Mechanistic insights of Rhodiola crenulata in treating diabetic kidney disease via network pharmacology

Rhodiola crenulata (RC) has been traditionally used for its therapeutic benefits, including alleviating high-altitude sickness, fatigue, and diabetes. Diabetic kidney disease (DKD), a severe complication of diabetes, often leads to progressive renal fibrosis. This study explored the protective effects of RC against kidney fibrosis in DKD rat models, identifying active compounds and their therapeutic targets, with a focus on salidroside (SAL), a key component of RC. After administering RC to DKD rats, network pharmacology analysis identified 22 core components and 141 DKD-related therapeutic targets, with TGFB1 emerging as a primary target in kidney fibrosis. In vivo experiments demonstrated that RC reduced fibrosis markers by decreasing glomerular mesangial expansion, collagen deposition, and myofibroblast proliferation, alongside lowering TGF-β1 levels. In vitro analyses revealed that SAL inhibited high glucose-induced fibroblast activation and suppressed TGF-β1 expression in proximal renal tubular epithelial cells (PTECs), suggesting its direct role in slowing fibrosis progression. These findings indicate that the antifibrotic effects of RC in DKD may be attributed to SAL's ability to regulate fibroblast activity and suppress TGF-β1, highlighting its potential as a therapeutic component for DKD management.