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

Abstract

Rhodiola crenulata (RC) has long been used in traditional medicine for its health benefits, including managing high-altitude sickness, fatigue, and diabetes. Diabetic kidney disease (DKD) is a severe diabetes consequence, often leading to progressive renal fibrosis. This study investigated how RC helps protect against kidney fibrosis in DKD rat models, focusing on identifying active compounds and their therapeutic targets, especially the effects of salidroside (SAL), a key component of RC. After administering RC to DKD rats, 22 core components were identified and analyzed via network pharmacology, leading to 141 DKD-related therapeutic targets. The compound SAL showed significant targeting capability, implicating TGFB1 as a primary therapeutic target in kidney fibrosis. In vivo, the study assessed RC's effects on fibrosis markers, while in vitro analyses explored SAL's role in fibroblast activation and TGF-β1 regulation in proximal renal tubular epithelial cells (PTECs). We found that RC treatment effectively reduced fibrosis markers in DKD rats by decreasing glomerular mesangial expansion, collagen deposition, and myofibroblast proliferation, alongside decreasing TGF-β1 levels. In vitro, SAL inhibited high glucose-induced fibroblast activation and TGF-β1 expression in PTECs, suggesting its direct role in slowing fibrosis progression. We conclude that the antifibrotic effects of RC in DKD may be attributed to SAL's ability to regulate fibroblast activity and suppress TGF-β1. These findings highlight its potential as a therapeutic component for DKD management.