Andrographis paniculata

Andrographolide is the most abundant terpenoid of A. paniculata which is used in the treatment of diabetes. In this study, we investigated the effects of A. paniculata extract (APE) and andrographolide on the expression of drug-metabolizing enzymes in rat liver and determined whether modulation of these enzymes changed the pharmacokinetics of tolbutamide. Rats were intragastrically dosed with 2 g/kg/day APE or 50 mg/kg/day andrographolide for 5 days before a dose of 20 mg/kg tolbutamide was given. APE and andrographolide reduced the AUC0–12 h of tolbutamide by 37% and 18%, respectively, compared with that in controls. The protein and mRNA levels and enzyme activities of CYP2C6/11, CYP1A1/2, and CYP3A1/2 were increased by APE and andrographolide. To evaluate whether APE or andrographolide affected the hypoglycemic action of tolbutamide, high-fat diet-induced obese mice were used and treated in the same manner as the rats. APE and andrographolide increased CYP2C6/11 expression and decreased plasma tolbutamide levels. In a glucose tolerance test, however, the hypoglycemic effect of tolbutamide was not changed by APE or andrographolide. These results suggest that APE and andrographolide accelerate the metabolism rate of tolbutamide through increased expression and activity of drug-metabolizing enzymes. APE and andrographolide, however, do not impair the hypoglycemic effect of tolbutamide

SNOSite: Exploiting Maximal Dependence Decomposition to Identify Cysteine S-Nitrosylation with Substrate Site Specificity

S-nitrosylation, the covalent attachment of a nitric oxide to (NO) the sulfur atom of cysteine, is a selective and reversible protein post-translational modification (PTM) that regulates protein activity, localization, and stability. Despite its implication in the regulation of protein functions and cell signaling, the substrate specificity of cysteine S-nitrosylation remains unknown. Based on a total of 586 experimentally identified S-nitrosylation sites from SNAP/L-cysteine-stimulated mouse endothelial cells, this work presents an informatics investigation on S-nitrosylation sites including structural factors such as the flanking amino acids composition, the accessible surface area (ASA) and physicochemical properties, i.e. positive charge and side chain interaction parameter. Due to the difficulty to obtain the conserved motifs by conventional motif analysis, maximal dependence decomposition (MDD) has been applied to obtain statistically significant conserved motifs. Support vector machine (SVM) is applied to generate predictive model for each MDD-clustered motif. According to five-fold cross-validation, the MDD-clustered SVMs could achieve an accuracy of 0.902, and provides a promising performance in an independent test set. The effectiveness of the model was demonstrated on the correct identification of previously reported S-nitrosylation sites of Bos taurus dimethylarginine dimethylaminohydrolase 1 (DDAH1) and human hemoglobin subunit beta (HBB). Finally, the MDD-clustered model was adopted to construct an effective web-based tool, named SNOSite (http://csb.cse.yzu.edu.tw/SNOSite/), for identifying S-nitrosylation sites on the uncharacterized protein sequences

Women with endometriosis have higher comorbidities: Analysis of domestic data in Taiwan

AbstractEndometriosis, defined by the presence of viable extrauterine endometrial glands and stroma, can grow or bleed cyclically, and possesses characteristics including a destructive, invasive, and metastatic nature. Since endometriosis may result in pelvic inflammation, adhesion, chronic pain, and infertility, and can progress to biologically malignant tumors, it is a long-term major health issue in women of reproductive age. In this review, we analyze the Taiwan domestic research addressing associations between endometriosis and other diseases. Concerning malignant tumors, we identified four studies on the links between endometriosis and ovarian cancer, one on breast cancer, two on endometrial cancer, one on colorectal cancer, and one on other malignancies, as well as one on associations between endometriosis and irritable bowel syndrome, one on links with migraine headache, three on links with pelvic inflammatory diseases, four on links with infertility, four on links with obesity, four on links with chronic liver disease, four on links with rheumatoid arthritis, four on links with chronic renal disease, five on links with diabetes mellitus, and five on links with cardiovascular diseases (hypertension, hyperlipidemia, etc.). The data available to date support that women with endometriosis might be at risk of some chronic illnesses and certain malignancies, although we consider the evidence for some comorbidities to be of low quality, for example, the association between colon cancer and adenomyosis/endometriosis. We still believe that the risk of comorbidity might be higher in women with endometriosis than that we supposed before. More research is needed to determine whether women with endometriosis are really at risk of these comorbidities

Вихретоковый анизотропный термоэлектрический первичный преобразователь лучистого потока

Представлена оригинальная конструкция первичного преобразователя лучистого потока, который может служить основой для создания приемника неселективного излучения с повышенной чувствительностью

Epigallocatechin-3-Gallate Reduces Hepatic Oxidative Stress and Lowers CYP-Mediated Bioactivation and Toxicity of Acetaminophen in Rats

Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol in green tea. To investigate the effects of dietary EGCG on oxidative stress and the metabolism and toxicity of acetaminophen in the liver, rats were fed diets with (0.54%) or without EGCG supplementation for four weeks and were then injected intraperitoneally with acetaminophen (1 g/kg). The results showed that EGCG lowered hepatic oxidative stress and cytochrome P450 (CYP) 1A2, 2E1, and 3A, and UDP-glucurosyltransferase activities prior to acetaminophen injection. After acetaminophen challenge, the elevations in plasma alanine aminotransferase activity and histological changes in the liver were ameliorated by EGCG treatment. EGCG reduced acetaminophen-induced apoptosis by lowering the Bax/Bcl2 ratio in the liver. EGCG mildly increased autophagy by increasing the LC3B II/I ratio. Lower hepatic acetaminophen–glutathione and acetaminophen–protein adducts contents were observed after EGCG treatment. EGCG increased glutathione peroxidase and NAD(P)H quinone 1 oxidoreductase activities and reduced organic anion-transporting polypeptides 1a1 expression in the liver after acetaminophen treatment. Our results indicate that EGCG may reduce oxidative stress and lower the metabolism and toxicity of acetaminophen. The reductions in CYP-mediated acetaminophen bioactivation and uptake transporter, as well as enhanced antioxidant enzyme activity, may limit the accumulation of toxic products in the liver and thus lower hepatotoxicity

Red algae (Gelidium amansii) hot-water extract ameliorates lipid metabolism in hamsters fed a high-fat diet

The purpose of this study was to investigate the effects of Gelidium amansii (GA) hot-water extracts (GHE) on lipid metabolism in hamsters. Six-week-old male Syrian hamsters were used as the experimental animals. Hamsters were divided into four groups: (1) control diet group (CON); (2) high-fat diet group (HF); (3) HF with GHE diet group (HF + GHE); (4) HF with probucol diet group (HF + PO). All groups were fed the experimental diets and drinking water ad libitum for 6 weeks. The results showed that GHE significantly decreased body weight, liver weight, and adipose tissue (perirenal and paraepididymal) weight. The HF diet induced an increase in plasma triacylglycerol (TG), total cholesterol (TC), low-density lipoprotein cholesterol and very-low-density lipoprotein cholesterol levels. However, GHE supplementation reversed the increase of plasma lipids caused by the HF diet. In addition, GHE increased fecal cholesterol, TG and bile acid excretion. Lower hepatic TC and TG levels were found with GHE treatment. GHE reduced hepatic sterol regulatory element-binding proteins (SREBP) including SREBP 1 and SREBP 2 protein expressions. The phosphorylation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) protein expression in hamsters was decreased by the HF diet; however, GHE supplementation increased the phosphorylation of AMPK protein expression. Our results suggest that GHE may ameliorate lipid metabolism in hamsters fed a HF diet

Red algae (Gelidium amansii) reduces adiposity via activation of lipolysis in rats with diabetes induced by streptozotocin-nicotinamide

Gelidium amansii (GA) is an edible red algae that is distributed mainly in northeastern Taiwan. This study was designed to investigate the effects of GA on plasma glucose, lipids, and adipocytokines in rats with streptozotocin-nicotinamide-induced diabetes. Rats were divided into four groups: (1) rats without diabetes fed a high-fat diet (control group); (2) rats with diabetes fed a high-fat diet; (3) rats with diabetes fed a high-fat diet with thiazolidinedione in the diet; and (4) rats with diabetes fed a high-fat diet and GA. The experimental diet and drinking water were available ad libitum for 11 weeks. After the 11-week feeding study, plasma glucose, triglyceride, and cholesterol concentrations were lower in rats with diabetes fed the GA diet than in animals with diabetes fed the control diet. In addition, cholesterol and triglyceride excretion were significantly higher in rats with diabetes fed the GA diet. Moreover, GA feeding induced lipolysis in both paraepididymal and perirenal adipose tissues. Adipose tissue (paraepididymal and perirenal) weight and triglyceride contents were lower after GA treatment. Plasma adipocytokines including tumor necrosis factor-alpha, interleukin-6, and plasminogen activator inhibitor-1 were reduced by GA feeding in rats with diabetes. The results of the current study suggest that GA feeding may regulate plasma glucose and lipid levels and prevent adipose tissue accumulation in rats with diabetes

Beverage–Drug Interaction: Effects of Green Tea Beverage Consumption on Atorvastatin Metabolism and Membrane Transporters in the Small Intestine and Liver of Rats

Green tea (GT) beverages are popular worldwide and may prevent the development of many chronic diseases including cardiovascular disease and cancer. To investigate whether the consumption of a GT beverage causes drug interactions, the effects of GT beverage consumption on atorvastatin metabolism and membrane transporters were evaluated. Male rats were fed a chow diet with tap water or the GT beverage for 3 weeks. Then, the rats were given a single oral dose (10 mg/kg body weight (BW)) of atorvastatin (ATV), and blood was collected at various time points within 6 h. The results show that GT consumption increased the plasma concentrations (AUC0–6h) of ATV (+85%) and 2-OH ATV (+93.3%). GT also increased the 2-OH ATV (+40.9%) and 4-OH ATV (+131.6%) contents in the liver. Decreased cytochrome P450 (CYP) 3A enzyme activity, with no change in P-glycoprotein expression in the intestine, was observed in rats treated with GT. Additionally, GT increased hepatic CYP3A-mediated ATV metabolism and decreased organic anion transporting polypeptides (OATP) 2 membrane protein expression. There was no significant difference in the membrane protein expression of OATP2B1 and P-glycoprotein in the intestine and liver after the GT treatment. The results show that GT consumption may lower hepatic OATP2 and, thus, limit hepatic drug uptake and increase plasma exposure to ATV and 2-OH ATV