Oxybaphus himalaicus alleviates diabetic kidney disease by suppressing the lipid metabolism and inflammation via PPARα signaling

Diabetic kidney disease (DKD) is a common complication in patients with diabetes, and glycolipid metabolism disorders are an important cause of DKD. The root of Oxybaphus himalaicus (Edgew.) Heimerl is a traditional Tibetan medicine commonly used to treat kidney-related diseases. Nevertheless, contemporary pharmacological investigations into O. himalaicus, especially those associated with the treatment of renal disorders, remain scarce. The objective of this research was to explore the pharmaceutical impacts and mechanisms of action of O. himalaicus in the treatment of DKD. The active fraction and potential pharmacological effects of O. himalaicus were determined through network pharmacology. Then, in vivo and in vitro efficacy and mechanism studies were conducted through streptozotocin-induced DKD mice and high glucose-induced HK-2 cells. Network pharmacology research speculated the ethyl acetate (EA) fraction as the main active component of O. himalaicus for treating DKD. In vivo and in vitro experiments showed that EA reduces renal lipotoxicity by upregulating PPARα pathway proteins, enhancing fatty acid oxidation (FAO), and downregulating inflammatory factors such as TNF-α and IL-6. Molecular docking studies revealed that the active components of EA with a high affinity for PPARα are mainly rotenoid compounds. EA mitigates DKD through the activation of PPARα, which serves to augment FAO, abate lipid accumulation, and impede the expression of inflammatory factors. Among these, rotenoids may be the main active components that exert pharmacological effects.