<italic>Moringa oleifera</italic> leaves extract improving disorders of glucolipid metabolism in type II diabetic rats through FXR-FGF15-FGFR4 pathway

Moringa oleifera leaf is a novel resource food with various activities such as hypoglycemic, lipid-lowering, and anti-inflammatory effects. However, its mechanism for improving glucose and lipid metabolism disorders in type II diabetes remains unclear. This study focuses on the extract of Moringa oleifera leaves, using STZ-induced SD rats as a type II diabetes model, to investigate the effects and mechanisms of the extract on glucose and lipid metabolism disorders in type II diabetic rats. The results indicate that the extract significantly reduces the levels of TC, TG, LDL-C, and NEFA in the serum of type II diabetic rats, increases HDL-C levels, and lowers fasting and random blood glucose levels. Additionally, it enhances SOD and GSH-Px activities while reducing MDA, IL-6, and MCP-1 levels, leading to a marked improvement in oxidative stress and inflammation in the serum. The intervention with the extract effectively ameliorates structural lesions in the liver, kidneys, and pancreatic tissues of the rats. By examining bile acids and proteins related to glucose and lipid metabolism, it is preliminarily clarified that the extract inhibits ileal FXR, thereby suppressing the FXR-FGF15-FGFR4 bile acid enterohepatic circulation pathway. This upregulates the expression of hepatic CYP7A1, promotes bile acid synthesis in the liver, and further activates hepatic FXR. Subsequently, it enhances fatty acid oxidation via the PPAR-α pathway, alleviates gluconeogenesis through the FOXO1 pathway, and modulates the expression of SREBP1 to regulate downstream ACC and FAS expression, thereby inhibiting excessive fatty acid synthesis and improving glucose and lipid metabolism disorders in type II diabetic rats. In conclusion, this study elucidates the mechanism by which Moringa oleifera leaf extract improves glucose and lipid metabolism disorders in type II diabetes, providing a scientific basis for further development and utilization of Moringa oleifera leaves.