Alcoholic fatty liver disease (AFLD) is characterized by excessive lipid accumulation in the liver. This study aimed to investigate the protective effects and mechanisms of Polygala fallax Hemsl polysaccharides (PFPs) on AFLD. PFPs were purified and structurally characterized. An AFLD model was established in mice using alcohol and a high-fat diet. A significant reduction in hepatic steatosis was observed following PFPs treatment, evidenced by decreased fat deposition in liver tissues. Additionally, PFPs reduced various liver injury markers, increased levels of antioxidant enzymes, and improved significantly liver function. RNA sequencing revealed that PFPs improved lipid and CYP450 metabolic pathway abnormalities in AFLD mice. Furthermore, PFPs activated the AMPK pathway, reducing lipid accumulation and enhancing lipid metabolism. A HepG2 cell model treated with ethanol and oleic acid showed significant biochemical improvements with PFPs pretreatment, including reduced lipid accumulation and lower reactive oxygen species (ROS) levels. To further elucidate the AMPK and PFPs correlation in AFLD, an AMPK inhibitor (compound C) was used. In vitro and in vivo qRT-PCR and Western blot results confirmed that PFPs protected against AFLD by activating AMPK phosphorylation, regulating lipid synthesis, and inhibiting lipid accumulation. PFPs also modulated CYP2E1 and oxidative stress-related gene expression, affecting liver metabolism.
Diabetic cardiomyopathy (DCM) is a prevalent complication of diabetes mellitus characterized by cardiac dysfunction and myocardial remodeling. Farrerol (FA), an active ingredient in Rhododendron with various pharmacological activities, has an unclear specific role in DCM. Therefore, this study aims to investigate the effects of FA on DCM rats and elucidate its mechanism. The type 2 diabetes mellitus (T2DM) model was induced in adult male Sprague-Dawley rats by administering a high-fat diet for 8 weeks along with STZ injection. Subsequent to successful modeling, FA and the positive drug Dapagliflozin (Dapa) were orally administered via gavage for an additional 8-week period. After administration, the rats’ body weight, fasting blood glucose, fasting insulin, and blood lipid profiles were quantified. Cardiac function was assessed through evaluation of cardiac function parameters, histopathological examination and measurement of myocardial enzyme markers were conducted to assess myocardial injury and fibrosis, Oil red O staining was utilized to evaluate myocardial lipid accumulation, wheat germ agglutinin (WGA) staining was used for assessing cardiomyocyte hypertrophy, and Western blot analysis was used to detect the proteins expression level of AMP-activated protein kinase (AMPK) pathway. The rat cardiomyocyte H9c2 were induced with palmitic acid to establish an in vitro cell model of myocardial lipid toxicity. Subsequently, the cells were subjected to treatment with FA and AMPK inhibitor Compound C, followed by assessment of lipid formation and expression levels of proteins related to the AMPK signaling pathway. The findings demonstrated that both FA and Dapa exhibited efficacy in ameliorating diabetic symptoms, cardiac dysfunction, myocardial fibrosis, cardiomyocyte hypertrophy, and lipid accumulation in T2DM rats. Additionally, they were found to enhance AMPK phosphorylation and PPARα expression while down-regulating CD36. Similarly, FA was observed to inhibit lipid formation in H9c2 and activate the AMPK signaling pathway. However, the improved effect of FA on lipotoxic cardiomyocytes induced by palmitic acid was partially reversed by Compound C. Therefore, the activation of the AMPK signaling pathway by FA may enhance cardiac lipid metabolism, thereby improving cardiac dysfunction and myocardial fibrosis in DCM rats.
危险品化学品经营许可证（带存储）