thermogravimetry and infrared spectroscopy, differential scanning calorimetry, and variable temperature-powder X-ray diffraction, in order to know their physicochemical properties, specially the thermal stability in solid state. The results demonstrated that the raw materials of quercetin analyzed present distinct crystalline structures, ascribed to the different degree of hydration of their crystal lattice. The thermal stability of these quercetin raw materials in the solid state was highly dependent on their degree of hydration, where QCTa (quercetin dihydrate) was thermodynamically more stable than the other two samples.

Research Progress in the Modification of Quercetin Leading to Anticancer Agents

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Alessandro Massi

2017-07-01

Full Text Available The flavonoid quercetin (3,3′,4′,5,7-pentahydroxyflavone is widely distributed in plants, foods, and beverages. This polyphenol compound exhibits varied biological actions such as antioxidant, radical-scavenging, anti-inflammatory, antibacterial, antiviral, gastroprotective, immune-modulator, and finds also application in the treatment of obesity, cardiovascular diseases and diabetes. Besides, quercetin can prevent neurological disorders and exerts protection against mitochondrial damages. Various in vitro studies have assessed the anticancer effects of quercetin, although there are no conclusive data regarding its mode of action. However, low bioavailability, poor aqueous solubility as well as rapid body clearance, fast metabolism and enzymatic degradation hamper the use of quercetin as therapeutic agent, so intense research efforts have been focused on the modification of the quercetin scaffold to obtain analogs with potentially improved properties for clinical applications. This review gives an overview of the developments in the synthesis and anticancer-related activities of quercetin derivatives reported from 2012 to 2016.

Characteristics of liver tissue for attenuate the gamma radiation

International Nuclear Information System (INIS)

Arcos P, A.; Rodriguez N, S.; Pinedo S, A.; Amador V, P.; Chacon R, A.; Vega C, H.R.

2005-01-01

It was determined the lineal attenuation coefficient of hepatic tissue before gamma radiation of a source of 137 Cs. When exposing organic material before X or gamma radiation fields, part of the energy of the photons is absorbed by the material, while another part crosses it without producing any effect. The quantity of energy that is absorbed is a measure of the dose that receives the material. The three main mechanisms by means of which the gamma rays interacting with the matter are: The Photoelectric Effect, the Compton dispersion and the Even production; the sum of these three processes is translated in the attenuation coefficient of the radiation. In this work we have used hepatic tissue of bovine, as substitute of the human hepatic tissue, and we have measured the lineal attenuation coefficient for photons of 0.662 MeV. Through a series of calculations we have determined the lineal attenuation coefficient for photons from 10 -3 to 10 -5 MeV and the measured coefficient was compared with the one calculated. (Author)

Quercetin Prevents Diastolic Dysfunction Induced by a High-Cholesterol Diet: Role of Oxidative Stress and Bioenergetics in Hyperglycemic Rats

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Rodrigo L. Castillo

2018-01-01

Full Text Available Alterations in cardiac energy metabolism play a key role in the pathogenesis of diabetic cardiomyopathy. Hypercholesterolemia associated with bioenergetic impairment and oxidative stress has not been well characterized in the cardiac function under glycemic control deficiency conditions. This work aimed to determine the cardioprotective effects of quercetin (QUE against the damage induced by a high-cholesterol (HC diet in hyperglycemic rats, addressing intracellular antioxidant mechanisms and bioenergetics. Quercetin reduced HC-induced alterations in the lipid profile and glycemia in rats. In addition, QUE attenuated cardiac diastolic dysfunction (increased E:A ratio, prevented cardiac cholesterol accumulation, and reduced the increase in HC-induced myocyte density. Moreover, QUE reduced HC-induced oxidative stress by preventing the decrease in GSH/GSSG ratio, Nrf2 nuclear translocation, HO-1 expression, and antioxidant enzymatic activity. Quercetin also counteracted HC-induced bioenergetic impairment, preventing a reduction in ATP levels and alterations in PGC-1α, UCP2, and PPARγ expression. In conclusion, the mechanisms that support the cardioprotective effect of QUE in rats with HC might be mediated by the upregulation of antioxidant mechanisms and improved bioenergetics on the heart. Targeting bioenergetics with QUE can be used as a pharmacological approach to modulate structural and functional changes of the heart under hypercholesterolemic and hyperglycemic conditions.

Role of necroptosis in autophagy signaling during hepatic ischemia and reperfusion

Energy Technology Data Exchange (ETDEWEB)

Hong, Jeong-Min; Kim, Seok-Joo; Lee, Sun-Mee, E-mail: sunmee@skku.edu

2016-10-01

Ischemia and reperfusion (I/R) is a complex phenomenon involving massive inflammation and cell death. Necroptosis refers to a newly described cell death as “programmed necrosis” that is controlled by receptor-interacting protein kinase (RIP) 1 and RIP3, which is involved in the pathogenesis of several inflammatory diseases. Autophagy is an essential cytoprotective system that is rapidly activated in response to various stimuli and involves crosstalk between different modes of cell death and inflammation. In this study, we investigated pattern changes in necroptosis and its role in autophagy signaling during hepatic I/R. Male C57BL/6 mice were subjected to 60 min of ischemia followed by 3 h reperfusion. Necrostatin-1 (Nec-1, a necroptosis inhibitor; 1.65 mg/kg) was administered intraperitoneally 5 min before reperfusion. Hepatic I/R significantly increased the level of RIP3, phosphorylated RIP1 and RIP3 protein expression, and RIP1/RIP3 necrosome formation, which were attenuated by Nec-1. I/R also significantly increased serum levels of alanine aminotransferase, tumor necrosis factor-α, and interleukin-6, which were attenuated by Nec-1. Meanwhile, hepatic I/R activated autophagy and mitophagy, as evidenced by increased LC3-II, PINK1, and Parkin, and decreased sequestosome 1/p62 protein expression. Nec-1 attenuated these changes and attenuated the increased levels of autophagy-related protein (ATG) 3, ATG7, Rab7, and cathepsin B protein expression during hepatic I/R. Moreover, hepatic I/R activated the extracellular signal-regulated kinase (ERK) pathway, and Nec-1 attenuated this increase. Taken together, our findings suggest that necroptosis contributes to hepatic damage during I/R, which induces autophagy via ERK activation. - Highlights: • Hepatic I/R induces RIP1/RIP3-dependent necroptosis. • Necroptosis contributes to hepatic I/R injury. • Necroptosis activates autophagic flux via ERK activation during hepatic I/R.

Quercetin topical application, from conventional dosage forms to nanodosage forms.

Science.gov (United States)

Hatahet, T; Morille, M; Hommoss, A; Devoisselle, J M; Müller, R H; Bégu, S

2016-11-01

Skin is a multifunctional organ with activities in protection, metabolism and regulation. Skin is in a continuous exposure to oxidizing agents and inflammogens from the sun and from the contact with the environment. These agents may overload the skin auto-defense capacity. To strengthen skin defense mechanisms against oxidation and inflammation, supplementation of exogenous antioxidants is a promising strategy. Quercetin is a flavonoid with very pronounced effective antioxidant and antiinflammatory activities, and thus a candidate of first choice for such skin supplementation. Quercetin showed interesting actions in cellular and animal based models, ranging from protecting cells from UV irradiation to support skin regeneration in wound healing. However, due to its poor solubility, quercetin has limited skin penetration ability, and various formulation approaches were taken to increase its dermal penetration. In this article, the quercetin antioxidant and antiinflammatory activities in wound healing and supporting skin against aging are discussed in detail. In addition, quercetin topical formulations from conventional emulsions to novel nanoformulations in terms of skin penetration enhancement are also presented. This article gives a comprehensive review of quercetin for topical application from biological effects to pharmaceutical formulation design for the last 25 years of research. Copyright © 2016 Elsevier B.V. All rights reserved.

The scavenging effects of tea polyphenol and quercetin on active oxygen species

International Nuclear Information System (INIS)

Fang Ruoying; Cheng Jiwu; Hu Tianxi; Tu Tiechen; Dong Jirong; Wang Wenfeng; Lin Nianyun

1993-01-01

The abilities of scavenging active oxygen species, O 2 free radical and OH., by tea polyphenols and quercetin have been studied by chemiluminescence, ESR and pulse radiolysis. Tea polyphenols and quercetin are all phenolic antioxidants. The synergetic studies show that both tea polyphenols and quercetin are strong free radical scavengers. Tea polyphenols are better than quercetin. the results from CL studies are in good accord with those from ESR and PR studies

Quercetin

DEFF Research Database (Denmark)

Harrison, Adrian Paul; Cooper, Ross G.

2008-01-01

With increasing interest among the general public for using natural and herbal remedies, there is a great need to document and list ancient medical texts and practices, as well as to investigate the efficacy of a number of 'ancient' compounds that are currently reputed to have medicinal benefits...... for human health. Our report not only provides clear evidence for the flavonoid quercetin as an anti-inflammatory, which may well have been used in antiquity to treat arthritic swelling and pain, it also serves to re-educate the general public and scientific community to the fact that natural and herbal...

Troxerutin Attenuates Enhancement of Hepatic Gluconeogenesis by Inhibiting NOD Activation-Mediated Inflammation in High-Fat Diet-Treated Mice.

Science.gov (United States)

Zhang, Zifeng; Wang, Xin; Zheng, Guihong; Shan, Qun; Lu, Jun; Fan, Shaohua; Sun, Chunhui; Wu, Dongmei; Zhang, Cheng; Su, Weitong; Sui, Junwen; Zheng, Yuanlin

2016-12-25

Recent evidence suggests that troxerutin, a trihydroxyethylated derivative of natural bioflavonoid rutin, exhibits beneficial effects on diabetes-related symptoms. Here we investigated the effects of troxerutin on the enhancement of hepatic gluconeogenesis in high-fat diet (HFD)-treated mice and the mechanisms underlying these effects. Mice were divided into four groups: Control group, HFD group, HFD + Troxerutin group, and Troxerutin group. Troxerutin was treated by daily oral administration at doses of 150 mg/kg/day for 20 weeks. Tauroursodeoxycholic acid (TUDCA) was used to inhibit endoplasmic reticulum stress (ER stress). Our results showed that troxerutin effectively improved obesity and related metabolic parameters, and liver injuries in HFD-treated mouse. Furthermore, troxerutin significantly attenuated enhancement of hepatic gluconeogenesis in HFD-fed mouse. Moreover, troxerutin notably suppressed nuclear factor-κB (NF-κB) p65 transcriptional activation and release of inflammatory cytokines in HFD-treated mouse livers. Mechanismly, troxerutin dramatically decreased Nucleotide oligomerization domain (NOD) expression, as well as interaction between NOD1/2 with interacting protein-2 (RIP2), by abating oxidative stress-induced ER stress in HFD-treated mouse livers, which was confirmed by TUDCA treatment. These improvement effects of troxerutin on hepatic glucose disorders might be mediated by its anti-obesity effect. In conclusion, troxerutin markedly diminished HFD-induced enhancement of hepatic gluconeogenesis via its inhibitory effects on ER stress-mediated NOD activation and consequent inflammation, which might be mediated by its anti-obesity effect.

Troxerutin Attenuates Enhancement of Hepatic Gluconeogenesis by Inhibiting NOD Activation-Mediated Inflammation in High-Fat Diet-Treated Mice

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Zifeng Zhang

2016-12-01

Full Text Available Recent evidence suggests that troxerutin, a trihydroxyethylated derivative of natural bioflavonoid rutin, exhibits beneficial effects on diabetes-related symptoms. Here we investigated the effects of troxerutin on the enhancement of hepatic gluconeogenesis in high-fat diet (HFD-treated mice and the mechanisms underlying these effects. Mice were divided into four groups: Control group, HFD group, HFD + Troxerutin group, and Troxerutin group. Troxerutin was treated by daily oral administration at doses of 150 mg/kg/day for 20 weeks. Tauroursodeoxycholic acid (TUDCA was used to inhibit endoplasmic reticulum stress (ER stress. Our results showed that troxerutin effectively improved obesity and related metabolic parameters, and liver injuries in HFD-treated mouse. Furthermore, troxerutin significantly attenuated enhancement of hepatic gluconeogenesis in HFD-fed mouse. Moreover, troxerutin notably suppressed nuclear factor-κB (NF-κB p65 transcriptional activation and release of inflammatory cytokines in HFD-treated mouse livers. Mechanismly, troxerutin dramatically decreased Nucleotide oligomerization domain (NOD expression, as well as interaction between NOD1/2 with interacting protein-2 (RIP2, by abating oxidative stress-induced ER stress in HFD-treated mouse livers, which was confirmed by TUDCA treatment. These improvement effects of troxerutin on hepatic glucose disorders might be mediated by its anti-obesity effect. In conclusion, troxerutin markedly diminished HFD-induced enhancement of hepatic gluconeogenesis via its inhibitory effects on ER stress-mediated NOD activation and consequent inflammation, which might be mediated by its anti-obesity effect.

MEASUREMENT OF CONTROLLED ATTENUATION PARAMETER: A SURROGATE MARKER OF HEPATIC STEATOSIS IN PATIENTS OF NONALCOHOLIC FATTY LIVER DISEASE ON LIFESTYLE MODIFICATION - A PROSPECTIVE FOLLOW-UP STUDY

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Jayanta PAUL

Full Text Available ABSTRACT BACKGROUND: Liver biopsy is a gold standard method for hepatic steatosis assessment. However, liver biopsy is an invasive and painful procedure and can cause severe complications therefore it cannot be frequently used in case of follow-up of patients. Non-invasive assessment of steatosis and fibrosis is of growing relevance in non-alcoholic fatty liver disease (NAFLD. To evaluate hepatic steatosis, transient elastography with controlled attenuation parameter (CAP measurement is an option now days. OBJECTIVE: Aim of this study is to evaluate role of measurement of controlled attenuation parameter, a surrogate marker of hepatic steatosis in patients of nonalcoholic fatty liver disease on lifestyle modification. METHODS: In this study, initially 37 participants were included who were followed up after 6 months with transient elastography, blood biochemical tests and anthropometric measurements. The results were analyzed by Multivariate linear regression analysis and paired samples t-test (Dependent t-test with 95% confidence interval. Correlation is calculated by Pearson correlation coefficients. RESULTS: Mean CAP value for assessing hepatic steatosis during 1st consultation (278.57±49.13 dB/m was significantly improved (P=0.03 after 6 months of lifestyle modification (252.91±62.02 dB/m. Only fasting blood sugar (P=0.008, weight (P=0.000, body mass index (BMI (P=0.000 showed significant positive correlation with CAP. Only BMI (P=0.034 and weight (P=0.035 were the independent predictor of CAP value in NAFLD patients. CONCLUSION: Lifestyle modification improves the hepatic steatosis, and CAP can be used to detect the improvement of hepatic steatosis during follow-up in patients with NAFLD on lifestyle modification. There is no relation between CAP and Fibroscan score in NAFLD patients. Only BMI and weight can predict CAP value independently.

MEASUREMENT OF CONTROLLED ATTENUATION PARAMETER: A SURROGATE MARKER OF HEPATIC STEATOSIS IN PATIENTS OF NONALCOHOLIC FATTY LIVER DISEASE ON LIFESTYLE MODIFICATION - A PROSPECTIVE FOLLOW-UP STUDY.

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Paul, Jayanta; Venugopal, Raj Vigna; Peter, Lorance; Shetty, Kula Naresh Kumar; Shetti, Mohit P

2018-01-01

Liver biopsy is a gold standard method for hepatic steatosis assessment. However, liver biopsy is an invasive and painful procedure and can cause severe complications therefore it cannot be frequently used in case of follow-up of patients. Non-invasive assessment of steatosis and fibrosis is of growing relevance in non-alcoholic fatty liver disease (NAFLD). To evaluate hepatic steatosis, transient elastography with controlled attenuation parameter (CAP) measurement is an option now days. Aim of this study is to evaluate role of measurement of controlled attenuation parameter, a surrogate marker of hepatic steatosis in patients of nonalcoholic fatty liver disease on lifestyle modification. In this study, initially 37 participants were included who were followed up after 6 months with transient elastography, blood biochemical tests and anthropometric measurements. The results were analyzed by Multivariate linear regression analysis and paired samples t-test (Dependent t-test) with 95% confidence interval. Correlation is calculated by Pearson correlation coefficients. Mean CAP value for assessing hepatic steatosis during 1st consultation (278.57±49.13 dB/m) was significantly improved (P=0.03) after 6 months of lifestyle modification (252.91±62.02 dB/m). Only fasting blood sugar (P=0.008), weight (P=0.000), body mass index (BMI) (P=0.000) showed significant positive correlation with CAP. Only BMI (P=0.034) and weight (P=0.035) were the independent predictor of CAP value in NAFLD patients. Lifestyle modification improves the hepatic steatosis, and CAP can be used to detect the improvement of hepatic steatosis during follow-up in patients with NAFLD on lifestyle modification. There is no relation between CAP and Fibroscan score in NAFLD patients. Only BMI and weight can predict CAP value independently.

Antioxidant Activity of Phyllanthus niruri Extract, Rutin and Quercetin

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Djaja Rusmana

2017-08-01

Full Text Available BACKGROUND: Normal metabolism of oxygen and exogenous factors constantly generate free radicals which could be harmful to the human body. Human need antioxidants to provide protection against free radicals, thus plants are a good source of natural antioxidants. Phyllanthus niruri (P. niruri has been known to possess several medicinal properties and contain numerous active phytochemical. In this research, we conducted phytochemical screening and antioxidant assay of P. niruri extract along with the compounds rutin and quercetin, which are flavonoids possessing medicinal properties. This study was conducted to determine P. niruri, rutin and quercetin as antioxidant. METHODS: In this study, qualitative phytochemical screening was performed to detect phenol, flavonoid, saponin, tannin, steroid/triterpenoid, terpenoid and alkaloid in P. niruri extract. Antioxidant analysis of P. niruri, rutin and quercetin was conducted using total measured phenolic content, 2,2-diphenyl-1-picrylhydrazil (DPPH, 2,2’-azinobis-3-ethylbenzo-thiazoline-6-sulfonic acid (ABTS and ferric reducing antioxidant power (FRAP assays. RESULTS:  The study revealed that P. niruri extract contained saponin, phenol, flavonoid and tannin based on phytochemical screening. In DPPH and ABTS assays quercetin possessed highest antioxidant activity with IC50 value of 0.55 and 1.17 μg/ml respectively. Meanwhile, P. niruri extract showed the highest FRAP activity which was 373.95 μM Fe(II/μg extract. Rutin possessed the lowest antioxidant activity in all antioxidant assays. CONCLUSION: This study confirmed that P. niruri extract and quercetin have great potential as a natural antioxidant source. KEYWORDS: asntioxidant, phytochemical, Phyllanthus niruri, quercetin, rutin, free radical

Quercetin suppresses heat shock-induced nuclear translocation of Hsp72

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Antoni Gawron

2011-08-01

Full Text Available The effect of quercetin and heat shock on the Hsp72 level and distribution in HeLa cells was studied by Western blotting, indirect immunofluorescence and immunogold electron microscopy. In control cells and after quercetin treatment, Hsp72 was located both in the cytoplasm and in the nucleus in comparable amounts. After hyperthermia, the level of nuclear Hsp72 raised dramatically. Expression of Hsp72 in cytoplasm was also higher but not to such extent as that observed in the nucleus. Preincubation of heated cells with quercetin inhibited strong Hsp72 expression observed after hyperthermia and changed the intracellular Hsp72 distribution. The cytoplasmic level of protein exceeded the nuclear one, especially around the nucleus, where the coat of Hsp72 was noticed. Observations indicating that quercetin was present around and in the nuclear envelope suggested an involvement of this drug in the inhibition of nuclear translocation. Our results indicate that pro-apoptotic activity of quercetin may be correlated not only with the inhibition of Hsp72 expression but also with suppression of its migration to the nucleus.

A novel solid fluorescence method for the fast determination of quercetin in biological samples based on the quercetin-Al(III) complex imprinted polymer

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Hu, Yufei; Feng, Ting; Li, Gongke

2014-01-01

In this work, a novel solid fluorescence method was proposed and applied to the fast determination of quercetin in urine and onion skin samples by using metal coordination imprinted polymer membrane, which was regarded as a recognition element. The quercetin-Al(III) imprinted polymer was immobilized in the microporous polypropylene fiber membrane via consecutive in situ polymerization. The CIP membrane had the porous, loose and layer upon layer structure. The CIP membrane was characterized by electron microscope photographs, infrared spectra, thermogravimetric analysis and solvent-resistant investigation. The extraction conditions including extraction solvent, extraction time, desorption solvent were optimized. Compared with MIP and NIP membrane, CIP membrane had been proved to be peculiar selective for quercetin even in presence of the structurally similar compounds such as kaempferol, rutin, naringenin and alpinetin. The CIP membrane was characteristic of high selectivity, stable and sensitive response to quercetin in polar environment. Under the optimum condition, there was a linear relationship between the state fluorescent response and the concentration of quercetin. The linear calibration range was over 0.02 mg L-1-0.80 mg L-1 with a detection limit of 5 μg L-1. The method was characteristic of flexible and good repeatability with relative standard deviation (RSD) of 4.1%. The proposed method was also successfully applied for the determination of quercetin in urine and onion skin samples without complicated pretreatment. The recoveries were 84.0-112.4% and RSDs varied from 1.5% to 6.8%. The results obtained by the proposed method agreed well with those obtained by HPLC method.

Effect of quercetin on radiosensitivity of human uterine cervix cancer HeLa cells

International Nuclear Information System (INIS)

Liang Xiaofang; Hong Chengjiao; Zhang Baoguo

2009-01-01

In order to investigate the effects of Quercetin on radiosensitivity of human Uterine Cervix Cancer HeLa cells, MTT assay and clonogenic assay were performed to evaluate the cytotoxicity of Quercetin on the cells. Clonogenic assay was used to observe its effects on the radiosensitivity of the cells. MTT result shows that the inhibition of Quercetin on the cells is in the dose-dependent and time-dependent. And the clonogenic assay result shows that the effect of Quercetin on HeLa cells can be divided into two parts, one for the inhibition of HeLa cells and another for the induction of HeLa cell death. The other clonogenic assay result also shows Quercetin can decrease clonogenic survival rate of HeLa cells exposed to X rays. The study shows Quercetin might enhance the radiosensitivity of the HeLa cell line. And it may provide a useful evaluation to combination of ionizing radiation and Quercetin for cancer patients. (authors)

Splenectomy attenuates murine liver fibrosis with hypersplenism stimulating hepatic accumulation of Ly-6C(lo) macrophages.

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Yada, Akito; Iimuro, Yuji; Uyama, Naoki; Uda, Yugo; Okada, Toshihiro; Fujimoto, Jiro

2015-10-01

Splenectomy in cirrhotic patients has been reported to improve liver function; however the underlying mechanism remains obscure. In the present study, we investigated the mechanism using a murine model, which represents well the compensated liver cirrhosis. C57BL/6 male mice were allowed to drink water including thioacetamide (TAA: 300 mg/L) ad libitum for 32 weeks. After splenectomy at 32 weeks, mice were sacrificed on days one, seven, and 28, respectively, while TAA-administration was continued. Perioperative changes in peripheral blood and liver tissues were analyzed. TAA treatment of mice for 32 weeks reproducibly achieved advanced liver fibrosis with splenomegaly, thrombocytopenia, and leukocytopenia. After splenectomy, liver fibrosis was attenuated, and macrophages/monocytes were significantly increased in peripheral blood, as well as in the liver. Progenitor-like cells expressing CK-19, EpCAM, or CD-133 appeared in the liver after TAA treatment, and gradually disappeared after splenectomy. Macrophages/monocytes accumulated in the liver, most of which were negative for Ly-6C, were adjacent to the hepatic progenitor-like cells, and quantitative RT-PCR indicated increased canonical Wnt and decreased Notch signals. As a result, a significant amount of β-catenin accumulated in the progenitor-like cells. Moreover, relatively small Ki67-positive hepatic cells were significantly increased. Protein expression of MMP-9, to which Ly-6G-positive neutrophils contributed, was also increased in the liver after splenectomy. The hepatic accumulation of macrophages/monocytes, most of which are Ly-6C(lo), the reduction of fibrosis, and the gradual disappearance of hepatic progenitor-like cells possibly play significant roles in the tissue remodeling process in cirrhotic livers after splenectomy. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Cardioprotective Effects of Quercetin in Cardiomyocyte under Ischemia/Reperfusion Injury

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Yi-Wen Chen

2013-01-01

Full Text Available Quercetin, a polyphenolic compound existing in many vegetables, fruits, has antiinflammatory, antiproliferation, and antioxidant effect on mammalian cells. Quercetin was evaluated for protecting cardiomyocytes from ischemia/reperfusion injury, but its protective mechanism remains unclear in the current study. The cardioprotective effects of quercetin are achieved by reducing the activity of Src kinase, signal transducer and activator of transcription 3 (STAT3, caspase 9, Bax, intracellular reactive oxygen species production, and inflammatory factor and inducible MnSOD expression. Fluorescence two-dimensional differential gel electrophoresis (2D-DIGE and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS can reveal the differentially expressed proteins of H9C2 cells treated with H2O2 or quercetin. Although 17 identified proteins were altered in H2O2-induced cells, these proteins such as alpha-soluble NSF attachment protein (α-SNAP, Ena/VASP-like protein (Evl, and isopentenyl-diphosphate delta-isomerase 1 (Idi-1 were reverted by pretreatment with quercetin, which correlates with kinase activation, DNA repair, lipid, and protein metabolism. Quercetin dephosphorylates Src kinase in H2O2-induced H9C2 cells and likely blocks the H2O2-induced inflammatory response through STAT3 kinase modulation. This probably contributes to prevent ischemia/reperfusion injury in cardiomyocytes.

Quercetin-induced changes in femoral bone microstructure of adult male rabbits

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Ramona Babosová

2016-06-01

Full Text Available Flavonoids are a group of plant metabolites with antioxidant effects. One of the most abundant flavonoids in the human diet is quercetin. It is found widely in fruits, vegetables and has a lot of beneficial effects on human health. Quercetin has a positive pharmacological effect on bone metabolism and it prevents the organism against bone loss. However, its impact on the size of basic structural units of the compact bone is still unknown. Therefore, the aim of present study was to investigate the impact of the quercetin on femoral bone microstructure in 5-month-old male rabbits. Five rabbits of Californian broiler line were randomly divided into two groups. In the experimental group (E group; n=3, animals were intramuscularly injected with quercetin at dose 1000 μg.kg-1 body weight (bw for 90 days, 3 times per week. Two rabbits without quercetin administration served as a control group (C group. According to our results, intramuscular application of quercetin had an insignificant effect on cortical bone thickness in male rabbits. In these rabbits, changes in qualitative histological characteristics were present in the middle part of the compacta, where primary vascular longitudinal bone tissue was present and expanded there from the periosteum. Also, a lower number of secondary osteons was found in these animals. From the histomorphometrical point of view, significantly decreased sizes of primary osteons' vascular canals and secondary osteons (p <0.05 were found in rabbits administered by quercetin. Our findings indicate that subchronic administration of quercetin at the dose used in our study had considerable impact on both qualitative and quantitative histological characteristics of the compact bone in adult male rabbits.

Effects of Quercetin in a Mouse Model of Experimental Dry Eye.

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Oh, Ha Na; Kim, Chae Eun; Lee, Ji Hyun; Yang, Jae Wook

2015-09-01

To evaluate the effect of treatment with quercetin in a mouse model of dry eye. 0.5% quercetin eye drops were prepared and an experimental dry eye model was induced in NOD.B10.H2(b) mice through desiccation stress. The mice were divided into 3 groups according to the treatment regimen: the DS 10D group (desiccation stress for 10 days), the phosphate buffered saline (PBS) group, and the quercetin group. Tear volumes and corneal irregularity scores were measured at 3, 5, 7, and 10 days after treatment. Hematoxylin and eosin staining, periodic acid-Schiff staining, and immunohistochemistry were performed at the end of the experiment. The quercetin group had increased tear volumes (0.2 ± 0.03 μm, P lacrimal gland than did the PBS group. Topical application of quercetin can help to improve ocular surface disorders of dry eye not only by decreasing the corneal surface irregularity but also by increasing the tear volume and goblet cell density. Moreover, quercetin has the potential for use in eye drops as a treatment for dry eye disease with antiinflammatory effects on the lacrimal functional unit.

Influence of quercetin and nanohydroxyapatite modifications of decellularized goat-lung scaffold for bone regeneration

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Gupta, Sweta K. [Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, 247667 (India); Kumar, Ritesh [Center for Computational Biology, University of Kansas, Kansas 66045 (United States); Mishra, Narayan C., E-mail: mishrawise@gmail.com [Department of Polymer and Process Engineering, Indian Institute of Technology Roorkee, 247667 (India)

2017-02-01

In the present study, goat-lung scaffold was fabricated by decellularization of lung tissue and verified for complete cell removal by DNA quantification, DAPI and H&E staining. The scaffold was then modified by crosslinking with quercetin and nanohydroxyapatite (nHAp), and characterized to evaluate the suitability of quercetin-crosslinked nHAp-modified scaffold for regeneration of bone tissue. The crosslinking chemistry between quercetin and decellularized scaffold was established theoretically by AutoDock Vina program (in silico docking study), which predicted multiple intermolecular hydrogen bonding interactions between quercetin and decellularized scaffold, and FTIR spectroscopy analysis also proved the same. From MTT assay and SEM studies, it was found that the quercetin-crosslinked nHAp-modified decellularized scaffold encouraged better growth and proliferation of bone-marrow derived mesenchymal stem cells (BMMSCs) in comparison to unmodified decellularized scaffold, quercetin-crosslinked decellularized scaffold and nHAp-modified decellularized scaffold. Alkaline Phosphatase (ALP) assay results showed highest expression of ALP over quercetin-crosslinked nHAp-modified scaffold among all the tested scaffolds (unmodified decellularized scaffold, quercetin-crosslinked decellularized scaffold and nHAp-modified decellularized scaffold) − indicating that quercetin and nHAp is very much efficient in stimulating the differentiation of BMMSCs into osteoblast cells. Alizarin red test quantified in vitro mineralization (calcium deposits), and increased expression of alizarin red over quercetin-crosslinked nHAp-modified scaffold indicating better stimulation of osteogenesis in BMMSCs. The above findings suggest that quercetin-crosslinked nHAp-modified decellularized goat-lung scaffold provides biomimetic bone-like microenvironment for BMMSCs to differentiate into osteoblast and could be applied as a potential promising biomaterial for bone regeneration. - Highlights: �

Naringenin and quercetin--potential anti-HCV agents for NS2 protease targets.

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Lulu, S Sajitha; Thabitha, A; Vino, S; Priya, A Mohana; Rout, Madhusmita

2016-01-01

Nonstructural proteins of hepatitis C virus had drawn much attention for the scientific fraternity in drug discovery due to its important role in the disease. 3D structure of the protein was predicted using molecular modelling protocol. Docking studies of 10 medicinal plant compounds and three drugs available in the market (control) with NS2 protease were employed by using rigid docking approach of AutoDock 4.2. Among the molecules tested for docking study, naringenin and quercetin revealed minimum binding energy of - 7.97 and - 7.95 kcal/mol with NS2 protease. All the ligands were docked deeply within the binding pocket region of the protein. The docking study results showed that these compounds are potential inhibitors of the target; and also all these docked compounds have good inhibition constant, vdW+Hbond+desolv energy with best RMSD value.

Method validation and stability study of quercetin in topical emulsions

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Rúbia Casagrande

2009-01-01

Full Text Available This study validated a high performance liquid chromatography (HPLC method for the quantitative evaluation of quercetin in topical emulsions. The method was linear within 0.05 - 200 μg/mL range with a correlation coefficient of 0.9997, and without interference in the quercetin peak. The detection and quantitation limits were 18 and 29 ng/mL, respectively. The intra- and inter-assay precisions presented R.S.D. values lower than 2%. An average of 93% and 94% of quercetin was recovered for non-ionic and anionic emulsions, respectively. The raw material and anionic emulsion, but not non-ionic emulsion, were stable in all storage conditions for one year. The method reported is a fast and reliable HPLC technique useful for quercetin determination in topical emulsions.

Quercetin as colorimetric reagent for determination of zirconium

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Grimaldi, F.S.; White, C.E.

1953-01-01

Methods described in the literature for the determination of zirconium are generally designed for relatively large amounts of this element. A good procedure using colorimetric reagent for the determination of trace amounts is desirable. Quercetin has been found to yield a sensitive color reaction with zirconium suitable for the determination of from 0.1 to 50?? of zirconium dioxide. The procedure developed involves the separation of zirconium from interfering elements by precipitation with p-dimethylaminoazophenylarsonic acid prior to its estimation with quercetin. The quercetin reaction is carried out in 0.5N hydrochloric acid solution. Under the operating conditions it is indicated that quercetin forms a 2 to 1 complex with zirconium; however, a 2 to 1 and a 1 to 1 complex can coexist under special conditions. Approximate values for the equilibrium constants of the complexes are K1 = 0.33 ?? 10-5 and K2 = 1.3 ?? 10-9. Seven Bureau of Standards samples of glass sands and refractories were analyzed with excellent results. The method described should find considerable application in the analysis of minerals and other materials for macro as well as micro amounts of zirconium.

Dermal quercetin smartCrystals®: Formulation development, antioxidant activity and cellular safety.

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Hatahet, T; Morille, M; Hommoss, A; Dorandeu, C; Müller, R H; Bégu, S

2016-05-01

Flavonoids are natural plant pigments, which possess high antioxidative and antiradical activities. However, their poor water solubility led to a limited bioavailability. To overcome this major hurdle, quercetin nanocrystals were produced implementing smartCrystals® technology. This process combines bead milling and subsequent high-pressure homogenization at relatively low pressure (300bar). To test the possibility to develop a dermal formulation from quercetin smartCrystals®, quercetin nanosuspensions were admixed to Lutrol® F127 and hydroxythylcellulose nonionic gels. The physicochemical properties (morphology, size and charge), saturation solubility, dissolution velocity and the antioxidant properties (DPPH assay) as well as the cellular interaction of the produced quercetin smartCrystals® were studied and compared to crude quercetin powder. Quercetin smartCrystals® showed a strong increase in the saturation solubility and the dissolution velocity (7.6 fold). SmartCrystals® loaded or not into gels proved to be physically stable over a period of three months at 25°C. Interestingly, in vitro DPPH assay confirmed the preservation of quercetin antioxidative properties after nanonization. In parallel, the nanocrystalline form did not display cellular toxicity, even at high concentration (50μg/ml), as assayed on an epithelial cell line (VERO cells). In addition, the nanocrystalline form confirmed a protective activity for VERO cells against hydrogen peroxide induced toxicity in vitro. This new formulation presents a promising approach to deliver quercetin efficiently to skin in well-tolerated formulations. Copyright © 2016 Elsevier B.V. All rights reserved.

Quercetin as natural stabilizing agent for bio-polymer

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Morici, Elisabetta [Dipartimento di Ingegneria Chimica, Gestionale, Informatica, Meccanica, Università di Palermo, 90128 Palermo (Italy); Arrigo, Rossella; Dintcheva, Nadka Tzankova [Dipartimento di Ingegneria Civile, Ambientale, Aerospaziale, dei Materiali, Università di Palermo, 90128 Palermo (Italy)

2014-05-15

The introduction of antioxidants in polymers is the main way to prevent or delay the degradation process. In particular natural antioxidants receive attention in the food industry also because of their presumed safety. In this work bio-polymers, i.e. a commercial starch-based polymer (Mater-Bi®) and a bio-polyester (PLA), and a bio-polyether (PEO) were additivated with quercetin, a natural flavonoid antioxidants, in order to formulate bio-based films for ecosustainable packaging and outdoor applications. The photo-oxidation behavior of unstabilized and quercetin stabilized films was analyzed and compared with the behavior of films additivated with a commercial synthetic light stabilizer. The quercetin is able to slow down the photo-degradation rate of all bio-polymeric films investigated in similar way to the synthetic stabilizer.

Quercetin as natural stabilizing agent for bio-polymer

Science.gov (United States)

Morici, Elisabetta; Arrigo, Rossella; Dintcheva, Nadka Tzankova

2014-05-01

The introduction of antioxidants in polymers is the main way to prevent or delay the degradation process. In particular natural antioxidants receive attention in the food industry also because of their presumed safety. In this work bio-polymers, i.e. a commercial starch-based polymer (Mater-Bi®) and a bio-polyester (PLA), and a bio-polyether (PEO) were additivated with quercetin, a natural flavonoid antioxidants, in order to formulate bio-based films for ecosustainable packaging and outdoor applications. The photo-oxidation behavior of unstabilized and quercetin stabilized films was analyzed and compared with the behavior of films additivated with a commercial synthetic light stabilizer. The quercetin is able to slow down the photo-degradation rate of all bio-polymeric films investigated in similar way to the synthetic stabilizer.

Quercetin as natural stabilizing agent for bio-polymer

International Nuclear Information System (INIS)

Morici, Elisabetta; Arrigo, Rossella; Dintcheva, Nadka Tzankova

2014-01-01

The introduction of antioxidants in polymers is the main way to prevent or delay the degradation process. In particular natural antioxidants receive attention in the food industry also because of their presumed safety. In this work bio-polymers, i.e. a commercial starch-based polymer (Mater-Bi®) and a bio-polyester (PLA), and a bio-polyether (PEO) were additivated with quercetin, a natural flavonoid antioxidants, in order to formulate bio-based films for ecosustainable packaging and outdoor applications. The photo-oxidation behavior of unstabilized and quercetin stabilized films was analyzed and compared with the behavior of films additivated with a commercial synthetic light stabilizer. The quercetin is able to slow down the photo-degradation rate of all bio-polymeric films investigated in similar way to the synthetic stabilizer

Dietary quercetin exacerbates the development of estrogen-induced breast tumors in female ACI rats

International Nuclear Information System (INIS)

Singh, Bhupendra; Mense, Sarah M.; Bhat, Nimee K.; Putty, Sandeep; Guthiel, William A.; Remotti, Fabrizio; Bhat, Hari K.

2010-01-01

Phytoestrogens are plant compounds that structurally mimic the endogenous estrogen 17β-estradiol (E 2 ). Despite intense investigation, the net effect of phytoestrogen exposure on the breast remains unclear. The objective of the current study was to examine the effects of quercetin on E 2 -induced breast cancer in vivo. Female ACI rats were given quercetin (2.5 g/kg food) for 8 months. Animals were monitored weekly for palpable tumors, and at the end of the experiment, rats were euthanized, breast tumor and different tissues excised so that they could be examined for histopathologic changes, estrogen metabolic activity and oxidant stress. Quercetin alone did not induce mammary tumors in female ACI rats. However, in rats implanted with E 2 pellets, co-exposure to quercetin did not protect rats from E 2 -induced breast tumor development with 100% of the animals developing breast tumors within 8 months of treatment. No changes in serum quercetin levels were observed in quercetin and quercetin + E 2 -treated groups at the end of the experiment. Tumor latency was significantly decreased among rats from the quercetin + E 2 group relative to those in the E 2 group. Catechol-O-methyltransferase (COMT) activity was significantly downregulated in quercetin-exposed mammary tissue. Analysis of 8-isoprostane F 2α (8-iso-PGF 2α ) levels as a marker of oxidant stress showed that quercetin did not decrease E 2 -induced oxidant stress. These results indicate that quercetin (2.5 g/kg food) does not confer protection against breast cancer, does not inhibit E 2 -induced oxidant stress and may exacerbate breast carcinogenesis in E 2 -treated ACI rats. Inhibition of COMT activity by quercetin may expose breast cells chronically to E 2 and catechol estrogens. This would permit longer exposure times to the carcinogenic metabolites of E 2 and chronic exposure to oxidant stress as a result of metabolic redox cycling to estrogen metabolites, and thus quercetin may exacerbate E 2 -induced

Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

International Nuclear Information System (INIS)

Wu, Weibin; Zhu, Bo; Peng, Xiaomin; Zhou, Meiling; Jia, Dongwei; Gu, Jianxin

2014-01-01

Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients

Activation of farnesoid X receptor attenuates hepatic injury in a murine model of alcoholic liver disease

Energy Technology Data Exchange (ETDEWEB)

Wu, Weibin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China); Zhu, Bo; Peng, Xiaomin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Zhou, Meiling, E-mail: meilingzhou2012@gmail.com [Department of Radiology, Zhongshan Hospital of Fudan University and Shanghai Institute of Medical Imaging, Shanghai 200032 (China); Jia, Dongwei, E-mail: jiadongwei@fudan.edu.cn [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Gu, Jianxin [Department of Biochemistry and Molecular Biology, Shanghai Medical College, Fudan University, Shanghai 200032 (China); Institutes of Biomedical Science, Fudan University, Shanghai 200032 (China)

2014-01-03

Highlights: •FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. •Activation of FXR attenuated alcohol-induced liver injury and steatosis. •Activation of FXR attenuated cholestasis and oxidative stress in mouse liver. -- Abstract: Alcoholic liver disease (ALD) is a common cause of advanced liver disease, and considered as a major risk factor of morbidity and mortality worldwide. Hepatic cholestasis is a pathophysiological feature observed in all stages of ALD. The farnesoid X receptor (FXR) is a member of the nuclear hormone receptor superfamily, and plays an essential role in the regulation of bile acid, lipid and glucose homeostasis. However, the role of FXR in the pathogenesis and progression of ALD remains largely unknown. Mice were fed Lieber-DeCarli ethanol diet or an isocaloric control diet. We used a specific agonist of FXR WAY-362450 to study the effect of pharmacological activation of FXR in alcoholic liver disease. In this study, we demonstrated that FXR activity was impaired by chronic ethanol ingestion in a murine model of ALD. Activation of FXR by specific agonist WAY-362450 protected mice from the development of ALD. We also found that WAY-362450 treatment rescued FXR activity, suppressed ethanol-induced Cyp2e1 up-regulation and attenuated oxidative stress in liver. Our results highlight a key role of FXR in the modulation of ALD development, and propose specific FXR agonists for the treatment of ALD patients.

Quercetin in Cancer Treatment, Alone or in Combination with Conventional Therapeutics?

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Brito, Ana Filipa; Ribeiro, Marina; Abrantes, Ana Margarida; Pires, Ana Salomé; Teixo, Ricardo Jorge; Tralhão, José Guilherme; Botelho, Maria Filomena

2015-01-01

Cancer is a problem of global importance, since the incidence is increasing worldwide and therapeutic options are generally limited. Thus, it becomes imperative to find new therapeutic targets as well as new molecules with therapeutic potential for tumors. Flavonoids are polyphenolic compounds that may be potential therapeutic agents. Several studies have shown that these compounds have a higher anticancer potential. Among the flavonoids in the human diet, quercetin is one of the most important. In the last decades, several anticancer properties of quercetin have been described, such as cell signaling, pro-apoptotic, anti-proliferative and anti-oxidant effects, growth suppression. In fact, it is now well known that quercetin has diverse biological effects, inhibiting multiple enzymes involved in cell proliferation, as well as, in signal transduction pathways. On the other hand, there are also studies reporting potential synergistic effects when combined quercetin with chemotherapeutic agents or radiotherapy. In fact, several studies which aim to explore the anticancer potential of these combined treatments have already been published, the majority with promising results. Actually it is well known that quercetin can act on the chemosensitization and radiosensitization but also as chemoprotective and radioprotective, protecting normal cells of the side effects that results from chemotherapy and radiotherapy, which obviously provides notable advantages in their use in anticancer treatment. Thus, all these data indicate that quercetin may have a key role in anticancer treatment. In this context, this review is focused on the relationship between flavonoids and cancer, with special emphasis on the role of quercetin.

Ultrasonication-Assisted Solvent Extraction of Quercetin Glycosides from ‘Idared’ Apple Peels

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Gwendolyn M. Huber

2011-11-01

Full Text Available Quercetin and quercetin glycosides are physiologically active flavonol molecules that have been attributed numerous health benefits. Recovery of such molecules from plant matrices depends on a variety of factors including polarity of the extraction solvent. Among the solvents of a wide range of dielectric constants, methanol recovered the most quercetin and its glycosides from dehydrated ‘Idared’ apple peels. When ultra-sonication was employed to facilitate the extraction, exposure of 15 min of ultrasound wavelengths of dehydrated apple peel powder in 80% to 100% (v/v methanol in 1:50 (w:v solid to solvent ratio provided the optimum extraction conditions for quercetin and its glycosides. Acidification of extraction solvent with 0.1% (v/v or higher concentrations of HCl led to hydrolysis of naturally occurring quercetin glycosides into the aglycone as an extraction artifact.

Quercetin prevents pyrrolizidine alkaloid clivorine-induced liver injury in mice by elevating body defense capacity.

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Lili Ji

Full Text Available Quercetin is a plant-derived flavonoid that is widely distributed in nature. The present study is designed to analyze the underlying mechanism in the protection of quercetin against pyrrolizidine alkaloid clivorine-induced acute liver injury in vivo. Serum transaminases, total bilirubin analysis, and liver histological evaluation demonstrated the protection of quercetin against clivorine-induced liver injury. Terminal dUTP nick end-labeling assay demonstrated that quercetin reduced the increased amount of liver apoptotic cells induced by clivorine. Western-blot analysis of caspase-3 showed that quercetin inhibited the cleaved activation of caspase-3 induced by clivorine. Results also showed that quercetin reduced the increase in liver glutathione and lipid peroxidative product malondialdehyde induced by clivorine. Quercetin reduced the enhanced liver immunohistochemical staining for 4-hydroxynonenal induced by clivorine. Results of the Mouse Stress and Toxicity PathwayFinder RT2 Profiler PCR Array demonstrated that the expression of genes related with oxidative or metabolic stress and heat shock was obviously altered after quercetin treatment. Some of the alterations were confirmed by real-time PCR. Our results demonstrated that quercetin prevents clivorine-induced acute liver injury in vivo by inhibiting apoptotic cell death and ameliorating oxidative stress injury. This protection may be caused by the elevation of the body defense capacity induced by quercetin.

Quercetin Prevents Pyrrolizidine Alkaloid Clivorine-Induced Liver Injury in Mice by Elevating Body Defense Capacity

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Ji, Lili; Ma, Yibo; Wang, Zaiyong; Cai, Zhunxiu; Pang, Chun; Wang, Zhengtao

2014-01-01

Quercetin is a plant-derived flavonoid that is widely distributed in nature. The present study is designed to analyze the underlying mechanism in the protection of quercetin against pyrrolizidine alkaloid clivorine-induced acute liver injury in vivo. Serum transaminases, total bilirubin analysis, and liver histological evaluation demonstrated the protection of quercetin against clivorine-induced liver injury. Terminal dUTP nick end-labeling assay demonstrated that quercetin reduced the increased amount of liver apoptotic cells induced by clivorine. Western-blot analysis of caspase-3 showed that quercetin inhibited the cleaved activation of caspase-3 induced by clivorine. Results also showed that quercetin reduced the increase in liver glutathione and lipid peroxidative product malondialdehyde induced by clivorine. Quercetin reduced the enhanced liver immunohistochemical staining for 4-hydroxynonenal induced by clivorine. Results of the Mouse Stress and Toxicity PathwayFinder RT2 Profiler PCR Array demonstrated that the expression of genes related with oxidative or metabolic stress and heat shock was obviously altered after quercetin treatment. Some of the alterations were confirmed by real-time PCR. Our results demonstrated that quercetin prevents clivorine-induced acute liver injury in vivo by inhibiting apoptotic cell death and ameliorating oxidative stress injury. This protection may be caused by the elevation of the body defense capacity induced by quercetin. PMID:24905073

Quercetin reduces markers of oxidative stress and inflammation in sarcoidosis

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Boots, Agnes W.; Drent, Marjolein; de Boer, Vincent C. J.; Bast, Aalt; Haenen, Guido R. M. M.

2011-01-01

Oxidative stress and low antioxidant levels are implicated in the aetiology of sarcoidosis, an inflammatory disease. Quercetin is a potent dietary antioxidant that also displays anti-inflammatory activities. Consequently, the aim is to examine the effect of quercetin supplementation on markers of

Onion skin waste as a valorization resource for the by-products quercetin and biosugar.

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Choi, In Seong; Cho, Eun Jin; Moon, Jae-Hak; Bae, Hyeun-Jong

2015-12-01

Onion skin waste (OSW), which is produced from processed onions, is a major industrial waste. We evaluated the use of OSW for biosugar and quercetin production. The carbohydrate content of OSW was analyzed, and the optimal conversion conditions were evaluated by varying enzyme mixtures and loading volumes for biosugar production and quercetin extraction. The enzymatic conversion rate of OSW to biosugar was 98.5% at 0.72 mg of cellulase, 0.16 mg of pectinase, and 1.0mg of xylanase per gram of dry OSW. Quercetin extraction also increased by 1.61-fold after complete enzymatic hydrolysis. In addition, the newly developed nano-matrix (terpyridine-immobilized silica-coated magnetic nanoparticles-zinc (TSMNP-Zn matrix) was utilized to separate quercetin from OSW extracts. The nano-matrix facilitated easy separation and purification of quercetin. Using the TSMNP-Zn matrix the quercetin was approximately 90% absorbed. In addition, the recovery yield of quercetin was approximately 75% after treatment with ethylenediaminetetraacetic acid. Copyright © 2015 Elsevier Ltd. All rights reserved.

Possible stimulatory effect of quercetin on secretion of selected pituitary hormones

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Eva Tušimová

2017-05-01

Full Text Available Quercetin is found in various types of foods such as apples, red onions, grapes, berries, citrus fruits, cherries, broccoli, tea etc. It is characterized by antioxidative, anti-carcinogenic, bacteriostatic and anti-inflammatory effects on the animal organism. The aim of our study was to examine its effect on endocrine system of the rabbit in vivo. Twenty healthy adult female rabbits were divided into four groups (control group and three experimental groups. Various concentrations of quercetin (10, 100 and 1000 µg/kg body weight were intramuscularly administrated to rabbits in experimental groups during 30 days. A sensitive, biochemical method, ELISA was used to determine the concentrations of selected hormones (follicle-stimulating hormone - FSH, luteinizing hormone – LH, prolactin – PRL after 30 days of administration. Non-significant differences between groups were found after application of different quercetin concentrations. Stimulatory effect was observed on FSH secretion by higher dose of quercetin. Similarly, LH and PRL increased at concentration 100 µg/kg and 1000 µg/kg. Our results indicate the possible effect of quercetin on secretion of selected pituitary hormones.

EFFECT OF QUERCETIN ON ANTIOXIDANT STATUS OF RABBITS AFTER ONE MONTH EXPOSURE

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Peter Petruška

2014-02-01

Full Text Available The aim of the present study was to investigate the short-term effect of quercetin in various doses on level of antioxidant enzymes in rabbit’s blood. Adult rabbits were divided into three experimental groups (E1, E2 and E3 and the control group without quercetin addition. Quercetin was applied intramuscularly in various concentrations; 10 µg.kg-1 in E1 group, 100 µg.kg-1 in E2 group, and 1000 µg.kg-1 in E3 group for 30 days, 3 times per week. Application of quercetin insignificantly increased the level of SOD in the experimental groups in comparison with the control group. Gender comparison showed higher level of SOD in all experimental male groups in comparison with the female groups. The level of GPx activity decreased in all experimental groups but without significant differences. In gender comparison we found higher activity of GPx in female groups in comparison with the male groups. In conclusion, as the quercetin serves in organism as antioxidant with the ability to scavenge free radicals, our results could contribute to the positive effect of quercetin on antioxidant balance, however further studies are needed.

Protective Effect of Quercetin against Oxidative Stress-Induced Cytotoxicity in Rat Pheochromocytoma (PC-12) Cells.

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Bao, Dengke; Wang, Jingkai; Pang, Xiaobin; Liu, Hongliang

2017-07-06

Oxidative stress has been implicated in the pathogenesis of many kinds of neurodegenerative disorders, particularly Parkinson's disease. Quercetin is a bioflavonoid found ubiquitously in fruits and vegetables, and has antioxidative activity. However, the underlying mechanism of the antioxidative effect of quercetin in neurodegenerative diseases has not been well explored. Here, we investigated the antioxidative effect and underlying molecular mechanisms of quercetin on PC-12 cells. We found that PC-12 cells pretreated with quercetin exhibited an increased cell viability and reduced lactate dehydrogenase (LDH) release when exposed to hydrogen peroxide (H₂O₂). The significantly-alleviated intracellular reactive oxygen species (ROS), malondialdehyde (MDA), and lipoperoxidation of the cell membrane of PC-12 cells induced by H₂O₂ were observed in the quercetin pretreated group. Furthermore, quercetin pretreatment markedly reduced the apoptosis of PC-12 cells and hippocampal neurons. The inductions of antioxidant enzyme catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) in PC-12 cells exposed to H₂O₂ were significantly reduced by preatment with quercetin. In addition, quercetin pretreatment significantly increased Bcl-2 expression, and reduced Bax, cleaved caspase-3 and p53 expressions. In conclusion, this study demonstrated that quercetin exhibited a protective effect against oxidative stress-induced apoptosis in PC-12 cells. Our findings suggested that quercetin may be developed as a novel therapeutic agent for neurodegenerative diseases induced by oxidative stress.

Adenoviral overexpression of Lhx2 attenuates cell viability but does not preserve the stem cell like phenotype of hepatic stellate cells.

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Genz, Berit; Thomas, Maria; Pützer, Brigitte M; Siatkowski, Marcin; Fuellen, Georg; Vollmar, Brigitte; Abshagen, Kerstin

2014-11-01

Hepatic stellate cells (HSC) are well known initiators of hepatic fibrosis. After liver cell damage, HSC transdifferentiate into proliferative myofibroblasts, representing the major source of extracellular matrix in the fibrotic organ. Recent studies also demonstrate a role of HSC as progenitor or stem cell like cells in liver regeneration. Lhx2 is described as stem cell maintaining factor in different organs and as an inhibitory transcription factor in HSC activation. Here we examined whether a continuous expression of Lhx2 in HSC could attenuate their activation and whether Lhx2 could serve as a potential target for antifibrotic gene therapy. Therefore, we evaluated an adenoviral mediated overexpression of Lhx2 in primary HSC and investigated mRNA expression patterns by qRT-PCR as well as the activation status by different in vitro assays. HSC revealed a marked increase in activation markers like smooth muscle actin alpha (αSMA) and collagen 1α independent from adenoviral transduction. Lhx2 overexpression resulted in attenuated cell viability as shown by a slightly hampered migratory and contractile phenotype of HSC. Expression of stem cell factors or signaling components was also unaffected by Lhx2. Summarizing these results, we found no antifibrotic or stem cell maintaining effect of Lhx2 overexpression in primary HSC. Copyright © 2014 Elsevier Inc. All rights reserved.

Potential improvement of Lymantria dispar L. management by quercetin

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Perić-Mataruga Vesna

2014-01-01

Full Text Available Lymantria dispar, a polyphagous insect pest, copes with a wide variety of host-specific allelochemicals. Glutathione S-transferases (GST are important for catalyzing detoxification in L. dispar. Larval mortality, GST activity in midgut tissue and mass of L. dispar with different trophic adaptations (originating from two forests with a suitable host, Quercus robur, and an unsuitable host, Robinia pseudoacacia, differed after feeding on quercetin supplemented diets (2% or 5% w/w. Quercetin inhibited GST most potently in oak forest larvae that were less adapted to flavonoids in their diet. The larvicidal effect of quercetin on L. dispar larvae depended on the host-use history. We believe this is important in strategies for sustainable control of insect pests. [Projekat Ministarstva nauke Republike Srbije, br. 173027

Quercetin does not alter the oral bioavailability of Atorvastatin in rats.

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Koritala, Rekha; Challa, Siva Reddy; Ragam, Satheesh Kumar; Geddam, Lal Babu; Venkatesh Reddy Challa, Venkatesh Reddy; Devi, Renuka; Sattenapalli, Srinu; Babu, Narendra

2015-09-01

The study was undertaken to evaluate the effect of Quercetin on the pharmacokinetics of Atorvastatin Calcium. In-vivo Pharmacokinetic studies were performed on rats in a single dose study and multiple dose study. Rats were treated with Quercetin (10 mg/kg) and Atorvastatin Calcium (20 mg/kg) orally and blood samples were collected at (0) pretreatment and 0.5, 1, 1.5, 2, 2.5, 3, 4, 8, 12, 24 hours post treatment. Plasma concentrations of Atorvastatin were estimated by HPLC method. Quercetin treatment did not significantly alter the pharmacokinetic parameters of atorvastatin like AUC(0-24), AUC(0-α) , T(max), C(max) and T(½) in both single dose and multiple dose studies of Atorvastatin Calcium. Quercetin does not alter the oral bioavailability of Atorvastatin Calcium in rats.

Quercetin targets cysteine string protein (CSPalpha and impairs synaptic transmission.

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Fenglian Xu

2010-06-01

Full Text Available Cysteine string protein (CSPalpha is a synaptic vesicle protein that displays unique anti-neurodegenerative properties. CSPalpha is a member of the conserved J protein family, also called the Hsp40 (heat shock protein of 40 kDa protein family, whose importance in protein folding has been recognized for many years. Deletion of the CSPalpha in mice results in knockout mice that are normal for the first 2-3 weeks of life followed by an unexplained presynaptic neurodegeneration and premature death. How CSPalpha prevents neurodegeneration is currently not known. As a neuroprotective synaptic vesicle protein, CSPalpha represents a promising therapeutic target for the prevention of neurodegenerative disorders.Here, we demonstrate that the flavonoid quercetin promotes formation of stable CSPalpha-CSPalpha dimers and that quercetin-induced dimerization is dependent on the unique cysteine string region. Furthermore, in primary cultures of Lymnaea neurons, quercetin induction of CSPalpha dimers correlates with an inhibition of synapse formation and synaptic transmission suggesting that quercetin interfers with CSPalpha function. Quercetin's action on CSPalpha is concentration dependent and does not promote dimerization of other synaptic proteins or other J protein family members and reduces the assembly of CSPalpha:Hsc70 units (70kDa heat shock cognate protein.Quercetin is a plant derived flavonoid and popular nutritional supplement proposed to prevent memory loss and altitude sickness among other ailments, although its precise mechanism(s of action has been unclear. In view of the therapeutic promise of upregulation of CSPalpha and the undesired consequences of CSPalpha dysfunction, our data establish an essential proof of principle that pharmaceutical agents can selectively target the neuroprotective J protein CSPalpha.

Controlled attenuation parameter for the detection and quantification of hepatic steatosis in nonalcoholic fatty liver disease.

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Chan, Wah-Kheong; Nik Mustapha, Nik Raihan; Mahadeva, Sanjiv

2014-01-01

Controlled attenuation parameter (CAP) has been suggested as a noninvasive method for detection and quantification of hepatic steatosis. We aim to study the diagnostic performance of CAP in nonalcoholic fatty liver disease (NAFLD) patients. Transient elastography was performed in consecutive NAFLD patients undergoing liver biopsy and non-NAFLD controls. The accuracy of CAP for the detection and quantification of hepatic steatosis was assessed based on histological findings according to the Nonalcoholic Steatohepatitis Clinical Research Network Scoring System. Data for 101 NAFLD patients (mean age 50.3 ± 11.3 years old, 51.5% male) and 60 non-NAFLD controls were analyzed. CAP was associated with steatosis grade (odds ratio [OR] = 29.16, P steatosis grades S0, S1, S2, and S3 were 184 dB/m, 305 dB/m, 320 dB/m, and 324 dB/m, respectively. The areas under receiver operating characteristics curves (AUROC) for estimation of steatosis grades ≥ S1, S2, and S3 were 0.97, 0.86, and 0.75, respectively. The optimal CAP cutoffs for estimation of steatosis grades ≥ S1, S2, and S3 were 263 dB/m, 281 dB/m, and 283 dB/m, respectively. Among non-obese patients, the AUROC for estimation of steatosis grades ≥ S1 and S2 were 0.99 and 0.99, respectively. Among obese patients, the AUROC for estimation of steatosis grades ≥ S1, S2, and S3 were 0.92, 0.64, and 0.58, respectively. CAP is excellent for the detection of significant hepatic steatosis. However, its accuracy is impaired by an increased BMI, and it is less accurate to distinguish between the different grades of hepatic steatosis. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.

Evaluation of anti-fatigue and immunomodulating effects of quercetin in strenuous exercise mice

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Zhang, Wei-qiang

2017-04-01

The purpose of the present study was to investigate the anti-fatigue and immunomodulating effects of quercetin in strenuous exercise mice. Mice were given orally either corn oil or quercetin (20, 40 and 60 mg/kg body weight suspended in corn oil) by gavage once a day for 28 day. All mice were sacrificed after rotarod test and the major biochemical parameters were analyzed in serum and liver. The results indicated that quercetin possessed anti-fatigue effects by prolonging retention times, decreasing levels of blood lactate and serum urea nitrogen, and increasing levels of blood glucose, tissue glycogen and serum glucagon. Furthermore, quercetin could improve the immune function of fatigue mice by decreasing tumor necrosis factor-α levels, and elevated interleukin-10 levels. Quercetin possessed anti-fatigue effects may be related to its immunomodulating effects.

Study of anti-oxidation and scavenging effects on free radicals of quercetin

International Nuclear Information System (INIS)

Wang Chongdao; Qiang Yizhong; Lao Qinhua; Shao Yuan

1999-01-01

The effects of Quercetin on the contents of lipid peroxides (LPO) in the mice caused by γ-whole-body irradiation by method of the modified spectrophotometry of TBA, and the scavenging effects of Quercetin on the free radicals of DNA induced by radiation exposure by means of ESR technique were investigated. The results demonstrates that Quercetin has a good anti-oxidation effect and is very effective in scavenging of free radicals

Protective Effect of Quercetin against Oxidative Stress-Induced Cytotoxicity in Rat Pheochromocytoma (PC-12 Cells

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Dengke Bao

2017-07-01

Full Text Available Oxidative stress has been implicated in the pathogenesis of many kinds of neurodegenerative disorders, particularly Parkinson’s disease. Quercetin is a bioflavonoid found ubiquitously in fruits and vegetables, and has antioxidative activity. However, the underlying mechanism of the antioxidative effect of quercetin in neurodegenerative diseases has not been well explored. Here, we investigated the antioxidative effect and underlying molecular mechanisms of quercetin on PC-12 cells. We found that PC-12 cells pretreated with quercetin exhibited an increased cell viability and reduced lactate dehydrogenase (LDH release when exposed to hydrogen peroxide (H2O2. The significantly-alleviated intracellular reactive oxygen species (ROS, malondialdehyde (MDA, and lipoperoxidation of the cell membrane of PC-12 cells induced by H2O2 were observed in the quercetin pretreated group. Furthermore, quercetin pretreatment markedly reduced the apoptosis of PC-12 cells and hippocampal neurons. The inductions of antioxidant enzyme catalase (CAT, superoxide dismutase (SOD, and glutathione peroxidase (GSH-Px in PC-12 cells exposed to H2O2 were significantly reduced by preatment with quercetin. In addition, quercetin pretreatment significantly increased Bcl-2 expression, and reduced Bax, cleaved caspase-3 and p53 expressions. In conclusion, this study demonstrated that quercetin exhibited a protective effect against oxidative stress-induced apoptosis in PC-12 cells. Our findings suggested that quercetin may be developed as a novel therapeutic agent for neurodegenerative diseases induced by oxidative stress.

Antibody response in animals immunized after oral delivery of attenuated liver hepatitis a vaccine

International Nuclear Information System (INIS)

Long Runxiang; Hou Zongliu; Xie Zhongping; Ding Xuefeng; Pan Yue; Huang Cheng; Zhang Ming; Yang Lixian

2006-01-01

The microspheres were prepared by encapsulating live attenuated hepatitis A vaccine with PLA/PLG, and the rhesus monkeys and mice were immunized by such microspheres through oral route. Then serum was collected to detect the HAV-IgM, HAV-IgG, HAV-IgA with EIA, so as to find a convenient immunization way. Results showed that HAV-IgG in rhesus monkeys was detected in the 3rd week and reached a peak value (1267mlU/mL), and then decreased by degrees. HAV-IgM titer was 1:4000. After an oral booster was given, the HAV-IgG level increased, and HAV-IgM titer was 1:1000. The level reached 1244mIU/mL after challenge with wild virus strain, and HAV-IgM was 1:100. HAV-IgM was detected in the control group only after challenge with wild virus strain. HAV-IgG in mice was detected in the 2nd week and reached a peak value in the 4th week. HAV S-IgA was detected in the 1st week and reached a peak value in the 4th week. Antibody response was induced in the rhesus monkeys after oral delivery of the biodegradable microspheres containing live attenuated HA vaccine. The results in mice were similar with the report but the anti-HAV was present earlier as compared with rhesus monkeys. (authors)

Influence of plasma on the physical properties of ointments with quercetin.

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Szulc-Musioł, Beata; Dolińska, Barbara; Kołodziejska, Justyna; Ryszka, Florian

2017-12-20

Effects of two independent variables - the content of quercetin (0 or 1 or 1.5 or 5 %) and the content of plasma (0 or 2 or 4 or 6 %) - on the organoleptic properties and rheological parameters of model formulations prepared on an amphiphilic base were estimated. The consistency of all ointments was uniform, and the content of quercetin and plasma lay within the predefined range. Tested ointments are non-Newtonian systems. The content of quercetin and plasma was found to have a significant effect on the rheological properties of the ointments. An increase in the content of plasma in ointments was accompanied by a significant increase in their hardness, viscosity and shear stress and a reduction of their spreadability. The best rheological properties were shown by formulation F-3, containing 1.5 % of quercetin and 2 % of plasma.

Acyl/free carnitine ratio is a risk factor for hepatic steatosis after pancreatoduodenectomy and total pancreatectomy.

Science.gov (United States)

Nakamura, Masafumi; Nakata, Kohei; Matsumoto, Hideo; Ohtsuka, Takao; Yoshida, Koji; Tokunaga, Shoji; Hino, Keisuke

Hepatic steatosis, one of the most frequent long-term complications of pancreatectomy, influences not only hepatic function but also survival rate. However, its risk factors and pathogenesis have not been established. The purpose of this study was to clarify the risk factors for hepatic steatosis after pancreatectomy. In this retrospective study of 21 patients who had undergone pancreatectomy (19 cases of pancreatoduodenectomy and 2 cases of total pancreatectomy), serum carnitine concentrations, fractions of carnitine, and hepatic attenuation on computed tomography images were analyzed with the aim of identifying risk factors for hepatic steatosis. Thirteen (61.9%) of the 21 patients were diagnosed as having hypocarnitinemia after pancreatectomy. Average hepatic attenuation was as low as 42.2HU (±21.3 SD). A high ratio of acyl/free carnitine was associated with less pronounced hepatic attenuation according to both univariate (P pancreatectomy in some patients. The statistical analyses suggest that a high ratio of acyl/free carnitine is an independent risk factor for hepatic steatosis after pancreatectomy. Copyright © 2016 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Quercetin-3-O-glucuronide induces ABCA1 expression by LXRα activation in murine macrophages

Energy Technology Data Exchange (ETDEWEB)

Ohara, Kazuaki, E-mail: Kazuaki_Ohara@kirin.co.jp [Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan); Wakabayashi, Hideyuki [Laboratory for New Product Development, Kirin Beverage Company Limited, 1-17-1 Namamugi, Tsurumi-ku, Yokohama 230-8628 (Japan); Taniguchi, Yoshimasa [Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan); Shindo, Kazutoshi [Department of Food and Nutrition, Japan Women’s University, 2-8-1 Mejirodai, Bunkyo-ku, Tokyo 112-8681 (Japan); Yajima, Hiroaki [Research Laboratories for Health Science and Food Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan); Yoshida, Aruto [Central Laboratories for Key Technologies, Kirin Company Limited, 1-13-5 Fukuura, Kanazawa-ku, Yokohama 236-0004 (Japan)

2013-11-29

Highlights: •The major circulating quercetin metabolite (Q3GA) activated LXRα. •Q3GA induced ABCA1 via LXRα activation in macrophages. •Nelumbo nucifera leaf extracts contained quercetin glycosides. •N. nucifera leaf extract feeding elevated HDLC in mice. -- Abstract: Reverse cholesterol transport (RCT) removes excess cholesterol from macrophages to prevent atherosclerosis. ATP-binding cassette, subfamily A, member 1 (ABCA1) is a crucial cholesterol transporter involved in RCT to produce high density lipoprotein-cholesterol (HDLC), and is transcriptionally regulated by liver X receptor alpha (LXRα), a nuclear receptor. Quercetin is a widely distributed flavonoid in edible plants which prevented atherosclerosis in an animal model. We found that quercetin-3-O-glucuronide (Q3GA), a major quercetin metabolite after absorption from the digestive tract, enhanced ABCA1 expression, in vitro, via LXRα in macrophages. In addition, leaf extracts of a traditional Asian edible plant, Nelumbo nucifera (NNE), which contained abundant amounts of quercetin glycosides, significantly elevated plasma HDLC in mice. We are the first to present experimental evidence that Q3GA induced ABCA1 in macrophages, and to provide an alternative explanation to previous studies on arteriosclerosis prevention by quercetin.

Oral and intraperitoneal administration of quercetin decreased lymphocyte DNA damage and plasma lipid peroxidation induced by TSA in vivo.

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Chan, Shu-Ting; Lin, Yi-Chin; Chuang, Cheng-Hung; Shiau, Rong-Jen; Liao, Jiunn-Wang; Yeh, Shu-Lan

2014-01-01

Our previous study showed that quercetin enhances the anticancer effect of trichostatin A (TSA) in xenograft mice given quercetin intraperitoneally (10 mg/kg, 3 times/week). Herein, we investigate whether quercetin administered orally exerts such an effect and prevents the cytotoxic side effects of TSA. We found that quercetin given orally (20 and 100 mg/kg, 3 times/week) failed to enhance the antitumor effect of TSA although it increased the total quercetin concentration more than quercetin administered intraperitoneally in the plasma. The compound quercetin-3-glucuronide (Q3G) increased the most. However, quercetin administered intraperitoneally increased the total quercetin level in tumor tissues more than oral quercetin. Oral and intraperitoneal administration of quercetin similarly decreased lymphocyte DNA damage and plasma lipid peroxidation level induced by TSA. Furthermore, we found that the enhancing effect of Q3G on the antitumor effect of TSA and the incorporation of Q3G was less than that of quercetin in A549 cells. However, we found that A549 cells possessed the ability to convert Q3G to quercetin. In conclusion, different from quercetin administered intraperitoneally, quercetin administered orally failed to enhance the antitumor effect of TSA because of its metabolic conversion. However, it prevented TSA-induced DNA damage and lipid peroxidation.

Steamed bread enriched with quercetin as an antiglycative food product: its quality attributes and antioxidant properties.

Science.gov (United States)

Lin, Jing; Gwyneth Tan, Yuan Xin; Leong, Lai Peng; Zhou, Weibiao

2018-06-06

Quercetin, a natural antiglycative agent, was incorporated into steamed bread to produce a functional food that has high potential to lower the risk of diabetes. With the incorporation of quercetin at 1.20, 2.40, and 3.60%, the volume of steamed bread significantly decreased and the hardness of the crumb correspondingly increased with incremental quercetin content, while incorporation levels below 1.20% had no impact. Within this range of enrichment (1.2-3.6%), quercetin negatively affected the yeast activity with significantly less CO2 produced in dough during proofing. The wheat protein structure was altered by quercetin in terms of a higher level of β-sheets and a lower level of β-turns. The antioxidant capacity of the steamed bread with quercetin (0.05-0.2%) was significantly enhanced dose-dependently. A high inhibitory activity of quercetin-enriched steamed bread (0.05-0.2%) against fluorescent advanced glycation endproducts (AGEs) via several different mechanisms was observed. The inhibition of total AGEs from 0.2% quercetin-enriched steamed bread was around 40% during in vitro protein glycation. Overall, the results support quercetin-enriched steamed bread to be a promising functional food with high antioxidant and antiglycation properties.

Quercetin-induced downregulation of phospholipase D1 inhibits proliferation and invasion in U87 glioma cells

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Park, Mi Hee [Department of Molecular Biology, College of Natural Science, Pusan National University, 30 Jangjeon dong, Geumjeong gu, Busan 609-735 (Korea, Republic of); Min, Do Sik, E-mail: minds@pusan.ac.kr [Department of Molecular Biology, College of Natural Science, Pusan National University, 30 Jangjeon dong, Geumjeong gu, Busan 609-735 (Korea, Republic of)

2011-09-09

Highlights: {yields} Quercetin, a bioactive flavonoid, suppresses expression and enzymatic activity of phospholipase D1. {yields} Quercetin abolishes NFkB-induced phospholipase D1 expression via inhibition of NFkB transactivation. {yields} Quercetin-induced suppression of phospholipase D1 inhibits invasion and proliferation of human glioma cells. -- Abstract: Phospholipase D (PLD) has been recognized as a regulator of cell proliferation and tumorigenesis, but little is known about the molecules regulating PLD expression. Thus, the identification of small molecules inhibiting PLD expression would be an important advance in PLD-mediated physiology. Quercetin, a ubiquitous bioactive flavonoid, is known to inhibit proliferation and induce apoptosis in a variety of cancer cells. In the present study, we examined the effect of quercetin on the expression of PLD in U87 glioma cells. Quercetin significantly suppressed the expression of PLD1 at the transcriptional level. Moreover, quercetin abolished the protein expression of PLD1 in a time and dose-dependent manner, as well as inhibited PLD activity. Quercetin suppressed NF{kappa}B-induced PLD1 expression via inhibition of NFkB transactivation. Furthermore, quercetin inhibited activation and invasion of metalloproteinase-2 (MMP-2), a key modulator of glioma cell invasion, induced by phosphatidic acid (PA), a product of PLD activity. Taken together these data demonstrate that quercetin abolishes PLD1 expression and subsequently inhibits invasion and proliferation of glioma cells.

Disruption of quercetin metabolism by fungicide affects energy production in honey bees (Apis mellifera).

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Mao, Wenfu; Schuler, Mary A; Berenbaum, May R

2017-03-07

Cytochrome P450 monooxygenases (P450) in the honey bee, Apis mellifera , detoxify phytochemicals in honey and pollen. The flavonol quercetin is found ubiquitously and abundantly in pollen and frequently at lower concentrations in honey. Worker jelly consumed during the first 3 d of larval development typically contains flavonols at very low levels, however. RNA-Seq analysis of gene expression in neonates reared for three days on diets with and without quercetin revealed that, in addition to up-regulating multiple detoxifying P450 genes, quercetin is a negative transcriptional regulator of mitochondrion-related nuclear genes and genes encoding subunits of complexes I, III, IV, and V in the oxidative phosphorylation pathway. Thus, a consequence of inefficient metabolism of this phytochemical may be compromised energy production. Several P450s metabolize quercetin in adult workers. Docking in silico of 121 pesticide contaminants of American hives into the active pocket of CYP9Q1, a broadly substrate-specific P450 with high quercetin-metabolizing activity, identified six triazole fungicides, all fungal P450 inhibitors, that dock in the catalytic site. In adults fed combinations of quercetin and the triazole myclobutanil, the expression of five of six mitochondrion-related nuclear genes was down-regulated. Midgut metabolism assays verified that adult bees consuming quercetin with myclobutanil metabolized less quercetin and produced less thoracic ATP, the energy source for flight muscles. Although fungicides lack acute toxicity, they may influence bee health by interfering with quercetin detoxification, thereby compromising mitochondrial regeneration and ATP production. Thus, agricultural use of triazole fungicides may put bees at risk of being unable to extract sufficient energy from their natural food.

A Molecularly Imprinted Polymer with Incorporated Graphene Oxide for Electrochemical Determination of Quercetin

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Xiwen He

2013-04-01

Full Text Available The molecularly imprinted polymer based on polypyrrole film with incorporated graphene oxide was fabricated and used for electrochemical determination of quercetin. The electrochemical behavior of quercetin on the modified electrode was studied in detail using differential pulse voltammetry. The oxidation peak current of quercetin in B-R buffer solution (pH = 3.5 at the modified electrode was regressed with the concentration in the range from 6.0 × 10−7 to 1.5 × 10−5 mol/L (r2 = 0.997 with a detection limit of 4.8 × 10−8 mol/L (S/N = 3. This electrode showed good stability and reproducibility. In the above mentioned range, rutin or morin which has similar structures and at the same concentration as quercetin did not interfere with the determination of quercetin. The applicability of the method for complex matrix analysis was also evaluated.

8-C-(E-phenylethenyl)quercetin from onion/beef soup induces autophagic cell death in colon cancer cells through ERK activation.

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Zhao, Yueliang; Fan, Daming; Zheng, Zong-Ping; Li, Edmund T S; Chen, Feng; Cheng, Ka-Wing; Wang, Mingfu

2017-02-01

Quercetin, a flavonoid, widely distributed in edible fruits and vegetables, was reported to effectively inhibit 2-amino-1-methyl-6-phenylimidazo[4, 5-b]pyridine (PhIP) formation in a food model (roast beef patties) with itself being converted into a novel compound 8-C-(E-phenylethenyl)quercetin (8-CEPQ). Here we investigated whether 8-CEPQ could be formed in a real food system, and tested its anticancer activity in human colon cancer cell lines. LC-MS was applied for the determination of 8-CEPQ formation in onion/beef soup. Anticancer activity of 8-CEPQ was evaluated by using cell viability assay and flow cytometry. Results showed that 8-CEPQ suppressed proliferation and caused G 2 phase arrest in colon cancer cells. Based on immunofluorescent staining assay, western blot assay, and RNA knockdown data, we found that 8-CEPQ did not cause apoptotic cell death. Instead, it induced autophagic cell death. Moreover, treatment with 8-CEPQ induced phosphorylation of extracellular signal-regulated kinase (ERK). Inhibition of ERK phosphorylation by the mitogen-activated protein kinase kinase (MEK)/ERK inhibitor U0126 attenuated 8-CEPQ-induced autophagy and reversed 8-CEPQ-mediated cell growth inhibition. Our results demonstrate that 8-CEPQ, a novel quercetin derivative, could be formed in onion/beef soup. 8-CEPQ inhibited colon cancer cell growth by inducing autophagic cell death through ERK activation. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Protective role of quercetin against copper(II)-induced oxidative stress: A spectroscopic, theoretical and DNA damage study.

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Jomova, Klaudia; Lawson, Michael; Drostinova, Lenka; Lauro, Peter; Poprac, Patrik; Brezova, Vlasta; Michalik, Martin; Lukes, Vladimir; Valko, Marian

2017-12-01

The radical scavenging and metal chelating properties of flavonoids indicate that they may play a protective role in diseases with perturbed metal homeostasis such as Alzheimer's disease. In this work we investigated the effect of the coordination of quercetin to copper(II) in view of the formation of ROS in Cu-catalyzed Fenton reaction. ABTS and DPPH assays confirmed that the copper(II)-quercetin complex exhibits a stronger radical scavenging activity than does quercetin alone. EPR spin trapping experiments have shown that chelation of quercetin to copper significantly suppressed the formation of hydroxyl radicals in the Cu(II)-Fenton reaction. DNA damage experiments revealed a protective effect for quercetin, but only at higher stoichiometric ratios of quercetin relative to copper. DNA protective effect of quercetin against ROS attack was described by two mechanisms. The first mechanism lies in suppressed formation of ROS due to the decreased catalytic action of copper in the Fenton reaction, as a consequence of its chelation and direct scavenging of ROS by free quercetin. Since the Cu-quercetin complex intercalates into DNA, the second mechanism was attributed to a suppressed intercalating ability of the Cu-quercetin complex due to the mildly intercalating free quercetin into DNA, thus creating a protective wall against stronger intercalators. Copyright © 2017 Elsevier Ltd. All rights reserved.

Hepatic iron overload: Quantitative MR imaging

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Gomori, J.M.; Horev, G.; Tamary, H.; Zandback, J.; Kornreich, L.; Zaizov, R.; Freud, E.; Krief, O.; Ben-Meir, J.; Rotem, H.

1991-01-01

Iron deposits demonstrate characteristically shortened T2 relaxation times. Several previously published studies reported poor correlation between the in vivo hepatic 1/T2 measurements made by means of midfield magnetic resonance (MR) units and the hepatic iron content of iron-overloaded patients. In this study, the authors assessed the use of in vivo 1/T2 measurements obtained by means of MR imaging at 0.5 T using short echo times (13.4 and 30 msec) and single-echo-sequences as well as computed tomographic (CT) attenuation as a measure of liver iron concentration in 10 severely iron-overloaded patients with beta-thalassemia major. The iron concentrations in surgical wedge biopsy samples of the liver, which varied between 3 and 9 mg/g of wet weight (normal, less than or equal to 0.5 mg/g), correlated well (r = .93, P less than or equal to .0001) with the preoperative in vivo hepatic 1/T2 measurements. The CT attenuation did not correlate with liver iron concentration. Quantitative MR imaging is a readily available noninvasive method for the assessment of hepatic iron concentration in iron-overloaded patients, reducing the need for needle biopsies of the liver

Quercetin, a natural product supplement, impairs mitochondrial bioenergetics and locomotor behavior in larval zebrafish (Danio rerio).

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Zhang, Ji-Liang; Laurence Souders, Christopher; Denslow, Nancy D; Martyniuk, Christopher J

2017-07-15

Quercetin is a natural product that is sold as a supplement in health food stores. While there are reported benefits for this flavonoid as a dietary supplement due to antioxidant properties, the full scope of its biological interactions has not been fully addressed. To learn more about the mechanisms of action related to quercetin, we exposed zebrafish (Danio rerio) embryos to 1 and 10μg/L quercetin for 96h starting at 3h post fertilization. Quercetin up to 10μg/L did not induce significant mortality in developing fish, but did increase prevalence of an upward-curved dorsal plane in hatched larvae. To determine whether this developmental defect was potentially related to mitochondrial bioenergetics during development, we measured oxygen consumption rate in whole embryos following a 24-hour exposure to quercetin. Basal mitochondrial and ATP-linked respiration were decreased at 1 and 10μg/L quercetin, and maximal respiration was decreased at 10μg/L quercetin, suggesting that quercetin impairs mitochondrial bioenergetics. This is proposed to be related to the deformities observed during development. Due to the fact that ATP production was affected by quercetin, larval behaviors related to locomotion were investigated, as well as transcriptional responses of six myogenesis transcripts. Quercetin at 10μg/L significantly reduced the swimming velocity of zebrafish larvae. The expression levels of both myostatin A (mstna) and myogenic differentiation (myoD) were also altered by quercetin. Mstna, an inhibitory factor for myogenesis, was significantly increased at 1μg/L quercetin exposure, while myoD, a stimulatory factor for myogenesis, was significantly increased at 10μg/L quercetin exposure. There were no changes in transcripts related to apoptosis (bcl2, bax, casp3, casp7), but we did observe a decrease in mRNA levels for catalase (cat) in fish exposed to each dose, supporting an oxidative stress response. Our data support the hypothesis that quercetin may affect

The critical role of quercetin in autophagy and apoptosis in HeLa cells.

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Wang, Yijun; Zhang, Wei; Lv, Qiongying; Zhang, Juan; Zhu, Dingjun

2016-01-01

In recent years, the effects of quercetin on autophagy and apoptosis of cancer cells have been widely reported, while effects on HeLa cells are still unclear. Here, HeLa cells were subjected to quercetin treatment, and then proliferation, apoptosis, and autophagy were evaluated using MTT, flow cytometry, and MDC staining, respectively. The LC3-I/II, Beclin 1, active caspase-3, and S6K1 phosphorylation were detected using Western blot assay. The ultrastructure of HeLa was observed via transmission electron microscope (TEM). Our findings showed that quercetin can dose-dependently inhibit the growth of HeLa cells. The MDC fluorescence was enhanced with increased concentration of quercetin and hit a plateau at 50 μmol/l. Western blot assay revealed that LC3-I/II ratio, Beclin 1, and active caspase-3 protein were enforced in a dose-dependent method. However, the phosphorylation of S6K1 gradually decreased, concomitant with an increase of autophagy. In addition, TEM revealed that the number of autophagic vacuoles was peaked at 50 μmol/l of quercetin. Besides, interference of autophagy with 3-MA led to proliferation inhibition and increased apoptosis in HeLa cells, accompanied by the decreased LC3-I/II conversion and the increased active caspase-3. In conclusion, quercetin can inhibit HeLa cell proliferation and induce protective autophagy at low concentrations; thus, 3-MA plus quercetin would suppress autophagy and effectively increased apoptosis.

Quercetin oxidation by horseradish peroxidase: The effect of UV-B irradiation

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Savić Saša R.

2013-01-01

Full Text Available Horseradish peroxidase (HRP, a highly-investigated member of the peroxidase family has been known, among many other biological activities, to catalyze the oxidation of flavonoids and phenolic substrates overall, including quercetin. On the other hand, quercetin is very well known for its antioxidant activities, which in the case of UV external radiation is exibited partly in a preventive manner since it is an excellent UV-absorber. Therefore the aim of this investigation is to study quercetin oxidation by HRP in phosphate buffer under the conditions of UV-stress, i.e. continuous, prolonged UV-B irradiation. The results show that while UV-B irradiation affects the activity of HRP, and the overal rate of quercetin oxidation by HRP, it probably has very little effect on it for longer UV-B-irradiation periods (>30 min. [Acknowledgements. This work was supported by the Ministry of Education and Science of the Republic of Serbia under Project No.TR-34012 and OI-172044

Ebselen pretreatment attenuates ischemia/reperfusion injury and prevents hyperglycemia by improving hepatic insulin signaling and β-cell survival in gerbils.

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Park, S; Kang, S; Kim, D S; Shin, B K; Moon, N R; Daily, J W

2014-08-01

Transient carotid artery occlusion causes ischemia/reperfusion (I/R) injury resulting in neuron and pancreatic β-cell death with consequential post-stroke hyperglycemia, which can lead to diabetes and may accelerate the development of Alzheimer's disease. Antioxidants have been shown to protect against the I/R injury and destruction of neurons. However, it is unknown whether the protection against I/R injury extends to the pancreatic β-cells. Therefore, we investigated whether treatment with ebselen, a glutathione peroxidase mimic, prevents neuronal and β-cell death following I/R in gerbils susceptible to stroke. After 28 days post artery occlusion, there was widespread neuronal cell death in the CA1 of the hippocampus and elevated IL-1β and TNF-α levels. Pretreatment with ebselen prevented the death by 56% and attenuated neurological damage (abnormal eyelid drooping, hair bristling, muscle tone, flexor reflex, posture, and walking patterns). Ischemic gerbils also exhibited impaired glucose tolerance and insulin sensitivity which induced post-stroke hyperglycemia associated with decreased β-cell mass due to increased β-cell apoptosis. Ebselen prevented the increased β-cell apoptosis, possibly by decreasing IL-1β and TNF-α in islets. Ischemia also attenuated hepatic insulin signaling, and expression of GLUT2 and glucokinase, whereas ebselen prevented the attenuation and suppressed gluconeogenesis by decreasing PEPCK expression. In conclusion, antioxidant protection by ebselen attenuated I/R injury of neurons and pancreatic β-cells and prevented subsequent impairment of glucose regulation that could lead to diabetes and Alzheimer's disease.

Hypereosinophilic syndrome: CT findings in patients with hepatic lobar or segmental involvement

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Lim, Jae Hoon; Lee, Won Jae [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Lee, Dong Ho [Kyunghee University Hospital, Seoul (Korea, Republic of); Nam, Kyung Jin [Donga University College of Medicine, Pusan (Korea, Republic of)

2000-06-01

The purpose of this study was to describe the CT findings of hepatic hypereosinophilic syndrome in which hepatic lobes or segments were involved. Seven patients with hypereosinophilic syndrome with hepatic lobar or segmental involvement were included in our study. In all seven, diagnosis was based on liver biopsy and the results of corticosteroid treatment. CT findings were retrospectively reviewed by three radiologists, who reached a consensus. Biopsy specimens were examined, with special reference to portal and periportal inflammation. CT demonstrated well-defined, homogeneous or heterogeneous low attenuation with a straight margin limited to a hepatic lobe (n = 2), segments (n = 3), or subsegments (n = 2), particularly during the portal phase. Where there was subsegmental involvement, lesions were multiple, ovoid or wedge-shaped, and showed low attenuation. In two patients with lobar or segmental involvement, segmental portal vein narrowing was observed. Histopathologic examination disclosed eosinophilic infiltration in the periportal area, sinusoids and central veins, as well as portal phlebitis. Hypereosinophilic syndrome may involve the presence of hepatic lobar, segmental, or subsegmental low-attenuated lesions, as seen on CT images. Their presence may be related to damage of the liver parenchyma and to portal phlebitis.

Hypereosinophilic syndrome: CT findings in patients with hepatic lobar or segmental involvement

International Nuclear Information System (INIS)

Lim, Jae Hoon; Lee, Won Jae; Lee, Dong Ho; Nam, Kyung Jin

2000-01-01

The purpose of this study was to describe the CT findings of hepatic hypereosinophilic syndrome in which hepatic lobes or segments were involved. Seven patients with hypereosinophilic syndrome with hepatic lobar or segmental involvement were included in our study. In all seven, diagnosis was based on liver biopsy and the results of corticosteroid treatment. CT findings were retrospectively reviewed by three radiologists, who reached a consensus. Biopsy specimens were examined, with special reference to portal and periportal inflammation. CT demonstrated well-defined, homogeneous or heterogeneous low attenuation with a straight margin limited to a hepatic lobe (n = 2), segments (n = 3), or subsegments (n = 2), particularly during the portal phase. Where there was subsegmental involvement, lesions were multiple, ovoid or wedge-shaped, and showed low attenuation. In two patients with lobar or segmental involvement, segmental portal vein narrowing was observed. Histopathologic examination disclosed eosinophilic infiltration in the periportal area, sinusoids and central veins, as well as portal phlebitis. Hypereosinophilic syndrome may involve the presence of hepatic lobar, segmental, or subsegmental low-attenuated lesions, as seen on CT images. Their presence may be related to damage of the liver parenchyma and to portal phlebitis

Effect of quercetin and 17-AAG on radiosensitivity of rat peripheral blood lymphocyte

International Nuclear Information System (INIS)

Chu Xuegang; Hong Chengjiao; Zhang Baoguo

2012-01-01

To investigate the effect of quercetin and 17-AAG on proliferation and on radiosensitivity of blood lymphocyte cells. CCK-8 assay is performed to evaluate the cytotoxicity of Quercetin on proliferation of blood lymphocyte cells. CCK-8 assay employed to observe its effects on the radiosensitivity of the cells quantified by calculating the sensitive enhancement ratio (SER). CCK-8 results showed that the inhibition of Quercetin on the cells was the dose-dependent and time-dependent, and the results of assay showed the inhibition of 17-AAG on blood lymphocyte cells was the dose-dependent and time-dependent. The study showed that Quercetin and 17-AAG have no effect on the radiosensitivity of the blood lymphocyte cells. (authors)

Fulminant hepatic failure in children: Etiology, histopathology and MDCT findings

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Cakir, Banu; Kirbas, Ismail; Demirhan, Beyhan; Tarhan, Nefise Cagla; Bozkurt, Alper; Ozcay, Figen; Coskun, Mehmet

2009-01-01

Introduction: The purpose of this study is to determine the etiologies, histopathology and MDCT findings of children with fulminant hepatic failure admitted to our institution. Materials and methods: Between June 2004 and November 2006, 15 children with fulminant hepatic failure who underwent MDCT were included retrospectively in this study. Twelve patients had liver biopsies. The patients were divided into three groups as hyperacute (Group I), acute (Group II) and subacute (Group III) depending on onset of hepatic encephalopathy. Results: Hepatitis A in 4 patients, non-A, non-E hepatitis in 4; mushroom poisoning in 3; fulminant Wilson's disease in 2; autoimmune hepatitis in 1; and both hepatitis B and toxic hepatitis (with leflunomide treatment) in 1 patient were detected. MDCT of all three groups revealed diffuse reduction in hepatic attenuation in 11 patients; ascites in 9; periportal edema in 6; edema of gallbladder wall in 6; splenomegaly in 6; heterogeneous hepatic parenchyma in 6; hepatomegaly in 3; irregular contours of liver in 2; multiple micronodules in 1 and necrotic areas and regeneration in liver parenchyma in 2 patients. Histopathologic evaluation of liver biopsies showed massive hepatic necrosis, inflammatory cell infiltration and ductular proliferation in 8 patients, periportal edema in 6, edema of gallbladder wall in 5, regenerating nodules and fibrous septa consistent with cirrhotic pattern in 2, and regenerating nodules and necrotic areas in 2 patients. Conclusion: The most common MDCT findings in fulminant hepatic failure were diffuse reduction in hepatic attenuation and ascites. Massive hepatic necrosis was the most common histopathologic finding.

Fulminant hepatic failure in children: Etiology, histopathology and MDCT findings

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Cakir, Banu [Baskent University Faculty of Medicine Department of Radiology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: banutopcu@yahoo.com; Kirbas, Ismail [Baskent University Faculty of Medicine Department of Radiology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: drismailk@yahoo.com; Demirhan, Beyhan [Baskent University Faculty of Medicine Department of Pathology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: beyhand@baskent-ank.edu.tr; Tarhan, Nefise Cagla [Baskent University Faculty of Medicine Department of Radiology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: caglat@gmail.com; Bozkurt, Alper [Baskent University Faculty of Medicine Department of Radiology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: abozkurt78@hotmail.com; Ozcay, Figen [Baskent University Faculty of Medicine Department of Pediatric Gastroenterology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: fozcay@baskent.edu.tr; Coskun, Mehmet [Baskent University Faculty of Medicine Department of Radiology, Fevzi Cakmak Cd. 10, Sok. No: 45, Bahcelievler, Ankara 06490 (Turkey)], E-mail: mcoskun@baskent-ank.edu.tr

2009-11-15

Introduction: The purpose of this study is to determine the etiologies, histopathology and MDCT findings of children with fulminant hepatic failure admitted to our institution. Materials and methods: Between June 2004 and November 2006, 15 children with fulminant hepatic failure who underwent MDCT were included retrospectively in this study. Twelve patients had liver biopsies. The patients were divided into three groups as hyperacute (Group I), acute (Group II) and subacute (Group III) depending on onset of hepatic encephalopathy. Results: Hepatitis A in 4 patients, non-A, non-E hepatitis in 4; mushroom poisoning in 3; fulminant Wilson's disease in 2; autoimmune hepatitis in 1; and both hepatitis B and toxic hepatitis (with leflunomide treatment) in 1 patient were detected. MDCT of all three groups revealed diffuse reduction in hepatic attenuation in 11 patients; ascites in 9; periportal edema in 6; edema of gallbladder wall in 6; splenomegaly in 6; heterogeneous hepatic parenchyma in 6; hepatomegaly in 3; irregular contours of liver in 2; multiple micronodules in 1 and necrotic areas and regeneration in liver parenchyma in 2 patients. Histopathologic evaluation of liver biopsies showed massive hepatic necrosis, inflammatory cell infiltration and ductular proliferation in 8 patients, periportal edema in 6, edema of gallbladder wall in 5, regenerating nodules and fibrous septa consistent with cirrhotic pattern in 2, and regenerating nodules and necrotic areas in 2 patients. Conclusion: The most common MDCT findings in fulminant hepatic failure were diffuse reduction in hepatic attenuation and ascites. Massive hepatic necrosis was the most common histopathologic finding.

Uso de quercetina a longo prazo em ratos cirróticos The long term use of quercetin in cirrhotic rats

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Aline Miltersteiner

2003-06-01

Full Text Available OBJETIVO: Avaliar o uso a longo prazo do flavonóide quercetina em ratos cirróticos por ligadura de ducto biliar comum (LDB. MÉTODOS: Foram utilizados 32 ratos machos Wistar, sendo submetidos à LDB ou simulação, e distribuídos em 4 grupos: 1 controle, 2 cirróticos, 3 cirróticos tratados com quercetina 50mg/kg, intraperitonealmente, desde o segundo dia após o procedimento cirúrgico; e 4 cirróticos tratados após o décimo quarto dia do procedimento cirúrgico. Analisou-se a função hepática por meio de testes bioquímicos (BT e BD e atividade enzimática (ALT, AST, FA e GGT. Na análise anatomopatológica, utilizou-se a coloração de Hematoxilina & Eosina (H&E e de Picrosírius para fibrose. A análise estatística para avaliação de sobrevivência foi realizada pelo teste Kaplan-Meier. RESULTADOS: Os resultados de sobrevivência dos oito animais de cada grupo foram: Grupo 1 = 200 dias de sobrevivência; Grupo 2 = 46 dias; Grupo 3 = 71 dias; e o Grupo 4 = 90 dias. Nos animais com ligadura de ducto biliar comum houve aumento das provas de função hepática e enzimáticas que se reduziu hipoteticamente com o tratamento com quercetina. Foram identificadas cirrose, congestão vascular porta e centrolobular na análise histopatológica por H&E e Picrosírius. CONCLUSÃO: O uso da quercetina diminuiu de maneira significante as alterações bioquímicas provocadas pela cirrose, aumentando o tempo de sobrevivência dos animais com cirrose biliar secundária à LDB, como verificado pelo teste de análise de sobrevivência.PURPOSE: The long term use of quercetin flavonoid was evaluated in cirrhotic rats by common biliary duct bondage (LDB. METHODS: 32 male Wistar rats were submitted to LDB or simulation, and distributed in 4 groups: 1 control, 2 cirrhotic, 3 cirrhotic treated with quercetin the second day after the surgical procedure; and 4 cirrhotic treated with quercetin after the fourteenth day of the surgical procedure. The hepatic

USE OF COMPUTED TOMOGRAPHY FOR INVESTIGATION OF HEPATIC LIPIDOSIS IN CAPTIVE CHELONOIDIS CARBONARIA (SPIX, 1824).

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Marchiori, Adriano; da Silva, Ieverton Cleiton Correia; de Albuquerque Bonelli, Marília; de Albuquerque Zanotti, Luciana Carla Rameh; Siqueira, Daniel B; Zanotti, Alexandre Pinheiro; Costa, Fabiano Séllos

2015-06-01

Computed tomography is a sensitive and highly applicable technique for determining the degree of radiographic attenuation of the hepatic parenchyma. Radiodensity measurements of the liver can help in the diagnosis of hepatic lipidosis in humans and animals. The objective was to investigate the presence of hepatic lipidosis in captive red-footed tortoises (Chelonoidis carbonaria) using computed tomography. Computed tomography was performed in 10 male red-footed tortoises. Mean radiographic attenuation values for the hepatic parenchyma were 11.2±3.0 Hounsfield units (HU). Seven red-footed tortoises had values lower than 20 HU, which is compatible with C. carbonaria hepatic lipidosis. These results allowed an early diagnosis of the hepatic changes and suggested corrective measures regarding feeding and management protocols.

Antioxidant study of quercetin and their metal complex and determination of stability constant by spectrophotometry method.

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Ravichandran, R; Rajendran, M; Devapiriam, D

2014-03-01

Quercetin found chelate cadmium ions, scavenge free radicals produced by cadmium. Hence new complex, quercetin with cadmium was synthesised, and the synthesised complex structures were determined by UV-vis spectrophotometry, infrared spectroscopy, thermogravimetry and differential thermal analysis techniques (UV-vis, IR, TGA and DTA). The equilibrium stability constants of quercetin-cadmium complex were determined by Job's method. The determined stability constant value of quercetin-cadminum complex at pH 4.4 is 2.27×10(6) and at pH 7.4 is 7.80×10(6). It was found that the quercetin and cadmium ion form 1:1 complex in both pH 4.4 and pH 7.4. The structure of the compounds was elucidated on the basis of obtained results. Furthermore, the antioxidant activity of the free quercetin and quercetin-cadmium complexes were determined by DPPH and ABTS assays. Copyright © 2013 Elsevier Ltd. All rights reserved.

Preventive effect of dietary quercetin on disuse muscle atrophy by targeting mitochondria in denervated mice.

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Mukai, Rie; Matsui, Naoko; Fujikura, Yutaka; Matsumoto, Norifumi; Hou, De-Xing; Kanzaki, Noriyuki; Shibata, Hiroshi; Horikawa, Manabu; Iwasa, Keiko; Hirasaka, Katsuya; Nikawa, Takeshi; Terao, Junji

2016-05-01

Quercetin is a major dietary flavonoid in fruits and vegetables. We aimed to clarify the preventive effect of dietary quercetin on disuse muscle atrophy and the underlying mechanisms. We established a mouse denervation model by cutting the sciatic nerve in the right leg (SNX surgery) to lack of mobilization in hind-limb. Preintake of a quercetin-mixed diet for 14days before SNX surgery prevented loss of muscle mass and atrophy of muscle fibers in the gastrocnemius muscle (GM). Phosphorylation of Akt, a key phosphorylation pathway of suppression of protein degradation, was activated in the quercetin-mixed diet group with and without SNX surgery. Intake of a quercetin-mixed diet suppressed the generation of hydrogen peroxide originating from mitochondria and elevated mitochondrial peroxisome proliferator-activated receptor-γ coactivator 1α mRNA expression as well as NADH dehydrogenase 4 expression in the GM with SNX surgery. Quercetin and its conjugated metabolites reduced hydrogen peroxide production in the mitochondrial fraction obtained from atrophied muscle. In C2C12 myotubes, quercetin reached the mitochondrial fraction. These findings suggest that dietary quercetin can prevent disuse muscle atrophy by targeting mitochondria in skeletal muscle tissue through protecting mitochondria from decreased biogenesis and reducing mitochondrial hydrogen peroxide release, which can be related to decreased hydrogen peroxide production and/or improvements on antioxidant capacity of mitochondria. Copyright © 2016 Elsevier Inc. All rights reserved.

The flavonoid quercetin induces apoptosis and inhibits JNK activation in intimal vascular smooth muscle cells

International Nuclear Information System (INIS)

Perez-Vizcaino, Francisco; Bishop-Bailley, David; Lodi, Federica; Duarte, Juan; Cogolludo, Angel; Moreno, Laura; Bosca, Lisardo; Mitchell, Jane A.; Warner, Timothy D.

2006-01-01

Quercetin, the most abundant dietary flavonol, exerts vasodilator, anti-hypertensive, and anti-atherogenic effects and reduces the vascular remodelling associated with elevated blood pressure. Here, we have compared the effects of quercetin in intimal- and medial-type rat vascular smooth muscle cells (VSMC) in culture. After 48 h, quercetin reduced the viability of a polyclonal intimal-type cell line derived from neonatal aorta but not of a medial-type cell line derived from adult aorta. These differential effects were similar in both proliferating and quiescent VSMC. Quercetin also preferentially reduced the viability of intimal-type over medial-type VSMC in primary cultures derived from balloon-injured carotid arteries. The effects of quercetin on cell viability were mainly dependent upon induction of apoptosis, as demonstrated by nuclear condensation and fragmentation, and were unrelated to PPARγ, pro-oxidant effects or nitric oxide. The expression of MAPKs (ERK, p38, and JNK) and ERK phosphorylation were not different between intimal- and medial-type VSMC. p38 phosphorylation was negligible in both cell types. Medial-type showed a weak JNK phosphorylation while this was markedly increased in intimal-type cells. Quercetin reduced JNK phosphorylation but had no consistent effect on ERK phosphorylation. In conclusion, quercetin preferentially produced apoptosis in intimal-type compared to medial-type VSMC. This might play a role in the anti-atherogenic and anti-hypertensive effects of quercetin

Effects of 2 adenosine antagonists, quercetin and caffeine, on vigilance and mood.

Science.gov (United States)

Olson, Craig A; Thornton, Jennifer A; Adam, Gina E; Lieberman, Harris R

2010-10-01

Quercetin, a phenolic flavonoid found in small quantities in some fruits and vegetables, is an adenosine receptor antagonist in vitro marketed as a dietary supplement for purported caffeine-like effects. A double-blind, placebo-controlled, between-subjects study was conducted to compare the behavioral effects of quercetin to a central adenosine receptor antagonist, caffeine. Fifty-seven volunteers received either 2000 mg of quercetin dihydrate (a dose estimated based on in vitro receptor binding to be equivalent in potency to 200 mg of caffeine), placebo, or 200 mg of caffeine. One hour later, a 45-minute visual vigilance task was administered. The Profile of Mood States questionnaire was completed before treatment and immediately after vigilance testing. On the vigilance task, caffeine increased the number of stimuli detected (P mood disturbance Profile of Mood States scores compared with placebo. Quercetin did not significantly alter any parameter, but values were typically intermediate between caffeine and placebo on those tests affected by caffeine. Quercetin is unlikely to have any effects when consumed by humans in quantities present in the diet or in dietary supplements. Caffeine (200 mg) administration resulted in the expected effects on vigilance and mood.

Caffeic acid, morin hydrate and quercetin partially attenuate sulfur mustard-induced cell death by inhibiting the lipoxygenase pathway.

Science.gov (United States)

Kim, Shin; Jeong, Kwang-Joon; Cho, Sung Kweon; Park, Joo-Won; Park, Woo-Jae

2016-11-01

Sulfur mustard (SM) is an alkylating agent, which has been used as in chemical warfare in a number of conflicts. As the generation of reactive oxygen species (ROS), and adducts in DNA and proteins have been suggested as the mechanism underlying SM‑induced cytotoxicity, the present study screened several antioxidant candidates, including tannic acid, deferoxamine mesylate, trolox, vitamin C, ellagic acid and caffeic acid (CA) to assess their potential as therapeutic agents for SM‑induced cell death. Among several antioxidants, CA partially alleviated SM‑induced cell death in a dose‑dependent manner. Although CA treatment decreased the phosphorylation of p38 mitogen‑activated protein (MAP) kinase and p53, p38 MAP kinase inhibition by SB203580 did not affect SM‑induced cell death. As CA has also been reported as a 15‑lipoxygenase (15‑LOX) inhibitor, the role of 15‑LOX in SM‑induced cytotoxicity was also examined. Similar to the results observed with CA, treatment with PD146176, a specific 15‑LOX inhibitor, decreased SM‑induced cytotoxicity, accompanied by decreases in the production of tumor necrosis factor‑α and 15‑hydroxyeicosatetraenoic acid. Furthermore, the present study investigated the protective effects of two natural 15‑LOX inhibitors, morin hydrate and quercetin, in SM‑induced cytotoxicity. As expected, these inhibitors had similar protective effects against SM‑induced cytotoxicity. These antioxidants also reduced the generation of ROS and nitrate/nitrite. Therefore, the results of the present study indicated that the natural products, CA, quercetin and morin hydrate, offer potential as adjuvant therapeutic agents for SM‑induced toxicity, not only by reducing inflammation mediated by the p38 and LOX signaling pathways, but also by decreasing the generation of ROS and nitrate/nitrite.

Release kinetics of tocopherol and quercetin from binary antioxidant controlled-release packaging films.

Science.gov (United States)

Chen, Xi; Lee, Dong Sun; Zhu, Xuntao; Yam, Kit L

2012-04-04

This paper investigated the feasibility of manipulating packaging polymers with various degrees of hydrophobicity to release two antioxidants, tocopherol and quercetin, at rates suitable for long-term inhibition of lipid oxidation in food. For example, one antioxidant can be released at a fast rate to provide short-term/intermediate protection, whereas the other antioxidant can be released at a slower rate to provide intermediate/long-term protection of lipid oxidation. Controlled-release packaging films containing tocopherol and quercetin were produced using ethylene vinyl alcohol (EVOH), ethylene vinyl acetate (EVA), low-density polyethylene (LDPE), and polypropylene (PP) polymers; the release of these antioxidants to 95% ethanol (a fatty food simulant) was measured using UV-vis spectrophotometry, and Fickian diffusion models with appropriate initial and boundary conditions were used to fit the data. For films containing only quercetin, the results show that the release of quercetin was much faster but lasted for a much shorter time for hydrophilic polymers (EVOH and EVA) than for hydrophobic polymers (LDPE and PP). For binary antioxidant films containing tocopherol and quercetin, the results show that tocopherol released more rapidly but for a shorter period of time than quercetin in LDPE and EVOH films, and the difference is more pronounced for LDPE films than EVOH films. The results also show the presence of tocopherol can accelerate the release of quercetin. Although none of the films produced is acceptable for long-term lipid oxidation inhibition, the study provides encouraging results suggesting that acceptable films may be produced in the future using polymer blend films.

Liposomes, lipid nanocapsules and smartCrystals®: A comparative study for an effective quercetin delivery to the skin.

Science.gov (United States)

Hatahet, T; Morille, M; Hommoss, A; Devoisselle, J M; Müller, R H; Bégu, S

2018-05-05

Quercetin is a flavonoid with strong antioxidant and antiinflammatory activities considered as a potential drug candidate for skin exogenous supplementation. Nevertheless, crude quercetin suffers from poor water solubility and consequently topical inactivity. Therefore, quercetin formulation within a suitable system that overcomes its solubility limitation is a matter of investigation. Three approaches were tested to improve quercetin delivery to skin: liposomes, lipid nanocapsules (LNC) and smartCrystals®. These nanoformulations were compared in terms of average particle size, homogeneity (PDI), quercetin loading and cellular interactions with HaCaT (keratinocytes) and TPH-1 (monocytes) cell lines. Finally, two formulations were selected for testing quercetin delivery to human skin in vivo using stripping test. Different size distribution was obtained with each strategy starting from 26 nm with quercetin LNC, 179 nm with liposomes to 295 nm with quercetin smartCrystals®. The drug loading varied with each formulation from 0.56 mg/ml with liposomes, 10.8 mg/ml with LNC to 14.4 mg/ml with smartCrystals®. No toxicity was observed in HaCaT cells with quercetin and free radical scavenging ability was established at 5 µg/ml. The safety of quercetin at 5 µg/ml was further confirmed on THP-1 cells with efficient free radical scavenging ability. Finally, skin penetration evidenced different behavior between the two selected forms (LNC and SmartCrystals®), which could lead to different promising strategies for skin protection. On one side, quercetin smartCrystals® seems to enable the superficial deposition of quercetin on top of the skin, which presents a good strategy for a quercetin-based sunscreen product. On the other side, LNC seems to allow quercetin delivery to viable epidermis that holds the promise for skin inflammatory disorders such as psoriasis. Copyright © 2018. Published by Elsevier B.V.

Bacteriostatic Effect of Quercetin as an Antibiotic Alternative In Vivo and Its Antibacterial Mechanism In Vitro.

Science.gov (United States)

Wang, Shengan; Yao, Jiaying; Zhou, Bo; Yang, Jiaxin; Chaudry, Maria T; Wang, Mi; Xiao, Fenglin; Li, Yao; Yin, Wenzhe

2018-01-01

Quercetin, a ubiquitous flavonoid, is known to have antibacterial effects. The purpose of this study was to investigate the effect of quercetin on cecal microbiota of Arbor Acre (AA) broiler chickens in vivo and the bacteriostatic effect and antibacterial mechanism of quercetin in vitro. In vivo, 480 AA broilers (1 day old) were randomly allotted to four treatments (negative control and 0.2, 0.4, or 0.6 g of quercetin per kg of diet) for 42 days. Cecal microbial population and distribution were measured at the end of the experiment. The cecal microflora in these broilers included Proteobacteria, Fimicutes, Bacteroidetes, and Deferribacteres. Compared with the negative control, quercetin significantly decreased the copies of Pseudomonas aeruginosa ( P 0.05). These results suggest that quercetin has potential as an alternative antibiotic feed additive in animal production.

Phenylbutyric acid protects against carbon tetrachloride-induced hepatic fibrogenesis in mice

Energy Technology Data Exchange (ETDEWEB)

Wang, Jian-Qing [School of Pharmacy, Anhui Medical University, Hefei, 230032 (China); Second Affiliated Hospital, Anhui Medical University, Hefei 230601 (China); Chen, Xi [First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China); Zhang, Cheng [Department of Toxicology, Anhui Medical University, Hefei, 230032 (China); Tao, Li [First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China); Zhang, Zhi-Hui; Liu, Xiao-Qian [Department of Toxicology, Anhui Medical University, Hefei, 230032 (China); Xu, Yuan-Bao [Department of Toxicology, Anhui Medical University, Hefei, 230032 (China); First Affiliated Hospital, Anhui Medical University, Hefei 230022 (China); Wang, Hua [Department of Toxicology, Anhui Medical University, Hefei, 230032 (China); Li, Jun, E-mail: lijun@ahmu.edu.cn [School of Pharmacy, Anhui Medical University, Hefei, 230032 (China); Xu, De-Xiang, E-mail: xudex@126.com [Department of Toxicology, Anhui Medical University, Hefei, 230032 (China)

2013-01-15

A recent report showed that the unfolded protein response (UPR) signaling was activated in the pathogenesis of carbon tetrachloride (CCl{sub 4})-induced hepatic fibrosis. Phenylbutyric acid (PBA) is a well-known chemical chaperone that inhibits endoplasmic reticulum (ER) stress and unfolded protein response (UPR) signaling. In the present study, we investigated the effects of PBA on CCl{sub 4}-induced hepatic fibrosis in mice. All mice were intraperitoneally (i.p.) injected with CCl{sub 4} (0.15 ml/kg BW, twice per week) for 8 weeks. In CCl{sub 4} + PBA group, mice were i.p. injected with PBA (150 mg/kg, twice per day) from the beginning of CCl{sub 4} injection to the end. As expected, PBA significantly attenuated CCl{sub 4}-induced hepatic ER stress and UPR activation. Although PBA alleviated, only to a less extent, hepatic necrosis, it obviously inhibited CCl{sub 4}-induced tumor necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-β). Moreover, PBA inhibited CCl{sub 4}-induced hepatic nuclear factor kappa B (NF-κB) p65 translocation and extracellular signal-regulated kinase (ERK) and c-Jun N-terminal Kinase (JNK) phosphorylation. Interestingly, CCl{sub 4}-induced α-smooth muscle actin (α-SMA), a marker for the initiation phase of HSC activation, was significantly attenuated in mice pretreated with PBA. Correspondingly, CCl{sub 4}-induced hepatic collagen (Col)1α1 and Col1α2, markers for the perpetuation phase of HSC activation, were inhibited in PBA-treated mice. Importantly, CCl{sub 4}-induced hepatic fibrosis, as determined using Sirius red staining, was obviously attenuated by PBA. In conclusion, PBA prevents CCl{sub 4}-induced hepatic fibrosis through inhibiting hepatic inflammatory response and HSC activation. Highlights: ► CCl{sub 4} induces hepatic ER stress, inflammation, HSC activation and hepatic fibrosis. ► PBA alleviates CCl{sub 4}-induced hepatic ER stress and UPR signaling activation. ► PBA inhibits CCl{sub 4}-induced

Effect of quercetin on chronic enhancement of spatial learning and memory of mice

Institute of Scientific and Technical Information of China (English)

LIU; Jiancai; YU; Huqing

2006-01-01

In this study we evaluated the effect of quercetin on D-galactose-induced aged mice using the Morris water maze (MWM) test. Based on the free radical theory of aging, experiments were performed to study the possible biochemical mechanisms of glutathione (GSH) level and hydroxyl radical (OH-) in the hippocampus and cerebral cortex and the brain tissue enzyme activity of the mice. The results indicated that quercetin can enhance the exploratory behavior, spatial learning and memory of the mice. The effects relate with enhancing the brain functions and inhibiting oxidative stress by quercetin, and relate with increasing the GSH level and decreasing the OH- content. These findings suggest that quercetin can work as a possible natural anti-aging pharmaceutical product.

Mood and Vigilance Following Quercetin Supplementation

National Research Council Canada - National Science Library

Olson, Craig

2002-01-01

.... Based on group assignment, each subject received a one-time dose of 200 mg caffeine plus 1,800 mg placebo, 2,000 mg quercetin or 2,000 mg placebo 1 hour prior to completing a 45-minute scanning visual vigilance task...

Quercetin Decreases Insulin Resistance in a Polycystic Ovary Syndrome Rat Model by Improving Inflammatory Microenvironment.

Science.gov (United States)

Wang, Zhenzhi; Zhai, Dongxia; Zhang, Danying; Bai, Lingling; Yao, Ruipin; Yu, Jin; Cheng, Wen; Yu, Chaoqin

2017-05-01

Insulin resistance (IR) is a clinical feature of polycystic ovary syndrome (PCOS). Quercetin, derived from Chinese medicinal herbs such as hawthorn, has been proven practical in the management of IR in diabetes. However, whether quercetin could decrease IR in PCOS is unknown. This study aims to observe the therapeutic effect of quercetin on IR in a PCOS rat model and explore the underlying mechanism. An IR PCOS rat model was established by subcutaneous injection with dehydroepiandrosterone. The body weight, estrous cycle, and ovary morphology of the quercetin-treated rats were observed. Serum inflammatory cytokines were analyzed using enzyme-linked immunosorbent assay. In ovarian tissues, the expression of key genes involved in the inflammatory signaling pathway was detected through Western blot, real-time polymerase chain reaction, or immunohistochemistry. The nuclear translocation of nuclear factor κB (NF-κB) was also observed by immunofluorescence. The estrous cycle recovery rate of the insulin-resistant PCOS model after quercetin treatment was 58.33%. Quercetin significantly reduced the levels of blood insulin, interleukin 1β, IL-6, and tumor necrosis factor α. Quercetin also significantly decreased the granulosa cell nuclear translocation of NF-κB in the insulin-resistant PCOS rat model. The treatment inhibited the expression of inflammation-related genes, including the nicotinamide adenine dinucleotide phosphate oxidase subunit p22phox, oxidized low-density lipoprotein, and Toll-like receptor 4, in ovarian tissue. Quercetin improved IR and demonstrated a favorable therapeutic effect on the PCOS rats. The underlying mechanism of quercetin potentially involves the inhibition of the Toll-like receptor/NF-κB signaling pathway and the improvement in the inflammatory microenvironment of the ovarian tissue of the PCOS rat model.

Protective Effects of Quercetin against Dimethoate-Induced Cytotoxicity and Genotoxicity in Allium sativum Test.

Science.gov (United States)

Ahmad, Waseem; Shaikh, Sibhghatulla; Nazam, Nazia; Lone, Mohammad Iqbal

2014-01-01

The present investigation was directed to study the possible protective activity of quercetin-a natural antioxidant against dimethoate-induced cyto- and genotoxicity in meristematic cells of Allium sativum. So far there is no report on the biological properties of quercetin in plant test systems. Chromosome breaks, multipolar anaphase, stick chromosome, and mitotic activity were undertaken in the current study as markers of cyto- and genotoxicity. Untreated control, quercetin controls (@ 5, 10 and 20 μg/mL for 3 h), and dimethoate exposed groups (@ 100 and 200 μg/mL for 3 h) were maintained. For protection against cytogenotoxicity, the root tip cells treated with dimethoate at 100 and 200 μg/mL for 3 h and quercetin treatment at 5, 10, and 20 μg/mL for 16 h, prior to dimethoate treatment, were undertaken. Quercetin was found to be neither cytotoxic nor genotoxic in Allium sativum control at these doses. A significant increase (P Allium. Pretreatment of Allium sativum with quercetin significantly (P Allium sativum that resides, at least in part, on its antioxidant effects.

Newcastle disease virus-attenuated vaccine co-contaminated with fowl adenovirus and chicken infectious anemia virus results in inclusion body hepatitis-hydropericardium syndrome in poultry.

Science.gov (United States)

Su, Qi; Li, Yang; Meng, Fanfeng; Cui, Zhizhong; Chang, Shuang; Zhao, Peng

2018-05-01

Inclusion body hepatitis-hydropericardium syndrome (IBH-HPS) induced by fowl adenovirus type 4 (FAdV-4) has caused huge economic losses to the poultry industry of China, but the source of infection for different flocks, especially flocks with high biological safety conditions, has remained unclear. This study tested the pathogenicity of Newcastle disease virus (NDV)-attenuated vaccine from a large-scale poultry farm in China where IBH-HPS had appeared with high mortality. Analysis revealed that the NDV-attenuated vaccine in use from the abovementioned poultry farm was simultaneously contaminated with FAdV-4 and chicken infectious anemia virus (CIAV). The FAdV and CIAV isolated from the vaccine were purified for the artificial preparation of an NDV-attenuated vaccine singly contaminated with FAdV or CIAV, or simultaneously contaminated with both of them. Seven-day-old specific pathogen-free chicks were inoculated with the artificially prepared contaminated vaccines and tested for corresponding indices. The experiments showed that no hydropericardium syndrome (HPS) and corresponding death occurred after administering the NDV-attenuated vaccine singly contaminated with FAdV or CIAV, but a mortality of 75% with IBH-HPS was commonly found in birds after administering the NDV-attenuated vaccine co-contaminated with FAdV and CIAV. In conclusion, this study found the co-contamination of FAdV-4 and CIAV in the same attenuated vaccine and confirmed that such a contaminated attenuated vaccine was a significant source of infection for outbreaks of IBH-HPS in some flocks. Copyright © 2018 Elsevier B.V. All rights reserved.

Hepatic infarction in HELLP syndrome; a case report

Energy Technology Data Exchange (ETDEWEB)

Kim, Mi Jeong; Kim, Hong [Keimyung Univ. School of Medicine, Taegu (Korea, Republic of)

2000-11-01

Hepatic infarction is a rare but potentially life-threatening complication of pregnancy-associated preeclampsia or HELLP (hemolysis, elevated liver function tests, low platelets) syndrome. We present a case of hepatic infarction subsequent to HELLP syndrome and occurring during the immediate postpartum, and the associated radiologic findings. Sonography revealed poorly defined hypoechoic zones of infarction. Computed tomography(CT) demonstrated the characteristic features of nonenhancing, low attenuation, relatively well-defined, wedge shaped or geographic hepatic lesions, without mass effect.

Hepatic infarction in HELLP syndrome; a case report

International Nuclear Information System (INIS)

Kim, Mi Jeong; Kim, Hong

2000-01-01

Hepatic infarction is a rare but potentially life-threatening complication of pregnancy-associated preeclampsia or HELLP (hemolysis, elevated liver function tests, low platelets) syndrome. We present a case of hepatic infarction subsequent to HELLP syndrome and occurring during the immediate postpartum, and the associated radiologic findings. Sonography revealed poorly defined hypoechoic zones of infarction. Computed tomography(CT) demonstrated the characteristic features of nonenhancing, low attenuation, relatively well-defined, wedge shaped or geographic hepatic lesions, without mass effect

Histidine augments the suppression of hepatic glucose production by central insulin action.

Science.gov (United States)

Kimura, Kumi; Nakamura, Yusuke; Inaba, Yuka; Matsumoto, Michihiro; Kido, Yoshiaki; Asahara, Shun-Ichiro; Matsuda, Tomokazu; Watanabe, Hiroshi; Maeda, Akifumi; Inagaki, Fuyuhiko; Mukai, Chisato; Takeda, Kiyoshi; Akira, Shizuo; Ota, Tsuguhito; Nakabayashi, Hajime; Kaneko, Shuichi; Kasuga, Masato; Inoue, Hiroshi

2013-07-01

Glucose intolerance in type 2 diabetes is related to enhanced hepatic glucose production (HGP) due to the increased expression of hepatic gluconeogenic enzymes. Previously, we revealed that hepatic STAT3 decreases the expression of hepatic gluconeogenic enzymes and suppresses HGP. Here, we show that increased plasma histidine results in hepatic STAT3 activation. Intravenous and intracerebroventricular (ICV) administration of histidine-activated hepatic STAT3 reduced G6Pase protein and mRNA levels and augmented HGP suppression by insulin. This suppression of hepatic gluconeogenesis by histidine was abolished by hepatic STAT3 deficiency or hepatic Kupffer cell depletion. Inhibition of HGP by histidine was also blocked by ICV administration of a histamine H1 receptor antagonist. Therefore, histidine activates hepatic STAT3 and suppresses HGP via central histamine action. Hepatic STAT3 phosphorylation after histidine ICV administration was attenuated in histamine H1 receptor knockout (Hrh1KO) mice but not in neuron-specific insulin receptor knockout (NIRKO) mice. Conversely, hepatic STAT3 phosphorylation after insulin ICV administration was attenuated in NIRKO but not in Hrh1KO mice. These findings suggest that central histidine action is independent of central insulin action, while both have additive effects on HGP suppression. Our results indicate that central histidine/histamine-mediated suppression of HGP is a potential target for the treatment of type 2 diabetes.

Dermal quercetin lipid nanocapsules: Influence of the formulation on antioxidant activity and cellular protection against hydrogen peroxide.

Science.gov (United States)

Hatahet, T; Morille, M; Shamseddin, A; Aubert-Pouëssel, A; Devoisselle, J M; Bégu, S

2017-02-25

Quercetin is a plant flavonoid with strong antioxidant and antiinflammatory properties interesting for skin protection. However, its poor water solubility limits its penetration and so its efficiency on skin. For this purpose, quercetin lipid nanocapsules were formulated implementing phase inversion technique wherein several modifications were introduced to enhance quercetin loading. Quercetin lipid nanocapsules were formulated with two particle size range, (50nm and 20nm) allowing a drug loading of 18.6 and 32mM respectively. The successful encapsulation of quercetin within lipid nanocapsules increased its apparent water solubility by more than 5000 fold (from 0.5μg/ml to about 5mg/ml). The physicochemical properties of these formulations such as surface charge, stability and morphology were characterized. Lipid nanocapsules had spherical shape and were stable for 28days at 25°C. Quercetin release from lipid nanocapsules was studied and revealed a prolonged release kinetics during 24h. Using DPPH assay, we demonstrated that the formulation process of lipid nanocapsules did not modify the antioxidant activity of quercetin in vitro (92.3%). With the goal of a future dermal application, quercetin lipid nanocapsules were applied to THP-1 monocytes and proved the cellular safety of the formulation up to 2μg/ml of quercetin. Finally, formulated quercetin was as efficient as the crude form in the protection of THP-1 cells from oxidative stress by exogenous hydrogen peroxide. With its lipophilic nature and occlusive effect on skin, lipid nanocapsules present a promising strategy to deliver quercetin to skin tissue and can be of value for other poorly water soluble drug candidates. Copyright © 2016 Elsevier B.V. All rights reserved.

Pretreatment with quercetin prevents changes in lymphocytes E-NTPDase/E-ADA activities and cytokines secretion in hyperlipidemic rats.

Science.gov (United States)

Braun, Josiane B S; Ruchel, Jader B; Manzoni, Alessandra G; Abdalla, Fátima H; Casalli, Emerson A; Castilhos, Lívia G; Passos, Daniela F; Leal, Daniela B R

2017-11-29

Hyperlipidemia (HL) is a condition associated with endothelial dysfunction and inflammatory disorders. Purinergic system ectoenzymes play an important role in modulating the inflammatory and immune response. This study investigated whether the preventive treatment with quercetin is able to prevent changes caused by hyperlipidemia in the purinergic system, through the activities of E-NTPDase and E-ADA in lymphocytes, and quantify the nucleotides and nucleoside, and the secretion of anti- and proinflammatory cytokines. Animals were divided into saline/control, saline/quercetin 5 mg/kg, saline/quercetin 25 mg/kg, saline/quercetin 50 mg/kg, saline/simvastatin (0.04 mg/kg), hyperlipidemia, hyperlipidemia/quercetin 5 mg/kg, hyperlipidemia/quercetin 25 mg/kg, hyperlipidemia/quercetin 50 mg/kg, and hyperlipidemia/simvastatin. Animals were pretreated with quercetin for 30 days and hyperlipidemia was subsequently induced by intraperitoneal administration of 500 mg/kg of poloxamer-407. Simvastatin was administered after the induction of hyperlipidemia. Lymphocytes were isolated and E-NTPDase and E-ADA activities were determined. Serum was separated for the cytokines and nucleotide/nucleoside quantification. E-NTPDase and E-ADA activities were increased in lymphocytes from hyperlipidemic rats and pretreatment with quercetin was able to prevent the increase in the activities of these enzymes caused by hyperlipidemia. Hyperlipidemic rats when receiving pretreatment with quercetin and treatment with simvastatin showed decreased levels of ATP and ADP when compared to the untreated hyperlipidemic group. The IFN-γ and IL-4 cytokines were increased in the hyperlipidemic group when compared with control group, and decreased when hyperlipidemic rats received the pretreatment with quercetin. However, pretreatment with quercetin was able to prevent the alterations caused by hyperlipidemia probably by regulating the inflammatory process. We can suggest that the quercetin is a

The impact of quercetin on wound healing relates to changes in αV and β1 integrin expression.

Science.gov (United States)

Doersch, Karen M; Newell-Rogers, M Karen

2017-08-01

Overly fibrotic wound healing can lead to excess scar formation, causing functional impairment and undesirable cosmetic results. However, there are few successful treatments available to prevent or remediate scars. This study sought to explore the molecular mechanisms by which quercetin, a naturally-occurring antifibrotic agent, diminishes scar formation. Using both mice and fibroblast cells, we examined quercetin's impact on fibrosis and the wound healing rate, and potential molecular mechanisms underlying the quercetin-mediated reduction of fibrosis. While cultured fibroblasts demonstrated normal growth in response to quercetin, quercetin increased surface αV integrin and decreased β1 integrin. These changes in surface integrin expression may impact factors that contribute to fibrosis including cell migration, proliferation, and extracellular matrix production. In both quercetin-treated and control mice, wounds healed in about 14 days. Masson's trichrome stain revealed diminished fibrosis at the wound site in quercetin-treated animals despite the normal healing rate, indicating the potential for better cosmetic results without delaying healing. An in vitro scratch wound model using cells plated on an artificial extracellular matrix demonstrated delayed closure following quercetin treatment. The extracellular matrix also ameliorated quercetin's effect on αV integrin. Thus, αV integrin recruitment in response to quercetin treatment may promote the quercetin-mediated decrease extracellular matrix because cells require less extracellular matrix to migrate into a wound. With added extracellular matrix, β1 integrin remained diminished in response to quercetin, indicating that quercetin's effect on β1 integrin expression is independent of extracellular matrix -mediated signaling and is likely driven by inhibition of the intracellular mechanisms driving β1 expression. These findings suggest that quercetin could alter the cells' interactions with the extracellular

The effect of quercetin dietary supplementation on meat oxidation processes and texture of fattening lambs.

Science.gov (United States)

Andrés, S; Huerga, L; Mateo, J; Tejido, M L; Bodas, R; Morán, L; Prieto, N; Rotolo, L; Giráldez, F J

2014-02-01

Thirty two lambs were fed a total mixed ration (TMR) formulated either with palm oil (CTRL; 34 g palm oil kg(-1) TMR) or whole flaxseed (+FS, 85 g flaxseed kg(-1) TMR) alone or enriched with quercetin (+QCT, 34 g palm oil plus 2 g quercetin kg(-1) TMR; +FS+QCT, 85 g flaxseed plus 2 g quercetin kg(-1) TMR). Dietary flaxseed did not affect, in a significant manner, the lipid peroxidation of meat samples. Quercetin treatment reduced oxysterol content (P0.05) the level of lipid-derived volatiles in the headspace of the light-exposed stored cooked meat. Sensory evaluation showed flaxseed as being responsible for a negative effect on meat flavour, probably associated with a modification of the fatty acid profile whereas, unexpectedly, quercetin seemed to worsen meat tenderisation. © 2013.

Nilotinib counteracts thioacetamide-induced hepatic oxidative stress and attenuates liver fibrosis progression.

Science.gov (United States)

Shaker, Mohamed E; Salem, Hatem A; Shiha, Gamal E; Ibrahim, Tarek M

2011-04-01

The aim of this study was to evaluate and compare the effects of imatinib and nilotinib to that of silymarin on established liver fibrosis and oxidative stress in a thioacetamide (TAA) rat model. Male Wistar rats received intraperitoneal (i.p.) injections of TAA (150mg/kg, twice weekly) for 12weeks. Daily treatments with imatinib (10mg/kg), nilotinib (10mg/kg), and silymarin (100mg/kg) were administered orally during the last 4weeks of TAA-administration. At the end of the study, hepatic damage was evaluated by analysis of liver function tests in serum. Hepatic histopathology and collagen content were employed to quantify liver fibrosis. Hepatic oxidative stress was assessed by measuring malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), total nitrate/nitrite (NOx), and reduced glutathione (GSH) contents, as well as myeloperoxidase (MPO) and superoxide dismutase (SOD) activities. Nilotinib, silymarin and, to a lesser extent, imatinib treatments ameliorated TAA-induced hepatic oxidative stress and damage as indicated by hepatic MDA, 4-HNE, NOx, GSH, MPO and SOD levels, as well as liver function tests. Hepatic histopathology results revealed that nilotinib, imatinib, and silymarin treatments decreased the mean score of fibrosis in TAA-treated rats by 24, 14, and 3%, respectively. However, nilotinib and silymarin, but not imatinib, treatments decreased hepatic collagen content in TAA-treated rats by 17 and 36%, respectively. In conclusion, we demonstrated for the first time that nilotinib not only protected against hepatic oxidative stress, but also slowed down liver fibrosis progression. Thus, we provide the first evidence that nilotinib might be a promising anti-fibrotic drug. © 2010 The Authors Fundamental and Clinical Pharmacology © 2010 Société Française de Pharmacologie et de Thérapeutique.

Magnetic nanoparticles for a new drug delivery system to control quercetin releasing for cancer chemotherapy

International Nuclear Information System (INIS)

Barreto, A. C. H.; Santiago, V. R.; Mazzetto, S. E.; Denardin, J. C.; Lavín, R.; Mele, Giuseppe; Ribeiro, M. E. N. P.; Vieira, Icaro G. P.; Gonçalves, Tamara; Ricardo, N. M. P. S.

2011-01-01

Quercetin belongs to the chemical class of flavonoids and can be found in many common foods, such as apples, nuts, berries, etc. It has been demonstrated that quercetin has a wide array of biological effects that are considered beneficial to health treatment, mainly as anticancer. However, therapeutic applications of quercetin have been restricted to oral administration due to its sparing solubility in water and instability in physiological medium. A drug delivery methodology was proposed in this work to study a new quercetin release system in the form of magnetite–quercetin–copolymer (MQC). These materials were characterized through XRD, TEM, IR, and Thermal analysis. In addition, the magnetization curves and quercetin releasing experiments were performed. It was observed a nanoparticle average diameter of 11.5 and 32.5 nm at Fe 3 O 4 and MQC, respectively. The presence of magnetic nanoparticles in this system offers the promise of targeting specific organs within the body. These results indicate the great potential for future applications of the MQC to be used as a new quercetin release system.

Quercetin as an Emerging Anti-Melanoma Agent: A four-focus area therapeutic development strategy

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Zoey Harris

2016-10-01

Full Text Available Replacing current refractory treatments for melanoma with new prevention and therapeutic approaches is crucial in order to successfully treat this aggressive cancer form. Melanoma develops from neural crest cells, which express tyrosinase -- a key enzyme in the pigmentation pathway. The tyrosinase enzyme is highly active in melanoma cells and metabolizes polyphenolic compounds; tyrosinase expression thus makes a feasible a target for polyphenol-based therapies. For example, quercetin (3,3′,4′,5,7-pentahydroxyflavone is a highly ubiquitous and well-classified dietary polyphenol found in various fruits, vegetables and other plant products including onions, broccoli, kale, oranges, blueberries, apples, and tea. Quercetin has demonstrated anti-proliferative and pro-apoptotic activity in various cancer cell types. Quercetin is readily metabolized by tyrosinase into various compounds that promote anti-cancer activity; additionally, given that tyrosinase expression increases during tumorigenesis, and its activity is associated with pigmentation changes in both early- and late-stage melanocytic lesions, it suggests that quercetin can be used to target melanoma. In this review we explore the potential of Quercetin as an anti-melanoma agent utilizing and extrapolating on evidence from previous in vitro studies in various human malignant cell lines and propose a four-focus area strategy to develop quercetin as a targeted anti-melanoma compound for use as either a preventative or therapeutic agent. The four areas of focus include utilizing quercetin to i modulate cellular bioreduction potential and associated signaling cascades, ii affect transcription of relevant genes, iii regulate epigenetic processes, and iv develop effective combination therapies and delivery modalities/protocols. In general, quercetin could be used to exploit tyrosinase activity to prevent, and/or treat, melanoma with minimal additional side effects.

Selecting optimal monochromatic level with spectral CT imaging for improving imaging quality in hepatic venography

International Nuclear Information System (INIS)

Sun Jun; Luo Xianfu; Wang Shou'an; Wang Jun; Sun Jiquan; Wang Zhijun; Wu Jingtao

2013-01-01

Objective: To investigate the effect of spectral CT monochromatic images for improving imaging quality in hepatic venography. Methods: Thirty patients underwent spectral CT examination on a GE Discovery CT 750 HD scanner. During portal phase, 1.25 mm slice thickness polychromatic images and optimal monochromatic images were obtained, and volume rendering and maximum intensity projection were created to show the hepatic veins respectively. The overall imaging quality was evaluated on a five-point scale by two radiologists. Inter-observer agreement in subjective image quality grading was assessed by Kappa statistics. Paired-sample t test were used to compare hepatic vein attenuation, hepatic parenchyma attenuation, CT value difference between the hepatic vein and the liver parenchyma, image noise, vein-to-liver contrast-to-noise ratio (CNR), the image quality score of hepatic venography between the two image data sets. Results: The monochromatic images at 50 keV were found to demonstrate the best CNR for hepatic vein.The hepatic vein attenuation [(329 ± 47) HU], hepatic parenchyma attenuation [(178 ± 33) HU], CT value difference between the hepatic vein and the liver parenchyma [(151 ± 33) HU], image noise (17.33 ± 4.18), CNR (9.13 ± 2.65), the image quality score (4.2 ± 0.6) of optimal monochromatic images were significantly higher than those of polychromatic images [(149 ± 18) HU], [(107 ± 14) HU], [(43 ±11) HU], 12.55 ± 3.02, 3.53 ± 1.03, 3.1 ± 0.8 (t values were 24.79, 13.95, 18.85, 9.07, 13.25 and 12.04, respectively, P < 0.01). In the comparison of image quality, Kappa value was 0.81 with optimal monochromatic images and 0.69 with polychromatic images. Conclusion: Monochromatic images of spectral CT could improve CNR for displaying hepatic vein and improve the image quality compared to the conventional polychromatic images. (authors)

Quercetin suppresses insulin receptor signaling through inhibition of the insulin ligand–receptor binding and therefore impairs cancer cell proliferation

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Wang, Feng [Department of Gastroenterology, The Tenth People’s Hospital of Shanghai, Tongji University, Shanghai 200072 (China); Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Yang, Yong, E-mail: yyang@houstonmethodist.org [Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Department of Medicine, Weill Cornell Medical College, New York, NY 10065 (United States)

2014-10-03

Graphical abstract: - Highlights: • Quercetin inhibits insulin ligand–receptor interactions. • Quercetin reduces downstream insulin receptor signaling. • Quercetin blocks insulin induced glucose uptake. • Quercetin suppresses insulin stimulated cancer cell proliferation and tumor growth. - Abstract: Although the flavonoid quercetin is known to inhibit activation of insulin receptor signaling, the inhibitory mechanism is largely unknown. In this study, we demonstrate that quercetin suppresses insulin induced dimerization of the insulin receptor (IR) through interfering with ligand–receptor interactions, which reduces the phosphorylation of IR and Akt. This inhibitory effect further inhibits insulin stimulated glucose uptake due to decreased cell membrane translocation of glucose transporter 4 (GLUT4), resulting in impaired cancer cell proliferation. The effect of quercetin in inhibiting tumor growth was also evident in an in vivo model, indicating a potential future application for quercetin in the treatment of cancers.

Quercetin suppresses insulin receptor signaling through inhibition of the insulin ligand–receptor binding and therefore impairs cancer cell proliferation

International Nuclear Information System (INIS)

Wang, Feng; Yang, Yong

2014-01-01

Graphical abstract: - Highlights: • Quercetin inhibits insulin ligand–receptor interactions. • Quercetin reduces downstream insulin receptor signaling. • Quercetin blocks insulin induced glucose uptake. • Quercetin suppresses insulin stimulated cancer cell proliferation and tumor growth. - Abstract: Although the flavonoid quercetin is known to inhibit activation of insulin receptor signaling, the inhibitory mechanism is largely unknown. In this study, we demonstrate that quercetin suppresses insulin induced dimerization of the insulin receptor (IR) through interfering with ligand–receptor interactions, which reduces the phosphorylation of IR and Akt. This inhibitory effect further inhibits insulin stimulated glucose uptake due to decreased cell membrane translocation of glucose transporter 4 (GLUT4), resulting in impaired cancer cell proliferation. The effect of quercetin in inhibiting tumor growth was also evident in an in vivo model, indicating a potential future application for quercetin in the treatment of cancers

Inhibition of soluble epoxide hydrolase attenuates hepatic fibrosis and endoplasmic reticulum stress induced by carbon tetrachloride in mice

International Nuclear Information System (INIS)

Harris, Todd R.; Bettaieb, Ahmed; Kodani, Sean; Dong, Hua; Myers, Richard; Chiamvimonvat, Nipavan; Haj, Fawaz G.; Hammock, Bruce D.

2015-01-01

Liver fibrosis is a pathological condition in which chronic inflammation and changes to the extracellular matrix lead to alterations in hepatic tissue architecture and functional degradation of the liver. Inhibitors of the enzyme soluble epoxide hydrolase (sEH) reduce fibrosis in the heart, pancreas and kidney in several disease models. In this study, we assess the effect of sEH inhibition on the development of fibrosis in a carbon tetrachloride (CCl 4 )-induced mouse model by monitoring changes in the inflammatory response, matrix remolding and endoplasmic reticulum stress. The sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was administered in drinking water. Collagen deposition in the liver was increased five-fold in the CCl 4 -treated group, and this was returned to control levels by TPPU treatment. Hepatic expression of Col1a2 and 3a1 mRNA was increased over fifteen-fold in the CCl 4 -treated group relative to the Control group, and this increase was reduced by 50% by TPPU treatment. Endoplasmic reticulum (ER) stress observed in the livers of CCl 4 -treated animals was attenuated by TPPU treatment. In order to support the hypothesis that TPPU is acting to reduce the hepatic fibrosis and ER stress through its action as a sEH inhibitor we used a second sEH inhibitor, trans-4-(4-[3-(4-trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy)-benzoic acid (t-TUCB), and sEH null mice. Taken together, these data indicate that the sEH may play an important role in the development of hepatic fibrosis induced by CCl 4 , presumably by reducing endogenous fatty acid epoxide chemical mediators acting to reduce ER stress. - Highlights: • We administer an inhibitor of sEH in a CCl4 murine model. • sEH inhibition reduces liver collagen deposition and pro-fibrotic gene expression. • sEH inhibition induces MMP-1a activity

Inhibition of soluble epoxide hydrolase attenuates hepatic fibrosis and endoplasmic reticulum stress induced by carbon tetrachloride in mice

Energy Technology Data Exchange (ETDEWEB)

Harris, Todd R. [Department of Entomology and Comprehensive Cancer Center, University of California, Davis, CA 95616 (United States); Bettaieb, Ahmed [Department of Nutrition, University of California, Davis, CA 95616 (United States); Kodani, Sean; Dong, Hua [Department of Entomology and Comprehensive Cancer Center, University of California, Davis, CA 95616 (United States); Myers, Richard; Chiamvimonvat, Nipavan [Department of Internal Medicine: Cardiovascular, University of California, Davis, CA 95616 (United States); Haj, Fawaz G. [Department of Nutrition, University of California, Davis, CA 95616 (United States); Department of Internal Medicine: Endocrinology, Diabetes and Metabolism, University of California, Davis, CA 95616 (United States); Hammock, Bruce D., E-mail: bdhammock@ucdavis.edu [Department of Entomology and Comprehensive Cancer Center, University of California, Davis, CA 95616 (United States)

2015-07-15

Liver fibrosis is a pathological condition in which chronic inflammation and changes to the extracellular matrix lead to alterations in hepatic tissue architecture and functional degradation of the liver. Inhibitors of the enzyme soluble epoxide hydrolase (sEH) reduce fibrosis in the heart, pancreas and kidney in several disease models. In this study, we assess the effect of sEH inhibition on the development of fibrosis in a carbon tetrachloride (CCl{sub 4})-induced mouse model by monitoring changes in the inflammatory response, matrix remolding and endoplasmic reticulum stress. The sEH inhibitor 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) was administered in drinking water. Collagen deposition in the liver was increased five-fold in the CCl{sub 4}-treated group, and this was returned to control levels by TPPU treatment. Hepatic expression of Col1a2 and 3a1 mRNA was increased over fifteen-fold in the CCl{sub 4}-treated group relative to the Control group, and this increase was reduced by 50% by TPPU treatment. Endoplasmic reticulum (ER) stress observed in the livers of CCl{sub 4}-treated animals was attenuated by TPPU treatment. In order to support the hypothesis that TPPU is acting to reduce the hepatic fibrosis and ER stress through its action as a sEH inhibitor we used a second sEH inhibitor, trans-4-(4-[3-(4-trifluoromethoxy-phenyl)-ureido]-cyclohexyloxy)-benzoic acid (t-TUCB), and sEH null mice. Taken together, these data indicate that the sEH may play an important role in the development of hepatic fibrosis induced by CCl{sub 4}, presumably by reducing endogenous fatty acid epoxide chemical mediators acting to reduce ER stress. - Highlights: • We administer an inhibitor of sEH in a CCl4 murine model. • sEH inhibition reduces liver collagen deposition and pro-fibrotic gene expression. • sEH inhibition induces MMP-1a activity.

Attenuation of the gamma rays in tissues; Atenuacion de los rayos gamma en tejidos

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Arcos P, A.; Rodriguez N, S.; Pinedo S, A.; Amador V, P.; Chacon R, A.; Vega C, H.R. [Unidad Academica de Estudios Nucleares, Cipres 10, Fracc. La Penuela, 98068 Zacatecas (Mexico)

2005-07-01

The mass and lineal attenuation coefficient and of hepatic tissue, muscular, osseous and of brain before gamma rays of 10{sup -3} to 10{sup 5} MeV were calculated. For the case of the osseous tissue the calculation was made for the cartilage, the cortical tissue and the bone marrow. During the calculations the elementary composition of the tissues of human origin was used. The calculations include by separate the Photoelectric effect, the Compton scattering and the Pair production, as well as the total. For to establish a comparison with the attenuation capacities, the coefficients of the water, the aluminum and the lead also were calculated. The study was complemented measuring the attenuation coefficient of hepatic tissue of bovine before gamma rays of 0.662 MeV of a source of {sup 137} Cs. The measurement was made through of an experiment of photons transmission through samples frozen of hepatic tissue and with a Geiger-Mueller detector. (Author)

Factors modulating bioavailability of quercetin-related flavonoids and the consequences of their vascular function.

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Terao, Junji

2017-09-01

Nowadays dietary flavonoids attract much attention in the prevention of chronic diseases. Epidemiological and intervention studies strongly suggest that flavonoid intake has beneficial effects on vascular health. It is unlikely that flavonoids act as direct antioxidants, although oxidative stress profoundly contributes to vascular impairment leading to cardiovascular diseases. Instead, flavonoids may exert their function by tuning the cellular redox state to an adaptive response or tolerable stress. However, the optimum intake of flavonoids from supplements or diet has not been clarified yet, because a number of exogenous and endogenous factors modulating their bioavailability affect their vascular function. This review will focus on the current knowledge of the bioavailability and vascular function of quercetin as a representative of antioxidative flavonoids. Current intervention studies imply that intake of quercetin-rich onion improves vascular health. Onion may be superior to quercetin supplement from the viewpoint of quercetin bioavailability, probably because the food matrix enhances the intestinal absorption of quercetin. α-Glucosylation increases its bioavailability by elevating the accessibility to the absorptive cells. Prenylation may enhance bioaccumulation at the target site by increasing the cellular uptake. However, these chemical modifications do not guarantee health benefits to the vascular system. Dietary quercetin is exclusively present as their conjugated form in the blood stream. Quercetin may exert its vascular function as an aglycone within macrophage cells after inflammation-induced deconjugation and as conjugated metabolites by targeting endothelial cells. The relationship between the bioavailability and bio-efficacy should be clarified, to evaluate the vascular function of a wide variety of dietary flavonoids. Copyright © 2017 Elsevier Inc. All rights reserved.

Hepatitis C virus core protein induces hepatic steatosis via Sirt1-dependent pathway.

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Zhang, Chuanhai; Wang, Jingjing; Zhang, Hanlin; Liu, Shunai; Lee, Hyuek Jong; Jin, Wanzhu; Cheng, Jun

2018-05-01

Hepatic steatosis is a common feature of patients with chronic hepatitis C. Previous reports have shown that the overexpression of hepatitis C virus core-encoding sequences (hepatitis C virus genotypes 3a and 1b) significantly induces intracellular triglyceride accumulation. However, the underlying mechanism has not yet been revealed. To investigate whether Sirt1 is involved in hepatitis C virus-mediated hepatic steatosis, the overexpression of hepatitis C virus core 1b protein and Sirt1 and the knockdown of Sirt1 in HepG2 cells were performed. To confirm the results of the cellular experiment liver-specific Sirt1 KO mice with lentivirus-mediated hepatitis C virus core 1b overexpression were studied. Our results show that hepatitis C virus core 1b protein overexpression led to the accumulation of triglycerides in HepG2 cells. Notably the expression of PPARγ2 was dramatically increased at both the mRNA and protein levels by hepatitis C virus core 1b overexpression. The protein expression of Sirt1 is an upstream regulator of PPARγ2 and was also significantly increased after core 1b overexpression. In addition, the overexpression or knockdown of Sirt1 expression alone was sufficient to modulate p300-mediated PPARγ2 deacetylation. In vivo studies showed that hepatitis C virus core protein 1b-induced hepatic steatosis was attenuated in liver-specific Sirt1 KO mice by downregulation of PPARγ2 expression. Sirt1 mediates hepatitis C virus core protein 1b-induced hepatic steatosis by regulation of PPARγ2 expression. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Quercetin Impacts Expression of Metabolism- and Obesity-Associated Genes in SGBS Adipocytes

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Andreas Leiherer

2016-05-01

Full Text Available Obesity is characterized by the rapid expansion of visceral adipose tissue, resulting in a hypoxic environment in adipose tissue which leads to a profound change of gene expression in adipocytes. As a consequence, there is a dysregulation of metabolism and adipokine secretion in adipose tissue leading to the development of systemic inflammation and finally resulting in the onset of metabolic diseases. The flavonoid quercetin as well as other secondary plant metabolites also referred to as phytochemicals have anti-oxidant, anti-inflammatory, and anti-diabetic effects known to be protective in view of obesity-related-diseases. Nevertheless, its underlying molecular mechanism is still obscure and thus the focus of this study was to explore the influence of quercetin on human SGBS (Simpson Golabi Behmel Syndrome adipocytes’ gene expression. We revealed for the first time that quercetin significantly changed expression of adipokine (Angptl4, adipsin, irisin and PAI-1 and glycolysis-involved (ENO2, PFKP and PFKFB4 genes, and that this effect not only antagonized but in part even overcompensated the effect mediated by hypoxia in adipocytes. Thus, these results are explained by the recently proposed hypothesis that the protective effect of quercetin is not solely due to its free radical-scavenging activity but also to a direct effect on mitochondrial processes, and they demonstrate that quercetin might have the potential to counteract the development of obesity-associated complications.

Benzbromarone, Quercetin, and Folic Acid Inhibit Amylin Aggregation

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Laura C. López

2016-06-01

Full Text Available Human Amylin, or islet amyloid polypeptide (hIAPP, is a small hormone secreted by pancreatic β-cells that forms aggregates under insulin deficiency metabolic conditions, and it constitutes a pathological hallmark of type II diabetes mellitus. In type II diabetes patients, amylin is abnormally increased, self-assembled into amyloid aggregates, and ultimately contributes to the apoptotic death of β-cells by mechanisms that are not completely understood. We have screened a library of approved drugs in order to identify inhibitors of amylin aggregation that could be used as tools to investigate the role of amylin aggregation in type II diabetes or as therapeutics in order to reduce β-cell damage. Interestingly, three of the compounds analyzed—benzbromarone, quercetin, and folic acid—are able to slow down amylin fiber formation according to Thioflavin T binding, turbidimetry, and Transmission Electron Microscopy assays. In addition to the in vitro assays, we have tested the effect of these compounds in an amyloid toxicity cell culture model and we have found that one of them, quercetin, has the ability to partly protect cultured pancreatic insulinoma cells from the cytotoxic effect of amylin. Our data suggests that quercetin can contribute to reduce oxidative damage in pancreatic insulinoma β cells by modulating the aggregation propensity of amylin.

Preparation of Essential Oil-Based Microemulsions for Improving the Solubility, pH Stability, Photostability, and Skin Permeation of Quercetin.

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Lv, Xia; Liu, Tiantian; Ma, Huipeng; Tian, Yan; Li, Lei; Li, Zhen; Gao, Meng; Zhang, Jianbin; Tang, Zeyao

2017-11-01

Quercetin can bring many benefits to skin based on its various bioactivities. However, the therapeutic effect of quercetin is limited due to the poor water solubility, pH instability, light instability, and skin permeation. The aim of the present work was applying essential oil-based microemulsions to improve the solubility, pH stability, photostability, and skin permeation of quercetin for topical application. Peppermint oil (PO-ME), clove oil (CO-ME), and rosemary oil (RMO-ME) were selected as model essential oils. Microemulsions composed of Cremophor EL/1,2-propanediol/essential oils (47:23:30, w/w) were selected as model formulations, based on the pseudo-ternary phase diagram and the characterizations. In the solubility study, the solubility of quercetin was improved dozens of times by microemulsions. Quercetin was found instable under alkaline condition, with 50% degraded in the solution of pH 13. However, PO-ME, CO-ME, and RMO-ME could protect quercetin from the hydroxide ions, with 47, 9, and 12% of quercetin degraded. In the photostability study, the essential oil-based microemulsions showed the capability of protecting quercetin from degradation under UV radiation. Where more than 67% of quercetin was degraded in aqueous solution, while less than 7% of quercetin degraded in microemulsions. At last, the in vitro skin permeation study showed that the essential oil-based microemulsions could enhance the permeation capacity of quercetin by 2.5-3 times compared to the aqueous solution. Hence, the prepared essential oil microemulsions could improve the solubility, pH stability, photostability, and skin permeation of quercetin, which will be beneficial for its topical application.

Quercetin protects human hepatoma HepG2 against oxidative stress induced by tert-butyl hydroperoxide

International Nuclear Information System (INIS)

Alia, Mario; Ramos, Sonia; Mateos, Raquel; Granado-Serrano, Ana Belen; Bravo, Laura; Goya, Luis

2006-01-01

Flavonols such as quercetin, have been reported to exhibit a wide range of biological activities related to their antioxidant capacity. The objective of the present study was to investigate the protective effect of quercetin on cell viability and redox status of cultured HepG2 cells submitted to oxidative stress induced by tert-butyl hydroperoxide. Concentrations of reduced glutathione and malondialdehyde, generation of reactive oxygen species and activity and gene expression of antioxidant enzymes were used as markers of cellular oxidative status. Pretreatment of HepG2 with 10 μM quercetin completely prevented lactate dehydrogenase leakage from the cells. Pretreatment for 2 or 20 h with all doses of quercetin (0.1-10 μM) prevented the decrease of reduced glutathione and the increase of malondialdehyde evoked by tert-butyl hydroperoxide in HepG2 cells. Reactive oxygen species generation induced by tert-butyl hydroperoxide was significantly reduced when cells were pretreated for 2 or 20 h with 10 μM and for 20 h with 5 μM quercetin. Finally, some of the quercetin treatments prevented the significant increase of glutathione peroxidase, superoxide dismutase, glutathione reductase and catalase activities induced by tert-butyl hydroperoxide. Gene expression of antioxidant enzymes was also affected by the treatment with the polyphenol. The results of the biomarkers analyzed clearly show that treatment of HepG2 cells in culture with the natural dietary antioxidant quercetin strongly protects the cells against an oxidative insult

Oxidative Stability in Oil-in-Water Emulsions with Quercetin or Rutin Under Iron Catalysis or Riboflavin Photosensitization.

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Yi, BoRa; Ka, HaeJung; Kwon, YongJun; Choi, HyungSeok; Kim, Sunghwa; Kim, Jisu; Kim, Mi-Ja; Lee, JaeHwan

2017-04-01

The effects of quercetin and rutin on the oxidative stability of oil-in-water (O/W) emulsions were tested under riboflavin (RF) photosensitization in the presence or absence of FeCl 2 . The degree of oxidation in O/W emulsions was determined by headspace oxygen content, conjugated dienes, and lipid hydroperoxides. Quercetin chelated more metal than did rutin in iron catalyzed O/W emulsions. Generally, 0.1 mM quercetin and rutin was oxidative while 0.5 and 1.0 mM quercetin and rutin was antioxidative in O/W emulsions under RF photosensitization. Depending on the analysis method, the antioxidants had different strengths. The antioxidative or oxidative properties of quercetin and rutin vary in O/W emulsions and depend the quercetin and rutin concentrations and oxidative forces like transition metals, RF photosensitization, or a combination thereof. © 2017 Institute of Food Technologists®.

The role of quinone reductase (NQO1) and quinone chemistry in quercetin cytotoxicity

NARCIS (Netherlands)

Gliszczynska-Swiglo, A.; Woude, van der H.; Haan, de L.H.J.; Tyrakowska, B.; Aarts, J.M.M.J.G.; Rietjens, I.M.C.M.

2003-01-01

The effects of quercetin on viability and proliferation of Chinese Hamster Ovary (CHO) cells and CHO cells overexpressing human quinone reductase (CHO+NQO1) were studied to investigate the involvement of the pro-oxidant quinone chemistry of quercetin. The toxicity of menadione was significantly

Hypothyroidism Enhanced Ectonucleotidases and Acetylcholinesterase Activities in Rat Synaptosomes can be Prevented by the Naturally Occurring Polyphenol Quercetin.

Science.gov (United States)

Baldissarelli, Jucimara; Santi, Adriana; Schmatz, Roberta; Abdalla, Fátima Husein; Cardoso, Andréia Machado; Martins, Caroline Curry; Dias, Glaecir R Mundstock; Calgaroto, Nicéia Spanholi; Pelinson, Luana Paula; Reichert, Karine Paula; Loro, Vania Lucia; Morsch, Vera Maria Melchiors; Schetinger, Maria Rosa Chitolina

2017-01-01

Thyroid hormones have an influence on the functioning of the central nervous system. Furthermore, the cholinergic and purinergic systems also are extensively involved in brain function. In this context, quercetin is a polyphenol with antioxidant and neuroprotective properties. This study investigated the effects of (MMI)-induced hypothyroidism on the NTPDase, 5'-nucleotidase, adenosine deaminase (ADA), and acetylcholinesterase (AChE) activities in synaptosomes of rats and whether the quercetin can prevent it. MMI at a concentration of 20 mg/100 mL was administered for 90 days in the drinking water. The animals were divided into six groups: control/water (CT/W), control/quercetin 10 mg/kg, control/quercetin 25 mg/kg, methimazole/water (MMI/W), methimazole/quercetin 10 mg/kg (MMI/Q10), and methimazole/quercetin 25 mg/kg (MMI/Q25). On the 30th day, hormonal dosing was performed to confirm hypothyroidism, and the animals were subsequently treated with 10 or 25 mg/kg quercetin for 60 days. NTPDase activity was not altered in the MMI/W group. However, treatment with quercetin decreased ATP and ADP hydrolysis in the MMI/Q10 and MMI/Q25 groups. 5'-nucleotidase activity increased in the MMI/W group, but treatments with 10 or 25 mg/kg quercetin decreased 5'-nucleotidase activity. ADA activity decreased in the CT/25 and MMI/Q25 groups. Furthermore, AChE activity was reduced in all groups with hypothyroidism. In vitro tests also demonstrated that quercetin per se decreased NTPDase, 5'-nucleotidase, and AChE activities. This study demonstrated changes in the 5'-nucleotidase and AChE activities indicating that purinergic and cholinergic neurotransmission are altered in this condition. In addition, quercetin can alter these parameters and may be a promising natural compound with important neuroprotective actions in hypothyroidism.

Protective Effect of Quercetin against Oxidative Stress-Induced Cytotoxicity in Rat Pheochromocytoma (PC-12) Cells

OpenAIRE

Dengke Bao; Jingkai Wang; Xiaobin Pang; Hongliang Liu

2017-01-01

Oxidative stress has been implicated in the pathogenesis of many kinds of neurodegenerative disorders, particularly Parkinson’s disease. Quercetin is a bioflavonoid found ubiquitously in fruits and vegetables, and has antioxidative activity. However, the underlying mechanism of the antioxidative effect of quercetin in neurodegenerative diseases has not been well explored. Here, we investigated the antioxidative effect and underlying molecular mechanisms of quercetin on PC-12 cells. We found t...

The antioxidants curcumin and quercetin inhibit inflammatory processes associated with arthritis.

Science.gov (United States)

Jackson, J K; Higo, T; Hunter, W L; Burt, H M

2006-04-01

Curcumin and quercetin are antioxidant molecules with anti-proliferative, anti-inflammatory and immunosuppressive activities. The objective of this study was to investigate the inhibitory activity of these agents using four assays of inflammatory aspects of arthritis. Crystal-induced neutrophil activation was measured by luminol-dependent chemiluminescence. Synoviocyte proliferation was measured by an MTS assay using HIG-82 rabbit synoviocytes in cell culture. Chondrocyte (cultured primary cells) expression of the matrix metalloproteinases collagenase and stromelysin was measured by Northern Blot analysis. Angiogenesis was measured using the chorioallantoic membrane of the chick embryo. Both agents inhibited neutrophil activation, synoviocyte proliferation and angiogenesis. Curcumin strongly inhibited collagenase and stromelysin expression at micromolar concentrations whereas quercetin had no effect in this assay. These studies suggest that curcumin and to a lesser extent quercetin may offer therapeutic potential for the treatment of crystal-induced arthritis or rheumatoid arthritis.

Wedged-shaped, segmental changes in the liver caused by occlusion of a single hepatic vein

International Nuclear Information System (INIS)

Kanazawa, Susumu; Akaki, Shiro; Yasui, Kotaro; Tanaka, Akio; Hiraki, Yoshio

1997-01-01

We evaluated wedged-shaped, segmental changes in the liver caused by occlusion of a single hepatic vein in seven patients. The causes of occlusion were due to liver tumors in three patients, metastasis of the right adrenal gland in one, and postoperative changes in three. Changes included low attenuating on unenhanced CT, high attenuation on enhanced CT, low signal intensity on T1-weighted MRI, high signal intensity on T2-weighted MRI, high signal intensity on enhanced MRI, dense hepatogram and retrograde arterioportal shunt on hepatic arteriography. MRI and hepatic arteriography are more sensitive than CT in demonstration of those changes. (author)

Protective effects of Bombyx mori, quercetin and benazepril against doxorubicin induced cardiotoxicity and nephrotoxicity

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Abdul S. Nazmi

2016-09-01

Full Text Available The present study was conducted with the aim of evaluating the protective effects of Bombyx mori, quercetin and benazepril on doxorubicin (DXR induced cardiotoxicity and nephrotoxicity in rats. B. mori, quercetin and benazepril were administered for 7 days, and a single intravenous injection of 10 mg/kg body weight of DXR on day five. The animals were sacrificed 48 h after DXR administration. DXR produced a significant elevation in the malondialdehyde (MDA level and significantly inhibited the activity of glutathione (GSH in the heart and the kidney followed by the activity of catalase (CAT in the heart tissue with a significant rise in the serum levels of aspartate transaminase (AST, lactate dehydrogenase (LDH, blood urea nitrogen (BUN, creatinine and a reduction in serum GSH levels indicating acute cardiac toxicity. B. mori, quercetin and benazepril pretreatment significantly reduced the MDA concentration and ameliorated the inhibition of cardiac GSH and CAT activity. B. mori, quercetin and benazepril also significantly improved the serum levels of AST, LDH, BUN, creatinine and GSH in DXR-treated rats. Furthermore, histological examination of the heart sections confirmed the myocardial injury with DXR administration, and the near normal pattern with B. mori, quercetin and benazepril pretreatment. The results provide clear evidence that the B. mori, quercetin and benazepril pretreatments offer significant protection against DXR-induced enzymatic changes in serum, cardiac and renal tissue damage.

Fibroblast growth factor 21 participates in adaptation to endoplasmic reticulum stress and attenuates obesity-induced hepatic metabolic stress.

Science.gov (United States)

Kim, Seong Hun; Kim, Kook Hwan; Kim, Hyoung-Kyu; Kim, Mi-Jeong; Back, Sung Hoon; Konishi, Morichika; Itoh, Nobuyuki; Lee, Myung-Shik

2015-04-01

Fibroblast growth factor 21 (FGF21) is an endocrine hormone that exhibits anti-diabetic and anti-obesity activity. FGF21 expression is increased in patients with and mouse models of obesity or nonalcoholic fatty liver disease (NAFLD). However, the functional role and molecular mechanism of FGF21 induction in obesity or NAFLD are not clear. As endoplasmic reticulum (ER) stress is triggered in obesity and NAFLD, we investigated whether ER stress affects FGF21 expression or whether FGF21 induction acts as a mechanism of the unfolded protein response (UPR) adaptation to ER stress induced by chemical stressors or obesity. Hepatocytes or mouse embryonic fibroblasts deficient in UPR signalling pathways and liver-specific eIF2α mutant mice were employed to investigate the in vitro and in vivo effects of ER stress on FGF21 expression, respectively. The in vivo importance of FGF21 induction by ER stress and obesity was determined using inducible Fgf21-transgenic mice and Fgf21-null mice with or without leptin deficiency. We found that ER stressors induced FGF21 expression, which was dependent on a PKR-like ER kinase-eukaryotic translation factor 2α-activating transcription factor 4 pathway both in vitro and in vivo. Fgf21-null mice exhibited increased expression of ER stress marker genes and augmented hepatic lipid accumulation after tunicamycin treatment. However, these changes were attenuated in inducible Fgf21-transgenic mice. We also observed that Fgf21-null mice with leptin deficiency displayed increased hepatic ER stress response and liver injury, accompanied by deteriorated metabolic variables. Our results suggest that FGF21 plays an important role in the adaptive response to ER stress- or obesity-induced hepatic metabolic stress.

Effects of phyto-oestrogen quercetin on productive performance, hormones, reproductive organs and apoptotic genes in laying hens.

Science.gov (United States)

Yang, J X; Chaudhry, M T; Yao, J Y; Wang, S N; Zhou, B; Wang, M; Han, C Y; You, Y; Li, Y

2018-04-01

Quercetin, a polyphenolic flavonoid with diverse biological activities including anti-inflammatory and antiviral, inhibits lipid peroxidation, prevents oxidative injury and cell death. The purpose of the research was to investigate the effect of quercetin on productive performance, reproductive organs, hormones and apoptotic genes in laying hens between 37 and 45 weeks of age, because of the structure and oestrogenic activities similar to 17β-oestradiol. The trial was conducted using 240 Hessian laying hens (37 weeks old), housed in wire cages with two hens in each cage. These hens were randomly allotted to four treatments with six replicates, 10 hens in each replicate and fed with diets containing quercetin as 0, 0.2, 0.4 and 0.6 g/kg feed for 8 weeks. The results showed that dietary quercetin significantly increased (p feed-egg ratio was decreased (p  .05) on average egg weight and average daily feed intake. Compared with control, secretion of hormones, oestradiol (E 2 ) , progesterone (P4), follicle-stimulating hormone (FSH), luteinizing hormone (LH), insulin-like growth factors-1 (IGF-1) and growth hormone (GH), was found to be significantly higher (p  .05) by quercetin, whereas magnum index, isthmus index, magnum length, isthmus length and follicle numbers were significantly increased (p < .05) with quercetin supplementation. Additionally, expression of apoptotic genes was significantly (p < .05) up-regulated or down-regulated by quercetin. These results indicated that quercetin improved productive performance, and its mechanism may be due to the oestrogen-like activities of quercetin. © 2017 Blackwell Verlag GmbH.

Application of quercetin and its bio-inspired nanoparticles as anti-adhesive agents against Bacillus subtilis attachment to surface

Energy Technology Data Exchange (ETDEWEB)

Raie, Diana S., E-mail: raiediana@yahoo.com [Process Design and Development Department, Egyptian Petroleum Research Institute (EPRI), Nasr City, Cairo (Egypt); Mhatre, Eisha [Terrestrial Biofilms Group, Institute of Microbiology, Friedrich Schiller University Jena (FSU), Jena (Germany); Thiele, Matthias [Nanobiophotonic Department, Leibniz Institute of Photonic Technology Jena (IPHT), Jena (Germany); Labena, A. [Process Design and Development Department, Egyptian Petroleum Research Institute (EPRI), Nasr City, Cairo (Egypt); El-Ghannam, Gamal [National Institute of Laser Enhanced Sciences (NILES), Cairo University, Giza (Egypt); Farahat, Laila A. [Process Design and Development Department, Egyptian Petroleum Research Institute (EPRI), Nasr City, Cairo (Egypt); Youssef, Tareq [National Institute of Laser Enhanced Sciences (NILES), Cairo University, Giza (Egypt); Fritzsche, Wolfgang [Nanobiophotonic Department, Leibniz Institute of Photonic Technology Jena (IPHT), Jena (Germany); Kovács, Ákos T., E-mail: akos-tibor.kovacs@uni-jena.de [Terrestrial Biofilms Group, Institute of Microbiology, Friedrich Schiller University Jena (FSU), Jena (Germany)

2017-01-01

The aim of this study was directed to reveal the repulsive effect of coated glass slides by quercetin and its bio-inspired titanium oxide and tungsten oxide nanoparticles on physical surface attachment of Bacillus subtilis as an ab-initio step of biofilm formation. Nanoparticles were successfully synthesized using sol–gel and acid precipitation methods for titanium oxide and tungsten oxide, respectively (in the absence or presence of quercetin). The anti-adhesive impact of the coated-slides was tested through the physical attachment of B. subtilis after 24 h using Confocal Laser Scanning Microscopy (CLSM). Here, quercetin was presented as a bio-route for the synthesis of tungsten mixed oxides nano-plates at room temperature. In addition, quercetin had an impact on zeta potential and adsorption capacity of both bio-inspired amorphous titanium oxide and tungsten oxide nano-plates. Interestingly, our experiments indicated a contrary effect of quercetin as an anti-adhesive agent than previously reported. However, its bio-inspired metal oxide proved their repulsive efficiency. In addition, quercetin-mediated nano-tungsten and quercetin-mediated amorphous titanium showed anti-adhesive activity against B. subtilis biofilm. - Highlights: • Novel quercetin-mediated nanoparticles were tested for anti-adhesion against attachment of cells forming biofilms. • Quercetin showed a low-grade of protection level against bacterial attachment. • Bio-inspired nano-anatase showed a lower efficiency than amorphous titanium. • Thermally treated bio-inspired nano-tungsten gets an improved anti-adhesive activity.

Quercetin suppresses hypoxia-induced accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) through inhibiting protein synthesis.

Science.gov (United States)

Lee, Dae-Hee; Lee, Yong J

2008-10-01

Quercetin, a ubiquitous bioactive plant flavonoid, has been shown to inhibit the proliferation of cancer cells and induce the accumulation of hypoxia-inducible factor-1alpha (HIF-1alpha) in normoxia. In this study, under hypoxic conditions (1% O(2)), we examined the effect of quercetin on the intracellular level of HIF-1alpha and extracellular level of vascular endothelial growth factor (VEGF) in a variety of human cancer cell lines. Surprisingly, we observed that quercetin suppressed the HIF-1alpha accumulation during hypoxia in human prostate cancer LNCaP, colon cancer CX-1, and breast cancer SkBr3 cells. Quercetin treatment also significantly reduced hypoxia-induced secretion of VEGF. Suppression of HIF-1alpha accumulation during treatment with quercetin in hypoxia was not prevented by treatment with 26S proteasome inhibitor MG132 or PI3K inhibitor LY294002. Interestingly, hypoxia (1% O(2)) in the presence of 100 microM quercetin inhibited protein synthesis by 94% during incubation for 8 h. Significant quercetin concentration-dependent inhibition of protein synthesis and suppression of HIF-1alpha accumulation were observed under hypoxic conditions. Treatment with 100 microM cycloheximide, a protein synthesis inhibitor, replicated the effect of quercetin by inhibiting HIF-1alpha accumulation during hypoxia. These results suggest that suppression of HIF-1alpha accumulation during treatment with quercetin under hypoxic conditions is due to inhibition of protein synthesis. (c) 2008 Wiley-Liss, Inc.

Quercetin protects human brain microvascular endothelial cells from fibrillar β-amyloid1–40-induced toxicity

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Yongjie Li

2015-01-01

Full Text Available Amyloid beta-peptides (Aβ are known to undergo active transport across the blood-brain barrier, and cerebral amyloid angiopathy has been shown to be a prominent feature in the majority of Alzheimer׳s disease. Quercetin is a natural flavonoid molecule and has been demonstrated to have potent neuroprotective effects, but its protective effect on endothelial cells under Aβ-damaged condition is unclear. In the present study, the protective effects of quercetin on brain microvascular endothelial cells injured by fibrillar Aβ1–40 (fAβ1–40 were observed. The results show that fAβ1–40-induced cytotoxicity in human brain microvascular endothelial cells (hBMECs can be relieved by quercetin treatment. Quercetin increases cell viability, reduces the release of lactate dehydrogenase, and relieves nuclear condensation. Quercetin also alleviates intracellular reactive oxygen species generation and increases superoxide dismutase activity. Moreover, it strengthens the barrier integrity through the preservation of the transendothelial electrical resistance value, the relief of aggravated permeability, and the increase of characteristic enzyme levels after being exposed to fAβ1–40. In conclusion, quercetin protects hBMECs from fAβ1–40-induced toxicity.

Synergistic Effect of Quercetin and α-Lipoic Acid on Aluminium Chloride Induced Neurotoxicity in Rats

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Sooad Saud Al-Otaibi

2018-01-01

Full Text Available Objectives. The present study was carried out to study the protective effects of quercetin and α-lipoic acid alone and in combination against aluminum chloride induced neurotoxicity in rats. Materials and Methods. The study consisted of eight groups, namely, Group 1: control rats, Group 2: rats receiving aluminium chloride 7 mg/kg body weight intraperitoneal route (i.p for two weeks, Group 3: rats receiving quercetin 50 mg/kg body weight i.p. for two weeks, Group 4: rats receiving quercetin 50 mg/kg body weight followed by aluminium chloride 7 mg/kg body weight i.p. for two weeks, Group 5: rats receiving α-lipoic acid 20 mg/kg body weight i.p. for two weeks, Group 6: rats receiving lipoic acid 20 mg/kg body weight followed by aluminium chloride 7 mg/kg body weight i.p. for two weeks, Group 7: rats receiving α-lipoic acid 20 mg/kg body weight and quercetin 50 mg/kg body weight i.p. for two weeks, and Group 8: rats receiving α-lipoic acid 20 mg/kg body weight and quercetin 50 mg/kg body weight followed by aluminium chloride 7 mg/kg body weight i.p. for two weeks. The animals were killed after 24 hours of the last dose by cervical dislocation. Results. Aluminium chloride treatment of rats resulted in significant increases in lipid peroxidation, protein carbonyl levels, and acetylcholine esterase activity in the brain. This was accompanied with significant decreases in reduced glutathione, activities of the glutathione reductase, and superoxide dismutase. Pretreatment of AlCl3 exposed rats to either quercetin or α-lipoic acid also restored altered lipid peroxidation and superoxide dismutase to near normal levels. Quercetin or α-lipoic acid pretreatment of AlCl3 exposed rats improved the protein carbonyl and reduced glutathione, glutathione reductase, and acetylcholine esterase activities in rat brains towards normal levels. Combined pretreatment of AlCl3 exposed rats with quercetin and α-lipoic acid resulted in a

Quercetin - A Flavonoid Compound from Sarcopyramis bodinieri var ...

African Journals Online (AJOL)

The flavonoid compound was identified as quercetin by 1H-. NMR and ESI-MS ... phenolic compounds were isolated, and their .... scored under a fluorescence microscope (Carl. Zeiss .... Antioxidant Properties of Sarcopyramis bodinieri.

Specificity of unenhanced CT for non-invasive diagnosis of hepatic steatosis: implications for the investigation of the natural history of incidental steatosis

Energy Technology Data Exchange (ETDEWEB)

Pickhardt, Perry J.; Hahn, Luke [University of Wisconsin School of Medicine and Public Health, Department of Radiology, Madison, WI (United States); Park, Seong Ho [University of Ulsan College of Medicine, Asan Medical Center, Department of Radiology and Research Institute of Radiology, Seoul (Korea, Republic of); Lee, Sung-Gyu [University of Ulsan College of Medicine, Asan Medical Center, Division of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, Seoul (Korea, Republic of); Bae, Kyongtae T. [University of Pittsburgh, Department of Radiology, Pittsburgh, PA (United States); Yu, Eun Sil [University of Ulsan College of Medicine, Asan Medical Center, Department of Pathology, Seoul (Korea, Republic of)

2012-05-15

To determine a highly specific liver attenuation threshold at unenhanced CT for biopsy-proven moderate to severe hepatic steatosis ({>=}30% at histology). 315 asymptomatic adults (mean age {+-} SD, 31.5 {+-} 10.1 years; 207 men, 108 women) underwent same-day unenhanced liver CT and ultrasound-guided liver biopsy. Blinded to biopsy results, CT liver attenuation was measured using standard region-of-interest methodology. Multiple linear regression analysis was used to assess the relationship of CT liver attenuation with patient age, gender, BMI, CT system, and hepatic fat and iron content. Thirty-nine subjects had moderate to severe steatosis and 276 had mild or no steatosis. A liver attenuation threshold of 48 HU was 100% specific (276/276) for moderate to severe steatosis, with no false-positives. Sensitivity, PPV and NPV at this HU threshold was 53.8%, 100% and 93.9%. Hepatic fat content was the overwhelming determinant of liver attenuation values, but CT system (P < 0.001), and hepatic iron (P = 0.035) also had a statistically significant independent association. Unenhanced CT liver attenuation alone is highly specific for moderate to severe hepatic steatosis, allowing for confident non-invasive identification of large retrospective/prospective cohorts for natural history evaluation of incidental non-alcoholic fatty liver disease. Low sensitivity, however, precludes effective population screening at this threshold. (orig.)

Specificity of unenhanced CT for non-invasive diagnosis of hepatic steatosis: implications for the investigation of the natural history of incidental steatosis

International Nuclear Information System (INIS)

Pickhardt, Perry J.; Hahn, Luke; Park, Seong Ho; Lee, Sung-Gyu; Bae, Kyongtae T.; Yu, Eun Sil

2012-01-01

To determine a highly specific liver attenuation threshold at unenhanced CT for biopsy-proven moderate to severe hepatic steatosis (≥30% at histology). 315 asymptomatic adults (mean age ± SD, 31.5 ± 10.1 years; 207 men, 108 women) underwent same-day unenhanced liver CT and ultrasound-guided liver biopsy. Blinded to biopsy results, CT liver attenuation was measured using standard region-of-interest methodology. Multiple linear regression analysis was used to assess the relationship of CT liver attenuation with patient age, gender, BMI, CT system, and hepatic fat and iron content. Thirty-nine subjects had moderate to severe steatosis and 276 had mild or no steatosis. A liver attenuation threshold of 48 HU was 100% specific (276/276) for moderate to severe steatosis, with no false-positives. Sensitivity, PPV and NPV at this HU threshold was 53.8%, 100% and 93.9%. Hepatic fat content was the overwhelming determinant of liver attenuation values, but CT system (P < 0.001), and hepatic iron (P = 0.035) also had a statistically significant independent association. Unenhanced CT liver attenuation alone is highly specific for moderate to severe hepatic steatosis, allowing for confident non-invasive identification of large retrospective/prospective cohorts for natural history evaluation of incidental non-alcoholic fatty liver disease. Low sensitivity, however, precludes effective population screening at this threshold. (orig.)

Diagnostic value of CT on hepatic tuberculosis

International Nuclear Information System (INIS)

Zhang Fan; Zhang Xuelin; Qiu Shijun; Zhang Yuzhong; Wen Ge; Zhong Qun

2006-01-01

Objective: To assess CT manifestations and diagnostic value in patients with hepatic tuberculosis. Methods: Ten cases of hepatic tuberculosis proved by hepatic biopsy or surgical specimens were analyzed retrospectively. Results: This group of hepatic tuberculosis included three types. (1) Five cases of miliary hepatic tuberculosis demonstrated that the liver swelled diffusely associated with multiple miliary low attenuations, and showed no enhancement after contrast agents administration. (2) Three cases of tubercle hepatic tuberculosis depicted multiple hypodensity areas or mixed density regions in the liver. The extension of lesions reduced in arterial phase, and a ring-like enhancement was displayed in the portal phase. (3) One case of hepatic tuberculoma illustrated solitary space occupying lesion accompanied with central necrosis. The envelope was thin and smooth which enhanced slightly after injecting Gd-DTPA. Another one was hepatic abscess and depicted fluid-fluid level inside the lesion. Conclusions: The CT manifestations of miliary hepatic tuberculosis lack of characteristics, it is hard to make the diagnosis clear-cut unless integrating the medical history and lab test. The 'powder calcification' findings of tubercle hepatic tuberculosis is propitious to draw a qualitative diagnosis. And the feature of hepatic tuberculomas with fluid- fluid level is in favor of making a differential diagnosis against parallel tumors. (authors)

Stimulatory effects of curcumin and quercetin on posttranslational modifications of p53 during lung carcinogenesis.

Science.gov (United States)

Zhang, P; Zhang, Xy

2018-06-01

Lung cancer is responsible for increase in mortality due to cancer-related deaths, and new approaches are being explored for the betterment of the situation. In the present study, chemopreventive efficacy of curcumin and quercetin was investigated against benzo(a)pyrene (BP)-induced lung carcinogenesis. The mice were segregated into five groups, which included normal control, BP-treated, BP + curcumin-treated, BP + quercetin-treated, and BP + curcumin + quercetin-treated groups. The morphological and histological analyses of tumor nodules confirmed lung carcinogenesis22 weeks after weeks single intraperitoneal injection of BP at a dose of 100 mg/kg body weight to mice. Curcumin and quercetin when administered individually as well as in combination significantly elevated the expression of acetylated-p53, which was otherwise depressed due to BP treatment. Also, both the phytochemicals significantly reduced the BP-inflicted increased levels of phosphorylated-p53. Furthermore, observed increase in the number of apoptotic cells by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), assay and increased activities of caspase 3 and 9 confirmed the induction of apoptosis by curcumin and quercetin. Moreover, the histological slides also showed noticeable improvement in the histoarchitecture of lungs by phytochemicals. The present study concludes that prophylactic treatment with curcumin and quercetin induces apoptosis in the lungs by modulation of p53 posttranslational modifications.

Utilization of quercetin and quercetin glycosides from onion (Allium cepa L.) solid waste as an antioxidant, urease and xanthine oxidase inhibitors.

Science.gov (United States)

Nile, Shivraj Hariram; Nile, Arti Shivraj; Keum, Young Soo; Sharma, Kavita

2017-11-15

This study aimed to determine the flavonol glycosides from onion solid waste (OSW) using HPLC analysis, with antioxidant and enzyme inhibitory activities. We found considerable amount of quercetin-4'-O-monoglucoside (QMG: 254.85), quercetin-3,4'-O-diglucoside (QDG: 162.34), quercetin (Q: 60.44), and isorhamnetin-3-glucoside (IMG: 23.92) (mg/100g) dry weight (DW) of OSW. For OSW, the methanol and ethanol showed the strongest antioxidant activities, followed by ethyl acetate, chloroform, and n-hexane extracts. Among the flavonols, Q and QDG possessed higher antioxidant activities. OSW and flavonol glycosides displayed significant enzyme inhibitory activity, with IC 50 values ranging from 12.5±0.11 to 32.5±0.28 for OSW, 8.2±0.07 to 16.8±0.02 for flavonol glycosides, and 4.2±0.05μg/mL for thiourea (positive control) towards urease; while 15.2±0.8 to 35.8±0.2 (μg/mL) for OSW, 10.5±0.06 to 20.8±0.05 (μg/mL) for flavonol glycosides, and 6.5±0.05μg/mL for allopurinol (positive control) towards xanthine oxidase, respectively. The OSW and flavonol glycosides may thus be considered as potential antioxidant and antigout agents. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fast Disintegrating Quercetin-Loaded Drug Delivery Systems Fabricated Using Coaxial Electrospinning

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Xiao-Yan Li

2013-10-01

Full Text Available The objective of this study is to develop a structural nanocomposite of multiple components in the form of core-sheath nanofibres using coaxial electrospinning for the fast dissolving of a poorly water-soluble drug quercetin. Under the selected conditions, core-sheath nanofibres with quercetin and sodium dodecyl sulphate (SDS distributed in the core and sheath part of nanofibres, respectively, were successfully generated, and the drug content in the nanofibres was able to be controlled simply through manipulating the core fluid flow rates. Field emission scanning electron microscope (FESEM images demonstrated that the nanofibres prepared from the single sheath fluid and double core/sheath fluids (with core-to-sheath flow rate ratios of 0.4 and 0.7 have linear morphology with a uniform structure and smooth surface. The TEM images clearly demonstrated the core-sheath structures of the produced nanocomposites. Differential scanning calorimetry (DSC and X-ray diffraction (XRD results verified that quercetin and SDS were well distributed in the polyvinylpyrrolidone (PVP matrix in an amorphous state, due to the favourite second-order interactions. In vitro dissolution studies showed that the core-sheath composite nanofibre mats could disintegrate rapidly to release quercetin within 1 min. The study reported here provides an example of the systematic design, preparation, characterization and application of a new type of structural nanocomposite as a fast-disintegrating drug delivery system.

Clinical and Anamnestic Features of Hepatic Steatosis in Children

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N.Yu. Zavgorodnia

2015-11-01

Full Text Available The article is devoted to the study of clinical and anamnestic features of hepatic steatosis in children. The results of a comparative analysis of survey data of patients with evidence of hepatic steatosis and patients without steatosis were shown. The presence and degree of hepatic steatosis was found using FibroScan-touch-502 by measuring controlled attenuation parameter (CAP. The features of lifestyle and nutrition of children with steatosis were determined: hypodynamic lifestyle, the prevalence of fast food habits, insufficient consumption of liquid. It was established that hepatic steatosis is closely associated with obesity and hypothalamic disorders, increased both blood pressure and serum levels of atherogenic lipids.

Quercetin-glutamic acid conjugate with a non-hydrolysable linker; a novel scaffold for multidrug resistance reversal agents through inhibition of P-glycoprotein.

Science.gov (United States)

Kim, Mi Kyoung; Kim, Yunyoung; Choo, Hyunah; Chong, Youhoon

2017-02-01

Previously, we have reported remarkable effect of a quercetin-glutamic acid conjugate to reverse multidrug resistance (MDR) of cancer cells to a broad spectrum of anticancer agents through inhibition of P-glycoprotein (Pgp)-mediated drug efflux. Due to the hydrolysable nature, MDR-reversal activity of the quercetin conjugate was attributed to its hydrolysis product, quercetin. However, several lines of evidence demonstrated that the intact quercetin-glutamic acid conjugate has stronger MDR-reversal activity than quercetin. In order to evaluate this hypothesis and to identify a novel scaffold for MDR-reversal agents, we prepared quercetin conjugates with a glutamic acid attached at the 7-O position via a non-hydrolysable linker. Pgp inhibition assay, Pgp ATPase assay, and MDR-reversal activity assay were performed, and the non-hydrolysable quercetin conjugates showed significantly higher activities compared with those of quercetin. Unfortunately, the quercetin conjugates were not as effective as verapamil in Pgp-inhibition and thereby reversing MDR, but it is worth to note that the structurally modified quercetin conjugates with a non-cleavable linker showed significantly improved MDR-reversal activity compared with quercetin. Taken together, the quercetin conjugates with appropriate structural modifications were shown to have a potential to serve as a scaffold for the design of novel MDR-reversal agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinical Characteristics and Risk Factors for the Development of Postoperative Hepatic Steatosis After Total Pancreatectomy.

Science.gov (United States)

Hata, Tatsuo; Ishida, Masaharu; Motoi, Fuyuhiko; Sakata, Naoaki; Yoshimatsu, Gumpei; Naitoh, Takeshi; Katayose, Yu; Egawa, Shinichi; Unno, Michiaki

2016-03-01

The occurrence of hepatic steatosis after pancreatectomy is known to be associated with the remnant pancreatic function. However, other risk factors for hepatic steatosis after pancreatectomy remain unknown. The aims of this study were to identify other risk factors in addition to the remnant pancreatic function and elucidate the relationship between postoperative hepatic steatosis and pancreatic exocrine insufficiency in totally pancreatomized patients. Forty-three patients who underwent total pancreatectomy were analyzed. Hepatic steatosis was defined as the attenuation of unenhanced computed tomography values. Clinical findings and laboratory data were compared between patients with and without hepatic steatosis. Sixteen (37.2%) patients developed hepatic steatosis after total pancreatectomy, with marked declines in the Controlling Nutritional Status score and body mass index. Multiple linear regression analysis revealed that the attenuation of computed tomography values was correlated with female sex (P = 0.002), early postoperative serum albumin levels (P = 0.003), and pancreatic enzyme replacement therapy with high-dose pancrelipase (P = 0.032). Postoperative hepatic steatosis after pancreatectomy is associated with sex, malnutrition, and pancreatic exocrine insufficiency. High-dose pancreatic enzyme replacement therapy may have preventive effects on hepatic steatosis occurring after pancreatectomy.

Characteristics of liver tissue for attenuate the gamma radiation; Caracteristicas del tejido hepatico para atenuar la radiacion gamma

Energy Technology Data Exchange (ETDEWEB)

Arcos P, A.; Rodriguez N, S.; Pinedo S, A.; Amador V, P.; Chacon R, A.; Vega C, H.R. [Unidad Academica de Estudios Nucleares, Cipres No. 10, Fracc. La Penuela, 98068 Zacatecas (Mexico)

2005-07-01

It was determined the lineal attenuation coefficient of hepatic tissue before gamma radiation of a source of {sup 137} Cs. When exposing organic material before X or gamma radiation fields, part of the energy of the photons is absorbed by the material, while another part crosses it without producing any effect. The quantity of energy that is absorbed is a measure of the dose that receives the material. The three main mechanisms by means of which the gamma rays interacting with the matter are: The Photoelectric Effect, the Compton dispersion and the Even production; the sum of these three processes is translated in the attenuation coefficient of the radiation. In this work we have used hepatic tissue of bovine, as substitute of the human hepatic tissue, and we have measured the lineal attenuation coefficient for photons of 0.662 MeV. Through a series of calculations we have determined the lineal attenuation coefficient for photons from 10{sup -3} to 10{sup -5} MeV and the measured coefficient was compared with the one calculated. (Author)

Thermodynamic study of quercetin and rutin mixtures with alcohols

Science.gov (United States)

Szymczyk, Katarzyna; Taraba, Anna

2018-04-01

The paper presents interactions between quercetin (3,3‧,4‧,5,7-pentahydroxyflavone) and its glycoside, rutin with short chain alcohols, methanol, ethanol and 1-propanol studied by the surface tension measurements. An attempt was made to investigate the effect of flavonoid and alcohol concentrations as well as temperature on the thermodynamic parameters of alcohols adsorption at the water-air interface that is the standard free enthalpy, enthalpy and entropy of adsorption as well as the infinite dilution activity coefficient. The obtained results show that the mixtures of quercetin with methanol and rutin with ethanol are characterized by the best adsorption properties but all studied systems become less structured after adsorption.

Evaluation of the effect of quercetin treatment on CYP2C9 enzyme activity of diclofenac in healthy human volunteers.

Science.gov (United States)

Bedada, Satish Kumar; Neerati, Prasad

2018-02-01

The purpose of present study was to evaluate the effect of quercetin on pharmacokinetics of diclofenac sodium (DIC) in healthy volunteers. The open-label, 2 period, sequential study was conducted in 12 healthy volunteers. DIC 100 mg was administered during control and after quercetin phases. Quercetin 500 mg was administered twice daily for 10 days during quercetin phase. Treatment with quercetin significantly enhanced maximum plasma concentration (C max ) , area under the curve (AUC 0-∞ ), and half life, while significantly decreased elimination rate constant (k el ) and apparent oral clearance (CL/F) of DIC compared with control. On the other hand, C max and AUC 0-∞ of 4-hydroxydiclofenac (4-OHDIC) were decreased after quercetin treatment. In addition, geometric mean ratios and 90% confidence intervals for C max and AUC 0-∞ of DIC and 4-OHDIC were both out of the no-effect limits of 0.80-1.25, which indicates a significant pharmacokinetic interaction between quercetin and DIC. Furthermore, quercetin treatment significantly decreased metabolic ratios of C max and AUC 0-∞ suggesting that reduced formation of DIC to 4-OHDIC. The results suggest that quercetin might have inhibited CYP2C9-mediated metabolism of DIC. Accordingly, caution should be taken when quercetin is used in combination with therapeutic drugs metabolized by CYP2C9, and dose adjustment of CYP2C9 substrates may be necessary. Copyright © 2017 John Wiley & Sons, Ltd.

Effect of quercetin on metallothionein, nitric oxide synthases and cyclooxygenase-2 expression on experimental chronic cadmium nephrotoxicity in rats

International Nuclear Information System (INIS)

Morales, Ana I.; Vicente-Sanchez, Cesar; Jerkic, Mirjana; Santiago, Jose M.; Sanchez-Gonzalez, Penelope D.; Perez-Barriocanal, Fernando; Lopez-Novoa, Jose M.

2006-01-01

Inflammation can play a key role in Cd-induced dysfunctions. Quercetin is a potent oxygen free radical scavenger and a metal chelator. Our aim was to study the effect of quercetin on Cd-induced kidney damage and metallothionein expression. The study was performed in Wistar rats that were administered during 9 weeks with either cadmium (1.2 mg Cd/kg/day, s.c.), quercetin (50 mg/kg/day, i.p.) or cadmium + quercetin. Renal toxicity was evaluated by measuring blood urea nitrogen concentration and urinary excretion of enzymes marker of tubular damage. Endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) renal expression were assessed by Western blot. Renal expression of metallothionein 1 and 2 (MT-1, MT-2) and eNOS mRNA was assessed by Northern blot. Our data demonstrated that Cd-induced renal toxicity was markedly reduced in rats that also received quercetin. MT-1 and MT-2 mRNA levels in kidney were substantially increased during treatment with Cd, being even higher when the animals received Cd and quercetin. Renal eNOS expression was significantly higher in rats receiving Cd and quercetin than in animals receiving Cd alone or in control rats. In the group that received Cd, COX-2 and iNOS expression was markedly higher than in control rats. In the group Cd + quercetin, no changes in COX-2 and iNOS expression were observed compared with the control group. Our results demonstrate that quercetin treatment prevents Cd-induced overexpression of iNOS and COX-2, and increases MT expression. These effects can explain the protection by quercetin of Cd-induced nephrotoxicity

The influence of the flavonoid quercetin on the interaction of propranolol with human serum albumin: Experimental and theoretical approaches

Energy Technology Data Exchange (ETDEWEB)

Mohseni-Shahri, Fatemeh S., E-mail: fmohsenishahri@gmail.com [Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad (Iran, Islamic Republic of); Housaindokht, Mohammad R. [Department of Chemistry, Faculty of Science, Ferdowsi University of Mashhad, Mashhad (Iran, Islamic Republic of); Bozorgmehr, Mohammad R. [Department of Chemistry, Mashhad Branch, Islamic Azad University, Mashhad (Iran, Islamic Republic of); Moosavi-Movahedi, Ali A. [Institute of Biochemistry and Biophysics, University of Tehran, Tehran (Iran, Islamic Republic of)

2014-10-15

The binding of propranolol (PROP) to human serum albumin (HSA) in the absence and presence of quercetin (QUER) in aqueous solution was investigated by multiple techniques. The presence of quercetin (QUER) increased binding constant of propranolol (PROP) with HSA. Fluorescence spectroscopy showed that quercetin (QUER) could quench the HSA fluorescence spectra. The results of synchronous fluorescence, resonance light scattering (RLS) and three-dimensional fluorescence spectra showed that propranolol (PROP) and quercetin (QUER) would alter the micro-environment around tryptophan (Trp) and tyrosine (Tyr) residues. According molecular dynamics (MD) simulation results suggested that these ligands can interact with the protein, with affecting the secondary structure of HSA and with a modification of its tertiary structure. Molecular docking studies showed that the affinity and binding site of each of the ligands to HSA altered in the presence of the other. All above results may have related consequence in rationalizing the interferences of ordinary food to cardiac dysrhythmias treatments. - Highlights: • The presence of quercetin increased binding constant of propranolol with HSA. • Quercetin quenched the fluorescence of HSA through a static quenching mechanism. • The binding of propranolol and quercetin with HSA induced partial unfolding. • The tertiary structure of HSA changed after ligand binding. • After the binding of quercetin, the helix content of HSA declined.

Ligustrazine attenuates oxidative stress-induced activation of hepatic stellate cells by interrupting platelet-derived growth factor-β receptor-mediated ERK and p38 pathways

International Nuclear Information System (INIS)

Zhang, Feng; Ni, Chunyan; Kong, Desong; Zhang, Xiaoping; Zhu, Xiaojing; Chen, Li; Lu, Yin; Zheng, Shizhong

2012-01-01

Hepatic fibrosis represents a frequent event following chronic insult to trigger wound healing reactions with accumulation of extracellular matrix (ECM) in the liver. Activation of hepatic stellate cells (HSCs) is the pivotal event during liver fibrogenesis. Compelling evidence indicates that oxidative stress is concomitant with liver fibrosis irrespective of the underlying etiology. Natural antioxidant ligustrazine exhibits potent antifibrotic activities, but the mechanisms are poorly understood. Our studies were to investigate the ligustrazine effects on HSC activation stimulated by hydrogen peroxide (H 2 O 2 ), an in vitro model mimicking the oxidative stress in liver fibrogenesis, and to elucidate the possible mechanisms. Our results demonstrated that H 2 O 2 at 5 μM significantly stimulated HSC proliferation and expression of marker genes of HSC activation; whereas ligustrazine dose-dependently suppressed proliferation and induced apoptosis in H 2 O 2 -activated HSCs, and attenuated expression of fibrotic marker genes. Mechanistic investigations revealed that ligustrazine reduced platelet-derived growth factor-β receptor (PDGF-βR) expression and blocked the phosphorylation of extracellular regulated protein kinase (ERK) and p38 kinase, two downstream effectors of PDGF-βR. Further molecular evidence suggested that ligustrazine interruption of ERK and p38 pathways was dependent on the blockade of PDGF-βR and might be involved in ligustrazine reduction of fibrotic marker gene expression under H 2 O 2 stimulation. Furthermore, ligustrazine modulated some proteins critical for HSC activation and ECM homeostasis in H 2 O 2 -stimulated HSCs. These data collectively indicated that ligustrazine could attenuate HSC activation caused by oxidative stress, providing novel insights into ligustrazine as a therapeutic option for hepatic fibrosis. Highlights: ► Ligustrazine inhibits oxidative stress-induced HSC activation. ► Ligustrazine reduces fibrotic marker genes

Edaravone prevents lung injury induced by hepatic ischemia-reperfusion.

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Uchiyama, Munehito; Tojo, Kentaro; Yazawa, Takuya; Ota, Shuhei; Goto, Takahisa; Kurahashi, Kiyoyasu

2015-04-01

Lung injury is a major clinical concern after hepatic ischemia-reperfusion (I/R), due to the production of reactive oxygen species in the reperfused liver. We investigated the efficacy of edaravone, a potent free-radical scavenger, for attenuating lung injury after hepatic I/R. Adult male Sprague-Dawley rats were assigned to sham + normal saline (NS), I/R + NS, or I/R + edaravone group. Rats in the I/R groups were subjected to 90 min of partial hepatic I/R. Five minutes before reperfusion, 3 mg/kg edaravone was administered to the I/R + edaravone group. After 6 h of reperfusion, we evaluated lung histopathology and wet-to-dry ratio. We also measured malondialdehyde (MDA), an indicator of oxidative stress, in the liver and the lung, as well as cytokine messenger RNA expressions in the reperfused liver and plasma cytokine concentrations. Histopathology revealed lung damages after 6 h reperfusion of partial ischemic liver. Moreover, a significant increase in lung wet-to-dry ratio was observed. MDA concentration increased in the reperfused liver, but not in the lungs. Edaravone administration attenuated the lung injury and the increase of MDA in the reperfused liver. Edaravone also suppressed the reperfusion-induced increase of interleukin-6 messenger RNA expressions in the liver and plasma interleukin-6 concentrations. Edaravone administration before reperfusion of the ischemic liver attenuates oxidative stress in the reperfused liver and the subsequent lung injury. Edaravone may be beneficial for preventing lung injury induced by hepatic I/R. Copyright © 2015 Elsevier Inc. All rights reserved.

The Best Extraction Technique for Kaempferol and Quercetin Isolation from Guava Leaves (Psidium guajava)

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Batubara, I.; Suparto, I. H.; Wulandari, N. S.

2017-03-01

Guava leaves contain various compounds that have biological activity such as kaempferol and quercetin as anticancer. Twelve extraction techniques were performed to obtain the best extraction technique to isolate kaempferol and quercetin from the guava leaves. Toxicity of extracts was tested against Artemia salina larvae. All extracts were toxic (LC50 value less than 1000 ppm) except extract of direct soxhletation on guava leaves, and extract of sonication and soxhletation using n-hexane. The extract with high content of total phenols and total flavonoids, low content of tannins, intense color of spot on thin layer chromatogram was selected for high performance liquid chromatography analysis. Direct sonication of guava leaves was chosen as the best extraction technique with kampferol and quercetin content of 0.02% and 2.15%, respectively. In addition to high content of kaempferol and quercetin, direct sonication was chosen due to the shortest extraction time, lesser impurities and high toxicity.

Fast-dissolving core-shell composite microparticles of quercetin fabricated using a coaxial electrospray process.

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Chen Li

Full Text Available This study reports on novel fast-dissolving core-shell composite microparticles of quercetin fabricated using coaxial electrospraying. A PVC-coated concentric spinneret was developed to conduct the electrospray process. A series of analyses were undertaken to characterize the resultant particles in terms of their morphology, the physical form of their components, and their functional performance. Scanning and transmission electron microscopies revealed that the microparticles had spherical morphologies with clear core-shell structure visible. Differential scanning calorimetry and X-ray diffraction verified that the quercetin active ingredient in the core and sucralose and sodium dodecyl sulfate (SDS excipients in the shell existed in the amorphous state. This is believed to be a result of second-order interactions between the components; these could be observed by Fourier transform infrared spectroscopy. In vitro dissolution and permeation studies showed that the microparticles rapidly released the incorporated quercetin within one minute, and had permeation rates across the sublingual mucosa around 10 times faster than raw quercetin.

Prophylactic Hepatitis E Vaccine.

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Zhang, Jun; Zhao, Qinjian; Xia, Ningshao

2016-01-01

Hepatitis E has been increasingly recognized as an underestimated global disease burden in recent years. Subpopulations with more serious infection-associated damage or death include pregnant women, patients with basic liver diseases, and elderly persons. Vaccine would be the most effective means for prevention of HEV infection. The lack of an efficient cell culture system for HEV makes the development of classic inactive or attenuated vaccine infeasible. Hence, the recombinant vaccine approaches are explored deeply. The neutralizing sites are located almost exclusively in the capsid protein, pORF2, of the virion. Based on pORF2, many vaccine candidates showed potential of protecting primate animals; two of them were tested in human and evidenced to be well tolerated in adults and highly efficacious in preventing hepatitis E. The world's first hepatitis E vaccine, Hecolin ® (HEV 239 vaccine), was licensed in China and launched in 2012.

Can hydrogen peroxide and quercetin improve production of ...

African Journals Online (AJOL)

SAM

2014-07-09

Jul 9, 2014 ... racting with other molecules or plant hormones) effects. (Corrêa and Fett-Neto, .... after planting, the F interaction (time x quercetin x IBA) was not significantly ..... development and stress responses (Moschou et al.,. 2013).

Rapid dimerization of quercetin through an oxidative mechanism in the presence of serum albumin decreases its ability to induce cytotoxicity in MDA-MB-231 cells

Energy Technology Data Exchange (ETDEWEB)

Pham, Anh; Bortolazzo, Anthony [Department of Biological Sciences, San Jose State University, San Jose, CA 95192-0100 (United States); White, J. Brandon, E-mail: Brandon.White@sjsu.edu [Department of Biological Sciences, San Jose State University, San Jose, CA 95192-0100 (United States)

2012-10-19

Highlights: Black-Right-Pointing-Pointer Quercetin cannot be detected intracellularly despite killing MDA-MB-231 cells. Black-Right-Pointing-Pointer Quercetin forms a heterodimer through oxidation in media with serum. Black-Right-Pointing-Pointer The quercetin heterodimer does not kill MDA-MB-231 cells. Black-Right-Pointing-Pointer Ascorbic acid stabilizes quercetin increasing cell death in quercetin treated cells. Black-Right-Pointing-Pointer Quercetin, and not a modified form, is responsible for apoptosis and cell death. -- Abstract: Quercetin is a member of the flavonoid family and has been previously shown to have a variety of anti-cancer activities. We and others have reported anti-proliferation, cell cycle arrest, and induction of apoptosis of cancer cells after treatment with quercetin. Quercetin has also been shown to undergo oxidation. However, it is unclear if quercetin or one of its oxidized forms is responsible for cell death. Here we report that quercetin rapidly oxidized in cell culture media to form a dimer. The quercetin dimer is identical to a dimer that is naturally produced by onions. The quercetin dimer and quercetin-3-O-glucopyranoside are unable to cross the cell membrane and do not kill MDA-MB-231 cells. Finally, supplementing the media with ascorbic acid increases quercetin's ability to induce cell death probably by reduction oxidative dimerization. Our results suggest that an unmodified quercetin is the compound that elicits cell death.

Diagnostic accuracy of a noninvasive hepatic ultrasound score for non-alcoholic fatty liver disease (NAFLD in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil

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Alessandra Carvalho Goulart

Full Text Available CONTEXT AND OBJECTIVE: Noninvasive strategies for evaluating non-alcoholic fatty liver disease (NAFLD have been investigated over the last few decades. Our aim was to evaluate the diagnostic accuracy of a new hepatic ultrasound score for NAFLD in the ELSA-Brasil study. DESIGN AND SETTINGS: Diagnostic accuracy study conducted in the ELSA center, in the hospital of a public university. METHODS: Among the 15,105 participants of the ELSA study who were evaluated for NAFLD, 195 individuals were included in this sub-study. Hepatic ultrasound was performed (deep beam attenuation, hepatorenal index and anteroposterior diameter of the right hepatic lobe and compared with the hepatic steatosis findings from 64-channel high-resolution computed tomography (CT. We also evaluated two clinical indices relating to NAFLD: the fatty liver index (FLI and the hepatic steatosis index (HSI. RESULTS: Among the 195 participants, the NAFLD frequency was 34.4%. High body mass index, high waist circumference, diabetes and hypertriglyceridemia were associated with high hepatic attenuation and large anteroposterior diameter of the right hepatic lobe, but not with the hepatorenal index. The hepatic ultrasound score, based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe, presented the best performance for NAFLD screening at the cutoff point ≥ 1 point; sensitivity: 85.1%; specificity: 73.4%; accuracy: 79.3%; and area under the curve (AUC 0.85; 95% confidence interval, CI: 0.78-0.91]. FLI and HSI presented lower performance (AUC 0.76; 95% CI: 0.69-0.83 than CT. CONCLUSION: The hepatic ultrasound score based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe has good reproducibility and accuracy for NAFLD screening.

Diagnostic accuracy of a noninvasive hepatic ultrasound score for non-alcoholic fatty liver disease (NAFLD) in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

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Goulart, Alessandra Carvalho; Oliveira, Ilka Regina Souza de; Alencar, Airlane Pereira; Santos, Maira Solange Camara dos; Santos, Itamar Souza; Martines, Brenda Margatho Ramos; Meireles, Danilo Peron; Martines, João Augusto dos Santos; Misciagna, Giovanni; Benseñor, Isabela Martins; Lotufo, Paulo Andrade

2015-01-01

Noninvasive strategies for evaluating non-alcoholic fatty liver disease (NAFLD) have been investigated over the last few decades. Our aim was to evaluate the diagnostic accuracy of a new hepatic ultrasound score for NAFLD in the ELSA-Brasil study. Diagnostic accuracy study conducted in the ELSA center, in the hospital of a public university. Among the 15,105 participants of the ELSA study who were evaluated for NAFLD, 195 individuals were included in this sub-study. Hepatic ultrasound was performed (deep beam attenuation, hepatorenal index and anteroposterior diameter of the right hepatic lobe) and compared with the hepatic steatosis findings from 64-channel high-resolution computed tomography (CT). We also evaluated two clinical indices relating to NAFLD: the fatty liver index (FLI) and the hepatic steatosis index (HSI). Among the 195 participants, the NAFLD frequency was 34.4%. High body mass index, high waist circumference, diabetes and hypertriglyceridemia were associated with high hepatic attenuation and large anteroposterior diameter of the right hepatic lobe, but not with the hepatorenal index. The hepatic ultrasound score, based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe, presented the best performance for NAFLD screening at the cutoff point ≥ 1 point; sensitivity: 85.1%; specificity: 73.4%; accuracy: 79.3%; and area under the curve (AUC 0.85; 95% confidence interval, CI: 0.78-0.91)]. FLI and HSI presented lower performance (AUC 0.76; 95% CI: 0.69-0.83) than CT. The hepatic ultrasound score based on hepatic attenuation and the anteroposterior diameter of the right hepatic lobe has good reproducibility and accuracy for NAFLD screening.

HPLC identification and determination of myricetin, quercetin, kaempferol and total flavonoids in herbal drugs

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Svetlana Kulevanova

2003-05-01

Full Text Available A new and rapid HPLC method for identification and determination of myricetin, quercetin, kaempferol and total flavonoids in ten herbal drugs of Macedonian origin is presented. Preparation of samples (Uvae ursi folim, Pruni spinosae flos, Sambuci flos, Betulae folim, Primulae flos, Herniariae herba, Centaurii herba, Tiliae flos, Robiniae pseudoacaciae flos, Bursae pastoris herba included hydrolysis of glycosides and extraction of total aglycones with ethyl acetate. HPLC analysis with UV-diode array detection was carried out on RP C18 column, using 5% acetic acid and acetonitrile in agradient elution mode and column temperature of 30 o C. The monitoring of the elution is performed in the whole UV-range and the acquisition of data for quantitative analysis at 367 nm. Screening of the extracts showed presence of quercetin in nine, kaempferol in seven and myricetin in only one sample. The quantitative analysis showed that the content of quercetin ranged from 0.026-0.506 % (m/m, while for kaempferol it was from traces to 1.246 %. Uvaeursi folium and Pruni spinosae flos were rich in content of quercetin (0.482 % and 0.506 %, respectively, while Pruni spinosae flos and Robiniae pseudoaccaciae flos contained the highest amounts of kaempferol (1.246 % and 0.892 %, respectively. Myricetin was identified and determined only in Betulae folium (0.102 %. The content of total flavonoids in the investigated samples expressed in terms of quercetin ranged from 0.040 to 1.680 %. The proposed HPLC method is convenient for use in routine analysis of myricetin, quercetin and kaempferol, as well as for estimation of total flavonoids content in herbal drugs.

Psidium guajava Linn. leaf extract affects hepatic glucose transporter-2 to attenuate early onset of insulin resistance consequent to high fructose intake: An experimental study

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Mathur, R.; Dutta, Shagun; Velpandian, T.; Mathur, S.R.

2015-01-01

Background: Insulin resistance (IR) is amalgam of pathologies like altered glucos metabolism, dyslipidemia, impaired glucose tolerance, non-alcoholic fatty liver disease, and associated with type-II diabetes and cardiometabolic diseases. One of the reasons leading to its increased and early incidence is understood to be a high intake of processed fructose containing foods and beverages by individuals, especially, during critical developmental years. Objective: To investigate the preventive potential of aqueous extract of Psidium guajava leaves (PG) against metabolic pathologies, vis-à-vis, IR, dyslipidemia, hyperleptinemia and hypertension, due to excess fructose intake initiated during developmental years. Materials and Methods: Post-weaning (4 weeks old) male rats were provided fructose (15%) as drinking solution, ad libitum, for 8 weeks and assessed for food and water/fructose intake, body weight, fasting blood sugar, mean arterial pressure, lipid biochemistry, endocrinal (insulin, leptin), histopathological (fatty liver) and immunohistochemical (hepatic glucose transporter [GLUT2]) parameters. Parallel treatment groups were administered PG in doses of 250 and 500 mg/kg/d, po × 8 weeks and assessed for same parameters. Using extensive liquid chromatography-mass spectrometry protocols, PG was analyzed for the presence of phytoconstituents like Myrecetin, Luteolin, Kaempferol and Guavanoic acid and validated to contain Quercetin up to 9.9%w/w. Results: High fructose intake raised circulating levels of insulin and leptin and hepatic GLUT2 expression to promote IR, dyslipidemia, and hypertension that were favorably re-set with PG. Although PG is known for its beneficial role in diabetes mellitus, for the first time we report its potential in the management of lifelong pathologies arising from high fructose intake initiated during developmental years. PMID:25829790

Investigation of antineoplastic activity of chewing tablets based on dry oat extract and quercetin

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Ярослав Ростиславович Андрійчук

2015-07-01

Full Text Available One of the main goals of domestic pharmaceutical science is development of new medicines. Thus, new tablet drug was created based on dry oat extract and quercetin. Investigation of antineoplastic activity was performed. Antineoplastic activity of investigational drug based on dry oat extract and quercetin was experimentally proved.

Study of the radioprotective effect of flavonoid quercetin on human lymphocytes

International Nuclear Information System (INIS)

Siqueira, Williams Nascimento de

2013-01-01

Ionizing radiation has been used in various fields of study, as medicine, industry, energy production, surgical materials sterilization, preservation and sterilization of foods, among others. These radiations may be responsible for adverse effects at molecular level in living organisms, where most important damage occurs in deoxyribonucleic acid molecule, DNA. These harmful effects caused by radiation highlights the importance of acquiring knowledge about radioprotector substances because they can act as protector of living tissue of those effects. In this research was investigated the possible radioprotective effect 'in vitro' of the flavonoid quercetin in human lymphocytes exposed to gamma radiation. At first, test was performed to evaluate the antioxidant activity of quercetin by capturing DPPH free radical molecules. Then, it was collected peripheral blood of volunteers donors. Then the samples were irradiated from linear accelerator (Siemens Primus - energy of 6 MeV and dose rate of 200 cGy/min from IMIP-PE). After samples irradiation, lymphocytes were isolated from whole blood and then the culture was carried out to obtain lymphocyte in metaphases and subsequent, analysis of chromosomal abnormalities were done at optical microscope. Statistical analysis was used Student 't' test. The results showed that quercetin at a concentration of 37.5 μM presented radioprotective against damage from gamma radiation on human lymphocytes in vitro. Have been also observed that the irradiated lymphocytes showed morphologically unchanged after undergoing the presence of the flavonoid quercetin. (author)

Rapid dimerization of quercetin through an oxidative mechanism in the presence of serum albumin decreases its ability to induce cytotoxicity in MDA-MB-231 cells

International Nuclear Information System (INIS)

Pham, Anh; Bortolazzo, Anthony; White, J. Brandon

2012-01-01

Highlights: ► Quercetin cannot be detected intracellularly despite killing MDA-MB-231 cells. ► Quercetin forms a heterodimer through oxidation in media with serum. ► The quercetin heterodimer does not kill MDA-MB-231 cells. ► Ascorbic acid stabilizes quercetin increasing cell death in quercetin treated cells. ► Quercetin, and not a modified form, is responsible for apoptosis and cell death. -- Abstract: Quercetin is a member of the flavonoid family and has been previously shown to have a variety of anti-cancer activities. We and others have reported anti-proliferation, cell cycle arrest, and induction of apoptosis of cancer cells after treatment with quercetin. Quercetin has also been shown to undergo oxidation. However, it is unclear if quercetin or one of its oxidized forms is responsible for cell death. Here we report that quercetin rapidly oxidized in cell culture media to form a dimer. The quercetin dimer is identical to a dimer that is naturally produced by onions. The quercetin dimer and quercetin-3-O-glucopyranoside are unable to cross the cell membrane and do not kill MDA-MB-231 cells. Finally, supplementing the media with ascorbic acid increases quercetin’s ability to induce cell death probably by reduction oxidative dimerization. Our results suggest that an unmodified quercetin is the compound that elicits cell death.

Improvement of memory recall by quercetin in rodent contextual fear conditioning and human early-stage Alzheimer's disease patients.

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Nakagawa, Toshiyuki; Itoh, Masanori; Ohta, Kazunori; Hayashi, Yuichi; Hayakawa, Miki; Yamada, Yasushi; Akanabe, Hiroshi; Chikaishi, Tokio; Nakagawa, Kiyomi; Itoh, Yoshinori; Muro, Takato; Yanagida, Daisuke; Nakabayashi, Ryo; Mori, Tetsuya; Saito, Kazuki; Ohzawa, Kaori; Suzuki, Chihiro; Li, Shimo; Ueda, Masashi; Wang, Miao-Xing; Nishida, Emika; Islam, Saiful; Tana; Kobori, Masuko; Inuzuka, Takashi

2016-06-15

Patients with Alzheimer's disease (AD) experience a wide array of cognitive deficits, which typically include the impairment of explicit memory. In previous studies, the authors reported that a flavonoid, quercetin, reduces the expression of ATF4 and delays memory deterioration in an early-stage AD mouse model. In the present study, the effects of long-term quercetin intake on memory recall were assessed using contextual fear conditioning in aged wild-type mice. In addition, the present study examined whether memory recall was affected by the intake of quercetin-rich onion (a new cultivar of hybrid onion 'Quergold') powder in early-stage AD patients. In-vivo analysis indicated that memory recall was enhanced in aged mice fed a quercetin-containing diet. Memory recall in early-stage AD patients, determined using the Revised Hasegawa Dementia Scale, was significantly improved by the intake of quercetin-rich onion (Quergold) powder for 4 weeks compared with the intake of control onion ('Mashiro' white onion) powder. These results indicate that quercetin might influence memory recall.

Еvaluation of biocompatibility and antioxidant efficiency of chitosan-alginate nanoparticles loaded with quercetin.

Science.gov (United States)

Aluani, Denitsa; Tzankova, Virginia; Kondeva-Burdina, Magdalena; Yordanov, Yordan; Nikolova, Elena; Odzhakov, Feodor; Apostolov, Alexandar; Markova, Tzvetanka; Yoncheva, Krassimira

2017-10-01

The present study deals with development and evaluation of the safety profile of chitosan/alginate nanoparticles as a platform for delivery of a natural antioxidant quercetin. The nanoparticles were prepared by varying the ratios between both biopolymers giving different size and charge of the formulations. The biocompatibility was explored in vitro in cells from different origin: cultivated HepG2 cells, isolated primary rat hepatocytes, isolated murine spleen lymphocytes and macrophages. In vivo toxicological evaluation was performed after repeated 14-day oral administration to rats. The study revealed that chitosan/alginate nanoparticles did not change body weight, the relative weight of rat livers, liver histology, hematology and biochemical parameters. The protective effects of quercetin-loaded nanoparticles were investigated in the models of iron/ascorbic acid (Fe 2+ /AA) induced lipid peroxidation in microsomes and tert-butyl hydroperoxide oxidative stress in isolated rat hepatocytes. Interesting finding was that the empty chitosan/alginate nanoparticles possessed protective activity themselves. The antioxidant effects of quercetin loaded into the nanoparticles formulated with higher concentration of chitosan were superior compared to quercetin encapsulated in nanoparticles with higher amount of sodium alginate. In conclusion, chitosan/alginate nanoparticles can be considered appropriate carrier for quercetin, combining safety profile and improved protective activity of the encapsulated antioxidant. Copyright © 2017 Elsevier B.V. All rights reserved.

The effects of quercetin on microRNA and inflammatory gene expression in lipopolysaccharide-stimulated bovine neutrophils

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Phongsakorn Chuammitri

2017-04-01

Full Text Available Aim: To investigate gene expression of microRNA (miRNA milieus (MIRLET7E, MIR17, MIR24-2, MIR146A, and MIR181C, inflammatory cytokine genes (interleukin 1β [IL1B], IL6, CXCL8, and tumor necrosis factor [TNF], and the pathogen receptor toll-like receptor (TLR4 in bovine neutrophils under quercetin supplementation. Materials and Methods: Isolated bovine neutrophils were incubated with bacterial lipopolysaccharide under quercetin treatment or left untreated. Real-time polymerase chain reaction was performed to determine the expression of the miRNAs and messenger RNA (mRNA transcripts in neutrophils. Results: Quercetin-treated neutrophils exhibited a remarkable suppression in MIR24-2, MIR146A, and MIR181C expression. Similarly, mRNA expression of IL1B, IL6, CXCL8, TLR4, and TNF genes noticeably declined in the quercetin group. Many proinflammatory genes (IL1B, IL6, and CXCL8 and the pathogen receptor TLR4 had a negative correlation with MIR146A and MIR181C as revealed by Pearson correlation. Conclusion: Interaction between cognate mRNAs and miRNAs under quercetin supplementation can be summarized as a positive or negative correlation. This finding may help understand the effects of quercetin either on miRNA or gene expression during inflammation, especially as a potentially applicable indicator in bovine mastitis.

Quercetin decrease somatic cells count in mastitis of dairy cows.

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Burmańczuk, Artur; Hola, Piotr; Milczak, Andrzej; Piech, Tomasz; Kowalski, Cezary; Wojciechowska, Beata; Grabowski, Tomasz

2018-04-01

Quercetin is a dietary flavonoid which has an effect on inflammation, angiogenesis and vascular inflammation. In several other flavonoids (e.g. kaempferol, astragalin, alpinetin, baicalein, indirubin), anti-inflammatory mechanism was proven by using mice mastitis model. The aim of the current study was pilot analysis of quercetin tolerability and its impact on somatic cells count (SCC) after multiple intramammary treatment on dairy cows with clinical mastitis. Based on SCC and clinical investigation, 9 dairy cows with clinical mastitis of one quarter were selected for the pilot study. Baseline analysis (hematology, TNFα, SCC) was performed every 24h among all cows three days before the first dose (B1-B3). After the baseline monitoring (B1-B3) eight days treatment (D1-D8) was performed with a high and low dose. Selected blood parameters were analyzed. Starting from D1 to D8, a decrease of SCC in relation to baseline was characterized by declining trend. The presented results allowed the confirmation of the significant influence of quercetin on the reduction of SCC in mastitis in dairy cows after 8days of therapy. Copyright © 2018. Published by Elsevier Ltd.

Genetic Polymorphisms in Organic Cation Transporter 1 Attenuates Hepatic Metformin Exposure in Humans

DEFF Research Database (Denmark)

Sundelin, E. I.O.; Gormsen, Lars C; Jensen, J. B.

2017-01-01

the transporter protein OCT1, affect the hepatic distribution of metformin in humans. We performed noninvasive 11C-metformin positron emission tomography (PET)/computed tomography (CT) to determine hepatic exposure in 12 subjects genotyped for variants in SLC22A1. Hepatic distribution of metformin...... was significantly reduced after oral intake in carriers of M420del and R61C variants in SLC22A1 without being associated with changes in circulating levels of metformin. Our data show that genetic polymorphisms in transporter proteins cause variation in hepatic exposure to metformin, and it demonstrates......Metformin has been used successfully to treat type 2 diabetes for decades. However, the efficacy of the drug varies considerably from patient to patient and this may in part be due to its pharmacokinetic properties. The aim of this study was to examine if common polymorphisms in SLC22A1, encoding...

Quercetin Inhibits Pulmonary Arterial Endothelial Cell Transdifferentiation Possibly by Akt and Erk1/2 Pathways

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Shian Huang

2017-01-01

Full Text Available This study aimed to investigate the effects and mechanisms of quercetin on pulmonary arterial endothelial cell (PAEC transdifferentiation into smooth muscle-like cells. TGF-β1-induced PAEC transdifferentiation models were applied to evaluate the pharmacological actions of quercetin. PAEC proliferation was detected with CCK8 method and BurdU immunocytochemistry. Meanwhile, the identification and transdifferentiation of PAECs were determined by FVIII immunofluorescence staining and α-SMA protein expression. The related mechanism was elucidated based on the levels of Akt and Erk1/2 signal pathways. As a result, quercetin effectively inhibited the TGF-β1-induced proliferation and transdifferentiation of the PAECs and activation of Akt/Erk1/2 cascade in the cells. In conclusion, quercetin is demonstrated to be effective for pulmonary arterial hypertension (PAH probably by inhibiting endothelial transdifferentiation possibly via modulating Akt and Erk1/2 expressions.

Ingestion of onion soup high in quercetin inhibits platelet aggregation and essential components of the collagen-stimulated platelet activation pathway in man: a pilot study.

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Hubbard, Gary P; Wolffram, Siegfried; de Vos, Ric; Bovy, Arnaud; Gibbins, Jonathan M; Lovegrove, Julie A

2006-09-01

Epidemiological data suggest that those who consume a diet rich in quercetin-containing foods may have a reduced risk of CVD. Furthermore, in vitro and ex vivo studies have observed the inhibition of collagen-induced platelet activation by quercetin. The aim of the present study was to investigate the possible inhibitory effects of quercetin ingestion from a dietary source on collagen-stimulated platelet aggregation and signalling. A double-blind randomised cross-over pilot study was undertaken. Subjects ingested a soup containing either a high or a low amount of quercetin. Plasma quercetin concentrations and platelet aggregation and signalling were assessed after soup ingestion. The high-quercetin soup contained 69 mg total quercetin compared with the low-quercetin soup containing 5 mg total quercetin. Plasma quercetin concentrations were significantly higher after high-quercetin soup ingestion than after low-quercetin soup ingestion and peaked at 2.59 (sem 0.42) mumol/l. Collagen-stimulated (0.5 mug/ml) platelet aggregation was inhibited after ingestion of the high-quercetin soup in a time-dependent manner. Collagen-stimulated tyrosine phosphorylation of a key component of the collagen-signalling pathway via glycoprotein VI, Syk, was significantly inhibited by ingestion of the high-quercetin soup. The inhibition of Syk tyrosine phosphorylation was correlated with the area under the curve for the high-quercetin plasma profile. In conclusion, the ingestion of quercetin from a dietary source of onion soup could inhibit some aspects of collagen-stimulated platelet aggregation and signalling ex vivo. This further substantiates the epidemiological data suggesting that those who preferentially consume high amounts of quercetin-containing foods have a reduced risk of thrombosis and potential CVD risk.

Analysis of the association between periportal low attenuation, as seen on CT, after blunt abdominal trauma, and elevated central venous pressure

International Nuclear Information System (INIS)

Lee, Jae Hung; Lee, Hyeon Kyeong; Lee, Chae Kyeong; Ku, Kwan Min; Lee, Sung Woo; Kim, Miu Woon; Ahn, Woo Sub; Yoon, Ji Young

1999-01-01

To assess the causes of periportal low attenuation, as seen on CT, in patients with blunt abdominal trauma. From among 812 patients who underwent abdominal CT after blunt abdominal trauma, we retrospectively analysed the findings in 124 with evidence of periportal low attenuation. Among these, hepatic injury was noted in only 87. The presence or absence, and extent of hepatic injury, and of periportal low attenuation, as seen on CT, were carefully evaluated. In each case, the ratio of the transverse diameter of the inferior vena cava(IVC) to the aorta at the level of the right adrenal gland provided an indirect measurement of central venous pressure ; for control purposes, the ratio was also obtained in 21 non-traumatic patients with no abnormal abdominal CT findings. Of the 87 patients with hepatic injury, 46 showed no periportal low attenuation, and average value of the ratio between the IVC and aorta was 1.16±0.12, while the remaining 41 patients showed periportal low attenuation with a ratio of 1.51±0.21(p<0.05). In the 37 patients with periportal low attenuation but no evidence of concomitant hepatic injury, the average ratio was 1.52±0.25, while in 21 non-traumatic patients it was 1.15±0.16. For resuscitation, all patients had received 0.5-5.0 litre of IV fluid therapy before CT, and at the time of CT, were normotensive. Rapidly elevated central venous pressure following massive IV infusion therapy in patients with blunt abdominal trauma can be one of the causes of periportal low attenuation, as seen on CT

Analysis of the association between periportal low attenuation, as seen on CT, after blunt abdominal trauma, and elevated central venous pressure

Energy Technology Data Exchange (ETDEWEB)

Lee, Jae Hung; Lee, Hyeon Kyeong; Lee, Chae Kyeong; Ku, Kwan Min; Lee, Sung Woo; Kim, Miu Woon; Ahn, Woo Sub [Dongguk Univ. College of Medicine, Pohang (Korea, Republic of); Yoon, Ji Young [Sungkyunkwan Univ. College of Medicine, Seoul (Korea, Republic of)

1999-01-01

To assess the causes of periportal low attenuation, as seen on CT, in patients with blunt abdominal trauma. From among 812 patients who underwent abdominal CT after blunt abdominal trauma, we retrospectively analysed the findings in 124 with evidence of periportal low attenuation. Among these, hepatic injury was noted in only 87. The presence or absence, and extent of hepatic injury, and of periportal low attenuation, as seen on CT, were carefully evaluated. In each case, the ratio of the transverse diameter of the inferior vena cava(IVC) to the aorta at the level of the right adrenal gland provided an indirect measurement of central venous pressure ; for control purposes, the ratio was also obtained in 21 non-traumatic patients with no abnormal abdominal CT findings. Of the 87 patients with hepatic injury, 46 showed no periportal low attenuation, and average value of the ratio between the IVC and aorta was 1.16{+-}0.12, while the remaining 41 patients showed periportal low attenuation with a ratio of 1.51{+-}0.21(p<0.05). In the 37 patients with periportal low attenuation but no evidence of concomitant hepatic injury, the average ratio was 1.52{+-}0.25, while in 21 non-traumatic patients it was 1.15{+-}0.16. For resuscitation, all patients had received 0.5-5.0 litre of IV fluid therapy before CT, and at the time of CT, were normotensive. Rapidly elevated central venous pressure following massive IV infusion therapy in patients with blunt abdominal trauma can be one of the causes of periportal low attenuation, as seen on CT.

Focused radiation hepatitis after Bragg-peak proton therapy for hepatocellular carcinoma: CT findings

International Nuclear Information System (INIS)

Okumura, Toshiyuki; Itai, Yuji; Tsuji, Hiroshi

1994-01-01

Radiation hepatitis is clearly demonstrated by noncontrast and contrast enhanced CT following radiotherapy for liver diseases. Radiation hepatitis is dependent on dose distribution and is usually demonstrated as nonsegmental bandlike lesion after photon therapy. We report a case of focused, oval-shaped radiation hepatitis that was induced by photon therapy. The attenuation difference was localized in a high-dose area caused by Bragg-peak proton therapy. 17 refs., 2 figs

Novel insights into the antiproliferative effects and synergism of quercetin and menadione in human leukemia Jurkat T cells.

Science.gov (United States)

Baran, Irina; Ionescu, Diana; Filippi, Alexandru; Mocanu, Maria Magdalena; Iftime, Adrian; Babes, Ramona; Tofolean, Ioana Teodora; Irimia, Ruxandra; Goicea, Alexandru; Popescu, Valentin; Dimancea, Alexandru; Neagu, Andrei; Ganea, Constanta

2014-07-01

The flavonoid quercetin and menadione (vitamin K3) are known as potent apoptogens in human leukemia Jurkat T cells. We explored some underlying mechanisms and the potential relevance of the combination quercetin-menadione for clinical applications. In acute treatments, quercetin manifested a strong antioxidant character, but induced a transient loss of Δψm, likely mediated by opening of the mitochondrial permeability transition pore. After removal of quercetin, persistent mitochondrial hyperpolarization was generated via stimulation of respiratory Complex I. In contrast, menadione-induced Δψm dissipation was only partially and transiently reversed after menadione removal. Results indicate that Ca(2+) release is a necessary event in quercetin-induced cell death and that the survival response to quercetin is delineated within 1h from exposure. Depending on dose, the two agents exhibited either antagonistic or synergistic effects in reducing clonogenicity of Jurkat cells. 24-h combinatorial regimens at equimolar concentrations of 10-15 μM, which are compatible with a clinically achievable (and safe) scheme, reduced cell viability at efficient rates. Altogether, these findings support the idea that the combination quercetin-menadione could improve the outcome of conventional leukemia therapies, and warrant the utility of additional studies to investigate the therapeutic effects of this combination in different cellular or animal models for leukemia. Copyright © 2014 Elsevier Ltd. All rights reserved.

Inhibitory Effect of High Dose of the Flavonoid Quercetin on Amygdala Electrical Kindling in Rats

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Tourandokht Baluchnejadmojarad

2010-05-01

Full Text Available A B S T R A C T Introduction: Epilepsy is a chronic neurological disorder in which patients experience spontaneous recurrent seizures. Although the most commonly recommended therapy is drug treatment, some patients do not achieve adequate control of their seizures on existing drugs. New medications with novel mechanisms of action are needed to help those patients whose seizures are resistant to currently-available drugs. Therefore, the anti-convulsant effect of a high dose of quercetin was evaluated in amygdala kindling model in male rats. Methods: Rats were divided into sham-operated group, quercetintreated SH, kindled, and quercetin-treated kindled rats. Quercetin was administered i.p. one day before amygdale kindling for 3 weeks (40 mg/kg/day. The parameters seizure stage, AD duration, the latency to the onset of stage 4, and the duration of stage 5 were analyzed. Results: The results showed that quercetin pretreatment causes a lower seizure intensity in treated kindled rats (p<0.05-0.01, a lower after-discharge duration (p<0.05-0.01, and a higher latency to stage IV (p<0.05 as compared to untreated kindled ones. Discussion: To conclude, chronic administration of quercetin inhibits amygdala electrical kindling and more studies are warranted to clarify its underlying mechanisms.

Quercetin modulates activities of Taiwan cobra phospholipase A2 ...

Indian Academy of Sciences (India)

2012-04-25

Apr 25, 2012 ... Quercetin incorporation led to a reduction in PLA2 enzymatic activity and membrane-damaging activity ... membrane physical properties such as membrane fluidity or ..... eral blood mononuclear cells from diabetes patients.

[Correction of the endothelial function damaged by gamma-irradiation with free and liposomal quercetin].

Science.gov (United States)

Kyslova, O V; Sapatyĭ, A L; Kupnovyts'ka, I H; Moĭbenko, O O

2007-01-01

It has been investigation the action of solubil quercetin (corvitin) and quercetin filled liposomes (lipoflavon) on endothelium--dependent r-irradiated isolated rats aortic rings relaxations to acetylcholine. It has been showed, that corvitin addition directly to the buffer solution (0.1 mg/ml) increase endothelium--dependent vascular responses to acetylcholine on 35%, lipoflavon addition--on 25%.

Novel self-nanoemulsifying formulation of quercetin

DEFF Research Database (Denmark)

Jain, Amit K; Thanki, Kaushik; Jain, Sanyog

2014-01-01

. This appreciation was further supported by normalized levels of tumor angiogenesis markers (MMP-2, MMP-9, TNF-α and IL-6). At higher doses (100mg/kg) the pro-oxidant activity was noted and exhibited significantly higher therapeutic anticancer efficacy (~65% tumor suppression) in the same model as compared...... significantly higher therapeutic anticancer efficacy (~65% tumor suppression) was noted in the same model as compared to that of free quercetin (~20%)....

RP-HPLC Analysis of Quercetin in the Extract of Sambong (Blumea balsamifera (L DC Leaves

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Joanna V. Toralba

2015-06-01

Full Text Available Blumea balsamifera (L DC, known in the Philippines as sambong, is an herb valued for its health benef its especially in the management of urolithiasis. Various phytochemicals, including flavonoids such as quercetin, have been determined in sambong leaves. A reversed-phase high-performance liquid chromatographic method (RP-HPLC was developed for the quantitative determination of quercetin in the methanol extract of sambong leaves obtained from Leyte, Cotabato, and Nueva Ecija, Philippines. The methanol extracts of sambong were prepared by maceration followed by rotary evaporation. The solid phase extraction (SPE for the sample cleanup involved the use of a C18 SPE packing, a 0.5-mL sample load (50 mg/mL solution, and elution with 4-mL of 80:20 Methanol:0.5% H3PO4. The HPLC conditions for the determination of quercetin involved the use of a C18 4.6-mm x 250-mm column maintained at 30°C, 254-nm UV detection, and a mobile phase composition of 25 parts methanol and 75 parts mixture of 0.5% H3PO4 and 0.2% triethylamine with a 1 mL/min flow rate in gradient elution. A good linearity at the concentration range of 3.72–124 μg/mL of quercetin standard (r2=0.9989 was observed with the limits of detection (LOD and quantitation (LOQ at 0.68 ng/mL and 2.28 ng/mL, respectively. The intra-day (n=5- and inter-day (n=3 precision values were satisfactory (%RSD <2%. The recovery eff iciency of the SPE sample cleanup step, which was checked by spiking sambong solution with quercetin standard, was 102.41%. The quercetin contents are 0.2337mg, 0.1350mg, and 0.2940mg per gram of the powdered dried leaves of sambong from Nueva Ecija, Cotabato, and Leyte, respectively. This is the f irst report of quercetin content in the leaves of sambong collected from the Philippines.

Soothing and anti-itch effect of quercetin phytosome in human subjects: a single-blind study

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Maramaldi G

2016-02-01

Full Text Available Giada Maramaldi,1 Stefano Togni,1 Ivan Pagin,1 Luca Giacomelli,2 Roberta Cattaneo,3 Roberto Eggenhöffner,2 Samuele E Burastero4 1Indena S.p.A, Milan, 2Department of Surgical Sciences and Integrated Diagnostics, School of Medicine, Genova University, Genoa, 3Abich Srl, Verbania, 4San Raffaele Scientific Institute, Milan, ItalyBackground: We evaluated the ability of quercetin, a natural antioxidant formulated in a specific delivery system, to reduce skin inflammation induced by a variety of stimuli, including UV radiation, stimulation with a histamine solution, or contact with chemical irritants. In particular, we tested the soothing and anti-itch effect of Quercevita®, 1% cream for external use, a formulation characterized by a phospholipids-based delivery system.Patients and methods: The study was a monocentric, single blind trial that enrolled a group of 30 healthy volunteers. The back of each subject was examined to identify four quadrants with no previous skin damage or naevi that were treated in order to induce a controlled and reversible form of skin stress. The areas were treated as follows: no product; Quercevita® 1% cream, 2 mg/cm2; placebo; positive control (a commercially available topical formulation containing 1% dexchlorpheniramine.Results: Only quercetin phospholipids 1% and dexchlorpheniramine 1% achieved a significant reduction in erythema with comparable results: (–10.05% [P=0.00329] for quercetin phospholipids 1% vs –14.05% [P=0.00046] for the positive control. Moreover, quercetin phospholipids 1% and dexchlorpheniramine 1% were both associated with a significant decrease in mean wheal diameter: (–13.25% and –12.23% for dexchlorpheniramine 1%, respectively. Similar findings were reported for the other tested parameters.Conclusion: Quercetin has a skin protective effect against damage caused by a variety of insults, including UV radiation, histamine, or contact with toxic chemical compounds. Indeed, quercetin is able

Antioxidant Effects of the Quercetin in the Jejunal Myenteric Innervation of Diabetic Rats

OpenAIRE

de Souza, Sara R. Garcia; de Miranda Neto, Marc?lio Hubner; Martins Perles, Juliana Vanessa Colombo; Vieira Frez, Fl?via Cristina; Zignani, Isabela; Ramalho, Francielle Veiga; Hermes-Uliana, Catchia; Bossolani, Gleison Daion Piovezana; Zanoni, Jacqueline Nelisis

2017-01-01

Purpose Enteric glial cells (EGCs) exert a critical role in the structural integrity, defense, and metabolic function of enteric neurons. Diabetes mellitus is a chronic disease characterized by metabolic disorders and chronic autonomic neuropathy. Quercetin supplementation, which is a potent antioxidant, has been used in order to reduce the effects of diabetes-induced oxidative stress. The purpose of this research was to investigate the effects of quercetin supplementation in the drinking ...

Hepatic SIRT1 attenuates hepatic steatosis and controls energy balance in mice by inducing fibroblast growth factor 21.

Science.gov (United States)

Li, Yu; Wong, Kimberly; Giles, Amber; Jiang, Jianwei; Lee, Jong Woo; Adams, Andrew C; Kharitonenkov, Alexei; Yang, Qin; Gao, Bin; Guarente, Leonard; Zang, Mengwei

2014-02-01

The hepatocyte-derived hormone fibroblast growth factor 21 (FGF21) is a hormone-like regulator of metabolism. The nicotinamide adenine dinucleotide-dependent deacetylase SIRT1 regulates fatty acid metabolism through multiple nutrient sensors. Hepatic overexpression of SIRT1 reduces steatosis and glucose intolerance in obese mice. We investigated mechanisms by which SIRT1 controls hepatic steatosis in mice. Liver-specific SIRT1 knockout (SIRT1 LKO) mice and their wild-type littermates (controls) were divided into groups that were placed on a normal chow diet, fasted for 24 hours, or fasted for 24 hours and then fed for 6 hours. Liver tissues were collected and analyzed by histologic examination, gene expression profiling, and real-time polymerase chain reaction assays. Human HepG2 cells were incubated with pharmacologic activators of SIRT1 (resveratrol or SRT1720) and mitochondrion oxidation consumption rate and immunoblot analyses were performed. FGF21 was overexpressed in SIRT1 LKO mice using an adenoviral vector. Energy expenditure was assessed by indirect calorimetry. Prolonged fasting induced lipid deposition in livers of control mice, but severe hepatic steatosis in SIRT1 LKO mice. Gene expression analysis showed that fasting up-regulated FGF21 in livers of control mice but not in SIRT1 LKO mice. Decreased hepatic and circulating levels of FGF21 in fasted SIRT1 LKO mice were associated with reduced hepatic expression of genes involved in fatty acid oxidation and ketogenesis, and increased expression of genes that control lipogenesis, compared with fasted control mice. Resveratrol or SRT1720 each increased the transcriptional activity of the FGF21 promoter (-2070/+117) and levels of FGF21 messenger RNA and protein in HepG2 cells. Surprisingly, SIRT1 LKO mice developed late-onset obesity with impaired whole-body energy expenditure. Hepatic overexpression of FGF21 in SIRT1 LKO mice increased the expression of genes that regulate fatty acid oxidation, decreased

Determination quercetin content, antioxidant and antimicrobial activity of genotype mutant Samosir shallots irradiated by gamma rays

Science.gov (United States)

Sinuraya, M.; Hanafiah, D. S.; Romulo, A.; Barus, A.

2018-02-01

The aim of the research was to study the variation in antioxidant and antimicrobial activity as well as the total quercetin content of the fifth generation genotypes mutant Samosir shallot irradiated by gamma rays. The studies conducted included the assessment of quercetin content, antioxidant and antimicrobial activity in shallot bulbs after long-term storage (6 months in the room temperature). Quercetin content of 20 selected genotype mutants of irradiated shallot bulbs along with untreated populations were calculated using quercetin (QU) as a standard. Antioxidant activities of 8 genotype mutant were determined using DPPH. Antimicrobial activity of bulb extracts were tested against six bacteria including Staphylococcus aurous, Enterococcus faecalis, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, and Klebsiella pneumoniae and oneyeastCandida albicans. The results showed that population of genotype mutants irradiated with dosage 2Gy, 4 Gy, 5 Gy and 6 Gy have higher quercetin content than control samples. None of the genotype mutants exhibited antibacterial inhibitory against all microorganism tested except for the sample number 2 and 6 (bulbs generated from the plants irradiated by gamma rays with dosage at 2 Gy and 6 Gy). There was also none of the genotypes observed exhibited significant antioxidant efficacy.

The Protective Effects of Oral Low-dose Quercetin on Diabetic Nephropathy in Hypercholesterolemic Mice

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Isabele Beserra Santos Gomes

2015-09-01

Full Text Available Aims: Diabetic nephropathy (DN is one of the major causes of end-stage renal disease, and the incidence of DN is increasing worldwide. Considering our previous report indicating that chronic treatment with oral low-dose quercetin (10 mg/Kg demonstrated renoprotective, anti-oxidative and anti-apoptotic effects in the C57BL/6J model of diabetic nephropathy, we investigated whether this flavonoid could also have beneficial effects in concurrent DN and spontaneous atherosclerosis using the apolipoprotein E-deficient mouse (apoE-/-. Methods: DN was induced by streptozotocin (100 mg/kg/day, for 3 days in adult apoE-/-mice. Six weeks later, the mice were divided into the following groups: diabetic apoE-/- mice treated with quercetin (DQ, 10 mg/kg/day, 4 weeks, diabetic ApoE-/- mice treated with vehicle (DV and non-treated non-diabetic (ND mice.Results: Quercetin treatment caused a reduction in polyuria (~30%, glycemia (~25%, abolished the hypertriglyceridemia and had significant effects on renal function, including decreased proteinuria (~15% and creatininemia (~30%, which were accompanied by beneficial effects on the renal structural changes, including normalization of the index of glomerulosclerosis and kidney weight.Conclusions: Our data revealed that quercetin treatment significantly reduced DN in hypercholesterolemic mice by inducing biochemical and morphological modifications. Thus, this translational study highlights the importance of quercetin as a potential nutraceutical for the management of DN, including in diabetes associated with dyslipidemia.

Protective effects of atorvastatin and quercetin on isoprenaline-induced myocardial infarction in rats

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Mai A. Zaafan

2013-06-01

Full Text Available Myocardial infarction (MI continues to be a major public health problem in the world. Statins exhibit cardio-protective effects by several mechanisms beyond their lipid lowering activity. Quercetin is a natural flavonoid that possesses significant anti-oxidant and antiinflammatory activities. The present study aimed to investigate the effects of pretreatment with atorvastatin (10 mg/kg and quercetin (50 mg/kg, as well as their combination on isoprenaline-induced MI in rats. Markers chosen to assess cardiac damage included serum activity of creatine kinase-MB (CK-MB and serum level of cardiac troponin-I (cTn-I, as well as oxidative stress and inflammatory biomarkers including serum levels of C-reactive protein (CRP, tumor necrosis factor-alpha (TNF-α, and interleukin-10 (IL-10 as well as cardiac contents of lipid peroxides, reduced glutathione (GSH, and nitrite. Furthermore, ECG monitoring and histological examinations of cardiac tissues were done. Isoprenaline increased serum CK-MB activity and cTn-I level as well as inflammatory and oxidative stress biomarkers. In addition, it produced ST-segment elevation and degenerative changes in heart tissues. Pretreatment with atorvastatin suppressed significantly the elevated levels of cTn-I, CRP, TNF-α, and IL-10 in serum coupled with reduction in cardiac lipid peroxides; however, it increased cardiac nitrite content. Quercetin decreased isoprenaline-induced changes in oxidative stress and inflammatory biomarkers with marked improvement in ECG and histopathologic alterations. Combination of quercetin with atorvastatin resulted in similar protective effects. In conclusion, quercetin can be regarded as a promising cardio-protective natural agent in MI alone or combined with atorvastatin.

Dietary Niacin Supplementation Suppressed Hepatic Lipid Accumulation in Rabbits

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Lei Liu

2016-12-01

Full Text Available An experiment was conducted to investigate the effect of niacin supplementation on hepatic lipid metabolism in rabbits. Rex Rabbits (90 d, n = 32 were allocated to two equal treatment groups: Fed basal diet (control or fed basal diet with additional 200 mg/kg niacin supplementation (niacin. The results show that niacin significantly increased the levels of plasma adiponectin, hepatic apoprotein B and hepatic leptin receptors mRNA (p0.05. However, niacin treatment significantly inhibited the hepatocytes lipid accumulation compared with the control group (p<0.05. In conclusion, niacin treatment can decrease hepatic fatty acids synthesis, but does not alter fatty acids oxidation and triacylglycerol export. And this whole process attenuates lipid accumulation in liver. Besides, the hormones of insulin, leptin and adiponectin are associated with the regulation of niacin in hepatic lipid metabolism in rabbits.

Quercetin: A wonder bioflvonoid with therapeutic potential in disease management

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Alka Gupta

2016-03-01

Full Text Available In the last decade, considerable efforts have been made to develop health promising nutritional supplements. Quercetin is a plant-derived bioflavonoid which is recently gaining scientific interest for its antioxidant free radical scavenging effects and anti-inflammatory properties. This wonder flavanol exhibits therapeutic potential in various ailments like cancer, coronary artery, asthma and alzheimer (neurodegeneration diseases. Additional clinical uses include treatment of inflammatory conditions like gout, pancreatitis and prostatitis. It has been extensively studied for its gastroprotective effects, anti-obesity action, immune booster, reducing risk of cataract and reduction of diabetic complications. The present review briefly discusses about biological activity, mechanism of action and therapeutic potential of quercetin in prevention and mitigation of diseases.

Single-energy non-contrast hepatic steatosis criteria applied to virtual non-contrast images: is it still highly specific and positively predictive?

Science.gov (United States)

Haji-Momenian, S; Parkinson, W; Khati, N; Brindle, K; Earls, J; Zeman, R K

2018-06-01

To determine the sensitivity, specificity, and predictive values of single-energy non-contrast hepatic steatosis criteria on dual-energy virtual non-contrast (VNC) images. Forty-eight computed tomography (CT) examinations, which included single-energy non-contrast (TNC) and contrast-enhanced dual-energy CT angiography (CTA) of the abdomen, were enrolled. VNC images were reconstructed from the CTA. Region of interest (ROI) attenuations were measured in the right and left hepatic lobes, spleen, and aorta on TNC and VNC images. The right and left hepatic lobes were treated as separate samples. Steatosis was diagnosed based on TNC liver attenuation of ≤40 HU or liver attenuation index (LAI) of ≤-10 HU, which are extremely specific and predictive for moderate to severe steatosis. The sensitivity, specificity, and predictive values of VNC images for steatosis were calculated. VNC-TNC deviations were correlated with aortic enhancement and patient water equivalent diameter (PWED). Thirty-two liver ROIs met steatosis criteria based on TNC attenuation; VNC attenuation had sensitivity, specificity, and a positive predictive value of 66.7%, 100%, and 100%, respectively. Twenty-one liver ROIs met steatosis criteria based on TNC LAI. VNC LAI had sensitivity, specificity, and positive predictive values of 61.9%, 90.7%, and 65%, respectively. Hepatic and splenic VNC-TNC deviations did not correlate with one another (R 2 =0.08), aortic enhancement (R 2 predictive for moderate to severe steatosis on VNC reconstructions from the arterial phase. Hepatic attenuation performs better than LAI criteria. VNC deviations are independent of aortic enhancement and PWED. Copyright © 2018 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Quercetin And Exercise Treatment On The Morphology Of ...

African Journals Online (AJOL)

This study was therefore undertaken to investigate the effects of exercise and quercetin on lipid peroxidation (MDA), scavenging enzyme activity, and morphology of pancreatic β-cells as against experimentally-induced diabetes and oxidative stress by streptozotocin (STZ) treatment in Wistar rats. Diabetes was induced in ...

Identification of Flavonoids (Quercetin, Gallic acid and Rutin from Catharanthus roseus Plant Parts using Deep Eutectic Solvent

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Asma Nisar

2017-02-01

Full Text Available Green technology is the most important topic in the pharmaceutical field because it reduces the cost of medicines and minimizes the environmental impact of the field and is better for human health and safety. Green chemistry emphasizes that the solvent should be nontoxic, safe, cheap, green, readily available, recyclable, and biodegradable. Deep eutectic solvents, a new type of green solvent, have some renowned properties—for instance, high thermal stability, low vapor pressure, low cost, biodegradability, and high viscosity. In this study, deep eutectic solvents made up of choline chloride-glycerol (1:2 were used for the extraction and isolation of flavonoid (rutin, gallic acid, and quercetin from Catharanthus roseus plant parts, flower petal, leaves, stem, and root. The amounts of rutin and quercetin in flower petal are 29.46 and 6.51%, respectively, whereas, rutin, gallic acid, and quercetin amounts in leaves are 25.16, 8.57, and 10.47%, respectively. In stem the amounts of rutin, gallic acid, and quercetin are 13.02, 5.89, and 7.47%, respectively. In root, only quercetin has been obtained that is 13.49%. The HPLC is an analytical method, which was found to be an excellent technique for determination of rutin, gallic acid, and quercetin using deep eutectic solvent extraction from plant parts of Catharanthus roseus.

The oxidation mechanism of the antioxidant quercetin in nonaqueous media

Energy Technology Data Exchange (ETDEWEB)

Sokolova, Romana, E-mail: romana.sokolova@jh-inst.cas.cz [J. Heyrovsky Institute of Physical Chemistry, v.v.i., Academy of Sciences of the Czech Republic, Dolejskova 3, 18223 Prague (Czech Republic); Degano, Ilaria [Department of Chemistry and Industrial Chemistry, University of Pisa, Via Risorgimento 35, 56100 Pisa (Italy); Ramesova, Sarka; Bulickova, Jana; Hromadova, Magdalena; Gal, Miroslav; Fiedler, Jan [J. Heyrovsky Institute of Physical Chemistry, v.v.i., Academy of Sciences of the Czech Republic, Dolejskova 3, 18223 Prague (Czech Republic); Valasek, Michal [Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nam. 2, 16610 Prague 6 (Czech Republic)

2011-08-30

The knowledge of the degradation pathways of natural dyes used in medieval textiles is necessary for the restoration of their original color. Quercetin, one of such colorants, reportedly yields the wide spectrum of oxidation products in different types of media. This study deals with electrochemical oxidation mechanism of quercetin in nonaqueous solution, which has not been yet attempted. The final oxidation product at the first oxidation wave was identified by HPLC-DAD and GC-MS techniques as 2-(3',4'-dihydroxybenzoyl)-2,4,6-trihydroxybenzofuran-3(2H)-one. The apparent two-electron process at the potential of the first oxidation wave yields current-voltage shapes with one-electron characteristics. The in situ spectroelectrochemistry measurements proved the oxidation mechanism leading through a short-lived anion radical. Two possibilities of the oxidation mechanism are discussed: two one-electron transfers, which do not have identical but similar redox potentials, or the presence of a disproportionation chemical reaction following the first one electron transfer. The quinone formed in either case is stable only on the time scale of a fast spectroelectrochemistry and undergoes fast hydroxylation reaction, where 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxybenzofuran-3-one is formed. This compound is oxidized at the potential of the second oxidation wave of quercetin.

The oxidation mechanism of the antioxidant quercetin in nonaqueous media

International Nuclear Information System (INIS)

Sokolova, Romana; Degano, Ilaria; Ramesova, Sarka; Bulickova, Jana; Hromadova, Magdalena; Gal, Miroslav; Fiedler, Jan; Valasek, Michal

2011-01-01

The knowledge of the degradation pathways of natural dyes used in medieval textiles is necessary for the restoration of their original color. Quercetin, one of such colorants, reportedly yields the wide spectrum of oxidation products in different types of media. This study deals with electrochemical oxidation mechanism of quercetin in nonaqueous solution, which has not been yet attempted. The final oxidation product at the first oxidation wave was identified by HPLC-DAD and GC-MS techniques as 2-(3',4'-dihydroxybenzoyl)-2,4,6-trihydroxybenzofuran-3(2H)-one. The apparent two-electron process at the potential of the first oxidation wave yields current-voltage shapes with one-electron characteristics. The in situ spectroelectrochemistry measurements proved the oxidation mechanism leading through a short-lived anion radical. Two possibilities of the oxidation mechanism are discussed: two one-electron transfers, which do not have identical but similar redox potentials, or the presence of a disproportionation chemical reaction following the first one electron transfer. The quinone formed in either case is stable only on the time scale of a fast spectroelectrochemistry and undergoes fast hydroxylation reaction, where 2-(3,4-dihydroxybenzoyl)-2,4,6-trihydroxybenzofuran-3-one is formed. This compound is oxidized at the potential of the second oxidation wave of quercetin.

Antioxidant Effects of Quercetin and Catechin Encapsulated into PLGA Nanoparticles

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Hector Pool

2012-01-01

Full Text Available Polymeric nanoparticles (PLGA have been developed for the encapsulation and controlled release of quercetin and catechin. Nanoparticles were fabricated using a solvent displacement method. Physicochemical properties were measured by light scattering, scanning electron microscopy and ζ-potential, X-ray diffraction, infrared spectroscopy and differential scanning calorimetry. Encapsulation efficiency and in vitro release profiles were obtained from differential pulse voltammetry experiments. Antioxidant properties of free and encapsulated flavonoids were determined by TBARS, fluorescence spectroscopy and standard chelating activity methods. Relatively small (d≈ 400 nm polymeric nanoparticles were obtained containing quercetin or catechin in a non-crystalline form (EE ≈ 79% and the main interactions between the polymer and each flavonoid were found to consist of hydrogen bonds. In vitro release profiles were pH-dependant, the more acidic pH, the faster release of each flavonoid from the polymeric nanoparticles. The inhibition of the action of free radicals and chelating properties, were also enhanced when quercetin and catechin were encapsulated within PLGA nanoparticles. The information obtained from this study will facilitate the design and fabrication of polymeric nanoparticles as possible oral delivery systems for encapsulation, protection and controlled release of flavonoids aimed to prevent oxidative stress in human body or food products.

Quercetin Protects Primary Human Osteoblasts Exposed to Cigarette Smoke through Activation of the Antioxidative Enzymes HO-1 and SOD-1

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Karl F. Braun

2011-01-01

Full Text Available Smokers frequently suffer from impaired fracture healing often due to poor bone quality and stability. Cigarette smoking harms bone cells and their homeostasis by increased formation of reactive oxygen species (ROS. The aim of this study was to investigate whether Quercetin, a naturally occurring antioxidant, can protect osteoblasts from the toxic effects of smoking. Human osteoblasts exposed to cigarette smoke medium (CSM rapidly produced ROS and their viability decreased concentration- and time-dependently. Co-, pre- and postincubation with Quercetin dose-dependently improved their viability. Quercetin increased the expression of the anti-oxidative enzymes heme-oxygenase- (HO- 1 and superoxide-dismutase- (SOD- 1. Inhibiting HO-1 activity abolished the protective effect of Quercetin. Our results demonstrate that CSM damages human osteoblasts by accumulation of ROS. Quercetin can diminish this damage by scavenging the radicals and by upregulating the expression of HO-1 and SOD-1. Thus, a dietary supplementation with Quercetin could improve bone matter, stability and even fracture healing in smokers.

Antiatherogenic effect of quercetin is mediated by proteasome inhibition in the aorta and circulating leukocytes.

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Pashevin, Denis A; Tumanovska, Lesya V; Dosenko, Victor E; Nagibin, Vasyl S; Gurianova, Veronika L; Moibenko, Alexey A

2011-01-01

Quercetin, a plant-derived flavonoid, has attracted considerable attention as promising compound for heart disease prevention and therapy. It has been linked to decreased mortality from heart disease and decreased incidence of stroke. Here, we report new data showing the angioprotective properties of quercetin mediated by its effect on proteasomal proteolysis. This study was designed to investigate the ability of quercetin to modulate proteasomal activity in a rabbit model of cholesterol-induced atherosclerosis. First, we show proteasomal trypsin-like (TL) activity increased up to 2.4-fold, chymotrypsin-like (CTL) activity increased by up to 43% and peptidyl-glutamyl peptide-hydrolyzing (PGPH) activity increased by up to 10% after 8 weeks of a cholesterol-rich diet. A single intravenous injection of the water-soluble form of quercetin (Corvitin) significantly decreased proteasomal TL activity 1.85-fold in monocytes, and decreased the CTL and PGPH activities more than 2-fold in polymorphonuclear leukocytes (PMNL) after 2 h. Prolonged administration (1 month) of Corvitin to animals following a cholesterol-rich diet significantly decreased all types of proteolytic proteasome activities both in tissues and in circulating leukocytes and was associated with the reduction of atherosclerotic lesion areas in the aorta. Additionally, the pharmacological form of quercetin (Quertin) was shown to have an antiatherogenic effect and an ability to inhibit proteasome activities.

Genetic expression profile analysis of the temporal inhibition of quercetin and naringenin on Lactobacillus rhamnosus GG

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The plant polyphenols, quercetin and naringenin, are considered healthy dietary compounds; however, little is known of their effects on the probiotic Lactobacillus rhamnosus GG (LGG). In this study, it was discovered that both quercetin and naringenin produced temporary inhibition of LGG growth, par...

Apoptosis of murine melanoma B16-BL6 cells induced by quercetin targeting mitochondria, inhibiting expression of PKC-alpha and translocating PKC-delta.

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Zhang, Xian-Ming; Chen, Jia; Xia, Yu-Gui; Xu, Qiang

2005-03-01

In our previous study, quercetin was found to induce apoptosis of murine melanoma B16-BL6 cells. The cellular and molecular mechanism of quercetin-induced apoptosis was investigated in the present study. Nuclear morphology was determined by fluorescence microscopy. DNA fragmentation was analyzed by electrophoresis and quantified by the diphenylamine method. The transmembrane potential of mitochondria was measured by flow cytometry. Bcl-2, Bcl-X(L), PKC-alpha, PKC-beta, and PKC-delta were detected by Western blotting. Caspase activity was determined spectrophotometrically. Quercetin induced the condensation of nuclei of B16-BL6 cells in a dose-dependent pattern as visualized by Hoechst 33258 and propidium iodide dying. Phorbol 12-myristate 13-acetate (PMA), a PKC activator, significantly enhanced apoptosis induced by quercetin, while doxorubicin, a PKC inhibitor, markedly decreased it. Both PMA and doxorubicin showed a consistent effect on the fragmentation of nuclear DNA caused by various dosages of quercetin. Quercetin dose-dependently led to loss of the mitochondrial membrane potential, which was also significantly reinforced or antagonized by PMA and doxorubicin, respectively. Moreover, PMA showed reinforcement, while doxorubicin showed significant antagonization, of the quercetin-mediated decrease in the expression of Bcl-2. Quercetin promoted caspase-3 activity in a dose-dependent manner, which was also regulated by PMA and doxorubicin with a pattern similar to that seen in their effect on apoptosis, mitochondrial membrane potential and Bcl-2 expression, but none of these were directly affected by PMA and doxorubicin. Free fatty acid and chlorpromazine, a PKC activator and inhibitor, respectively, did not interfere with these effects of quercetin. B16-BL6 cells expressed PKC-alpha, PKC-beta, and PKC-delta. Quercetin dose-dependently inhibited the expression of PKC-alpha but not that of PKC-beta and PKC-delta. Doxorubicin almost completely blocked the effect of

Validation of an HPLC method for quantification of total quercetin in Calendula officinalis extracts

International Nuclear Information System (INIS)

Muñoz Muñoz, John Alexander; Morgan Machado, Jorge Enrique; Trujillo González, Mary

2015-01-01

Introduction: calendula officinalis extracts are used as natural raw material in a wide range of pharmaceutical and cosmetic preparations; however, there are no official methods for quality control of these extracts. Objective: to validate an HPLC-based analytical method for quantification total quercetin in glycolic and hydroalcoholic extracts of Calendula officinalis. Methods: to quantify total quercetin content in the matrices, it was necessary to hydrolyze flavonoid glycosides under optimal conditions. The chromatographic separation was performed on a C-18 SiliaChrom 4.6x150 mm 5 µm column, adapted to a SiliaChrom 5 um C-18 4.6x10 mm precolumn, with UV detection at 370 nm. The gradient elution was performed with a mobile phase consisting of methanol (MeOH) and phosphoric acid (H 3 PO 4 ) (0.08 % w/v). The quantification was performed through the external standard method and comparison with quercetin reference standard. Results: the studied method selectivity against extract components and degradation products under acid/basic hydrolysis, oxidation and light exposure conditions showed no signals that interfere with the quercetin quantification. It was statistically proved that the method is linear from 1.0 to 5.0 mg/mL. Intermediate precision expressed as a variation coefficient was 1.8 and 1.74 % and the recovery percentage was 102.15 and 101.32 %, for glycolic and hydroalcoholic extracts, respectively. Conclusions: the suggested methodology meets the quality parameters required for quantifying total quercetin, which makes it a useful tool for quality control of C. officinalis extracts. (author)

Urine recovery experiments with quercetin and other mutagens using the Ames test

Energy Technology Data Exchange (ETDEWEB)

Busch, D.B.; Hatcher, J.F.; Bryan, G.T.

1986-01-01

Recovery from urine of the mutagenic activity of 2-anthramine, cyclophosphamide, 7,12-dimethylbenz(a)anthracene, 6-chloro-9-((3-(2-chloroethylamino)-propyl)amino)-2-methoxyacridine dihydrochloride (ICR-191), mitomycin-C, nitrofurantoin, and quercetin was studied with several of the Ames tester strains using acetone-extracted XAD-2 columns with yields ranging from 27% to 79%. Dose responses of the pure chemicals were also studied, and results showed TA 97 to be far more susceptible to quercetin mutagenesis than TA 1537. Reducing pour plate agar volume enhanced mutagenesis.

Efficacy of quercetin flavonoid in recovering the postbleaching bond strength of orthodontic brackets: A preliminary study.

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Shamsedin, Mana; Arash, Valiollah; Jahromi, Masoud Babaei; Moghadamnia, Ali Akbar; Kamel, Manouchehr Rahmati; Ezoji, Fariba; Bijani, Ali; Kavoli, Samira; Ghasemi, Tania; Ramezani, Gholamhossein

2017-01-01

To evaluate comparatively the effect of quercetin on postbleaching shear bond strength (SBS) and adhesive remnant index (ARI). Intact maxillary premolars were divided randomly into 12 groups of 10 each: (1) bonding the bracket immediately after bleaching, (2) bonding 1 week after bleaching, (3-8) application of three experimental concentrations of quercetin (0.1%, 0.5%, and 1%) at two time durations (5 and 10 min), (9-10) application of the solvent of quercetin at two time periods (5 and 10 min), (11) application of 10% sodium ascorbate for 10 min, and (12) bonding the brackets on nonbleached teeth. Bleaching was performed using 15% carbamide peroxide gel for 5 days (6 h daily). After incubation and thermocycling, the SBS of brackets was measured. The ARI too was recorded at ×20. The data were analyzed statistically (α =0.05). Bleaching reduced the SBS below 10 Megapascal (MPa) level ( P 0.01). All eight postbleaching treatments had rather similar efficacies ( P = 0.1396). The concentration of quercetin (beta = 0.259, P = 0.042) but not its duration (beta = 0.213, P = 0.093) significantly improved its efficacy. Bleaching can weaken the bond strength of orthodontic brackets below acceptable levels. The application of quercetin or Vitamin C or delaying the bracket bonding improved the postbleaching SBS.

Antioxidant and bone repair properties of quercetin-functionalized hydroxyapatite: An in vitro osteoblast-osteoclast-endothelial cell co-culture study.

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Forte, Lucia; Torricelli, Paola; Boanini, Elisa; Gazzano, Massimo; Rubini, Katia; Fini, Milena; Bigi, Adriana

2016-03-01

Quercetin (3,3',4',5,7-pentahydroxy-flavone) is a flavonoid known for its pharmacological activities, which include antioxidant and anti-inflammatory properties, as well as possible beneficial action on diseases involving bone loss. In this work, we explored the possibility to functionalize hydroxyapatite (HA) with quercetin in order to obtain new materials for bone repair through local administration of the flavonoid. HA was synthesized in presence of different concentrations of quercetin according to two different procedures: direct synthesis and phase transition from monetite. Direct synthesis lead to composite nanocrystals containing up to 3.1 wt% quercetin, which provokes a reduction of the crystals mean dimensions and of the length of the coherently scattering domains. Synthesis conditions provoke a partial oxidation of quercetin and, as a consequence, a significant reduction of its radical scavenging activity (RSA). On the other hand, synthesis through phase transition yields samples containing up to 1.3 wt% of quercetin incorporated into hydroxyapatite, with minor structural modifications, which exhibit relevant anti-oxidant activities, as testified by their high RSA levels, (slightly lower than that of pure quercetin). The biological response to these materials was tested using an innovative triculture model involving osteoblast, osteoclast and endothelial cells, in order to mimic bone microenvironment. The results show that the presence of quercetin in the composite materials enhances human osteoblast-like MG63 proliferation and differentiation, whereas it downregulates osteoclastogenesis of osteoclast precursors 2T-110, and supports proliferation and differentiation of human umbilical vein endothelial cells (HUVEC). The pharmacological activities of the flavonoid quercetin include anti-oxidant and antiinflammatory properties, as well as capability to prevent bone loss. In this paper, we demonstrate that it is possible to synthesize hydroxyapatite

Identification of the Products of Oxidation of Quercetin by Air Oxygenat Ambient Temperature

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Viktor A Utsal

2007-03-01

Full Text Available Oxidation of quercetin by air oxygen takes place in water and aqueous ethanol solutions under mild conditions, namely in moderately-basic media (pH ∼ 8-10 at ambient temperature and in the absence of any radical initiators, without enzymatic catalysis or irradiation of the reaction media by light. The principal reaction products are typical of other oxidative degradation processes of quercetin, namely 3,4-dihydroxy-benzoic (proto-catechuic and 2,4,6-trihydroxybenzoic (phloroglucinic acids, as well as the decarboxylation product of the latter – 1,3,5-trihydroxybenzene (phloroglucinol. In accordance with the literature data, this process involves the cleavage of the γ-pyrone fragment (ring C of the quercetin molecule by oxygen, with primary formation of 4,6-dihydroxy-2-(3,4-dihydroxybenzoyloxybenzoic acid (depside. However under such mild conditions the accepted mechanism of this reaction (oxidative decarbonylation with formation of carbon monoxide, CO should be reconsidered as preferably an oxidative decarboxylation with formation of carbon dioxide, CO2. Direct head-space analysis of the gaseous components formed during quercetin oxidation in aqueous solution at ambient temperature indicates that the ratio of carbon dioxide/carbon monoxide in the gas phase after acidification of the reaction media is ca. 96:4 %. Oxidation under these mild conditions is typical for other flavonols having OH groups at C3 (e.g., kaempferol, but it is completely suppressed if this hydroxyl group is substituted by a glycoside fragment (as in rutin, or a methyl substituent. An alternative oxidation mechanism involving the direct cleavage of the C2-C3 bond in the diketo-tautomer of quercetin is proposed.

Influence of Quercetin in the Temporal Regulation of Redox Homeostasis in Drosophila melanogaster.

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Subramanian, Perumal; Kaliyamoorthy, Kanimozhi; Jayapalan, Jaime Jacqueline; Abdul-Rahman, Puteri Shafinaz; Haji Hashim, Onn

2017-01-01

Numerous biological processes are governed by the biological clock. Studies using Drosophila melanogaster (L.) are valuable that could be of importance for their effective applications on rodent studies. In this study, the beneficial role of quercetin (a flavonoid) on H2O2 induced stress in D. melanogaster was investigated. D. melanogaster flies were divided into four groups (group I - control, group II - H2O2 (acute exposure), group III - quercetin, and group IV - quercetin + H2O2 treated). Negative geotaxis assay, oxidative stress indicators (protein carbonyls, thiobarbituric reactive substances [TBARS]), and antioxidants (superoxide dismutase [SOD], catalase [CAT], glutathione-S-transferase [GST], glutathione peroxidase, and reduced glutathione [GSH]) were measured at 4 h intervals over 24 h and temporal expression of heat shock protein-70 (Hsp70), Upd1 (homolog of IL-6 in Drosophila), and nitric oxide synthase (Nos) was analyzed by Western blotting. Groups II and IV showed altered biochemical rhythms (compared with controls). Decreased mesor values of negative geotaxis, SOD, CAT, GST, and GSH were noticed in H2O2, increased mesor of oxidative stress indicators (TBARS and protein carbonyl content) and a reversibility of the rhythmic characteristics were conspicuous after quercetin treatment. The expression levels of Hsp70, Upd1, and Nos were noticeably maximum at 04:00. Significant elevation of expression by H2O2 was nearly normalized by quercetin treatment. The possible mechanism by which quercetin modulates oxidant-antioxidant imbalance under oxidative stress could be ascribed to the modulation of the rhythmic properties. Our results will be helpful to understand the molecular interlink between circadian rhythm and oxidative stress mechanism. © The Author 2017. Published by Oxford University Press on behalf of the Entomological Society of America.

Antioxidant Capacity of Flavonoids in Hepatic Microsomes Is not Reflected by Antioxidant Effects In Vivo

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Garry Duthie

2012-01-01

Full Text Available Flavonoids are polyphenolic compounds with potential antioxidant activity via multiple reduction capacities. Oxidation of cellular lipids has been implicated in many diseases. Consequently, this study has assessed the ability of several dietary flavonoid aglycones to suppress lipid peroxidation of hepatic microsomes derived from rats deficient in the major lipid soluble antioxidant, dα-tocopherol. Antioxidant effectiveness was galangin > quercetin > kaempferol > fisetin > myricetin > morin > catechin > apigenin. However, none of the flavonoids were as effective as dα-tocopherol, particularly at the lowest concentrations used. In addition, there appears to be an important distinction between the in vitro antioxidant effectiveness of flavonoids and their ability to suppress indices of oxidation in vivo. Compared with dα-tocopherol, repletion of vitamin E deficient rats with quercetin, kaempferol, or myricetin did not significantly affect indices of lipid peroxidation and tissue damage. Direct antioxidant effect of flavonoids in vivo was not apparent probably due to low bioavailability although indirect redox effects through stimulation of the antioxidant response element cannot be excluded.

Water Extract of Dolichos lablab Attenuates Hepatic Lipid Accumulation in a Cellular Nonalcoholic Fatty Liver Disease Model.

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Im, A-Rang; Kim, Yun Hee; Lee, Hye Won; Song, Kwang Hoon

2016-05-01

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease that is rising in prevalence worldwide. Therapeutic strategies for patients with NAFLD are limited by a lack of effective drugs. In this report, we show that Dolichos lablab water extract (DLL-Ex) protects against free fatty acid (FFA)-induced lipid accumulation and attenuates expression of genes involved in lipid droplet accumulation in cellular NAFLD models. The hepatoprotective effects and underlying mechanism of DLL-Ex were assessed using an in vitro cellular model in which NAFLD was simulated by inducing excessive FFA influx into hepatocytes. HepG2 cells were treated with DLL-Ex and FFAs for 24 h, after which intracellular lipid content was observed by using Nile Red and Oil Red O staining. Quantitative real-time polymerase chain reaction was used to measure expression levels of genes related to FFA-mediated cellular energy depletion. Western blotting was used to measure protein levels of phosphorylated c-Jun N-terminal kinase, AMP-activated protein kinase alpha (AMPKα), and peroxisome proliferator-activated receptor γ coactivator 1 alpha. In HepG2 cells, DLL-Ex inhibited expression of CD36, which regulates fatty acid uptake, as well as BODIPY-labeled fatty acid uptake. Additionally, DLL-Ex significantly attenuated FFA-mediated cellular energy depletion and mitochondrial membrane depolarization. Furthermore, DLL-Ex enhanced phosphorylation of AMPK, indicating that AMPK is a critical regulator of DLL-Ex-mediated inhibition of hepatic lipid accumulation, possibly through its antioxidative effect. These results demonstrate that DLL-Ex exerts potent anti-NAFLD activity, suggesting that it could be a potential adjuvant treatment for patients with NAFLD.

Protectin DX suppresses hepatic gluconeogenesis through AMPK-HO-1-mediated inhibition of ER stress.

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Jung, Tae Woo; Kim, Hyung-Chun; Abd El-Aty, A M; Jeong, Ji Hoon

2017-06-01

Several studies have shown that protectins, which are ω-3 fatty acid-derived proresolution mediators, may improve insulin resistance. Recently, protectin DX (PDX) was documented to attenuate insulin resistance by stimulating IL-6 expression in skeletal muscle, thereby regulating hepatic gluconeogenesis. These findings made us investigate the direct effects of PDX on hepatic glucose metabolism in the context of diabetes. In the current study, we show that PDX regulates hepatic gluconeogenesis in a manner distinct from its indirect glucoregulatory activity via IL-6. We found that PDX stimulated AMP-activated protein kinase (AMPK) phosphorylation, thereby inducing heme oxygenase 1 (HO-1) expression. This induction blocked hepatic gluconeogenesis by suppressing endoplasmic reticulum (ER) stress in hepatocytes under hyperlipidemic conditions. These effects were significantly dampened by silencing AMPK or HO-1 expression with small interfering RNA (siRNA). We also demonstrated that administration of PDX to high fat diet (HFD)-fed mice resulted in increased hepatic AMPK phosphorylation and HO-1 expression, whereas hepatic ER stress was substantially attenuated. Furthermore, PDX treatment suppressed the expression of gluconeogenic genes, thereby decreasing blood glucose levels in HFD-fed mice. In conclusion, our findings suggest that PDX inhibits hepatic gluconeogenesis via AMPK-HO-1-dependent suppression of ER stress. Thus, PDX may be an effective therapeutic target for the treatment of insulin resistance and type 2 diabetes through the regulation of hepatic gluconeogenesis. Copyright © 2017 Elsevier Inc. All rights reserved.

New benzophenone and quercetin galloyl glycosides from Psidium guajava L.

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Matsuzaki, Keiichi; Ishii, Rie; Kobiyama, Kaori

2010-01-01

New benzophenone and flavonol galloyl glycosides were isolated from an 80% MeOH extract of Psidium guajava L. (Myrtaceae) together with five known quercetin glycosides. The structures of the novel glycosides were elucidated to be 2,4,6-trihydroxybenzophenone 4-O-(6″-O-galloyl)-β-d-glucopyranoside (1, guavinoside A), 2,4,6-trihydroxy-3,5-dimethylbenzophenone 4-O-(6″-O-galloyl)-β-d-glucopyranoside (2, guavinoside B), and quercetin 3-O-(5″-O-galloyl)-α-l-arabinofuranoside (3, guavinoside C) by NMR, MS, UV, and IR spectroscopies. Isolated phenolic glycosides showed significant inhibitory activities against histamine release from rat peritoneal mast cells, and nitric oxide production from a murine macrophage-like cell line, RAW 264.7. PMID:20354804

Modulatory effects of quercetin on proliferation and differentiation of the human colorectal cell line Caco-2

NARCIS (Netherlands)

Dihal, A.A.; Woutersen, R.A.; Ommen, B.v.; Rietjens, I.M.C.M.; Stierum, R.H.

2006-01-01

The effect of the dietary flavonoid quercetin was investigated on proliferation and differentiation of the human colon cancer cell line Caco-2. Confluent Caco-2 monolayers exposed to quercetin showed a biphasic effect on cell proliferation and a decrease in cell differentiation (0.001

(Anti)mutagenic and immunomodulatory properties of quercetin glycosides

Czech Academy of Sciences Publication Activity Database

Valentová, Kateřina; Šíma, Petr; Rybková, Z.; Křižan, Jiří; Malachová, K.; Křen, Vladimír

2016-01-01

Roč. 96, č. 5 (2016), s. 1492-1499 ISSN 0022-5142 R&D Projects: GA ČR(CZ) GAP301/11/0767; GA MŠk(CZ) LD14096 Institutional support: RVO:61388971 Keywords : quercetin glycosides * (anti)mutagenicity * mice Subject RIV: EE - Microbiology, Virology Impact factor: 2.463, year: 2016

Can hydrogen peroxide and quercetin improve production of ...

African Journals Online (AJOL)

The aim of the present work was to determine if hydrogen peroxide in combination with quercetin or indole butyric acid, can modify some characteristics related to rooting and development in cuttings of Eucalyptus grandis x Eucalyptus urophylla. Cuttings were periodically evaluated at 30, 60 and 90 days according to the ...

Quercetin inhibits the invasion of murine melanoma B16-BL6 cells by decreasing pro-MMP-9 via the PKC pathway.

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Zhang, Xian-Ming; Huang, Shao-Peng; Xu, Qiang

2004-01-01

On the basis of the inhibitory effect of quercetin on the invasion of melanoma B16-BL6 cells previously reported by us, the mechanisms of quercetin-mediated inhibition of invasion were further investigated in the present study. The ability of B16-BL6 cells to invade and migrate was evaluated in terms of the numbers of cells penetrating a reconstituted basement membrane in the Transwell coculture system. The relative levels and activities of matrix metalloproteinase-9 (MMP-9) and MMP-2 were determined by gelatin zymography and quantified using LabWorks 4.0 software. The quercetin-mediated inhibition of invasion was partially blocked by phorbol-12,13-dibutyrate (PDB), a PKC (protein kinase C) activator, and by doxorubicin, a PKC inhibitor. Only the proforms of MMP-9 (92 kDa) and MMP-2 (72 kDa) were detected by gelatin zymography. Quercetin dose-dependently decreased the gelatinolytic activity of pro-MMP-9. Doxorubicin also markedly reversed the quercetin-induced decrease. Quercetin showed a dose-dependent antagonism of increases in gelatinolytic activity of pro-MMP-9 induced by PDB and free fatty acid (another PKC activator). Together with the report that quercetin directly reduces PKC activity, the results reported here suggest that quercetin may inhibit the invasion of B16-BL6 cells by decreasing pro-MMP-9 via the PKC pathway.

Combination of Quercetin and Kaempferol enhances in vitro Cytotoxicity on Human Colon Cancer (HCT-116 Cells

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Sara Jaramillo-Carmona

2014-05-01

Full Text Available Colon cancer is one of the most common types of cancer malignancy. Although flavonoids naturally occur as mixtures, little information is available regarding the additive or synergistic biochemical interactions between flavonoids. The objectives of this study were to examine the feasibility of combining two major structurally related flavonoids, quercetin and kaempferol, to affect the cell viability, cell cycle, and proliferation of the human colon cancer HCT-116 cell line. The combination of quercetin and kaempferol exhibited a greater cytotoxic efficacy than did either quercetin or kaempferol alone. This effect was highest and acted in a synergistic fashion in a 2-fold quercetin and 1-fold kaempferol IC50 combination, which also arrested cell growth in the G2/M phase and suppressed proliferation. Our observations support a structure-activity relationship based on the presence of 3’–OH moiety and/or 4’–OH moiety on the B-ring of flavonoids.

Neuroprotective effect of quercetin in a model of Parkinson’s disease in rat: A histochemical analysis

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Mehdi Mehdizadeh

2009-01-01

Full Text Available AbstractIntroduction: Parkinson's disease (PD is a neuropathological disorder involving the degeneration of dopaminergic neurons in the substantia nigra, with the subsequent loss of their terminals in the striatum. Quercetin, a natural flavonoid, is a strong antioxidant and radical scavenger. Therefore, its neuroprotective effect in a model of Parkinson’s disease in rat was evaluated.Methods: For this purpose, unilateral intrastriatal 6-hydroxydopamine (6-OHDA-lesioned rats were pretreated with quercetin (20 mg/kg; i.p. 1 hour before surgery and treated once a day for one month. Nissl-stained neurons of substantia nigra pars compacta (SNC were counted. Results: Number of Nissl-stained neurons in left side of SNC of lesion group was lower relative to sham-operated group (p<0.005 and it was higher in quercetin-treated lesion group as compared to untreated lesion group (p<0.01.Discussion: Flavonoid quercetin administration for one month could protect the neurons of SNC against 6-OHDA toxicity. 

Neuroprotective effect of quercetin in a model of Parkinson’s disease in rat: A histochemical analysis

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Mehdi Mehdizadeh

2009-01-01

Full Text Available AbstractIntroduction: Parkinson's disease (PD is a neuropathological disorder involving the degeneration of dopaminergic neurons in the substantia nigra, with the subsequent loss of their terminals in the striatum. Quercetin, a natural flavonoid, is a strong antioxidant and radical scavenger. Therefore, its neuroprotective effect in a model of Parkinson’s disease in rat was evaluated.Methods: For this purpose, unilateral intrastriatal 6-hydroxydopamine (6-OHDA-lesioned rats were pretreated with quercetin (20 mg/kg i.p. 1 hour before surgery and treated once a day for one month. Nissl-stained neurons of substantia nigra pars compacta (SNC were counted. Results: Number of Nissl-stained neurons in left side of SNC of lesion group was lower relative to sham-operated group (p<0.005 and it was higher in quercetin-treated lesion group as compared to untreated lesion group (p<0.01.Discussion: Flavonoid quercetin administration for one month could protect the neurons of SNC against 6-OHDA toxicity.

Neurite Outgrowth and Neuroprotective Effects of Quercetin from Caesalpinia mimosoides Lamk. on Cultured P19-Derived Neurons

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Napat Tangsaengvit

2013-01-01

Full Text Available Quercetin has been isolated for the first time from ethyl acetate extract of Caesalpinia mimosoides Lamk. C. mimosoides Lamk. (Fabaceae or Cha rueat (Thai name is an indigenous plant found in mixed deciduous forest in northern and north-eastern parts of Thailand. Thai rural people consume its young shoots and leaves as a fresh vegetable, as well as it is used for medicinal purposes.The antioxidant capacity in terms of radical scavenging activity of quercetin was determined as IC50 of 3.18 ± 0.07 µg/mL, which was higher than that of Trolox and ascorbic acid (12.54 ± 0.89 and 10.52 ± 0.48 µg/mL, resp.. The suppressive effect of quercetin on both purified and cellular acetylcholinesterase (AChE enzymes was investigated as IC50 56.84 ± 2.64 and 36.60 ± 2.78 µg/mL, respectively. In order to further investigate the protective ability of quercetin on neuronal cells, P19-derived neurons were used as a neuronal model in this study. As a result, quercetin at a very low dose of 1 nM enhanced survival and induced neurite outgrowth of P19-derived neurons. Furthermore, this flavonoid also possessed significant protection against oxidative stress induced by serum deprivation. Altogether, these findings suggest that quercetin is a multifunctional compound and promising valuable drugs candidate for the treatment of neurodegenerative disease.

Effect of Quercetin on Bone Mineral Status and Markers of Bone Turnover in Retinoic Acid-Induced Osteoporosis

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Oršolić Nada

2018-06-01

Full Text Available Retinoic acid-induced osteoporosis (RBM is one of the most common causes of secondary osteoporosis. This study tested the anti-osteoporetic effect of quercetin in RBM-induced bone loss model (RBM. After 14-day supplementation of 13cRA to induce RBM, rats were administered with quercetin (100 mg/kg or alendronate (40 mg/kg. We analysed changes in body and uterine weight of animals, femoral geometric characteristics, calcium and phosphorus content, bone weight index, bone hystology, bone mineral density (BMD, markers of bone turnover, lipid peroxidation, glutathione levels and SOD, CAT activity of liver, kidney spleen, and ovary as well as biochemical and haematological variables. In comparison to the control RBM rats, the treatment with quercetin increased bone weight index, BMD, osteocalcin level, femoral geometric characteristics, calcium and phosphorus content in the 13cRA-induced bone loss model. Histological results showed its protective action through promotion of bone formation. According to the results, quercetin could be an effective substitution for alendronate in 13cRA-induced osteoporosis. Good therapeutic potential of quercetin on rat skeletal system is based partly on its antioxidant capacity and estrogenic activity.

Comparison of the urinary excretion of quercetin glycosides from red onion and aglycone from dietary supplements in healthy subjects: a randomized, single-blinded, cross-over study.

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Shi, Yuanlu; Williamson, Gary

2015-05-01

Some intervention studies have shown that quercetin supplementation can regulate certain biomarkers, but it is not clear how the doses given relate to dietary quercetin (e.g. from onion). We conducted a two-period, two-sequence crossover study to compare the bioavailability of quercetin when administered in the form of a fresh red onion meal (naturally glycosylated quercetin) or dietary supplement (aglycone quercetin) under fasting conditions. Six healthy, non-smoking, adult males with BMI 22.7 ± 4.0 kg m(-2) and age 35.3 ± 12.3 y were grouped to take the two study meals in random order. In each of the 2 study periods, one serving of onion soup (made from 100 g fresh red onion, providing 156.3 ± 3.4 μmol (47 mg) quercetin) or a single dose of a quercetin dihydrate tablet (1800 ± 150 μmol (544 mg) of quercetin) were administered following 3 d washout. Urine samples were collected up to 24 h, and after enzyme deconjugation, quercetin was quantified by LC-MS. The 24 h urinary excretion of quercetin (1.69 ± 0.79 μmol) from red onion in soup was not significantly different to that (1.17 ± 0.44 μmol) for the quercetin supplement tablet (P = 0.065, paired t-test). This means that, in practice, 166 mg of quercetin supplement would be comparable to about 10 mg of quercetin aglycone equivalents from onion. These data allow intervention studies on quercetin giving either food or supplements to be more effectively compared.

Effect of Novel Quercetin Titanium Dioxide-Decorated Multi-Walled Carbon Nanotubes Nanocomposite on Bacillus subtilis Biofilm Development

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Diana S. Raie

2018-01-01

Full Text Available The present work was targeted to design a surface against cell seeding and adhering of bacteria, Bacillus subtilis. A multi-walled carbon nanotube/titanium dioxide nano-power was produced via simple mixing of carbon nanotube and titanium dioxide nanoparticles during the sol-gel process followed by heat treatment. Successfully, quercetin was immobilized on the nanocomposite via physical adsorption to form a quercetin/multi-walled carbon nanotube/titanium dioxide nanocomposite. The adhesion of bacteria on the coated-slides was verified after 24 h using confocal laser-scanning microscopy. Results indicated that the quercetin/multi-walled carbon nanotube/titanium dioxide nanocomposite had more negativity and higher recovery by glass surfaces than its counterpart. Moreover, coating surfaces with the quercetin-modified nanocomposite lowered both hydrophilicity and surface-attached bacteria compared to surfaces coated with the multi-walled carbon nanotubes/titanium dioxide nanocomposite.

Quercetin inhibits the poly(dA:dT)-induced secretion of IL-18 via down-regulation of the expressions of AIM2 and pro-caspase-1 by inhibiting the JAK2/STAT1 pathway in IFN-γ-primed human keratinocytes.

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Lee, Kyung-Mi; Kang, Jung Hoon; Yun, Mihee; Lee, Seong-Beom

2018-06-05

Quercetin, a polyphenol, belongs to a class of flavonoids that exerts anti-inflammatory effects. Interleukin (IL)-18 is a member of the IL-1 family cytokine that regulates immune responses and is implicated in various inflammatory skin diseases. Absent in melanoma 2 (AIM2) is a cytosolic double-stranded (ds) DNA sensor that recognizes the dsDNA of a microbial or host origin. Binding of dsDNA to AIM2 simulates caspase-1-dependent inflammasome activity, which leads to the production of IL-1β and IL-18. Increased levels of AIM2 have been observed in patients with inflammatory skin diseases. In the current study, we investigated the issue of whether or how Quercetin attenuates poly (dA:dT), a synthetic analog of microbial dsDNA, -induced IL-18 secretion in IFN-γ-primed human keratinocytes. Treatment with 5 and 10 μM of Quercetin inhibited the poly (dA:dT)-induced secretion of IL-18 after IFN-γ priming and before poly (dA:dT)-induced AIM2 activation. In addition, treatment with Quercetin at 10 μM, significantly inhibited the phosphorylation of JAK2 and STAT1, and the nuclear translocation of phosphorylated STAT1 in poly (dA:dT)-treated and IFN-γ-primed keratinocytes. These results suggest that treatment with Quercetin inhibits the poly (dA:dT)-induced secretion of IL-18 via down-regulation of the expressions of AIM2 and pro-caspase-1 by inhibiting the JAK2/STAT1 pathway in IFN-γ-primed keratinocytes. Copyright © 2018 Elsevier Inc. All rights reserved.

Anthocyanin indexes, quercetin, kaempferol, and myricetin concentration in leaves and fruit of Abutilon theophrasti Medik. genetic resources

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Anthocyanin indexes, quercetin, kaempferol, and myricetin may provide industry with potential new medicines or nutraceuticals. Velvetleaf (Abutilon theophrasti Medik) leaves from 42 accessions were analyzed for anthocyanin indexes while both leaves and fruit were used for quercetin, kaempferol, and ...

Cardioprotective effects of lipoic acid, quercetin and resveratrol on oxidative stress related to thyroid hormone alterations in long-term obesity.

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Cheserek, Maureen Jepkorir; Wu, Guirong; Li, Longnan; Li, Lirong; Karangwa, Eric; Shi, Yonghui; Le, Guowei

2016-07-01

This study investigated possible mechanisms for cardioprotective effects of lipoic acid (LA), quercetin (Q) and resveratrol (R) on oxidative stress related to thyroid hormone alterations in long-term obesity. Female C57BL/6 mice were fed on high-fat diet (HFD), HFD+LA, HFD+R, HFD+Q and normal diet for 26weeks. Body weight, blood pressure, thyroid hormones, oxidative stress markers, angiotensin converting enzyme (ACE), nitric oxide synthase (NOS) and ion pump activities were measured, and expression of cardiac genes was analyzed by real-time polymerase chain reaction. HFD induced marked increase (Pstress, while plasma triidothyronine levels reduced. ACE activity increased (Pobesity thereby restoring plasma thyroid hormone levels and attenuating oxidative stress in the heart and thus may have therapeutic potential in heart diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Quercetin Inhibits Peripheral and Spinal Cord Nociceptive Mechanisms to Reduce Intense Acute Swimming-Induced Muscle Pain in Mice

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Borghi, Sergio M.; Pinho-Ribeiro, Felipe A.; Fattori, Victor; Bussmann, Allan J. C.; Vignoli, Josiane A.; Camilios-Neto, Doumit; Casagrande, Rubia; Verri, Waldiceu A.

2016-01-01

The present study aimed to evaluate the effects of the flavonoid quercetin (3,3´,4´,5,7-pentahydroxyflavone) in a mice model of intense acute swimming-induced muscle pain, which resembles delayed onset muscle soreness. Quercetin intraperitoneal (i.p.) treatment dose-dependently reduced muscle mechanical hyperalgesia. Quercetin inhibited myeloperoxidase (MPO) and N-acetyl-β-D- glucosaminidase (NAG) activities, cytokine production, oxidative stress, cyclooxygenase-2 (COX-2) and gp91phox mRNA expression and muscle injury (creatinine kinase [CK] blood levels and myoblast determination protein [MyoD] mRNA expression) as well as inhibited NFκB activation and induced Nrf2 and HO-1 mRNA expression in the soleus muscle. Beyond inhibiting those peripheral effects, quercetin also inhibited spinal cord cytokine production, oxidative stress and glial cells activation (glial fibrillary acidic protein [GFAP] and ionized calcium-binding adapter molecule 1 [Iba-1] mRNA expression). Concluding, the present data demonstrate that quercetin is a potential molecule for the treatment of muscle pain conditions related to unaccustomed exercise. PMID:27583449

Red wine alcohol promotes quercetin absorption and directs its metabolism towards isorhamnetin and tamarixetin in rat intestine in vitro

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Dragoni, Stefania; Gee, Jennifer; Bennett, Richard; Valoti, Massimo; Sgaragli, Giampietro

2006-01-01

Moderate consumption of red wine has been associated with beneficial effects on human health, and this has been attributed to the flavonoid content. Factors that influence the bioavailability of this group of polyphenolic compounds are therefore important. Using the rat cannulated everted jejunal sac technique, we have investigated the effect of alcohol on the intestinal absorption of quercetin and its 3-O-glucoside from red wine. Tissue preparations were incubated in whole or dealcoholised red wine, diluted 1 : 1 with Krebs buffer for 20 min at 37°C, after which the mucosa was removed and processed for HPLC analysis. Tissues exposed to red wine had significantly higher amounts of both quercetin (× 3; P<0.001) and quercetin-3-O-glucoside (× 1.5; P<0.01) associated with them, compared with sacs incubated in the dealcoholised equivalent. In addition, both tamarixetin (T) and isorhamnetin (I), in the mucosal tissue from sacs exposed to the whole wine, were significantly elevated approximately two fold (P<0.05; P<0.01, respectively). Similar results were obtained when sacs were incubated in Krebs buffer containing a mixture of pure quercetin and quercetin-3-O-glucoside with or without alcohol, and, although effects on the apparent absorption of Q and Q-3-G were not so marked, concentrations of the metabolites quercetin-3-O-glucuronide and I were significantly increased by the presence of alcohol (P<0.01 and P<0.001, respectively). It is therefore plausible that the moderate alcohol content of red wine contributes to its beneficial health effects in humans by both increasing the absorption of quercetin and quercetin-3-O-glucoside and by channelling their metabolism towards O-methylation to yield compounds (T and I), which have potential protective effects against cancer and cardiovascular diseases. PMID:16444288

An Intestinal Farnesoid X Receptor–Ceramide Signaling Axis Modulates Hepatic Gluconeogenesis in Mice

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Xie, Cen; Shi, Jingmin; Gao, Xiaoxia; Sun, Dongxue; Sun, Lulu; Wang, Ting; Takahashi, Shogo; Anitha, Mallappa; Krausz, Kristopher W.; Patterson, Andrew D.

2017-01-01

Increasing evidence supports the view that intestinal farnesoid X receptor (FXR) is involved in glucose tolerance and that FXR signaling can be profoundly impacted by the gut microbiota. Selective manipulation of the gut microbiota–FXR signaling axis was reported to significantly impact glucose intolerance, but the precise molecular mechanism remains largely unknown. Here, caffeic acid phenethyl ester (CAPE), an over-the-counter dietary supplement and an inhibitor of bacterial bile salt hydrolase, increased levels of intestinal tauro-β-muricholic acid, which selectively suppresses intestinal FXR signaling. Intestinal FXR inhibition decreased ceramide levels by suppressing expression of genes involved in ceramide synthesis specifically in the intestinal ileum epithelial cells. The lower serum ceramides mediated decreased hepatic mitochondrial acetyl-CoA levels and pyruvate carboxylase (PC) activities and attenuated hepatic gluconeogenesis, independent of body weight change and hepatic insulin signaling in vivo; this was reversed by treatment of mice with ceramides or the FXR agonist GW4064. Ceramides substantially attenuated mitochondrial citrate synthase activities primarily through the induction of endoplasmic reticulum stress, which triggers increased hepatic mitochondrial acetyl-CoA levels and PC activities. These results reveal a mechanism by which the dietary supplement CAPE and intestinal FXR regulates hepatic gluconeogenesis and suggest that inhibiting intestinal FXR is a strategy for treating hyperglycemia. PMID:28223344

Antioxidant intervention of smoking-induced lung tumor in mice by vitamin E and quercetin

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Yang, Jie; Li, Jun-Wen; Wang, Lu; Chen, Zhaoli; Shen, Zhi-Qiang; Jin, Min; Wang, Xin-Wei; Zheng, Yufei; Qiu, Zhi-Gang; Wang, Jing-feng

2008-01-01

Epidemiological and in vitro studies suggest that antioxidants such as quercetin and vitamin E (VE) can prevent lung tumor caused by smoking; however, there is limited evidence from animal studies. In the present study, Swiss mouse was used to examine the potential of quercetin and VE for prevention lung tumor induced by smoking. Our results suggest that the incidence of lung tumor and tumor multiplicity were 43.5% and 1.00 ± 0.29 in smoking group; Quercetin has limited effects on lung tumor prevention in this in vivo model, as measured by assays for free radical scavenging, reduction of smoke-induced DNA damage and inhibition of apoptosis. On the other hand, vitamin E drastically decreased the incidence of lung tumor and tumor multiplicity which were 17.0% and 0.32 ± 0.16, respectively (p < 0.05); and demonstrated prominent antioxidant effects, reduction of DNA damage and decreased cell apoptosis (p < 0.05). Combined treatment with quercetin and VE in this animal model did not demonstrate any effect greater than that due to vitamin E alone. In addition, gender differences in the occurrence of smoke induced-lung tumor and antioxidant intervention were also observed. We conclude that VE might prevent lung tumor induced by smoking in Swiss mice

Fluorescence and picosecond induced absorption from the lowest singlet excited states of quercetin in solutions and polymer films

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Bondarev, S. L.; Tikhomirov, S. A.; Buganov, O. V.; Knyukshto, V. N.; Raichenok, T. F.

2017-03-01

The spectroscopic and photophysical properties of the biologically important plant antioxidant quercetin in organic solvents, polymer films of polyvinyl alcohol, and a buffer solution at pH 7.0 are studied by stationary luminescence and femtosecond laser spectroscopy at room temperature and 77 K. The large magnitude of the dipole moment of the quercetin molecule in the excited Franck-Condon state μ e FC = 52.8 C m indicates the dipolar nature of quercetin in this excited state. The transient induced absorption spectra S 1→ S n in all solvents are characterized by a short-wave band at λ abs max = 460 nm with exponential decay times in the range of 10.0-20.0 ps. In the entire spectral range at times of >100 ps, no residual induced absorption was observed that could be attributed to the triplet-triplet transitions T 1 → T k in quercetin. In polar solvents, two-band fluorescence was also recorded at room temperature, which is due to the luminescence of the initial enol form of quercetin ( 415 nm) and its keto form with a transferred proton (550 nm). The short-wave band is absent in nonpolar 2-methyltetrahydrofuran (2-MTHF). The spectra of fluorescence and fluorescence excitation exhibit a low dependence on the wavelength of excitation and detection, which may be related to the solvation and conformational changes in the quercetin molecule. Decreasing the temperature of a glassy-like freezing quercetin solution in ethanol and 2-MTHF to 77 K leads to a strong increase in the intensity (by a factor of 100) of both bands. The energy circuits for the proton transfer process are proposed depending on the polarity of the medium. The main channel for the exchange of electronic excitation energy in the quercetin molecule at room temperature is the internal conversion S 1 ⇝ S 0, induced by the state with a proton transfer.

Preliminary Study of Quercetin Affecting the Hypothalamic-Pituitary-Gonadal Axis on Rat Endometriosis Model

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Yang Cao

2014-01-01

Full Text Available In this study, the endometriosis rats model was randomly divided into 6 groups: model control group, ovariectomized group, Gestrinone group, and quercetin high/medium/low dose group. Rats were killed after 3 weeks of administration. The expression levels of serum FSH and LH were detected by ELISA. The localizations and quantities of ERα, ERβ, and PR were detected by immunohistochemistry and western blot. The results showed that the mechanism of quercetin inhibiting the growth of ectopic endometrium on rat endometriosis model may be through the decreasing of serum FSH and LH levels and then reducing local estrogen content to make the ectopic endometrium atrophy. Quercetin can decrease the expression of ERα, ERβ, and PR in hypothalamus, pituitary, and endometrium, thereby inhibiting estrogen and progesterone binding to their receptors to play the role of antiestrogen and progesterone.

Preparation of MIP grafts for quercetin by tandem aryl diazonium surface chemistry and photopolymerization

International Nuclear Information System (INIS)

Salmi, Zakaria; Benmehdi, Houcine; Lamouri, Aazdine; Decorse, Philippe; Jouini, Mohamed; Chehimi, Mohamed M.; Yagci, Yusuf

2013-01-01

The food antioxidant quercetin was used as a template in an ultrathin molecularly imprinted polymer (MIP) film prepared by photopolymerization. Indium tin oxide (ITO) plates were electrografted with aryl layers via a diazonium salt precursor bearing two terminal hydroxyethyl groups. The latter act as hydrogen donors for the photosensitizer isopropylthioxanthone and enabled the preparation of MIP grafts through radical photopolymerization of methacrylic acid (the functional monomer) and ethylene glycol dimethacrylate (the crosslinker) in the presence of quercetin (the template) on the ITO. The template was extracted, and the remaining ITO electrode used for the amperometric determination of quercetin at a working potential of 0.26 V (vs. SCE). The analytical range is from 5.10 −8 to 10 −4 mol L −1 , and the detection limit is 5.10 −8 mol L −1 . (author)

Ursolic acid inhibits superoxide production in activated neutrophils and attenuates trauma-hemorrhage shock-induced organ injury in rats.

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Tsong-Long Hwang

Full Text Available Neutrophil activation is associated with the development of organ injury after trauma-hemorrhagic shock. In the present study, ursolic acid inhibited the superoxide anion generation and elastase release in human neutrophils. Administration of ursolic acid attenuated trauma-hemorrhagic shock-induced hepatic and lung injuries in rats. In addition, administration of ursolic acid attenuated the hepatic malondialdehyde levels and reduced the plasma aspartate aminotransferase and alanine aminotransferase levels after trauma-hemorrhagic shock. In conclusion, ursolic acid, a bioactive natural compound, inhibits superoxide anion generation and elastase release in human neutrophils and ameliorates trauma-hemorrhagic shock-induced organ injury in rats.

Determination of quercetin using a photo-electrochemical sensor modified with titanium dioxide and a platinum(II)-porphyrin complex

International Nuclear Information System (INIS)

Tian, Li; Wang, Binbin; Chen, Ruizhan; Gao, Ye; Chen, Yanling; Li, Tianjiao

2015-01-01

A glassy carbon electrode (GCE) was modified with a film containing titanium dioxide and a Pt(II)-porphyrin complex, and its response to quercetin was investigated employing cyclic voltammetry and chronoamperometry. The oxidation current caused by quercetin is largely enhanced under UV illumination. The effects of pH value, mass of TiO 2 in the film, UV illumination time and applied potential were studied. Under optimized conditions, the peak current at a typically applied voltage of +0.4 V depends linearly on the concentration of quercetin in the 0.002 to 50 mg L −1 range. The detection limit (at an SNR of 3) is 0.8 μg L −1 . The method was successfully applied to the determination of quercetin in (spiked) samples of tea and apple juice. (author)

Maraviroc attenuates trauma-hemorrhage-induced hepatic injury through PPAR gamma-dependent pathway in rats.

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Fu-Chao Liu

Full Text Available Maraviroc is a CC-chemokine receptor 5 (CCR5 antagonist with potent antiviral and cancer preventive effects. Recent evidence suggests that the co-existence of CCR5 in various cell types is involved in inflammation. However, the effects that CCR5 antagonists produce in trauma-hemorrhage remain unknown. The peroxisome proliferator-activated receptor gamma (PPAR(γ pathway exerts anti-inflammatory effects in injury. In this study, we hypothesized that maraviroc administration in male rats, after trauma-hemorrhage, decreases cytokine production and protects against hepatic injury through a PPAR(γ-dependent pathway. Male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure maintained at approximately 35-40 mmHg for 90 minutes, followed by fluid resuscitation. During resuscitation, a single dose of maraviroc (3 mg/kg, intravenously with and without a PPAR(γ antagonist GW9662 (1 mg/kg, intravenously, GW9662 or vehicle was administered. Plasma alanine aminotransferase (ALT with aspartate aminotransferase (AST concentrations and various hepatic parameters were measured (n=8 rats/group at 24 hours after resuscitation. The results showed that trauma-hemorrhage increased hepatic myeloperoxidase activity, intercellular adhesion molecule-1 and interleukin-6 levels, and plasma ALT and AST concentrations. These parameters were significantly improved in the maraviroc-treated rats subjected to trauma-hemorrhage. Maraviroc treatment also increased hepatic PPAR(γ expression compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of GW9662 with maraviroc abolished the maraviroc-induced beneficial effects on the above parameters and hepatic injury. These results suggest that the protective effect of maraviroc administration on alleviation of hepatic injury after trauma-hemorrhage, which is, at least in part, through PPAR(γ-dependent pathway.

Protection by quercetin and quercetin-rich fruit juice against induction of oxidative DNA damage and formation of BPDE-DNA adducts in human lymphocytes

NARCIS (Netherlands)

Wilms, L.C.; Hollman, P.C.H.; Boots, A.W.; Kleinjans, J.C.S.

2005-01-01

Flavonoids are claimed to protect against cardiovascular disease, certain forms of cancer and ageing, possibly by preventing initial DNA damage. Therefore, we investigated the protective effects of the flavonoid quercetin against the formation of oxidative DNA damage and bulky DNA adducts in human

Quercetin and fisetin enhanced the small intestine cellular uptake and plasma levels of epi-catechins in in vitro and in vivo models.

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Chung, Jin-Oh; Lee, Seon-Bong; Jeong, Kang-Hyun; Song, Ji-Hoon; Kim, Su-Kyung; Joo, Kyung-Mi; Jeong, Hyun-Woo; Choi, Jin-Kyu; Kim, Jeong-Kee; Kim, Wan-Gi; Shin, Song-Seok; Shim, Soon-Mi

2018-01-24

Quercetin and fisetin, known as catechol-containing flavonoids, could positively affect the absorption of catechins due to their strong affinity for catechol-O-methyl transferase (COMT), which can methylate and cause the excretion of catechins. The current study examined the effect of quercetin and fisetin on the absorption of epi-catechins (ECs) by using a Caco-2 cell line and an in vivo model. The intestinal transport of total catechins by Caco-2 cells was enhanced from 1.3- to 1.6-fold and 1.4- to 1.7-fold by adding quercetin and fisetin, respectively, compared to the control. It was even higher in the treatment with a mixture of quercetin and fisetin. While EC had the highest value of intestinal transport (169% of the control) in 10% quercetin treatment, EGC (235%), EGCG (244%), and ECG (242%) were significantly transported in the treatment with a 5% mixture of quercetin and fisetin (p < 0.05). In an in vivo pharmacokinetic study, the values of the area under the plasma concentration-time curve (AUC, ng h mL -1 ) were also higher in rats orally administered EGCG with 10% quercetin (365.5 ± 25.5) or 10% fisetin (825.3 ± 46.7) than in those administered EGCG only (111.3 ± 13.1). Methylated quercetin and methylated fisetin were determined to be m/z 317.24 and m/z 301.25 [M + H] + with their own product ions, respectively. The results indicate that quercetin or fisetin is superior to ECs for methylation by COMT.

A combination of methylprednisolone and quercetin is effective for the treatment of cardiac contusion following blunt chest trauma in rats

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Demir, F. [Department of Pediatric Cardiology, Faculty of Medicine, Dicle University, Diyarbakır (Turkey); Güzel, A. [Department of Pediatrics, Faculty of Medicine, Ondokuz Mayıs University, Samsun (Turkey); Katı, C. [Department of Emergency Medicine, Faculty of Medicine, Ondokuz Mayıs University, Samsun (Turkey); Karadeniz, C. [Pediatric Cardiology Services, Behçet Uz Children' s Hospital, İzmir (Turkey); Akdemir, U. [Department of Emergency Medicine, Faculty of Medicine, Ondokuz Mayıs University, Samsun (Turkey); Okuyucu, A. [Department of Medical Biochemistry, Faculty of Medicine, Ondokuz Mayıs University, Samsun (Turkey); Gacar, A. [Department of Pathology, Faculty of Veterinary Medicine, Ondokuz Mayıs University, Samsun (Turkey); Özdemir, S. [Department of Pediatrics, Faculty of Medicine, Ondokuz Mayıs University, Samsun (Turkey); Güvenç, T. [Department of Pathology, Faculty of Veterinary Medicine, Ondokuz Mayıs University, Samsun (Turkey)

2014-08-01

Cardiac contusion is a potentially fatal complication of blunt chest trauma. The effects of a combination of quercetin and methylprednisolone against trauma-induced cardiac contusion were studied. Thirty-five female Sprague-Dawley rats were divided into five groups (n=7) as follows: sham, cardiac contusion with no therapy, treated with methylprednisolone (30 mg/kg on the first day, and 3 mg/kg on the following days), treated with quercetin (50 mg·kg{sup −1}·day{sup −1}), and treated with a combination of methylprednisolone and quercetin. Serum troponin I (Tn-I) and tumor necrosis factor-alpha (TNF-α) levels and cardiac histopathological findings were evaluated. Tn-I and TNF-α levels were elevated after contusion (P=0.001 and P=0.001). Seven days later, Tn-I and TNF-α levels decreased in the rats treated with methylprednisolone, quercetin, and the combination of methylprednisolone and quercetin compared to the rats without therapy, but a statistical significance was found only with the combination therapy (P=0.001 and P=0.011, respectively). Histopathological degeneration and necrosis scores were statistically lower in the methylprednisolone and quercetin combination group compared to the group treated only with methylprednisolone (P=0.017 and P=0.007, respectively). However, only degeneration scores were lower in the combination therapy group compared to the group treated only with quercetin (P=0.017). Inducible nitric oxide synthase positivity scores were decreased in all treatment groups compared to the untreated groups (P=0.097, P=0.026, and P=0.004, respectively). We conclude that a combination of quercetin and methylprednisolone can be used for the specific treatment of cardiac contusion.

Preparation and characterization of quercetin-loaded silica microspheres stabilized by combined multiple emulsion and sol-gel processes

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Kim Young Ho

2015-01-01

Full Text Available Despite exhibiting a wide spectrum of cosmeceutical properties, flavonoids and related compounds have some limitations related to their stability and solubility in distilledwater. In this project, we prepared silica microspheres using a novel method that uses polyol-in-oil-in-water (P/O/W emulsion and sol-gel methods as techniques for stabilizing quercetin. A stable microsphere suspension was successfully preparedusing a mixed solvent system comprising a polyol-phase medium for performing the sol-gel processing of tetraethyl orthosilicate (TEOS as an inorganic precursor with outer water phase. The morphology of the microsphere was evaluated using a scanning electron microscope (SEM, which showed a characteristic spherical particle shape with a smooth surface. Furthermore, SEM/EDSanalysis of a representative microsphere demonstrated that the inner structure of the silica microspheres was filled with quercetin. The mean diameter of the microsphere was in the range 20.6-35.0 μm, and the encapsulation efficiency ranged from 17.8% to 27.5%. The free and encapsulated quercetin samples were incubated in separateaqueous solutions at 25 and 42°C for 28 days. The residualcontent of the quercetin encapsulated by silica microspheres was 82% at 42°C. In contrast, that of the free quercetin stored at 42°C decreased to ~24%.

Quercetin postconditioning attenuates myocardial ischemia/reperfusion injury in rats through the PI3K/Akt pathway

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Y. Wang

2013-09-01

Full Text Available Quercetin (Que, a plant-derived flavonoid, has multiple benefical actions on the cardiovascular system. The current study investigated whether Que postconditioning has any protective effects on myocardial ischemia/reperfusion (I/R injury in vivo and its potential cardioprotective mechanisms. Male Sprague-Dawley rats were randomly allocated to 5 groups (20 animals/group: sham, I/R, Que postconditioning, Que+LY294002 [a phosphatidylinositol 3-kinase (PI3K/Akt signaling pathway inhibitor], and LY294002+I/R. I/R was produced by 30-min coronary occlusion followed by 2-h reperfusion. At the end of reperfusion, myocardial infarct size and biochemical changes were compared. Apoptosis was evaluated by both TUNEL staining and measurement of activated caspase-3 immunoreactivity. The phosphorylation of Akt and protein expression of Bcl-2 and Bax were determined by Western blotting. Que postconditioning significantly reduced infarct size and serum levels of creatine kinase and lactate dehydrogenase compared with the I/R group (all P<0.05. Apoptotic cardiomyocytes and caspase-3 immunoreactivity were also suppressed in the Que postconditioning group compared with the I/R group (both P<0.05. Akt phosphorylation and Bcl-2 expression increased after Que postconditioning, but Bax expression decreased. These effects were inhibited by LY294002. The data indicate that Que postconditioning can induce cardioprotection by activating the PI3K/Akt signaling pathway and modulating the expression of Bcl-2 and Bax proteins.

Quercetin postconditioning attenuates myocardial ischemia/reperfusion injury in rats through the PI3K/Akt pathway

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Wang, Y.; Zhang, Z.Z.; Wu, Y.; Ke, J.J.; He, X.H.; Wang, Y.L. [Department of Anesthesiology, Zhongnan Hospital, Wuhan University, Wuhan (China)

2013-09-24

Quercetin (Que), a plant-derived flavonoid, has multiple benefical actions on the cardiovascular system. The current study investigated whether Que postconditioning has any protective effects on myocardial ischemia/reperfusion (I/R) injury in vivo and its potential cardioprotective mechanisms. Male Sprague-Dawley rats were randomly allocated to 5 groups (20 animals/group): sham, I/R, Que postconditioning, Que+LY294002 [a phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway inhibitor], and LY294002+I/R. I/R was produced by 30-min coronary occlusion followed by 2-h reperfusion. At the end of reperfusion, myocardial infarct size and biochemical changes were compared. Apoptosis was evaluated by both TUNEL staining and measurement of activated caspase-3 immunoreactivity. The phosphorylation of Akt and protein expression of Bcl-2 and Bax were determined by Western blotting. Que postconditioning significantly reduced infarct size and serum levels of creatine kinase and lactate dehydrogenase compared with the I/R group (all P<0.05). Apoptotic cardiomyocytes and caspase-3 immunoreactivity were also suppressed in the Que postconditioning group compared with the I/R group (both P<0.05). Akt phosphorylation and Bcl-2 expression increased after Que postconditioning, but Bax expression decreased. These effects were inhibited by LY294002. The data indicate that Que postconditioning can induce cardioprotection by activating the PI3K/Akt signaling pathway and modulating the expression of Bcl-2 and Bax proteins.

Enhanced therapeutic benefit of quercetin-loaded phytosome nanoparticles in ovariectomized rats.

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Abd El-Fattah, Abeer I; Fathy, Mohamed M; Ali, Zeinab Y; El-Garawany, Abd El-Rahman A; Mohamed, Ehsan K

2017-06-01

Quercetin, a dietary flavonol phytoestrogen, has many health benefits but it is poorly absorbed when administered orally. To improve its bioavailability, we prepared quercetin-loaded phytosome nanoparticles (QP) using the thin film hydration method. The prepared nano-formulations were characterized using different techniques. Transmission electron microscopy revealed the homogeneously spherical, well and uniformly dispersed, nano-sized nature of QP. Dynamic light scattering measurements of QP (70 ± 7.44 nm) also confirmed this. Stability of the formed nanoparticles was established via zeta potential determination. The prepared QP exhibited very high encapsulation efficiency (98.4%). The estrogenic activity of QP, concerning inflammation, oxidative stress, bone, lipid profile, blood glucose level and weight gain, was investigated in ovariectomized rat model using 10 and 50 mg/kg/day oral doses for 4 weeks. Treatment with QP showed significant increase in serum calcium, inorganic phosphorus and glutathione content. Whereas, it significantly decreased serum alkaline phosphatase, acid phosphatase, malondialdehyde level, tumor necrosis factor-alpha and glucose level and improved lipid profile. Consequently, the results obtained confirm the superiority of QP over free quercetin at the same doses as a promising hormone replacement therapy. Copyright © 2017 Elsevier B.V. All rights reserved.

Chemoprevention by Quercetin of Oral Squamous Cell Carcinoma by Suppression of the NF-κB Signaling Pathway in DMBA-treated Hamsters.

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Zhang, Wen; Yin, Gang; Dai, Jianguo; Sun, Y U; Hoffman, Robert M; Yang, Zhijian; Fan, Yuan

2017-08-01

The aim of this study was to investigate the effects of the flavonoid quercetin on chemoprevention of oral squamous cell carcinoma (OSCC). The study involved molecular signaling pathways in 7,12-dimethylbenz(a) anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis. DMBA (0.5%) was painted at the right buccal pouches of hamsters for 14 weeks to induce carcinoma. DMBA-treated hamsters received simultaneous doses of quercetin. Animals without DMBA induction were used as normal controls. The incidence of OSCC and the severity of pre-malignant lesions were determined histologically. Apoptosis in the pouch tissue was determined by TUNEL staining. The mRNA and protein expression of NF-κB p50 and p65, as well as Bcl-2 and Bax genes were analyzed using RT-PCR and Western blotting, respectively. Quercetin, at various doses, significantly reduced OSCC incidence and severity of hyperplasia and dysplasia compared to the DMBA-induction-only group (p<0.01). Apoptosis was induced by quercetin treatment compared to the DMBA-induction-only group (p<0.01). mRNA and protein expression of NF-κB p50, p65 as well as Bcl-2 genes were significantly suppressed by quercetin at high doses compared to DMBA induction only (p<0.05). However, mRNA and protein expression of the Bax gene was increased by quercetin treatment at medium and high doses, compared to the DMBA-induction-only group (p<0.05). Quercetin significantly reduced body-weight loss compared to the DMBA-induction-only group (p<0.05). Quercetin reduced tumor incidence and induced apoptosis through modulation of NF-κB signaling and its target genes Bcl-2 and Bax in the DMBA-induced carcigenesis hamster model, suggesting the potential of quercetin as a candidate for OSCC chemoprevention. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Quercetin inhibits the invasion and mobility of murine melanoma B16-BL6 cells through inducing apoptosis via decreasing Bcl-2 expression.

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Zhang, X; Xu, Q; Saiki, I

2000-01-01

Quercetin has been known to have anti-tumor and anti-oxidation activities. In the present study, we have investigated its in vitro anti-metastatic activity. Quercetin inhibited the invasion and mobility of murine melanoma B16-BL6 cells in a dose-dependent manner but did not affect their adhesion to either laminin, fibronectin, or type VI collagen. Moreover, quercetin significantly inhibited the proliferation of B16-BL6 cells only in the case of time incubation longer than 48 h. Quercetin dose-dependently decreased the cell rates in S and G2-M phases of cell cycle. The effect of quercetin to cause a remarkable apoptosis of B16-BL6 cells was also demonstrated by flow cytometric assay as well as DNA fragmentation with a typical 180-bp ladder band in agarose electrophoresis and a quantitative analysis. Furthermore, quercetin markedly inhibited the expression of anti-apoptotic protein Bcl-2 but hardly influenced Bcl-XL. These results suggest that the inhibition of quercetin on invasiveness and migration of B16-BL6 cells are closely associated with the arrest of cell cycle as well as the induction of apoptosis by decreasing the Bcl-2 expression.

Quercetin treatment regulates the Na+,K+-ATPase activity, peripheral cholinergic enzymes, and oxidative stress in a rat model of demyelination.

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Carvalho, Fabiano B; Gutierres, Jessié M; Beckmann, Diego; Santos, Rosmarini P; Thomé, Gustavo R; Baldissarelli, Jucimara; Stefanello, Naiara; Andrades, Amanda; Aiello, Graciane; Ripplinger, Angel; Lucio, Bruna M; Ineu, Rafael; Mazzanti, Alexandre; Morsch, Vera; Schetinger, Maria Rosa; Andrade, Cinthia M

2018-07-01

Quercetin is reported to exert a plethora of health benefits through many different mechanisms of action. This versatility and presence in the human diet has attracted the attention of the scientific community, resulting in a huge output of in vitro and in vivo (preclinical) studies. Therefore, we hypothesized that quercetin can protect Na + ,K + -ATPase activity in the central nervous system, reestablish the peripheral cholinesterases activities, and reduce oxidative stress during demyelination events in rats. In line with this expectation, our study aims to find out how quercetin acts on the Na + ,K + -ATPase activity in the central nervous system, peripheral cholinesterases, and stress oxidative markers in an experimental model of demyelinating disease. Wistar rats were divided into 4 groups: vehicle, quercetin, ethidium bromide (EB), and EB plus quercetin groups. The animals were treated once a day with vehicle (ethanol 20%) or quercetin 50 mg/kg for 7 (demyelination phase, by gavage) or 21 days (remyelination phase) after EB (0.1%, 10 μL) injection (intrapontine).The encephalon was removed, and the pons, hypothalamus, cerebral cortex, hippocampus, striatum, and cerebellum were dissected to verify the Na + ,K + -ATPase activity. Our results showed that quercetin protected against reduction in Na + ,K + -ATPase in the pons and cerebellum in the demyelination phase, and it increased the activity of this enzyme in the remyelination phase. During the demyelination, quercetin promoted the increase in acetylcholinesterase activity in whole blood and lymphocytes induced by EB, and it reduced the increase in acetylcholinesterase activity in lymphocytes in the remyelination phase. On day 7, EB increased the superoxide dismutase and decreased catalase activities, as well as increased the thiobarbituric acid-reactive substance levels. Taken together, these results indicated that quercetin regulates the Na + ,K + -ATPase activity, affects the alterations of redox state

Plasma concentrations and urinary excretion of the antioxidant flavonols quercetin and kaempferol as biomarkers for dietary intake.

NARCIS (Netherlands)

Vries, de J.H.M.; Hollman, P.C.H.; Meyboom, S.; Buysman, M.N.C.P.; Zock, P.L.; Staveren, van W.A.; Katan, M.B.

1998-01-01

Flavonols are antioxidants that may reduce the risk of heart disease. Two major flavonols in the diet are quercetin and kaempferol, and their main sources in The Netherlands are tea and onions. We investigated whether plasma concentrations and urinary excretion of quercetin and kaempferol in humans

Protective effects of Bombyx mori, quercetin and benazepril against doxorubicin induced cardiotoxicity and nephrotoxicity

OpenAIRE

Abdul S. Nazmi; Shibli J. Ahmad; Krishna K. Pillai; Mohammad Akhtar; Aftab Ahmad; Abul K. Najmi

2016-01-01

The present study was conducted with the aim of evaluating the protective effects of Bombyx mori, quercetin and benazepril on doxorubicin (DXR) induced cardiotoxicity and nephrotoxicity in rats. B. mori, quercetin and benazepril were administered for 7 days, and a single intravenous injection of 10 mg/kg body weight of DXR on day five. The animals were sacrificed 48 h after DXR administration. DXR produced a significant elevation in the malondialdehyde (MDA) level and significantly inhibited ...

The effects of quercetin towards reactive oxygen species levels and glutathione in Toxoplasma gondii profilin-exposed adipocytes in vitro

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Yulia D.S.

2018-04-01

Full Text Available Toxoplasma gondii (T. gondii has been found to potentially cause adipocyte dysfunction by activating the inflammatory pathways through its profilin. In response to inflammation, adipocytes produce Reactive Oxygen Species (ROS. To scavenge ROS, endogenous or exogenous antioxidants are required. Glutathione (GSH is one of enzimatic antioxidant that abundant in all of body cells. Quercetin, an exogenous antioxidant, can be widely found in natural products. This research aims to explore the effects of quercetin towards ROS and GSH stimulated from T. gondii profilin-exposed adipocytes. To achieve this, adipocytes were exposed to 20 µM T. gondii profilin and treated with four doses of quercetin; 31.25, 62.5, 125, and 250 µM. The results showed that quercetin significantly reduced the ROS levels (p <0,001 and significantly increased GSH (p <0,001 in T. gondii profilin-exposed adipocytes compared to untreated cells, with an effective dose of 62.5µM. This study implies that quercetin might be a promising candidate for development of antioxidant treatment interventions to prevent toxoplasmosis-mediated adipocytopathy.

Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models

NARCIS (Netherlands)

Kleemann, R.; Verschuren, L.; Morrison, M.; Zadelaar, A.S.M.; Erk, M.J. van; Wielinga, P.Y.; Kooistra, T.

2011-01-01

Objective: Polyphenols such as quercetin may exert several beneficial effects, including those resulting from anti-inflammatory activities, but their impact on cardiovascular health is debated. We investigated the effect of quercetin on cardiovascular risk markers including human C-reactive protein

Neuroprotective role of quercetin in locomotor activities and cholinergic neurotransmission in rats experimentally demyelinated with ethidium bromide.

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Beckmann, Diego V; Carvalho, Fabiano B; Mazzanti, Cinthia M; Dos Santos, Rosmarini P; Andrades, Amanda O; Aiello, Graciane; Rippilinger, Angel; Graça, Dominguita L; Abdalla, Fátima H; Oliveira, Lizielle S; Gutierres, Jessié M; Schetinger, Maria Rosa C; Mazzanti, Alexandre

2014-05-17

The purpose of this study was to investigate whether the flavonoid quercetin can prevent alterations in the behavioral tests and of cholinergic neurotransmission in rats submitted to the ethidium bromide (EB) experimental demyelination model during events of demyelination and remyelination. Wistar rats were randomly distributed into four groups (20 animals per group): Control (pontine saline injection and treatment with ethanol), Querc (pontine saline injection and treatment with quercetin), EB (pontine 0.1% EB injection and treatment with ethanol), and EB+Querc (pontine 0.1% EB injection and treatment with quercetin). The groups Querc and Querc+EB were treated once daily with quercetin (50mg/kg) diluted in 25% ethanol solution (1ml/kg) and the animals of the control and EB groups were treated once daily with 25% ethanol solution (1ml/kg). Two stages were observed: phase of demyelination (peak on day 7) and phase of remyelination (peak on day 21 post-injection). Behavioral tests (beam walking, foot fault and inclined plane test), acetylcholinesterase (AChE) activity and lipid peroxidation in pons, cerebellum, hippocampus, hypothalamus, striatum and cerebral cortex were measured. The quercetin promoted earlier locomotor recovery, suggesting that there was demyelination prevention or further remyelination velocity as well as it was able to prevent the inhibition of AChE activity and the increase of lipidic peroxidation, suggesting that this compound can protect cholinergic neurotransmission. These results may contribute to a better understanding of the neuroprotective role of quercetin and the importance of an antioxidant diet in humans to provide benefits in neurodegenerative diseases such as MS. Copyright © 2014. Published by Elsevier Inc.

Quantitative analysis of vasodilatory action of quercetin on intramural coronary resistance arteries of the rat in vitro.

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Anna Monori-Kiss

Full Text Available BACKGROUND: Dietary quercetin improves cardiovascular health, relaxes some vascular smooth muscle and has been demonstrated to serve as a substrate for the cyclooxygenase enzyme. AIMS: 1. To test quantitatively a potential direct vasodilatory effect on intramural coronary resistance artery segments, in different concentrations. 2. To scale vasorelaxation at different intraluminal pressure loads on such vessels of different size. 3. To test the potential role of prostanoids in vasodilatation induced by quercetin. METHODS: Coronary arterioles (70-240 µm were prepared from 24 rats and pressurized in PSS, using a pressure microangiometer. RESULTS: The spontaneous tone that developed at 50 mmHg was relaxed by quercetin in the 10(-9 moles/lit concentration (p<0.05, while 10(-5 moles/lit caused full relaxation. Significant relaxation was observed at all pressure levels (10-100 mmHg at 10(-7 moles/lit concentration of quercetin. The cyclooxygenase blocker indomethacin (10(-5 moles/lit induced no relaxation but contraction when physiological concentrations of quercetin were present in the tissue bath (p<0.02 with Anova, this contraction being more prominent in smaller vessels and in the higher pressure range (p<0.05, Pearson correlation. A further 2-8% contraction could be elicited by the NO blocker L-NAME (10(-4 moles/lit. CONCLUSION: These results demonstrate that circulating levels of quercetin (10(-7 moles/lit exhibit a substantial coronary vasodilatory effect. The extent of it is commeasurable with that of several other physiological mechanisms of coronary blood flow control. At least part of this relaxation is the result of an altered balance toward the production of endogenous vasodilatory prostanoids in the coronary arteriole wall.

The dietary flavonoids naringenin and quercetin acutely impair glucose metabolism in rodents possibly via inhibition of hypothalamic insulin signalling.

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Koch, Christiane E; Ganjam, Goutham K; Steger, Juliane; Legler, Karen; Stöhr, Sigrid; Schumacher, Daniela; Hoggard, Nigel; Heldmaier, Gerhard; Tups, Alexander

2013-03-28

Secondary metabolites of herbs and spices are widely used as an alternative strategy in the therapy of various diseases. The polyphenols naringenin, quercetin and curcumin have been characterised as anti-diabetic agents. Conversely, in vitro, naringenin and quercetin are described to inhibit phosphoinositide-3-kinase (PI3K), an enzyme that is essential for the neuronal control of whole body glucose homoeostasis. Using both in vitro and in vivo experiments, we tested whether the inhibitory effect on PI3K occurs in neurons and if it might affect whole body glucose homoeostasis. Quercetin was found to inhibit basal and insulin-induced phosphorylation of Akt (Ser473), a downstream target of PI3K, in HT-22 cells, whereas naringenin and curcumin had no effect. In Djungarian hamsters (Phodopus sungorus) naringenin and quercetin (10 mg/kg administered orally) diminished insulin-induced phosphorylation of Akt (Ser473) in the arcuate nucleus, indicating a reduction in hypothalamic PI3K activity. In agreement with this finding, glucose tolerance in naringenin-treated hamsters (oral) and mice (oral and intracerebroventricular) was reduced compared with controls. Dietary quercetin also impaired glucose tolerance, whereas curcumin was ineffective. Circulating levels of insulin and insulin-like growth factor-binding protein were not affected by the polyphenols. Oral quercetin reduced the respiratory quotient, suggesting that glucose utilisation was impaired after treatment. These data demonstrate that low doses of naringenin and quercetin acutely and potently impair glucose homoeostasis. This effect may be mediated by inhibition of hypothalamic PI3K signalling. Whether chronic impairments in glucose homoeostasis occur after long-term application remains to be identified.

The protective role of nitric oxide and nitric oxide synthases in whole-body hyperthermia-induced hepatic injury in rats.

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Chen, Chao-Fuh; Wang, David; Leu, Fur-Jiang; Chen, Hsing I

2012-01-01

The present study was designed to elucidate the role of endothelial nitric oxide (NO) synthase (eNOS), inducible NOS (iNOS)-derived NO and heat-shock protein (Hsp70) in a rat model of whole-body hyperthermia (WBH)-induced liver injury. Real-time polymerase chain reaction, immunohistochemistry and western blot were used to observe the mRNA and protein expression of eNOS, iNOS and Hsp70. Rats were exposed to hyperthermia by immersion for 60 min at a conscious state in a water bath maintained at 41°C. Plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were used to assess liver injury 15 h after the hyperthermia challenge. Nitrosative and oxidative mediators, particularly NO and hydroxyl radical were measured. Plasma AST, ALT, hydroxyl radical, and NO were significantly increased after WBH. There were 4.14 ± 0.42, 2.82 ± 0.34 and 2.91 ± 0.16-fold increases in the mRNA expression of eNOS, iNOS and Hsp70. Immunohistochemistry and western blot showed up-regulation of eNOS, iNOS and Hsp70 protein. An eNOS inhibitor (N(ω)-nitro-L-arginine methyl ester (L-NAME)), or an iNOS inhibitor (aminoguanidine (AG)), significantly aggravated the liver injury. On the contrary, administration of NO precursor, L-arginine (L-ARG), attenuated the liver injury. Hsp70 inhibitor quercetin reduced Hsp70, while aggravating the WBH-induced hepatic changes. WBH induces increases in eNOS, iNOS and Hsp70 expression with increase in NO release. The deleterious effects of L-NAME and AG and the protective effects of L-ARG and Hsp70 inhibitor on the liver function and pathology suggest that NO and heat shock protein play a beneficial role in the WBH-induced hepatic injury.

Toyocamycin attenuates free fatty acid-induced hepatic steatosis and apoptosis in cultured hepatocytes and ameliorates nonalcoholic fatty liver disease in mice.

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Takahara, Ikuko; Akazawa, Yuko; Tabuchi, Maiko; Matsuda, Katsuya; Miyaaki, Hisamitsu; Kido, Youko; Kanda, Yasuko; Taura, Naota; Ohnita, Ken; Takeshima, Fuminao; Sakai, Yusuke; Eguchi, Susumu; Nakashima, Masahiro; Nakao, Kazuhiko

2017-01-01

A high serum level of saturated free fatty acids (FFAs) is associated with the development of nonalcoholic fatty liver disease (NAFLD). X-box binding protein-1 (XBP-1) is activated by FFA treatment upon splicing. XBP-1 is a transcription factor induced by the endoplasmic reticulum (ER) stress sensor endoribonuclease inositol-requiring enzyme 1 alpha (IRE1α). However, the role of XBP-1 in NAFLD remains relatively unexplored. Toyocamycin was recently reported to attenuate the activation of XBP-1, possibly by inducing a conformational change in IRE1α. In this study, we examined the effect of toyocamycin on hepatocyte lipoapoptosis and steatosis. We also explored the effects of toyocamycin in a mouse model of NAFLD. Huh-7 cells and isolated rat primary hepatocytes were treated with palmitic acid (PA), which is a saturated FFA, in the presence or absence of toyocamycin. In addition, male C57BL/6J mice were fed a diet rich in saturated fat, fructose, and cholesterol (FFC) for 4 months, after which the effect of toyocamycin was assessed. Toyocamycin attenuated FFA-induced steatosis. It also significantly reduced PA-induced hepatocyte lipoapoptosis. In addition, toyocamycin reduced the expression of cytosine-cytosine-adenosine-adenosine-thymidine enhancer-binding protein homologous protein (CHOP), which is a key player in ER stress-mediated apoptosis, as well as its downstream cell death modulator, death receptor 5. In the in vivo study, toyocamycin ameliorated the liver injury caused by FFC-induced NAFLD. It also reduced hepatic steatosis and the expression of lipogenic genes. The data we obtained suggest that toyocamycin attenuates hepatocyte lipogenesis and ameliorates NAFLD in vivo and may therefore be beneficial in the treatment of NAFLD in humans.

Carbon monoxide-Releasing Molecule-2 (CORM-2 attenuates acute hepatic ischemia reperfusion injury in rats

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Zhang Weihui

2010-05-01

Full Text Available Abstract Background Hepatic ischemia-reperfusion injury (I/Ri is a serious complication occurring during liver surgery that may lead to liver failure. Hepatic I/Ri induces formation of reactive oxygen species, hepatocyte apoptosis, and release of pro-inflammatory cytokines, which together causes liver damage and organ dysfunction. A potential strategy to alleviate hepatic I/Ri is to exploit the potent anti-inflammatory and cytoprotective effects of carbon monoxide (CO by application of so-called CO-releasing molecules (CORMs. Here, we assessed whether CO released from CORM-2 protects against hepatic I/Ri in a rat model. Methods Forty male Wistar rats were randomly assigned into four groups (n = 10. Sham group underwent a sham operation and received saline. I/R group underwent hepatic I/R procedure by partial clamping of portal structures to the left and median lobes with a microvascular clip for 60 minutes, yielding ~70% hepatic ischemia and subsequently received saline. CORM-2 group underwent the same procedure and received 8 mg/kg of CORM-2 at time of reperfusion. iCORM-2 group underwent the same procedure and received iCORM-2 (8 mg/kg, which does not release CO. Therapeutic effects of CORM-2 on hepatic I/Ri was assessed by measuring serum damage markers AST and ALT, liver histology score, TUNEL-scoring of apoptotic cells, NFkB-activity in nuclear liver extracts, serum levels of pro-inflammatory cytokines TNF-α and IL-6, and hepatic neutrophil infiltration. Results A single systemic infusion with CORM-2 protected the liver from I/Ri as evidenced by a reduction in serum AST/ALT levels and an improved liver histology score. Treatment with CORM-2 also up-regulated expression of the anti-apoptotic protein Bcl-2, down-regulated caspase-3 activation, and significantly reduced the levels of apoptosis after I/Ri. Furthermore, treatment with CORM-2 significantly inhibited the activity of the pro-inflammatory transcription factor NF-κB as measured in

Therapeutic potentials of Quercetin in management of polycystic ovarian syndrome using Letrozole induced rat model: a histological and a biochemical study.

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Jahan, Sarwat; Abid, Abira; Khalid, Sidra; Afsar, Tayyaba; Qurat-Ul-Ain; Shaheen, Ghazala; Almajwal, Ali; Razak, Suhail

2018-04-03

PCOS is a leading endocrinopathy of young women instigating androgens elevation, insulin resistance, obesity, cardiometabolic and menstrual complications. The study investigated the effects of quercetin in a letrozole induced rat model of polycystic ovarian syndrome, which displayed both clinical and metabolic features as in PCOS women. Female Sprague Dawley (SD) rats were divided into four groups; control group received aqueous solution of carboxymethyl (CMC 0.5%); PCOS group administered with letrozole (1 mg/kg) dissolved in solution (CMC 0.5%); Metformin group given with metformin (20 mg/kg) + letrozole (1 mg/kg); and Quercetin group provided with quercetin (30 mg/kg) + letrozole (1 mg/kg). All doses were given orally via gavage, for 21 consecutive days and colpocytological analysis was carried till end. After 21rst day, blood was taken out, centrifuged and plasma was kept for biochemical analysis (ELISA, anti-oxidant enzymes, lipid profile) and the reproductive organs were dissected out for histopathological evaluation. Quercetin as a chief member of flavonoid, showed beneficial effects by decreasing body weight, ovarian diameter, cysts and restoring healthy follicles, follicle's extra-glandular layers, and corpora lutea in contrast to the positive control. Additionally, lipid profile and anti-oxidant status were also maintained to baseline which was very high in diseased rats (p < 0.001).Quercetin depicted a mark regulation in steroidogenesis by decreasing the levels of testosterone (0.78 ng/ml ± 0.14 in quercetin vs. PCOS positive control 1.69 ng/ml ± 0.17, p < 0.001) and estradiol (8.85 pg/ml ± 0.19 in quercetin vs. PCOS positive 1.61 pg/ml ± 0.29) and increasing progesterone levels (34.47 ng/ml ± 1.65 in quercetin vs. 11.08 ng/ml ± 1.17 in PCOS positive). The effects of quercetin were moderately parallel to the standard drug available in market i.e. metformin. The present study has confirmed that

Accuracy of ultrasonography in the detection of severe hepatic lipidosis in cats.

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Yeager, A E; Mohammed, H

1992-04-01

The accuracy of ultrasonography in detection of feline hepatic lipidosis was studied retrospectively. The following ultrasonographic criteria were associated positively with severe hepatic lipidosis: the liver hyperechoic, compared with falciform fat; the liver isoechoic or hyperechoic, compared with omental fat; poor visualization of intrahepatic vessel borders; and increased attenuation of sound by the liver. In a group of 36 cats with clinically apparent hepatobiliary disease and in which liver biopsy was done, liver hyperechoic, compared with falciform fat, was the best criterion for diagnosis of severe hepatic lipidosis with 91% sensitivity, 100% specificity, and 100% positive predictive value.

Protection by the flavonoids quercetin and luteolin against peroxide- or menadione-induced oxidative stress in MC3T3-E1 osteoblast cells.

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Fatokun, Amos A; Tome, Mercedes; Smith, Robert A; Darlington, L Gail; Stone, Trevor W

2015-01-01

Potential protective effects of the flavonoids quercetin and luteolin have been examined against the oxidative stress of MC3T3-E1 osteoblast-like cells. Although hydrogen peroxide and menadione reduced cell viability, the toxicity was prevented by desferrioxamine or catalase but not superoxide dismutase, suggesting the involvement of hydrogen peroxide in both cases. Quercetin and luteolin reduced the oxidative damage, especially that caused by hydrogen peroxide. When cultures were pre-incubated with quercetin or luteolin, protection was reduced or lost. Protection was also reduced when a 24 h pre-incubation with the flavonoids was followed by exposure to menadione alone. Pretreating cultures with luteolin impaired protection by quercetin, whereas quercetin pretreatment did not affect protection by luteolin. It is concluded that quercetin and luteolin suppress oxidative damage to MC3T3-E1 cells, especially caused by peroxide. The reduction in protection by pretreatment implies a down-regulation of part of the toxic transduction pathway.

Quercetin, kaempferol, myricetin, and fatty acid content among several Hibiscus sabdariffa accession calyces based on maturity in a greenhouse

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Flavonols including quercetin, kaempferol, myricetin, and fatty acids in plants have many useful health attributes including antioxidants, cholesterol lowering, and cancer prevention. Six accessions of roselle, Hibiscus sabdariffa calyces were evaluated for quercetin, kaempferol, and myricetin conte...

Quercetin modulates activities of Taiwan cobra phospholipase A 2 ...

Indian Academy of Sciences (India)

Home; Journals; Journal of Biosciences; Volume 37; Issue 2. Quercetin modulates activities of Taiwan cobra phospholipase A2 via its effects on membrane structure and membrane-bound mode of phospholipase A2. Yi-Ling Chiou Shinne-Ren Lin Wan-Ping Hu Long-Sen Chang. Articles Volume 37 Issue 2 June 2012 pp ...

The effect of quercetin on plasma oxidative status, C-reactive protein and blood pressure in women with rheumatoid arthritis

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Fatemeh Javadi

2014-01-01

Conclusions: In this study, quercetin had no effect on oxidative and inflammatory status of plasma and blood pressure in patients with RA. Further studies are needed to ensure the effect of quercetin on oxidative stress and inflammation in human.

The Impact of Transient Hepatic Attenuation Differences in the Diagnosis of Pseudoaneurysm and Arteriovenous Fistula on Follow-Up CT Scans after Blunt Liver Trauma

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Andreas Hjelm Brandt

2014-09-01

Full Text Available A feared complication to liver trauma is delayed vascular complication, such as pseudoaneurysm and arteriovenous fistula (PS/AF seen as focal enhancement on contrast-enhanced computed tomography (CT in the arterial phase. A hyperdense area termed transient hepatic attenuation difference (THAD representing altered hepatic blood flow can be seen in the arterial phase near the liver lesion. The objective of this study was to describe THAD and PS/AF on follow-up CT after blunt liver trauma, and to evaluate if THAD influenced the evaluation of PS/AF. Three radiology residents retrospectively evaluated scans of 78 patients. The gold standard for PS/AF was an evaluation by an experienced senior radiologist, while THAD was a consensus between the residents. PS/AF was present in 14% and THAD in 54%. THAD was located in the periphery of the lesion with hazy borders and mean HU levels of 100, while PS/AF was located within the lesion with focal enhancement and mean HU levels of 170 (p < 0.05. In evaluation of PS/AF, the likelihood of agreement between the observers and the gold standard was 89% when THAD was present, and 98% when THAD was absent (p = 0.04. THAD is common and can hamper the evaluation of PS/AF.

Molecular mechanisms underlying protective effects of quercetin against mitochondrial dysfunction and progressive dopaminergic neurodegeneration in cell culture and MitoPark transgenic mouse models of Parkinson's Disease.

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Ay, Muhammet; Luo, Jie; Langley, Monica; Jin, Huajun; Anantharam, Vellareddy; Kanthasamy, Arthi; Kanthasamy, Anumantha G

2017-06-01

Quercetin, one of the major flavonoids in plants, has been recently reported to have neuroprotective effects against neurodegenerative processes. However, since the molecular signaling mechanisms governing these effects are not well clarified, we evaluated quercetin's effect on the neuroprotective signaling events in dopaminergic neuronal models and further tested its efficacy in the MitoPark transgenic mouse model of Parkinson's disease (PD). Western blot analysis revealed that quercetin significantly induced the activation of two major cell survival kinases, protein kinase D1 (PKD1) and Akt in MN9D dopaminergic neuronal cells. Furthermore, pharmacological inhibition or siRNA knockdown of PKD1 blocked the activation of Akt, suggesting that PKD1 acts as an upstream regulator of Akt in quercetin-mediated neuroprotective signaling. Quercetin also enhanced cAMP response-element binding protein phosphorylation and expression of the cAMP response-element binding protein target gene brain-derived neurotrophic factor. Results from qRT-PCR, Western blot analysis, mtDNA content analysis, and MitoTracker assay experiments revealed that quercetin augmented mitochondrial biogenesis. Quercetin also increased mitochondrial bioenergetics capacity and protected MN9D cells against 6-hydroxydopamine-induced neurotoxicity. To further evaluate the neuroprotective efficacy of quercetin against the mitochondrial dysfunction underlying PD, we used the progressive dopaminergic neurodegenerative MitoPark transgenic mouse model of PD. Oral administration of quercetin significantly reversed behavioral deficits, striatal dopamine depletion, and TH neuronal cell loss in MitoPark mice. Together, our findings demonstrate that quercetin activates the PKD1-Akt cell survival signaling axis and suggest that further exploration of quercetin as a promising neuroprotective agent for treating PD may offer clinical benefits. © 2017 International Society for Neurochemistry.

Korean Pine Nut Oil Attenuated Hepatic Triacylglycerol Accumulation in High-Fat Diet-Induced Obese Mice

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Soyoung Park

2016-01-01

Full Text Available Korean pine nut oil (PNO has been reported to influence weight gain and lipid metabolism. We examined whether PNO replacement in a high-fat diet (HFD can ameliorate HFD-induced hepatic steatosis. Five-week-old male C57BL mice were fed control diets containing 10% of the energy from fat from PNO or soybean oil (SBO (PC, SC or HFDs with 45% of the energy from fat, with 10% from PNO or SBO and 35% from lard (PHFD, SHFD, for 12 weeks. Body weight gain and amount of white adipose tissue were lower in PHFD (10% and 18% lower, respectively compared with SHFD. Hepatic triacylglycerol (TG level was significantly lower in PHFD than the SHFD (26% lower. PNO consumption upregulated hepatic ACADL mRNA levels. The hepatic PPARG mRNA level was lower in the PC than in the SC. Expression of the sirtuin (SIRT 3 protein in white adipose tissue was down-regulated in the SHFD and restored in the PHFD to the level in the lean control mice. SIRT 3 was reported to be upregulated under conditions of caloric restriction (CR and plays a role in regulating mitochondrial function. PNO consumption resulted in lower body fat and hepatic TG accumulation in HFD-induced obesity, which seemed to be associated with the CR-mimetic response.

Exploring the oxidation and iron binding profile of a cyclodextrin encapsulated quercetin complex unveiled a controlled complex dissociation through a chemical stimulus.

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Diamantis, Dimitrios A; Ramesova, Sarka; Chatzigiannis, Christos M; Degano, Ilaria; Gerogianni, Paraskevi S; Karadima, Constantina; Perikleous, Sonia; Rekkas, Dimitrios; Gerothanassis, Ioannis P; Galaris, Dimitrios; Mavromoustakos, Thomas; Valsami, Georgia; Sokolova, Romana; Tzakos, Andreas G

2018-06-07

Flavonoids possess a rich polypharmacological profile and their biological role is linked to their oxidation state protecting DNA from oxidative stress damage. However, their bioavailability is hampered due to their poor aqueous solubility. This can be surpassed through encapsulation to supramolecular carriers as cyclodextrin (CD). A quercetin- 2HP-β-CD complex has been formerly reported by us. However, once the flavonoid is in its 2HP-β-CD encapsulated state its oxidation potential, its decomplexation mechanism, its potential to protect DNA damage from oxidative stress remained elusive. To unveil this, an array of biophysical techniques was used. The quercetin-2HP-β-CD complex was evaluated through solubility and dissolution experiments, electrochemical and spectroelectrochemical studies (Cyclic Voltammetry) UV-Vis spectroscopy, HPLC-ESI-MS/MS and HPLC-DAD, fluorescence spectroscopy, NMR Spectroscopy, theoretical calculations (density functional theory (DFT)) and biological evaluation of the protection offered against H 2 O 2 -induced DNA damage. Encapsulation of quercetin inside the supramolecule's cavity enhanced its solubility and oxidation profile is retained in its encapsulated state. Although the protective ability of the quercetin-2HP-β-CD complex against H 2 O 2 was diminished, iron serves as a chemical stimulus to dissociate the complex and release quercetin. We found that in a quercetin-2HP-β-CD inclusion complex quercetin retains its oxidation profile similarly to its native state, while iron can operate as a chemical stimulus to release quercetin from its host cavity. The oxidation profile of a natural product once it is encapsulated in a supramolecular cyclodextrin carrier as also it was discovered that decomplexation can be triggered by a chemical stimulus. Copyright © 2018. Published by Elsevier B.V.

Soy compared with milk protein in a western diet changes fecal microbiota and decreases hepatic steatosis in obese OLETF rats

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Soy protein is effective at preventing hepatic steatosis; however, the mechanisms are poorly understood. We tested the hypothesis that soy versus dairy protein-based diet would alter microbiota and attenuate hepatic steatosis in hyperphagic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Male OLETF ...

Contrast enhancement of focal hepatic lesions in CT: effect of size and histology

International Nuclear Information System (INIS)

Burgener, F.A.; Hamlin, D.J.

1983-01-01

The effect of size and histology on the contrast enhancement of hepatic lesions has been analyzed in this clinical and experimental investigation yielding the following results: (1) The attenuation values of hepatic cysts in patients increase significantly and inversely with their size after contrast enhancement when the cysts measure less than twice the CT-slice thickness. This seems to be caused by partial-volume effect. (2) Experimental tumors of identical sizes and originating from the same cell line can demonstrate different contrast-enhancement patterns. (3) Peak contrast uptake in both experimental and human tumors seems to be inversely related to their size. (4) Compared to liver, contrast washout from experimental and human tumors (presumably the extravascular space) is delayed. The delay in the contrast washout from a tumor seems to correlate with tumor size. These findings suggest that in general, it is not possible to differentiate reliably among various hepatic neoplasms on the basis of their contrast enhancement patterns for the following reasons: (1) Attenuation values of small hepatic neoplasms are distorted by partial volume effect. (2) Tumors of different histologies can demonstrate the same enhancement pattern. (3) Tumors of identical histology and size can demonstrate different enhancement patterns. (4) The enhancement pattern of a tumor changes with growth or size

Arctigenin in combination with quercetin synergistically enhances the anti-proliferative effect in prostate cancer cells

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Wang, Piwen; Phan, Tien; Gordon, David; Chung, Seyung; Henning, Susanne M.; Vadgama, Jaydutt V.

2014-01-01

Scope We investigated whether a combination of two promising chemopreventive agents arctigenin and quercetin increases the anti-carcinogenic potency at lower concentrations than necessary when used individually in prostate cancer. Methods and results Androgen-dependent LAPC-4 and LNCaP prostate cancer cells were treated with low doses of arctigenin and quercetin alone or in combination for 48h. The anti-proliferative activity of arctigenin was 10-20 fold stronger than quercetin in both cell lines. Their combination synergistically enhanced the anti-proliferative effect, with a stronger effect in androgen receptor (AR) wild-type LAPC-4 cells than in AR mutated LNCaP cells. Arctigenin demonstrated a strong ability to inhibit AR protein expression in LAPC-4 cells. The combination treatment significantly inhibited both AR and PI3K/Akt pathways compared to control. A protein array analysis revealed that the mixture targets multiple pathways particularly in LAPC-4 cells including Stat3 pathway. The mixture significantly inhibited the expression of several oncogenic microRNAs including miR-21, miR-19b, and miR-148a compared to control. The mixture also enhanced the inhibition of cell migration in both cell lines compared to individual compounds tested. Conclusion The combination of arctigenin and quercetin, that target similar pathways, at low physiological doses, provides a novel regimen with enhanced chemoprevention in prostate cancer. PMID:25380086

Radioprotective effect of flavonoid quercetin on human lymphocytic cells; Efeito radioprotetor do flavonóide quercetina sobre células linfocitárias humanas

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Siqueira, Williams N.; Melo, Larissa S.A.; Lima, Maíra V.; Luna Filho, Ricardo L.C.; Melo, Ana M.M.A.; Silva, Edvane B., E-mail: williams.wns@gmail.com, E-mail: larissamelo.pe@gmail.com, E-mail: mairavasconceloslima@gmail.com, E-mail: ricardolclf@hotmail.com, E-mail: amdemelo@hotmail.com, E-mail: edvborges@yahoo.com [Universidade Federal de Pernambuco (UFPE), Recife (Brazil)

2017-07-01

Several substances of synthetic and natural origin have been studied in relation to their ability to protect the body from damage caused by ionizing radiation. Among these substances, quercetin has been shown to be a molecule of natural origin with high radioprotective potential due to its antioxidant properties. The objective of this study was to determine, in vitro, the radioprotective effect of quercetin on human lymphocytes exposed to gamma radiation. Blood was irradiated at the 2.5, 3.5 and 4.5 Gy doses and then lymphocyte culture with quercetin at preselected concentrations of 37.5 and 75 μM. Subsequently, slides were prepared for analysis and quantification of the metaphases present in lymphocyte cells. The results demonstrated that irradiated lymphocytes and later exposed to quercetin presented a lower number of chromosomal alterations compared to the control group which was irradiated and not exposed to quercetin. Therefore, the results suggest a radioprotective effect of flavonoid quercetin on human lymphocytes exposed, in vitro, to ionizing radiation.

Characterization of putative receptors specific for quercetin on bovine aortic smooth-muscle cells

International Nuclear Information System (INIS)

Yu, S.C.; Becker, C.G.

1986-01-01

The authors have reported that tobacco glycoprotein (TGP), rutin-bovine serum albumin conjugates (R-BSA), quercetin, and chlorogenic acid are mitogenic for bovine aortic smooth-muscle cells (SMC). To investigate whether there are binding sites or receptors for these polyphenol-containing molecules on SMC, the authors have synthesized 125 I-labeled rutin-bovine serum albumin ([ 125 I]R-BSA) of high specific activity (20 Ci/mmol). SMC were isolated from a bovine thoracic aorta and maintained in Eagle's minimum essential medium with 10% calf serum in culture. These SMC at early subpassages were suspended (3-5 x 10 7 cells/ml) in phosphate-buffered saline and incubated with [ 125 I]R-BSA (10 pmol) in the presence or absence of 200-fold unlabeled R-BSA, TGP, BSA, rutin, quercetin or related polyphenols, and catecholamines. Binding of [ 125 I]R-BSA to SMC was found to be reproducible and the radioligand was displaced by R-BSA, and also by TGP, rutin, quercetin, and chlorogenic acid, but not by BSA, ellagic acid, naringin, hesperetin, dopamine, epinephrine, or isoproterenol. The binding was saturable, reversible, and pH-dependent. These results demonstrate the presence of specific binding sites for quercetinon arterial SMC

Berberine Attenuates Development of the Hepatic Gluconeogenesis and Lipid Metabolism Disorder in Type 2 Diabetic Mice and in Palmitate-Incubated HepG2 Cells through Suppression of the HNF-4α miR122 Pathway.

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Wei, Shengnan; Zhang, Ming; Yu, Yang; Lan, Xiaoxin; Yao, Fan; Yan, Xin; Chen, Li; Hatch, Grant M

2016-01-01

Berberine (BBR) has been shown to exhibit protective effects against diabetes and dyslipidemia. Previous studies have indicated that BBR modulates lipid metabolism and inhibits hepatic gluconeogensis by decreasing expression of Hepatocyte Nuclear Factor-4α (HNF-4α). However, the mechanism involved in this process was unknown. In the current study, we examined the mechanism of how BBR attenuates hepatic gluconeogenesis and the lipid metabolism alterations observed in type 2 diabetic (T2D) mice and in palmitate (PA)-incubated HepG2 cells. Treatment with BBR for 4 weeks improve all biochemical parameters compared to T2D mice. Treatment of T2D mice for 4 weeks or treatment of PA-incubated HepG2 cells for 24 h with BBR decreased expression of HNF-4α and the microRNA miR122, the key gluconeogenesis enzymes Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase) and the key lipid metabolism proteins Sterol response element binding protein-1 (SREBP-1), Fatty acid synthase-1 (FAS-1) and Acetyl-Coenzyme A carboxylase (ACCα) and increased Carnitine palmitoyltransferase-1(CPT-1) compared to T2D mice or PA-incubated HepG2 cells. Expression of HNF-4α in HepG2 cells increased expression of gluconeogenic and lipid metabolism enzymes and BBR treatment or knock down of miR122 attenuated the effect of HNF-4α expression. In contrast, BBR treatment did not alter expression of gluconeogenic and lipid metabolism enzymes in HepG2 cells with knockdown of HNF-4α. In addition, miR122 mimic increased expression of gluconeogenic and lipid metabolism enzymes in HepG2 cells with knockdown of HNF-4α. These data indicate that miR122 is a critical regulator in the downstream pathway of HNF-4α in the regulation of hepatic gluconeogenesis and lipid metabolism in HepG2 cells. The effect of BBR on hepatic gluconeogenesis and lipid metabolism is mediated through HNF-4α and is regulated downstream of miR122. Our data provide new evidence to support HNF-4α and miR122

Effect of quercetin on cadmium chloride-induced impairments in sexual behaviour and steroidogenesis in male Wistar rats.

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Ujah, G A; Nna, V U; Agah, M I; Omue, L O; Leku, C B; Osim, E E

2018-03-01

Cadmium chloride (CdCl 2 ) has been reported to cause reproductive toxicity in male rats, mainly through oxidative stress. This study examined its effect on sexual behaviour, as one of the mechanisms of reproductive dysfunction, as well as the possible ameliorative effect of quercetin (QE) on same. Thirty male Wistar rats (10 weeks old), weighing 270-300 g, were used for this study. They were either orally administered 2% DMSO, CdCl 2 (5 mg/kg b.w.), QE (20 mg/kg b.w.) or CdCl 2 +QE, once daily for 4 weeks, before sexual behavioural studies. The 5th group received CdCl 2 for 4 weeks and allowed 4-week recovery period, before sexual behavioural test. Rats were sacrificed after sexual behavioural studies. The blood, testis and penis were collected for biochemical assays. Cadmium increased mount, intromission and ejaculatory latencies, but reduced their frequencies, compared to control. Serum nitric oxide increased, while penile cyclic guanosine monophosphate reduced in the CdCl 2 -exposed rats, compared to control. CdCl 2 increased testicular cholesterol, but reduced 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-HSD activities, and testosterone concentration. QE better attenuated these negative changes compared to withdrawal of CdCl 2 treatment. In conclusion, CdCl 2 suppressed steroidogenesis, penile erection and sexual behaviour, with poor reversal following withdrawal, while QE attenuated these effects. © 2017 Blackwell Verlag GmbH.

Mechanism of salutary effects of astringinin on rodent hepatic injury following trauma-hemorrhage: Akt-dependent hemeoxygenase-1 signaling pathways.

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Liu, Fu-Chao; Hwang, Tsong-Long; Lau, Ying-Tung; Yu, Huang-Ping

2011-01-01

Astringinin can attenuate organ injury following trauma-hemorrhage, the mechanism remains unknown. Protein kinase B/hemeoxygenase-1 (Akt/HO-1) pathway exerts potent anti-inflammatory effects in various tissues. The aim of this study is to elucidate whether Akt/HO-1 plays any role in astringinin-mediated attenuation of hepatic injury following trauma-hemorrhage. For study this, male Sprague-Dawley rats underwent trauma-hemorrhage (mean blood pressure 35-40 mmHg for 90 min) followed by fluid resuscitation. A single dose of astringinin (0.3 mg/kg body weight) with or without a PI3K inhibitor (wortmannin) or a HO antagonist (chromium-mesoporphyrin) was administered during resuscitation. Various parameters were measured at 24 h post-resuscitation. Results showed that trauma-hemorrhage increased plasma aspartate and alanine aminotransferases (AST and ALT) concentrations and hepatic myeloperoxidase activity, cytokine induced neutrophil chemoattractant (CINC)-1, CINC-3, intercellular adhesion molecule-1, and interleukin-6 levels. These parameters were significantly improved in the astringinin-treated rats subjected to trauma-hemorrhage. Astringinin treatment also increased hepatic Akt activation and HO-1 expression as compared with vehicle-treated trauma-hemorrhaged rats. Co-administration of wortmannin or chromium-mesoporphyrin abolished the astringinin-induced beneficial effects on post-resuscitation pro-inflammatory responses and hepatic injury. These findings collectively suggest that the salutary effects of astringinin administration on attenuation of hepatic injury after trauma-hemorrhage are likely mediated via Akt dependent HO-1 up-regulation.

Maternal resveratrol intake during lactation attenuates hepatic triglyceride and fatty acid synthesis in adult male rat offspring

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Masato Tanaka

2017-03-01

regulates the lipogenic pathway by activating genes involved in triglyceride and fatty acid synthesis. The present study showed significant downregulation of hepatic fatty acid synthase (FAS and acetyl-CoA carboxylase (ACC levels in the CR group. These results indicated that maternal resveratrol intake during lactation suppressed SREBP-1c cleavage and nuclear translocation and repressed SREBP-1c target gene expression such as FAS and ACC in the livers of adult male offspring. These changes attenuate hepatic triacylglycerol and fatty acid synthesis in adult male offspring.

Lycopene attenuated hepatic tumorigenesis via differential mechanisms depending on carotenoid cleavage enzyme in mice

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Ip, Blanche C.; Liu, Chun; Ausman, Lynne M.; von Lintig, Johannes; Wang, Xiang-Dong

2014-01-01

Obesity is associated with increased liver cancer risks and mortality. We recently showed that apo-10’-lycopenoic acid, a lycopene metabolite generated by beta-carotene-9’,10’-oxygenase (BCO2), inhibited carcinogen-initiated, high-fat diet (HFD)-promoted liver inflammation and hepatic tumorigenesis development. The present investigation examined the outstanding question of whether the lycopene could suppress HFD-promoted hepatocellular carcinoma (HCC) progression, and if BCO2 is important in BCO2-knockout (BCO2-KO) and wild-type male mice. Results showed that lycopene supplementation (100 mg/kg diet) for 24 weeks resulted in comparable accumulation of hepatic lycopene (19.4 vs 18.2 nmol/g) and had similar effects on suppressing HFD-promoted HCC incidence (19% vs 20%) and multiplicity (58% vs 62%) in wild-type and BCO2-KO mice, respectively. Intriguingly, lycopene chemopreventive effects in wild-type mice were associated with reduced hepatic pro-inflammatory signaling (phosphorylation of nuclear factor-κB p65 and signal transducer and activator of transcription 3; interleukin-6 protein) and inflammatory foci. In contrast, the protective effects of lycopene in BCO2-KO but not in wild-type mice were associated with reduced hepatic endoplasmic reticulum stress-mediated unfolded protein response (ERUPR), through decreasing ERUPR-mediated protein kinase RNA-activated like kinase– eukaryotic initiation factor 2α activation, and inositol requiring 1α–X-box binding protein 1 signaling. Lycopene supplementation in BCO2-KO mice suppressed oncogenic signals including Met mRNA, β-catenin protein, and mammalian target of rapamycin (mTOR) complex 1 activation, which was associated with increased hepatic microRNA (miR)-199a/b and miR-214 levels. These results provided novel experimental evidence that dietary lycopene can prevent HFD-promoted HCC incidence and multiplicity in mice, and may elicit different mechanisms depending on BCO2 expression. PMID:25293877

Haemodynamic changes in hepatocellular carcinoma and liver parenchyma under balloon occlusion of the hepatic artery

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Sugihara, Fumie; Murata, Satoru; Ueda, Tatsuo; Yasui, Daisuke; Yamaguchi, Hidenori; Miki, Izumi; Kumita, Shin-ichiro [Nippon Medical School, Department of Radiology, Center for Advanced Medical Technology, Tokyo (Japan); Kawamoto, Chiaki [Nippon Medical School, Department of Internal Medicine, Tokyo (Japan); Uchida, Eiji [Nippon Medical School, Department of Surgery, Tokyo (Japan)

2017-06-15

To investigate haemodynamic changes in hepatocellular carcinoma (HCC) and liver under hepatic artery occlusion. Thirty-eight HCC nodules in 25 patients were included. Computed tomography (CT) during hepatic arteriography (CTHA) with and without balloon occlusion of the hepatic artery was performed. CT attenuation and enhancement volume of HCC and liver with and without balloon occlusion were measured on CTHA. Influence of balloon position (segmental or subsegmental branch) was evaluated based on differences in HCC-to-liver attenuation ratio (H/L ratio) and enhancement volume of HCC and liver. In the segmental group (n = 20), H/L ratio and enhancement volume of HCC and liver were significantly lower with balloon occlusion than without balloon occlusion. However, in the subsegmental group (n = 18), H/L ratio was significantly higher and liver enhancement volume was significantly lower with balloon occlusion; HCC enhancement volume was similar with and without balloon occlusion. Rate of change in H/L ratio and enhancement volume of HCC and liver were lower in the segmental group than in the subsegmental group. There were significantly more perfusion defects in HCC in the segmental group. Hepatic artery occlusion causes haemodynamic changes in HCC and liver, especially with segmental occlusion. (orig.)

Quercetin protects against aluminium induced oxidative stress and promotes mitochondrial biogenesis via activation of the PGC-1α signaling pathway.

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Sharma, Deep Raj; Sunkaria, Aditya; Wani, Willayat Yousuf; Sharma, Reeta Kumari; Verma, Deepika; Priyanka, Kumari; Bal, Amanjit; Gill, Kiran Dip

2015-12-01

The present investigation was carried out to elucidate a possible molecular mechanism related to the protective effect of quercetin administration against aluminium-induced oxidative stress on various mitochondrial respiratory complex subunits with special emphasis on the role of PGC-1α and its downstream targets, i.e. NRF-1, NRF-2 and Tfam in mitochondrial biogenesis. Aluminium lactate (10mg/kg b.wt./day) was administered intragastrically to rats, which were pre-treated with quercetin 6h before aluminium (10mg/kg b.wt./day, intragastrically) for 12 weeks. We found a decrease in ROS levels, mitochondrial DNA oxidation and citrate synthase activity in the hippocampus (HC) and corpus striatum (CS) regions of rat brain treated with quercetin. Besides this an increase in the mRNA levels of the mitochondrial encoded subunits - ND1, ND2, ND3, Cyt b, COX1, COX3 and ATPase6 along with increased expression of nuclear encoded subunits COX4, COX5A and COX5B of electron transport chain (ETC). In quercetin treated group an increase in the mitochondrial DNA copy number and mitochondrial content in both the regions of rat brain was observed. The PGC-1α was up regulated in quercetin treated rats along with NRF-1, NRF-2 and Tfam, which act downstream from PGC-1α. Electron microscopy results revealed a significant decrease in the mitochondrial cross-section area, mitochondrial perimeter length and increase in mitochondrial number in case of quercetin treated rats as compared to aluminium treated ones. Therefore it seems quercetin increases mitochondrial biogenesis and makes it an almost ideal flavanoid to control or limit the damage that has been associated with the defective mitochondrial function seen in many neurodegenerative diseases. Copyright © 2015 Elsevier Inc. All rights reserved.

Glial cell line-derived neurotrophic factor protects against high-fat diet-induced hepatic steatosis by suppressing hepatic PPAR-γ expression.

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Mwangi, Simon Musyoka; Peng, Sophia; Nezami, Behtash Ghazi; Thorn, Natalie; Farris, Alton B; Jain, Sanjay; Laroui, Hamed; Merlin, Didier; Anania, Frank; Srinivasan, Shanthi

2016-01-15

Glial cell line-derived neurotrophic factor (GDNF) protects against high-fat diet (HFD)-induced hepatic steatosis in mice, however, the mechanisms involved are not known. In this study we investigated the effects of GDNF overexpression and nanoparticle delivery of GDNF in mice on hepatic steatosis and fibrosis and the expression of genes involved in the regulation of hepatic lipid uptake and de novo lipogenesis. Transgenic overexpression of GDNF in liver and other metabolically active tissues was protective against HFD-induced hepatic steatosis. Mice overexpressing GDNF had significantly reduced P62/sequestosome 1 protein levels suggestive of accelerated autophagic clearance. They also had significantly reduced peroxisome proliferator-activated receptor-γ (PPAR-γ) and CD36 gene expression and protein levels, and lower expression of mRNA coding for enzymes involved in de novo lipogenesis. GDNF-loaded nanoparticles were protective against short-term HFD-induced hepatic steatosis and attenuated liver fibrosis in mice with long-standing HFD-induced hepatic steatosis. They also suppressed the liver expression of steatosis-associated genes. In vitro, GDNF suppressed triglyceride accumulation in Hep G2 cells through enhanced p38 mitogen-activated protein kinase-dependent signaling and inhibition of PPAR-γ gene promoter activity. These results show that GDNF acts directly in the liver to protect against HFD-induced cellular stress and that GDNF may have a role in the treatment of nonalcoholic fatty liver disease.

Effect of quercetin on the number of blastomeres, zona pellucida thickness, and hatching rate of mouse embryos exposed to actinomycin D: An experimental study

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Hamid Reza Sameni

2018-02-01

Full Text Available Background: Quercetin is a flavonoid with the ability to improve the growth of embryos in vitro, and actinomycin D is an inducer of apoptosis in embryonic cells. Objective: The aim was to evaluate the effect of quercetin on the number of viable and apoptotic cells, the zona pellucida (ZP thickness and the hatching rate of preimplantation embryos exposed to actinomycin D in mice. Materials and Methods: Two-cell embryos were randomly divided into four groups (Control, Quercetin, actinomycin D, and Quercetin + actinomycin D group. Blastocysts percentage, hatched blastocysts, and ZP thickness of blastocysts was measured. The number of blastomeres was counted by Hoechst and propidium iodide staining and the apoptotic cells number was counted by TUNEL assay. Results: The results showed that the use of quercetin significantly improved the growth of embryos compared to the control group (p=0.037. Moreover, quercetin reduced the destructive effects of actinomycin D on the growth of embryos significantly (p=0.026. Conclusion: quercetin may protect the embryos against actinomycin D so that increases the number of viable cells and decreases the number of apoptotic cells, which can help the expansion of the blastocysts, thinning of the ZP thickness and increasing the hatching rate in mouse embryos.

TRIPLE PHASE SPIRAL C.T. IN THE EVALUATION OF HEPATIC MASSES

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Prasad

2015-10-01

Full Text Available BACKGROUND AND OBJECTIVE : The goal of the study is to determine the value of various phases of Triple, Helical CT, Hepatic arterial Phase (HAP, Portal venous phase (PVP and Equilibrium Phase (EP, is the detection and characterization of Hepatic Lesions and to evaluate whether u nenhanced and hepatic arterial phases when used in conjunction with porto venous phase would lead to detection of greater number of lesions or better characterization of lesion. METHODOLOGY : The study population consists of 50 Patients aged between 30 Years and 80 Years were examined with multiphase (plain, hepatic arterial, portal venous and equilibrium phases. Spiral CT of liver. Patients were referred for CT scan when liver diseases were suspected clinically, if ultrasound and other previous investi gations revealed lesions which had to be further evaluated by spiral CT and to detect liver metastases in known cases of primary extra hepatic malignancy. CT TECHNIQUE: Helical scanning of liver with Toshiba astein s4, continuous spiral run and the images were reconstructed at 5mm intervals. Contrast material 100ml was injected through 18 or 20G catheter at the rate of 3ml per second using automatic medrad power injector. Non - ionic contrast [IOHEXOl – 300mg perml was used in all the patients]. After obtaine d unenhanced CT scan HAP scanning was initiated 25 seconds after initiation of contrast injection. Portal venous phase scanning was initiated 60 - 65 seconds after start of contrast injection. Equilibrium phase scanning was initiated after 180 seconds after the start of contrast injection. IMAGE EVALUATION: All the images of 4 phases were reviewed. First Step : The presence, appearance and enhancement of each Lesion were noted in all phases and lesion were described Isodense, Hypodense Hyperdense based on thei r attenuation relative to liver parenchyma during that phase of scanning. Based on enhancement pattern of the lesion during various phases they were

HPLC Method for Simultaneous Quantitative Detection of Quercetin and Curcuminoids in Traditional Chinese Medicines

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Lee Fung Ang

2014-12-01

Full Text Available Objectives: Quercetin and curcuminoids are important bioactive compounds found in many herbs. Previously reported high performance liquid chromatography ultraviolet (HPLC-UV methods for the detection of quercetin and curcuminoids have several disadvantages, including unsatisfactory separation times and lack of validation according the standard guidelines of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. Methods: A rapid, specific, reversed phase, HPLC-UV method with an isocratic elution of acetonitrile and 2% v/v acetic acid (40% : 60% v/v (pH 2.6 at a flow rate of 1.3 mL/minutes, a column temperature of 35°C, and ultraviolet (UV detection at 370 nm was developed. The method was validated and applied to the quantification of different types of market available Chinese medicine extracts, pills and tablets. Results: The method allowed simultaneous determination of quercetin, bisdemethoxycurcumin, demethoxycurcumin and curcumin in the concentration ranges of 0.00488 ─ 200 μg/mL, 0.625 ─ 320 μg/mL, 0.07813 ─ 320 μg/mL and 0.03906 ─ 320 μg/mL, respectively. The limits of detection and quantification, respectively, were 0.00488 and 0.03906 μg/mL for quercetin, 0.62500 and 2.50000 μg/mL for bisdemethoxycurcumin, 0.07813 and 0.31250 μg/mL for demethoxycurcumin, and 0.03906 and 0.07813 μg/mL for curcumin. The percent relative intra day standard deviation (% RSD values were 0.432 ─ 0.806 μg/mL, 0.576 ─ 0.723 μg/ mL, 0.635 ─ 0.752 μg/mL and 0.655 ─ 0.732 μg/mL for quercetin, bisdemethoxycurcumin, demethoxycurcumin and curcumin, respectively, and those for intra day precision were 0.323 ─ 0.968 μg/mL, 0.805 ─ 0.854 μg/mL, 0.078 ─ 0.844 μg/mL and 0.275 ─ 0.829 μg/mL, respectively. The intra day accuracies were 99.589% ─ 100.821%, 98.588% ─ 101.084%, 9.289% ─ 100.88%, and 98.292% ─ 101.022% for quercetin, bisdemethoxycurcumin

HPLC method for simultaneous quantitative detection of quercetin and curcuminoids in traditional chinese medicines.

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Ang, Lee Fung; Yam, Mun Fei; Fung, Yvonne Tan Tze; Kiang, Peh Kok; Darwin, Yusrida

2014-12-01

Quercetin and curcuminoids are important bioactive compounds found in many herbs. Previously reported high performance liquid chromatography ultraviolet (HPLC-UV) methods for the detection of quercetin and curcuminoids have several disadvantages, including unsatisfactory separation times and lack of validation according the standard guidelines of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use. A rapid, specific, reversed phase, HPLC-UV method with an isocratic elution of acetonitrile and 2% v/v acetic acid (40% : 60% v/v) (pH 2.6) at a flow rate of 1.3 mL/minutes, a column temperature of 35°C, and ultraviolet (UV) detection at 370 nm was developed. The method was validated and applied to the quantification of different types of market available Chinese medicine extracts, pills and tablets. The method allowed simultaneous determination of quercetin, bisdemethoxycurcumin, demethoxycurcumin and curcumin in the concentration ranges of 0.00488 ─ 200 μg/mL, 0.625 ─ 320 μg/mL, 0.07813 ─ 320 μg/mL and 0.03906 ─ 320 μg/mL, respectively. The limits of detection and quantification, respectively, were 0.00488 and 0.03906 μg/mL for quercetin, 0.62500 and 2.50000 μg/mL for bisdemethoxycurcumin, 0.07813 and 0.31250 μg/mL for demethoxycurcumin, and 0.03906 and 0.07813 μg/mL for curcumin. The percent relative intra day standard deviation (% RSD) values were 0.432 ─ 0.806 μg/mL, 0.576 ─ 0.723 μg/mL, 0.635 ─ 0.752 μg/mL and 0.655 ─ 0.732 μg/mL for quercetin, bisdemethoxycurcumin, demethoxycurcumin and curcumin, respectively, and those for intra day precision were 0.323 ─ 0.968 μg/mL, 0.805 ─ 0.854 μg/mL, 0.078 ─ 0.844 μg/mL and 0.275 ─ 0.829 μg/mL, respectively. The intra day accuracies were 99.589% ─ 100.821%, 98.588% ─ 101.084%, 9.289% ─ 100.88%, and 98.292% ─ 101.022% for quercetin, bisdemethoxycurcumin, demethoxycurcumin and curcumin, respectively, and the

iPLA2β deficiency attenuates obesity and hepatic steatosis in ob/ob mice through hepatic fatty-acyl phospholipid remodeling.

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Deng, Xiuling; Wang, Jiliang; Jiao, Li; Utaipan, Tanyarath; Tuma-Kellner, Sabine; Schmitz, Gerd; Liebisch, Gerhard; Stremmel, Wolfgang; Chamulitrat, Walee

2016-05-01

PLA2G6 or GVIA calcium-independent PLA2 (iPLA2β) is identified as one of the NAFLD modifier genes in humans, and thought to be a target for NAFLD therapy. iPLA2β is known to play a house-keeping role in phospholipid metabolism and remodeling. However, its role in NAFLD pathogenesis has not been supported by results obtained from high-fat feeding of iPLA2β-null (PKO) mice. Unlike livers of human NAFLD and genetically obese rodents, fatty liver induced by high-fat diet is not associated with depletion of hepatic phospholipids. We therefore tested whether iPLA2β could regulate obesity and hepatic steatosis in leptin-deficient mice by cross-breeding PKO with ob/ob mice to generate ob/ob-PKO mice. Here we observed an improvement in ob/ob-PKO mice with significant reduction in serum enzymes, lipids, glucose, insulin as well as improved glucose tolerance, and reduction in islet hyperplasia. The improvement in hepatic steatosis measured by liver triglycerides, fatty acids and cholesterol esters was associated with decreased expression of PPARγ and de novo lipogenesis genes, and the reversal of β-oxidation gene expression. Notably, ob/ob livers contained depleted levels of lysophospholipids and phospholipids, and iPLA2β deficiency in ob/ob-PKO livers lowers the former, but replenished the latter particularly phosphatidylethanolamine (PE) and phosphatidylcholine (PC) that contained arachidonic (AA) and docosahexaenoic (DHA) acids. Compared with WT livers, PKO livers also contained increased PE and PC containing AA and DHA. Thus, iPLA2β deficiency protected against obesity and ob/ob fatty liver which was associated with hepatic fatty-acyl phospholipid remodeling. Our results support the deleterious role of iPLA2β in severe obesity associated NAFLD. Copyright © 2016 Elsevier B.V. All rights reserved.

Hepatic JAK2 protects against atherosclerosis through circulating IGF-1.

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Sivasubramaniyam, Tharini; Schroer, Stephanie A; Li, Angela; Luk, Cynthia T; Shi, Sally Yu; Besla, Rickvinder; Dodington, David W; Metherel, Adam H; Kitson, Alex P; Brunt, Jara J; Lopes, Joshua; Wagner, Kay-Uwe; Bazinet, Richard P; Bendeck, Michelle P; Robbins, Clinton S; Woo, Minna

2017-07-20

Atherosclerosis is considered both a metabolic and inflammatory disease; however, the specific tissue and signaling molecules that instigate and propagate this disease remain unclear. The liver is a central site of inflammation and lipid metabolism that is critical for atherosclerosis, and JAK2 is a key mediator of inflammation and, more recently, of hepatic lipid metabolism. However, precise effects of hepatic Jak2 on atherosclerosis remain unknown. We show here that hepatic Jak2 deficiency in atherosclerosis-prone mouse models exhibited accelerated atherosclerosis with increased plaque macrophages and decreased plaque smooth muscle cell content. JAK2's essential role in growth hormone signalling in liver that resulted in reduced IGF-1 with hepatic Jak2 deficiency played a causal role in exacerbating atherosclerosis. As such, restoring IGF-1 either pharmacologically or genetically attenuated atherosclerotic burden. Together, our data show hepatic Jak2 to play a protective role in atherogenesis through actions mediated by circulating IGF-1 and, to our knowledge, provide a novel liver-centric mechanism in atheroprotection.

Ab initio molecular dynamics of the reaction of quercetin with superoxide radical

International Nuclear Information System (INIS)

Lespade, Laure

2016-01-01

Highlights: • Ab initio molecular dynamics is performed to describe the reaction of quercetin and superoxide. • The reaction occurs near the sites 4′ and 7 when the system contains sufficiently water molecules. • The difference of reactivity of superoxide compared to commonly used radicals as DPPH · or ABTS ·+ is explained. - Abstract: Superoxide plays an important role in biology but in unregulated concentrations it is implicated in a lot of diseases such as cancer or atherosclerosis. Antioxidants like flavonoids are abundant in plant and are good scavengers of superoxide radical. The modeling of superoxide scavenging by flavonoids from the diet still remains a challenge. In this study, ab initio molecular dynamics of the reaction of the flavonoid quercetin toward superoxide radical has been carried out using Car–Parrinello density functional theory. The study has proven different reactant solvation by modifying the number of water molecules surrounding superoxide. The reaction consists in the gift of a hydrogen atom of one of the hydroxyl groups of quercetin to the radical. When it occurs, it is relatively fast, lower than 100 fs. Calculations show that it depends largely on the environment of the hydroxyl group giving its hydrogen atom, the geometry of the first water layer and the presence of a certain number of water molecules in the second layer, indicating a great influence of the solvent on the reactivity.

Quercetin suppresses DNA double-strand break repair and enhances the radiosensitivity of human ovarian cancer cells via p53-dependent endoplasmic reticulum stress pathway

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Gong C

2017-12-01

Full Text Available Cheng Gong,1 Zongyuan Yang,1 Lingyun Zhang,2 Yuehua Wang,2 Wei Gong,2 Yi Liu3 1Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 2Department of Oncology, XiangYang Central Hospital, Hubei University of Arts and Science, XiangYang, 3Department of Medicinal Chemistry, School of Pharmacy, Hubei University of Chinese Medicine, Wuhan, China Abstract: Quercetin is proven to have anticancer effects for many cancers. However, the role of tumor suppressor p53 on quercetin’s radiosensitization and regulation of endoplasmic reticulum (ER stress response in this process remains obscure. Here, quercetin exposure resulted in ER stress, prolonged DNA repair, and the expression of p53 protein; phosphorylation on serine 15 and 20 increased in combination with X-irradiation. Quercetin pretreatment could potentiate radiation-induced cell death. The combination of irradiation and quercetin treatment aggravated DNA damages and caused typical apoptotic cell death; as well the expression of Bax and p21 elevated and the expression of Bcl-2 decreased. Knocking down of p53 could reverse all the above effects under quercetin in combination with radiation. In addition, quercetin-induced radiosensitization was through stimulation of ATM phosphorylation. In human ovarian cancer xenograft model, combined treatment of quercetin and radiation significantly restrained the growth of tumors, accompanied with the activation of p53, CCAAT/enhancer-binding protein homologous protein, and γ-H2AX. Overall, these results indicated that quercetin acted as a promising radiosensitizer through p53-dependent ER stress signals. Keywords: quercetin, p53, endoplasmic reticulum stress, DNA double-strand breaks, eIF-2α (eukaryotic initiation factor 2α, ATM kinase

Heme Oxygenase Induction Suppresses Hepatic Hepcidin and Rescues Ferroportin and Ferritin Expression in Obese Mice

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Nitin Puri

2017-01-01

Full Text Available Hepcidin, a phase II reactant secreted by hepatocytes, regulates cellular iron levels by increasing internalization of ferroportin-a transmembrane protein facilitating egress of cellular iron. Chronic low-grade inflammatory states, such as obesity, have been shown to increase oxidative stress and enhance hepcidin secretion from hepatocytes and macrophages. Heme-heme oxygenase (HO is a stress response system which reduces oxidative stress. We investigated the effects of HO-1 induction on hepatic hepcidin levels and on iron homeostasis in hepatic tissues from lean and obese mice. Obese mice exhibited hyperglycemia (p<0.05; increased levels of proinflammatory cytokines (MCP-1, IL-6, p<0.05; oxidative stress (p<0.05; and increased hepatic hepcidin levels (p<0.05. Enhancement of hepcidin was reflected in the reduced expression of ferroportin in obese mice (p<0.05. However, this effect is accompanied by a significant decline in ferritin expression. Additionally, there are reduced insulin receptor phosphorylation and attenuation of metabolic regulators pAMPK, pAKT, and pLKB1. Cobalt protoporphyrin- (CoPP- induced HO-1 upregulation in obese mice reversed these alterations (p<0.05, while attenuating hepatic hepcidin levels. These effects of CoPP were prevented in obese mice concurrently exposed to an inhibitor of HO (SnMP (p<0.05. Our results highlight a modulatory effect of HO on iron homeostasis mediated through the suppression of hepatic hepcidin.

Quercetin inhibits epithelial–mesenchymal transition, decreases invasiveness and metastasis, and reverses IL-6 induced epithelial–mesenchymal transition, expression of MMP by inhibiting STAT3 signaling in pancreatic cancer cells

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Yu D

2017-09-01

Full Text Available Dinglai Yu,1 Tingting Ye,1 Yukai Xiang,1 Zhehao Shi,1 Jie Zhang,1 Bin Lou,1 Fan Zhang,1 Bicheng Chen,1,2 Mengtao Zhou1 1Department of Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 2Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Wenzhou, Zhejiang Province, People’s Republic of China Abstract: Quercetin, a flavone, is multifaceted, having anti-oxidative, anti-inflammatory, and anticancer properties. In the present study, we explored the effects of quercetin on the epithelial–mesenchymal transition (EMT and invasion of pancreatic cancer cells and the underlying mechanisms. We noted that quercetin exerted pronounced inhibitory effects in PANC-1 and PATU-8988 cells. Moreover, quercetin inhibited EMT and decreased the secretion of matrix metalloproteinase (MMP. Meanwhile, we determined the activity of STAT3 after quercetin treatment. STAT3 phosphorylation decreased following treatment with quercetin. We also used activating agent of STAT3, IL-6, to induce an increase in cell malignancy and to observe the effects of treatment with quercetin. As expected, the EMT and MMP secretion increased with activation of the STAT3 signaling pathway, and quercetin reversed IL-6-induced EMT, invasion, and migration. Therefore, our results demonstrate that quercetin triggers inhibition of EMT, invasion, and metastasis by blocking the STAT3 signaling pathway, and thus, quercetin merits further investigation. Keywords: quercetin, EMT, MMPs, STAT3, pancreatic cancer

Integrated assessment by multiple gene expression analysis of quercetin bioactivity on anticancer-related mechanisms in colon cancer cells in vitro

NARCIS (Netherlands)

Erk, van M.J.; Roepman, P.; Lende, van der T.R.; Stierum, R.H.; Aarts, J.M.M.J.G.; Bladeren, van P.J.; Ommen, van B.

2005-01-01

Background Many different mechanisms are involved in nutrient¿related prevention of colon cancer. In this study, a comprehensive assessment of the spectrum of possible biological actions of the bioactive compound quercetin is made using multiple gene expression analysis. Quercetin is a flavonoid

White Pitaya (Hylocereus undatus) Juice Attenuates Insulin Resistance and Hepatic Steatosis in Diet-Induced Obese Mice.

Science.gov (United States)

Song, Haizhao; Zheng, Zihuan; Wu, Jianan; Lai, Jia; Chu, Qiang; Zheng, Xiaodong

2016-01-01

Insulin resistance and hepatic steatosis are the most common complications of obesity. Pitaya is an important source of phytochemicals such as polyphenols, flavonoid and vitamin C which are related to its antioxidant activity. The present study was conducted to evaluate the influence of white pitaya juice (WPJ) on obesity-related metabolic disorders (e.g. insulin resistance and hepatic steatosis) in high-fat diet-fed mice. Forty-eight male C57BL/6J mice were assigned into four groups and fed low-fat diet with free access to water or WPJ, or fed high-fat diet with free access to water or WPJ for 14 weeks. Our results showed that administration of WPJ improved high-fat diet-induced insulin resistance, hepatic steatosis and adipose hypertrophy, but it exerted no influence on body weight gain in mice. Hepatic gene expression analysis indicated that WPJ supplement not only changed the expression profile of genes involved in lipid and cholesterol metabolism (Srebp1, HMGCoR, Cpt1b, HL, Insig1 and Insig2) but also significantly increased the expression levels of FGF21-related genes (Klb, FGFR2, Egr1 and cFos). In conclusion, WPJ protected from diet-induced hepatic steatosis and insulin resistance, which was associated with the improved FGF21 resistance and lipid metabolism.

Quantification of Quercetin and Rutin from Benincasa hispida Seeds and Carissa Congesta Roots by High-performance Thin Layer Chromatography and High-performance Liquid Chromatography.

Science.gov (United States)

Doshi, Gaurav Mahesh; Une, Hemant Devidas

2016-01-01

In Indian Ayurvedic system, Benincasa hispida (BH) and Carissa congesta (CC) are well-known plants used for major and minor ailments. BH has been regarded as Kushmanda, whereas CC has been used in immune-related disorders of the human system. Quercetin and rutin identified from the vast plethora of plant extracts have proved to possess ethnopharmacological relevance. In present studies, we have determined quercetin and rutin in terms of percentage in BH seeds and CC roots by high-performance thin layer chromatography (HPTLC) and high-performance liquid chromatography (HPLC). After extraction and phytochemical screening, the extracts were subjected to quantification for the presence of quercetin and rutin by HPTLC and HPLC. HPTLC showed quercetin as 44.60, 27.13% and rutin as 32.00, 36.31% w/w, whereas HPLC revealed quercetin as 34.00, 35.00% and rutin as 21.99, 45.03% w/v in BH and CC extracts, respectively. The BH and CC extracts have elucidated peaks that were corresponding with standard peaks on undertaking chromatographic studies. Quercetin and rutin are isolated from BH seeds and CC roots by High Performance. Thin Layer Chromatography and High Performance Liquid Chromatography. HPTLC revealed presence of quercetin as 44.60, 27.13 % and rutin as 32.00, 36.31 % w/w. HPLC revealed presence of quercetin as 34.00, 35.00 % and rutin as 21.99, 45.03 % w/v. Abbreviation Used: HPTLC: High Performance Thin Layer Chromatography; HPLC: High Pressure Liquid Chromatography, UV: Ultraviolet, CC: Carissa congesta, BH: Benincasa hispida.

Quantification of Quercetin and Rutin from Benincasa hispida Seeds and Carissa Congesta Roots by High-performance Thin Layer Chromatography and High-performance Liquid Chromatography

Science.gov (United States)

Doshi, Gaurav Mahesh; Une, Hemant Devidas

2016-01-01

Objective: In Indian Ayurvedic system, Benincasa hispida (BH) and Carissa congesta (CC) are well-known plants used for major and minor ailments. BH has been regarded as Kushmanda, whereas CC has been used in immune-related disorders of the human system. Quercetin and rutin identified from the vast plethora of plant extracts have proved to possess ethnopharmacological relevance. Materials and Methods: In present studies, we have determined quercetin and rutin in terms of percentage in BH seeds and CC roots by high-performance thin layer chromatography (HPTLC) and high-performance liquid chromatography (HPLC). After extraction and phytochemical screening, the extracts were subjected to quantification for the presence of quercetin and rutin by HPTLC and HPLC. Results: HPTLC showed quercetin as 44.60, 27.13% and rutin as 32.00, 36.31% w/w, whereas HPLC revealed quercetin as 34.00, 35.00% and rutin as 21.99, 45.03% w/v in BH and CC extracts, respectively. Conclusion: The BH and CC extracts have elucidated peaks that were corresponding with standard peaks on undertaking chromatographic studies. SUMMARY Quercetin and rutin are isolated from BH seeds and CC roots by High Performance. Thin Layer Chromatography and High Performance Liquid Chromatography. HPTLC revealed presence of quercetin as 44.60, 27.13 % and rutin as 32.00, 36.31 % w/w. HPLC revealed presence of quercetin as 34.00, 35.00 % and rutin as 21.99, 45.03 % w/v. Abbreviation Used: HPTLC: High Performance Thin Layer Chromatography; HPLC: High Pressure Liquid Chromatography, UV: Ultraviolet, CC: Carissa congesta, BH: Benincasa hispida PMID:26941534

Evaluation of diffuse hepatic disease by computed tomography, 1

International Nuclear Information System (INIS)

Tada, Akira; Shikae, Mikio; Morinaga, Kenichi; Morikawa, Toshihiro; Nei, Hirokazu.

1979-01-01

Liver attenuation values of 53 diffuse hepatic disease were measured, and compared with those of normal subjects. In normal subjects mean CT values of the liver was 62.3, that of the spleen was 53.2. But in diffuse hepatic disease, all group's mean CT values of the liver was decreased, especially at fatty liver and acute hepatitis. In all cases of fatty liver, CT values of the liver were lower than that of the spleen. In 39 cases of 53 patients, change of CT values of the liver were measured using biliary tract contrast agents. In another 39 cases of 53 patients, were evaluated histological fat deposit and CT values of the liver. Correlation between histological fat deposit and CT values was good. Diagnosis of the moderate fatty liver and quantitative analysis was possible by CT values alone. (author)

Benznidazole, the trypanocidal drug used for Chagas disease, induces hepatic NRF2 activation and attenuates the inflammatory response in a murine model of sepsis

International Nuclear Information System (INIS)

Lambertucci, Flavia; Motiño, Omar; Villar, Silvina; Rigalli, Juan Pablo; Luján Alvarez, María de; Catania, Viviana A; Martín-Sanz, Paloma; Carnovale, Cristina Ester; Quiroga, Ariel Darío; Francés, Daniel Eleazar; Ronco, María Teresa

2017-01-01

Molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity. Previous studies demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, has immunomodulatory effects, increasing survival in C57BL/6 mice in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). The mechanism by which BZL inhibits inflammatory response in sepsis is poorly understood. Also, our group recently reported that BZL is able to activate the nuclear factor erytroide-derived 2-Like 2 (NRF2) in vitro. The aim of the present work was to delineate the beneficial role of BZL during sepsis, analyzing its effects on the cellular redox status and the possible link to the innate immunity receptor TLR4. Specifically, we analyzed the effect of BZL on Nrf2 regulation and TLR4 expression in liver of mice 24 hours post-CLP. BZL was able to induce NRF2 nuclear protein localization in CLP mice. Also, we found that protein kinase C (PKC) is involved in the NRF2 nuclear accumulation and induction of its target genes. In addition, BZL prompted a reduction in hepatic CLP-induced TLR4 protein membrane localization, evidencing its immunomodulatory effects. Together, our results demonstrate that BZL induces hepatic NRF2 activation with the concomitant increase in the antioxidant defenses, and the attenuation of inflammatory response, in part, by inhibiting TLR4 expression in a murine model of sepsis. - Highlights: • BZL improves survival rate after polymicrobial sepsis • BZL enhances hepatic NRF2 nuclear accumulation in a model of sepsis, in part, by a mechanism dependent on PKC activation • BZL-enhanced NRF2 induction regulates antioxidant enzymes and increases antioxidant cellular defenses in sepsis • BZL blocks liver ROS production and ROS-induced TLR4 plasma membrane expression in septic mice

Benznidazole, the trypanocidal drug used for Chagas disease, induces hepatic NRF2 activation and attenuates the inflammatory response in a murine model of sepsis

Energy Technology Data Exchange (ETDEWEB)

Lambertucci, Flavia [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina); Motiño, Omar [Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Arturo Duperier 4, 28029 Madrid (Spain); Villar, Silvina [Instituto de Inmunología, Facultad de Ciencias Médicas, UNR, Suipacha 531, 2000 Rosario (Argentina); Rigalli, Juan Pablo; Luján Alvarez, María de; Catania, Viviana A [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina); Martín-Sanz, Paloma [Instituto de Investigaciones Biomédicas Alberto Sols, CSIC-UAM, Arturo Duperier 4, 28029 Madrid (Spain); Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Monforte de Lemos 3-5, 28029 Madrid (Spain); Carnovale, Cristina Ester; Quiroga, Ariel Darío; Francés, Daniel Eleazar [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina); Ronco, María Teresa, E-mail: ronco@ifise-conicet.gov.ar [Instituto de Fisiología Experimental (IFISE-CONICET), Suipacha 570, 2000 Rosario (Argentina)

2017-01-15

Molecular mechanisms on sepsis progression are linked to the imbalance between reactive oxygen species (ROS) production and cellular antioxidant capacity. Previous studies demonstrated that benznidazole (BZL), known for its antiparasitic action on Trypanosoma cruzi, has immunomodulatory effects, increasing survival in C57BL/6 mice in a model of polymicrobial sepsis induced by cecal ligation and puncture (CLP). The mechanism by which BZL inhibits inflammatory response in sepsis is poorly understood. Also, our group recently reported that BZL is able to activate the nuclear factor erytroide-derived 2-Like 2 (NRF2) in vitro. The aim of the present work was to delineate the beneficial role of BZL during sepsis, analyzing its effects on the cellular redox status and the possible link to the innate immunity receptor TLR4. Specifically, we analyzed the effect of BZL on Nrf2 regulation and TLR4 expression in liver of mice 24 hours post-CLP. BZL was able to induce NRF2 nuclear protein localization in CLP mice. Also, we found that protein kinase C (PKC) is involved in the NRF2 nuclear accumulation and induction of its target genes. In addition, BZL prompted a reduction in hepatic CLP-induced TLR4 protein membrane localization, evidencing its immunomodulatory effects. Together, our results demonstrate that BZL induces hepatic NRF2 activation with the concomitant increase in the antioxidant defenses, and the attenuation of inflammatory response, in part, by inhibiting TLR4 expression in a murine model of sepsis. - Highlights: • BZL improves survival rate after polymicrobial sepsis • BZL enhances hepatic NRF2 nuclear accumulation in a model of sepsis, in part, by a mechanism dependent on PKC activation • BZL-enhanced NRF2 induction regulates antioxidant enzymes and increases antioxidant cellular defenses in sepsis • BZL blocks liver ROS production and ROS-induced TLR4 plasma membrane expression in septic mice.

Quercetin inhibits angiogenesis through thrombospondin-1 upregulation to antagonize human prostate cancer PC-3 cell growth in vitro and in vivo.

Science.gov (United States)

Yang, Feiya; Jiang, Xian; Song, Liming; Wang, Huiping; Mei, Zhu; Xu, Zhiqing; Xing, Nianzeng

2016-03-01

The rapid growth, morbidity and mortality of prostate cancer, and the lack of effective treatment have attracted great interests of researchers to find novel cancer therapies aiming to inhibit angiogenesis and tumor growth. Quercetin is a flavonoid compound that widely exists in the nature. Our previous study preliminarily demonstrated that quercetin effectively inhibited human prostate cancer cell xenograft tumor growth by inhibiting angiogenesis. Thrombospondin-1 (TSP-1) is the first reported endogenous anti-angiogenic factor that can inhibit angiogenesis and tumorigenesis. However, the relationship between quercetin inhibiting angiogenesis and TSP-1 upregulation in prostate cancer has not been determined. Thus, we explored the important role of TSP-1 upregulation in reducing angiogenesis and anti-prostate cancer effect of quercetin both in vitro and in vivo for the first time. After the selected doses were used for a certain time, quercetin i) significantly inhibited PC-3 and human umbilical vein endothelial cells (HUVECs) proliferation, migration and invasion in a dose-dependent manner; ⅱ) effectively inhibited prostate cancer PC-3 cell xenograft tumor growth by 37.5% with 75 mg/kg as compared to vehicle control group, more effective than 25 (22.85%) and 50 mg/kg (29.6%); ⅲ) was well tolerated by BALB/c mice and no obvious toxic reactions were observed; ⅳ) greatly reduced angiogenesis and led to higher TSP-1 protein and mRNA expression both in vitro and in vivo in a dose-dependent manner. Therefore, quercetin could increase TSP-1 expression to inhibit angiogenesis resulting in antagonizing prostate cancer PC-3 cell and xenograft tumor growth. The present study can lay a good basis for the subsequent concrete mechanism study and raise the possibility of applying quercetin to clinical for human prostate cancer in the near future.

Psoralea corylifolia L. Attenuates Nonalcoholic Steatohepatitis in Juvenile Mouse

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Lishan Zhou

2017-11-01

Full Text Available Psoralea corylifolia L. (PC is a traditional Chinese herb used to treat yang deficiency of the spleen and kidney in pediatric disease. Recent studies have shown its liver protection and anti-oxidative effects. The aim of this study was to explore the effect and mechanism of PC on nonalcoholic steatohepatitis in juvenile mice. The juvenile mouse model of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH was established by being fed a high-fat diet in maternal-offspring manner. PC granules were prepared and the quality was assessed. The main components were identified by high performance liquid chromatography. Then, different dosages of PC were administered for 6 weeks. Homeostatic model assessment of insulin resistance, plasma liver enzymes, hepatic morphology, hepatic superoxide anion, and triglyceride/total cholesterol levels were examined. The changes of nuclear factor-κB (NF-κB activity phosphatidylinositol 3 kinase (PI3K/protein kinase B (Akt and protein kinase C-α (PKC-α/nicotinamide-adenine dinucleotide phosphate (NADPH oxidase signaling pathways in hepatic tissues were also determined. Our data demonstrated that PC significantly improved liver dysfunction, liver triglyceride/total cholesterol accumulation and insulin resistance in juvenile NAFLD/NASH mice. PC also alleviated hepatic steatosis, inflammatory cell infiltration, and fibroplasia in the portal area. Additionally, PC inhibited the activation of NF-κB and the mRNA expression of inflammatory factors while enhancing PI3K/Akt signaling in hepatic tissues. PC could also reduce hepatic superoxide anion levels, and NADPH oxidase activity as well as p47phox protein expression and PKCα activation in hepatic tissues. The results suggest that PC is effective in the treatment of NASH in juvenile mice. The mechanism may be related to the attenuation of hepatic oxidative stress through the PKC-α/NADPH oxidase signaling pathway.

Study on pretreatment of FPS-1 in rats with hepatic ischemia-reperfusion injury.

Science.gov (United States)

Lin, Shiqing; Liu, Kexuan; Wu, Weikang; Chen, Chao; Wang, Zhi; Zhang, Xuanhong

2009-01-01

This study was designed to determine whether FPS-1, the water-soluble polysaccharide isolated from fuzi, protected against hepatic damage in hepatic ischemia-reperfusion injury in rats, and its mechanism. SD rats were subjected to 60 min of hepatic ischemia, followed by 120 min reperfusion. FPS-1 (160 mg/kg/day) was administered orally for 5 days before ischemia-reperfusion injury in treatment group. Serum aspartate aminotransferase (AST), alanine aminotransferase (ALT) and albumin (ALB) were assayed to evaluate liver functions. Liver samples were taken for histological examination and determination of malondialdehyde (MDA), superoxide dismutase (SOD), that catalase (CAT) in liver. Na(+)-K(+)-ATPase and Ca(2+)-ATPase in mitochondria were measured with colorimetry method. Morphological changes were also investigated by using both light microscopy and electron microscopy (EM). In addition, apoptosis and oncosis were detected by Annexin V-FITC/PI immunofluorescent flow cytometry analysis. Serum AST and ALT levels were elevated in groups exposed to ischemia-reperfusion (p FPS-1 reversed all these biochemical parameters as well as histological alterations, evidently by increased SOD, CAT, reduced MDA and histological scores compared to the model group (p FPS-1 could attenuate the necrotic states by the detection of immunofluorescent flow cytometry analysis. Pretreatment with FPS-1 reduced hepatic ischemia-reperfusion injury through its potent antioxidative effects and attenuation of necrotic states.

Simultaneous determination by HPLC of quercetin and kaempferol in three Sedum medicinal plants harvested in different seasons.

Science.gov (United States)

Wang, Luyao; Mei, Qing; Wan, Dingrong

2014-04-01

A high-performance liquid chromatography method was established for the fast quantification of quercetin and kaempferol in three Sedum crude medicines: Sedi Herba (Sedum sarmentosum Bunge.), Sedi Linearis Herba (Sedum lineare Thunb.) and Sedi Emarginati Herba (Sedum emarginatum Migo.). The column used was a YMC-pack ODS-A (250 × 4.6 mm, 5 µm), the mobile phase was a solution of methanol-0.4% phosphoric acid (47:53) with a flow rate of 1.0 mL/min at 35°C and the detection wavelength was 360 nm. The calibration curves for quercetin and kaempferol were linear over the range of 0.01-0.62 µg for quercetin and 0.02-0.78 µg for kaempferol, and the average recoveries were 99.72% [relative standard deviation (RSD): 1.63% and 99.50% (RSD: 1.16%), respectively]. In conclusion, the method established in this paper is accurate and repeatable. It can be used for the determination of quercetin and kaempferol, controlling the quality of the three crude drugs. Furthermore, the experimental data showed that the best harvest season for the three Sedum medicinal species should be the full-bloom period between the end of April and the beginning of May.

Simultaneous determination of quercetin, kaempferol and isorhamnetin accumulated human breast cancer cells, by high-performance liquid chromatography.

Science.gov (United States)

Wang, Yi; Cao, Jiang; Weng, Jian-Hua; Zeng, Su

2005-09-01

Quercetin, kaempferol and isorhamnetin are the most important constituents in ginkgo flavonoids. A simple, rapid and sensitive high-performance liquid chromatography method was developed to simultaneously determine quercetin, kaempferol and isorhamnetin absorped by human breast cancer cells. Cells were treated with ginkgo flavonols and then lysed with Triton-X 100. The flavonols in the samples were measured by RP-HPLC with a C18 column after a simple extraction with a mixture of ether and acetone. The mobile phase contained phosphate buffer (pH 2.0; 10 mM) tetrahydrofuran, methanol and isopropanol (65:15:10:20, v/v/v/v). The ultraviolet detector was operated at 380 nm. The calibration curve was linear from 0.1 to 1.0 microM (r > 0.999) for each flavonol. The mean extraction efficiency was about 70%. The recovery of the assay was between 98.9 and 100.6%. The limit of detection was 0.01 microM for quercetin and kaempferol and 0.05 microM for isorhamnetin. The limit of quantitation was 0.1 microM (R.S.D.method was applied to quantify quercetin, kaempferol and isorhamnetin in human breast cancer Bcap37 and Bcap37/MDR1 cells.

Chemoenzymatic Preparation and Biophysical Properties of Sulfated Quercetin Metabolites

Czech Academy of Sciences Publication Activity Database

Valentová, Kateřina; Káňová, Kristýna; Di Meo, F.; Pelantová, Helena; Chambers, Christopher S.; Rydlová, Lenka; Petrásková, Lucie; Křenková, Alena; Cvačka, Josef; Trouillas, P.; Křen, Vladimír

2017-01-01

Roč. 18, č. 11 (2017), č. článku 2231. E-ISSN 1422-0067 R&D Projects: GA MŠk(CZ) LD15082; GA MŠk LTC17009; GA ČR(CZ) GBP208/12/G016 Institutional support: RVO:61388971 ; RVO:61388963 Keywords : quercetin * sulfotransferase * metabolites Subject RIV: CE - Biochemistry OBOR OECD: Biochemistry and molecular biology Impact factor: 3.226, year: 2016

Selection of the most powerful predictors for the evaluation of hepatic steatosis grade: An experimental study

International Nuclear Information System (INIS)

Su Zhongzhen; Shan Hong; He Bingjun; Lv Wentian; Meng Xiaochun; Wang Jin; Zhu Kangshun; Yang Yang; Chen Guihua

2009-01-01

Purpose: To select the most powerful predictors for the evaluation of hepatic steatosis grade. Methods and materials: Forty-five healthy New Zealand rabbits were randomly divided into one normal control group and three experimental groups. Hepatic steatosis models were established by feeding a high-fat, high-sugar diet and drinking water containing 5% ethanol. Twenty-two variable indexes were measured using general observation, biochemical examination, ultrasonography, computed tomography (CT), and proton magnetic resonance spectroscopy (MRS). Univariate analysis, correlation analysis, and stepwise regression analysis were used to make the selection of the most powerful predictors. ROC analysis was used to compare the diagnostic efficacy of single index with combined index (Y) expressed by a regression equation. Results: Based on statistical analysis, there were 12 variable indexes with significant differences among groups, which correlated with hepatic steatosis grade: liver weight, hepatic index, liver CT value, liver-to-muscle attenuation ratio, 1 H MRS fat peak value, fat peak area, fat-to-water peak area ratio, fat percentage, ultrasound attenuation coefficient, serum aspartate aminotransferase, total cholesterol (TC) and triglycerides. Among them hepatic index, liver CT value and serum TC were selected as the most powerful predictors for hepatic steatosis grade with correlation coefficients of 0.709, -0.764, and 0.886, respectively. The regression equation was: Y = 1.975 + 3.906 x 10 -2 X 1 + 0.369X 2 - 2.84 x 10 -2 X 3 , where Y = hepatic steatosis grade, X 1 = TC, X 2 = hepatic index, and X 3 = liver CT value. ROC analysis displayed PPV, NPV, curve area of combined index (Y) were superior to simple index (hepatic index, liver CT value and serum TC) in evaluating hepatic steatosis grade, and they were nearly 1.0000, 1.0000 and 1.000, respectively. Conclusions: Combined application of several diagnostic methods is superior to simple diagnostic method, and

Selection of the most powerful predictors for the evaluation of hepatic steatosis grade: An experimental study

Energy Technology Data Exchange (ETDEWEB)

Su Zhongzhen [Department of Radiology, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province (China); Shan Hong [Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province (China)], E-mail: gzshsums@public.guangzhou.gd.cn; He Bingjun; Lv Wentian; Meng Xiaochun; Wang Jin; Zhu Kangshun [Department of Radiology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province (China); Yang Yang; Chen Guihua [Department of Liver Transplantation, Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong Province (China)

2009-10-15

Purpose: To select the most powerful predictors for the evaluation of hepatic steatosis grade. Methods and materials: Forty-five healthy New Zealand rabbits were randomly divided into one normal control group and three experimental groups. Hepatic steatosis models were established by feeding a high-fat, high-sugar diet and drinking water containing 5% ethanol. Twenty-two variable indexes were measured using general observation, biochemical examination, ultrasonography, computed tomography (CT), and proton magnetic resonance spectroscopy (MRS). Univariate analysis, correlation analysis, and stepwise regression analysis were used to make the selection of the most powerful predictors. ROC analysis was used to compare the diagnostic efficacy of single index with combined index (Y) expressed by a regression equation. Results: Based on statistical analysis, there were 12 variable indexes with significant differences among groups, which correlated with hepatic steatosis grade: liver weight, hepatic index, liver CT value, liver-to-muscle attenuation ratio, {sup 1}H MRS fat peak value, fat peak area, fat-to-water peak area ratio, fat percentage, ultrasound attenuation coefficient, serum aspartate aminotransferase, total cholesterol (TC) and triglycerides. Among them hepatic index, liver CT value and serum TC were selected as the most powerful predictors for hepatic steatosis grade with correlation coefficients of 0.709, -0.764, and 0.886, respectively. The regression equation was: Y = 1.975 + 3.906 x 10{sup -2}X{sub 1} + 0.369X{sub 2} - 2.84 x 10{sup -2}X{sub 3}, where Y = hepatic steatosis grade, X{sub 1} = TC, X{sub 2} = hepatic index, and X{sub 3} = liver CT value. ROC analysis displayed PPV, NPV, curve area of combined index (Y) were superior to simple index (hepatic index, liver CT value and serum TC) in evaluating hepatic steatosis grade, and they were nearly 1.0000, 1.0000 and 1.000, respectively. Conclusions: Combined application of several diagnostic methods is

α-Amyrin attenuates high fructose diet-induced metabolic syndrome in rats.

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Prabhakar, Pankaj; Reeta, K H; Maulik, Subir Kumar; Dinda, Amit Kumar; Gupta, Yogendra Kumar

2017-01-01

This study investigated the effect of α-amyrin (a pentacyclic triterpene) on high-fructose diet (HFD)-induced metabolic syndrome in rats. Male Wistar rats were randomly distributed into different groups. The control group was fed normal rat chow diet. The HFD group was fed HFD (60%; w/w) for 42 days. Pioglitazone (10 mg/kg, orally, once daily) was used as a standard drug. α-Amyrin was administered in 3 doses (50, 100, and 200 mg/kg, orally, once daily along with HFD). Plasma glucose, total cholesterol, triglycerides, and high-density lipoprotein cholesterol (HDL-C) were estimated. Changes in blood pressure, oral glucose tolerance, and insulin tolerance were measured. Hepatic oxidative stress as well as messenger RNA (mRNA) and protein levels of peroxisome proliferator-activated receptor alpha (PPAR-α) were analyzed. A significant increase in systolic blood pressure, plasma glucose, total cholesterol, and plasma triglycerides and a significant decrease in HDL-C were observed in HFD rats as compared with control rats. Glucose tolerance and insulin tolerance were also significantly impaired with HFD. α-Amyrin prevented these changes in a dose-dependent manner. Hepatic oxidative stress as well as micro- and macrovesicular fatty changes in hepatocytes caused by HFD were also attenuated by α-amyrin. α-Amyrin preserved the hepatic mRNA and protein levels of PPAR-α, which was reduced in HFD group. This study thus demonstrates that α-amyrin attenuates HFD-induced metabolic syndrome in rats.

Effects of Quercetin on CYP450 and Cytokines in Aroclor 1254 Injured Endometrial Cells of the Pregnant Rats

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Lina Xu

2014-01-01

Full Text Available Polychlorinated biphenyls (PCBs are widespread persistent residual environmental pollutants, which affect seriously the growth and reproductive alterations in humans and animals. Aroclor 1254 is a commercial mixture of PCBs. Quercetin is a flavonoid, which acts on estrogen receptors and causes the development of estrogen-related diseases. In this paper, the primary cultured endometrial cells in the pregnant rats were isolated and Aroclor 1254 was used to induce the injured endometrial cells model. The cells were treated with gradient quercetin, the viability of the endometrial cells, the expressions of CYP450, the contents of TNF-α, IL-6, estradiol (E2, and progesterone (P4 were measured. It showed that the viability of the cultured endometrial cells, the expression of CYP1A1 and CYP2B1, and the contents of TNF-α, E2, and IL-6 in the injured endometrial cells increased with the treatment of quercetin. It shows that quercetin has protective effect on the injured endometrial cells in the pregnant rats, this provide a basis on herbal medicine protection for animal reproductive diseases caused by environmental endocrine disruptors.

Red wine alcohol promotes quercetin absorption and directs its metabolism towards isorhamnetin and tamarixetin in rat intestine in vitro.

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Dragoni, Stefania; Gee, Jennifer; Bennett, Richard; Valoti, Massimo; Sgaragli, Giampietro

2006-04-01

Moderate consumption of red wine has been associated with beneficial effects on human health, and this has been attributed to the flavonoid content. Factors that influence the bioavailability of this group of polyphenolic compounds are therefore important. Using the rat cannulated everted jejunal sac technique, we have investigated the effect of alcohol on the intestinal absorption of quercetin and its 3-O-glucoside from red wine. Tissue preparations were incubated in whole or dealcoholised red wine, diluted 1 : 1 with Krebs buffer for 20 min at 37 degrees C, after which the mucosa was removed and processed for HPLC analysis. Tissues exposed to red wine had significantly higher amounts of both quercetin (x 3; P wine, were significantly elevated approximately two fold (P moderate alcohol content of red wine contributes to its beneficial health effects in humans by both increasing the absorption of quercetin and quercetin-3-O-glucoside and by channelling their metabolism towards O-methylation to yield compounds (T and I), which have potential protective effects against cancer and cardiovascular diseases.

Quercetin derivatives as non-nucleoside inhibitors for dengue polymerase: molecular docking, molecular dynamics simulation, and binding free energy calculation.