A natural product of acteoside ameliorate kidney injury in diabetes db/db mice and HK‐2 cells via regulating NADPH/oxidase‐TGF‐β/Smad signaling pathway

This study was designed to investigate the protective effects and mechanisms of acteoside on DKD in diabetes male db/db mice and high glucose‐induced HK‐2 cells. The diabetes db/db mice were divided randomly into model group, metformin group, irbesartan group, and acteoside group. We observed the natural product of acteoside exhibiting a significant effect in renal protection through analyzing of biochemical indicators and endogenous metabolites, histopathological observations, and western blotting. HK‐2 cells subjected to high glucose were used in invitro experiments. The molecular mechanisms of them were investigated by RT‐PCR and western blot. Acteoside prevents high glucose‐induced HK‐2 cells and diabetes db/db mice by inhibiting NADPH/oxidase‐TGF‐β/Smad signaling pathway. Acteoside regulated the disturbed metabolic pathway of lipid metabolism, glyoxylate and dicarboxylate metabolism, and arachidonic acid metabolism. We discovered the natural product of acteoside exhibiting a significant effect in renal protection. This study paved the way for further exploration of pathogenesis, early diagnosis, and development of a new therapeutic agent for DKD.