3-methylquercetin and Body-Weight

To explore the role of isorhamnetin on polycystic ovary syndrome (PCOS) in rats.. Sprague Dawley (SD) rats were subcutaneously injected with dehydroepiandrosteron (DHEA) to establish PCOS model. Hematoxylin and eosin (H&E) staining and TdT-mediated dUTP Nick-End Labeling (TUNEL) were used to measure histological changes and apoptosis of ovary tissues. The levels of serum hormones and inflammatory factors in ovary tissues were measured by enzyme-linked immuno sorbent assay (ELISA).. In DHEA-induced PCOS rats, the levels of serum glucose, insulin, testosterone and luteinizing hormone (LH) were enhanced, estradiol (E2), sex hormone-binding globulin (SHBG), follicle stimulating hormone (FSH) levels were decreased, inflammatory levels and apoptosis of ovary tissues were increased. Additionally, DHEA increased the body weight, ovary weight, and ovary volume, cystic follicles, and decreased corpus luteum. Moreover, the tumor necrosis factor (TNF) signaling pathway was activated in PCOS rats. The levels of TNF receptor superfamily member 1 A (TNFR1), TNF-α, and fas cell surface death feceptor (FAS) were enhanced in ovary tissues of DHEA induced PCOS rats. Isorhamnetin (ISO) treatment after DHEA modeling markedly reduced serum levels of glucose, insulin, testosterone and LH, increased E2, SHBG, FSH level, decreased inflammatory levels, and inhibited apoptosis and decreased body weight, ovary weight, and ovary volume. The levels of TNFR1, TNF-α, and FAS were markedly decreased after ISO treatment in PCOS rats. Additionally, ISO alone had no significant effect on rats.. Isorhamnetin inhibits inflammatory response to alleviate DHEA-induced PCOS in rats by inactivating the TNF signaling pathway.

Topics: Animals; Body Weight; Dehydroepiandrosterone; Female; Follicle Stimulating Hormone; Insulin; Luteinizing Hormone; Polycystic Ovary Syndrome; Rats; Rats, Sprague-Dawley; Receptors, Tumor Necrosis Factor, Type I; Testosterone; Tumor Necrosis Factor-alpha

Isorhamnetin, a derivative of quercetin, exerts antioxidant and anti-inflammatory effects in different diseases, and we examined its protective effects against diabetes-related changes in the brain.. A single dose of a freshly prepared solution of streptozotocin (STZ) (60 mg/kg body weight) was intraperitoneally injected to establish STZ-induced diabetic model in male Wistar rats. The animals were randomly divided into four groups: control, control + isorhamnetin, diabetic, diabetic + isorhamnetin. Isorhamnetin at a dose of 10 mg/kg body weight was intraperitoneally administrated once a day for 12 weeks. Formalin and tail immersion tests were performed to evaluate the severity of pain. Astrogliosis markers such as GFAP and APO-E4, DNA fragments, MDA level, and TNFα expressions were evaluated using ELISA assay. Neuronal density in the hippocampus region was evaluated using Nissl staining. The method of Ellman and fluorescent probe 2, 7-dichlorofluorescein diacetate (DCFH-DA) was used to measure brain acetyl-cholinesterase activity and detect reactive nitrogen and oxygen species (RNS and ROS), respectively.. Isorhamnetin reduced pain, blood glucose levels, and increased body weight significantly compared to control. Moreover, isorhamnetin inhibited astroglial activation, acetyl-cholinesterase activity, oxidative stress, apoptosis, and inflammation.. These findings suggested that isorhamnetin has potential effects as neuroprotective agents against diabetes-related changes in the brain.

Topics: Animals; Apoptosis; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; DNA Fragmentation; Inflammation; Male; Malondialdehyde; Neurons; Neuroprotective Agents; Oxidative Stress; Pain; Pain Measurement; Quercetin; Rats; Rats, Wistar; Reactive Nitrogen Species; Reactive Oxygen Species

Nonalcoholic steatohepatitis (NASH) is the most severe and progressive form of nonalcoholic fatty liver disease (NAFLD), which can lead to life-threatening conditions, however, there is still no approved drug for the treatment of NASH. In this study we used human-like NASH mouse model and treated orally with isorhamnetin at a dose of 50 mg/kg to analyze the effect of isorhamnetin on the progression of NASH. NASH-induced mice represented severe steatosis with inflammation, and fibrosis in liver accompanied with high level of liver injury markers in serum. Isorhamnetin treatment reduced intrahepatic lipid accumulation and TG content by inhibiting de novo lipogenic pathway in NASH-induced mice. Consistent with this, isorhamnetin-treated NASH mice showed improved liver injury markers, reduced collagen deposition as well as decreased gene expression of fibrogenic markers. Taken together, here we showed for the first time that synthesized isorhamnetin alleviates pathologic features of NASH and thus can potentially contribute to NASH drug development.

Topics: Animals; Body Weight; Lipogenesis; Liver; Liver Cirrhosis; Macrophages; Male; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Organ Size; Oxidation-Reduction; Quercetin

Polyphenols, such as flavonoids, are secondary plant metabolites with potentially health-promoting properties. In newborn calves flavonoids may improve health status, but little is known about the systemically availability of flavonoids in calves to exert biological effects. The aim of this study was to investigate the oral bioavailability of the flavonol quercetin, applied either as quercetin aglycone (QA) or as its glucorhamnoside rutin (RU), in newborn dairy calves. Twenty-one male newborn German Holstein calves were fed equal amounts of colostrum and milk replacer according to body weight. On d 2 and 29 of life, 9 mg of quercetin equivalents/kg of body weight, either fed as QA or as RU, or no quercetin (control group) were fed together with the morning meal. Blood samples were taken before and 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 12, 24, and 48 h after feed intake. Quercetin and quercetin metabolites with an intact flavonol structure (isorhamnetin, tamarixetin, and kaempferol) were analyzed in blood plasma after treatment with glucuronidase or sulfatase by HPLC with fluorescence detection. Maximum individual plasma concentration was depicted from the concentration-time-curve on d 2 and 29, respectively. Additional blood samples were taken to measure basal plasma concentrations of total protein, albumin, urea, and lactate as well as pre- and postprandial plasma concentrations of glucose, nonesterified fatty acids, insulin, and cortisol. Plasma concentrations of quercetin and its metabolites were significantly higher on d 2 than on d 29 of life, and administration of QA resulted in higher plasma concentrations of quercetin and its metabolites than RU. The relative bioavailability of total flavonols (sum of quercetin and its metabolites isorhamnetin, tamarixetin, and kaempferol) from RU was 72.5% on d 2 and 49.6% on d 29 when compared with QA (100%). Calves fed QA reached maximum plasma concentrations of total flavonols much earlier than did RU-fed calves. Plasma metabolites and hormones were barely affected by QA and RU feeding in this experiment. Taken together, orally administrated QA resulted in a greater bioavailability of quercetin than RU on d 2 and 29, respectively, and quercetin bioavailability of quercetin and its metabolites differed markedly between calves aged 2 and 29 d.

Topics: Administration, Oral; Animals; Animals, Newborn; Biological Availability; Blood Glucose; Body Weight; Cattle; Disaccharides; Fatty Acids, Nonesterified; Female; Flavonoids; Flavonols; Insulin; Kaempferols; Male; Pregnancy; Quercetin; Rutin

Aflatoxin B(1) (AFB(1))-mediated hepatic damage is involved in production of AFB(1)-8,9-epoxide-bound DNA adducts and this is also affected by a pro-oxidant potential of the toxin. In this study we investigated the effects of quercetin on AFB(1)-treated HepG2 cells. We also examined the biochemical mechanisms associated with the effects of quercetin on AFB(1)-mediated liver damage in mice. Our results revealed that quercetin and isorhamnetin inhibit production of reactive oxygen species and cytotoxicity, and block the decrease of reduced glutathione (GSH) levels in AFB(1)-treated HepG2 cells. Isorhamnetin have inhibitory ability on lipid peroxidation stronger than quercetin in the cells. Oral supplementation with quercetin decreased serum lactate dehydrogenase levels, increased hepatic GSH levels and superoxide dismutase activity, and reduced lipid peroxidation in both the liver and kidney in AFB(1)-treated mice. However, quercetin did not show a significant reduction on serum levels of alkaline phosphate, alanine aminotransferase and aspartate aminotransferase that were increased in AFB(1)-treated mice. HPLC analysis revealed that quercetin in plasma is mainly present as glucoronides and/or sulfates of quercetin. Collectively, it is suggested that quercetin does not directly protect against AFB(1)-mediated liver damage in vivo, but exerts a partial role in promoting antioxidative defense systems and inhibiting lipid peroxidation.

Topics: Aflatoxin B1; Animals; Body Weight; Carcinoma, Hepatocellular; Cell Line, Tumor; Cell Survival; Chemical and Drug Induced Liver Injury; Chromatography, High Pressure Liquid; Flavonols; Glutathione; Humans; Liver; Male; Malondialdehyde; Mice; Mice, Inbred ICR; Organ Size; Quercetin; Reactive Oxygen Species