Liu Wei Di Huang Decoction Alleviates Renal Fibrosis by Inhibiting Endothelial Mesenchymal Transitions via Upregulating Sirt1 Expression and Inhibiting the Wnt/β-Catenin Signaling Pathway

作者：Hui Wang, Shuangshuang Chen, Yongxian Zhang, Haibo Gao, Bin Meng, Weixiang Wu, Qun Tang · 发表于：Drug Design Development and Therapy · 年份：2025 · DOI：10.2147/dddt.s517938 · 被引用次数：4 · 研究领域：Chronic Kidney Disease and Diabetes、Renal Diseases and Glomerulopathies、Renal cell carcinoma treatment

Background: Renal fibrosis (RF) is the final outcome of chronic kidney disease (CKD), which can be triggered by various factors. Liuwei Dihuang Decoction (LWDHD) has been clinically established as an effective treatment for CKD, demonstrating anti-inflammatory, antioxidant, and antifibrotic effects. However, the specific molecular mechanisms underlying the therapeutic effectiveness of LWDHD remain unknown. Aim: Prediction of key active ingredients, targets, and mechanistic pathways of LWDHD in RF treatment. Materials and Methods: The bioactive components of LWDHD were identified and quantified using ultra-performance liquid chromatography-tandem quadrupole mass spectrometry (UHPLC-MS/MS). A network pharmacology approach was employed to predict the key targets of these bioactive components. A rat model of renal tubulointerstitial fibrosis was created through unilateral ureteral obstruction (UUO). Rats were divided into six groups: sham operation, UUO, low-dose LWDHD (LW-L), medium-dose LWDHD (LW-M), high-dose LWDHD (LW-H), and enalapril group. Continuous gavage of treatments was administered for 2 weeks. The renal tissues were histopathologically assessed, including HE, Masson's trichrome, and Sirius red staining, immunohistochemistry, co-staining and Western blot analysis to evaluate the effects of LWDHD on renal fibrosis. Transforming growth factor beta-1 (TGF-β1) was employed to stimulate endothelial-mesenchymal transition (EndMT) in EA.hy926 cells. The inhibitory effect of...