The different effects of psyllium husk and orlistat on weight control, the amelioration of hypercholesterolemia and non-alcohol fatty liver disease in obese mice induced by a high-fat diet.

Obesity is a widespread medical problem, for which many drugs have been developed, each with its own limitations. Orlistat, a lipase inhibitor, functions as a fat absorption blocker and is a widely used over-the-counter drug in China. Psyllium husk, in contrast, is a food source rich in dietary fibre and is beneficial for weight loss because it reduces appetite. Here, it was investigated how psyllium husk treatments affect mice with a high-fat diet (HFD)-induced obesity, using obesity-related indices, metabolism indices, and gut microbiota, compared to orlistat treatments. Orlistat had a greater effect on weight loss, whereas psyllium husk had a greater effect at reducing serum and liver cholesterol and triglyceride levels. Treatments had similar effects on controlling the body fat rate, the expression level of farnesoid X receptor, sterol 27-hydroxylase and oxysterol 7-hydroxylase (CYP7B1) in the liver, and the regulation of major bile acids such as cholic acid, chenodeoxycholic acid, deoxycholic acid, and lithocholic acid in faecal content. However, the expression of CYP7A1 in the liver and the structures of faecal bile acids were different between the two drugs. Furthermore, although they also had similar effects on the gut microbiota at the phylum level, there were differences at the genus level for Roseburia, Bacteroides, Faecalibacterium, Coprobacillus, and Akkernansia, which led to the difference in the serum lipopolysaccharide (LPS) level. Orlistat increased the food intake of the obese mice that were fed a HFD, which led to an increase in water intake, serum triglyceride levels, and lower glucose tolerance. Although orlistat is considered a suitable drug for weight loss, psyllium husk is a comparatively more cost-effective choice for ameliorating hypercholesterolemia and non-alcoholic fatty liver disease caused by a HFD.

Pharmacokinetics-based comprehensive strategy to identify multiple effective components in Huangqi decoction against liver fibrosis.

BACKGROUND: Huangqi decoction (HQD) has been used to treat chronic liver diseases since the 11th century, but the effective components in HQD against liver fibrosis have not been definitively clarified. PURPOSE: To investigate and identify multiple effective components in HQD against liver fibrosis using a pharmacokinetics-based comprehensive strategy. METHODS: The absorbed representative components in HQD and their metabolites were detected in human plasma and urine using high-resolution mass spectrometry combined with a database-directed method, and then pharmacokinetics in multiple HQD components in human plasma was analyzed by ultra-performance liquid chromatography coupled with triple-quadruple mass spectrometry. Furthermore, the anti-fibrotic effect of potential effective HQD components was studied in LX-2 cells and that of a multi-component combination of HQD (MCHD) was verified in a mouse CCl4-induced hepatic fibrosis model. RESULTS: Twenty-four prototype components in HQD and 17 metabolites were identified in humans, and the pharmacokinetic characteristics of 14 components were elucidated. Among these components, astragaloside IV, cycloastragenol, glycyrrhizic acid, glycyrrhetinic acid, liquiritigenin, and isoliquiritigenin downregulated the mRNA expression of α-SMA; cycloastragenol, calycosin-7-O-ß-D-glucoside, formononetin, glycyrrhetinic acid, liquiritin, and isoliquiritin downregulated the mRNA expression of Col I; and calycosin, liquiritigenin, isoliquiritigenin, cycloastragenol, and glycyrrhetinic accelerated the apoptosis of LX-2 cells. MCHD reduced serum aminotransferase activity and hepatic collagen fibril deposition in mice with CCl4-induced hepatic fibrosis. CONCLUSION: Using the pharmacokinetics-based comprehensive strategy, we revealed that multiple effective HQD components act together against liver fibrosis.

Prenatal alcohol exposure and maternal glutamine supplementation alter the mTOR signaling pathway in ovine fetal cerebellum and skeletal muscle.

Prenatal alcohol exposure causes fetal neurodevelopmental damage and growth restriction. Among regions of the brain, the cerebellum is the most vulnerable to developmental alcohol exposure. Despite vast research in the field, there is still a need to identify specific mechanisms by which alcohol causes this damage in order to design effective therapeutic interventions. The mammalian target of rapamycin (mTOR) is known to be associated with axonal regeneration, dendritic arborization, synaptic plasticity, cellular growth, autophagy, and many other cellular processes. Glutamine and glutamine-related amino acids play a key role in fetal development and are known to alter the mTOR pathway; recent research has shown that disturbances in their bioavailability and signaling pathways may mediate adverse effects of prenatal alcohol exposure. This study investigated the role of the mTOR signaling pathway in the fetal cerebellum and skeletal muscle after third trimester-equivalent prenatal alcohol exposure and maternal l-glutamine (GLN) supplementation using a sheep model. Fetal cerebella and skeletal muscles were sampled for Western blot analysis of mTOR and its downstream targets S6 kinase and eukaryotic initiation factor 4E-bindin protein (4E-BP1). The expression of cerebellar phosphorylated mTOR relative to the total mTOR was elevated in the alcohol+GLN group compared to the saline and GLN groups. Alcohol exposure increased the ratio of phosphorylated S6K to total S6K in fetal cerebellum, and no significant effect of GLN supplementation was observed. On contrary, maternal GLN supplementation reduced the activation of mTOR and S6K in fetal skeletal muscle, possibly to make GLN and other amino acids available for use by other organs. These findings suggest prenatal alcohol exposure and maternal GLN supplementation during the third trimester-equivalent alter the mTOR signaling cascade, which plays a possible key role in alcohol-induced developmental damage.

Oxysophoridine attenuates the injury caused by acute myocardial infarction in rats through anti-oxidative, anti-inflammatory and anti-apoptotic pathways.

Oxysophoridine (OSR), a natural alkaloid derived from the traditional Chinese medicinal plant sophora alopecuroides, can perform a variety of pharmacological actions. The aim of the present study was to assess the cardioprotective effect of OSR against acute myocardial infarction (AMI) in rats. OSR markedly reduced infarction size and levels of specific myocardial enzymes, including creatine kinase, the MB isoenzyme of creatine kinase, lactate dehydrogenase and cardiac troponin T. A reduced level of malondialdehyde was observed, and elevated catalase, Cu/Zn-superoxide dismutase (SOD), Mn-SOD, non-enzymatic scavenger glutathione and glutathione peroxidase activity were also identified in the OSR-treated rats. Additionally, OSR inhibited the activities of various inflammatory cytokines in a dose-dependent manner. These included nuclear factor-κB p65, tumor necrosis factor-α, and interleukin-1ß, -6 and -10. Furthermore, OSR treatment suppressed caspase-3 activity in a dose-dependent manner. These results demonstrate that OSR ameliorates cardiac damage in a rat model of AMI and that this cardioprotection may be linked with its anti-oxidative, anti-apoptotic and anti-inflammatory properties.