Shenbing Decoction III and Apigenin Improve Peritoneal Fibrosis Mediated by Epithelial–Mesenchymal Transition Through TAK1/p38MAPK/NF-κB Pathways

Abstract

Background: This study aimed to evaluate the effect of Shenbing Decoction III (SBD III) and its key Apigenin on peritoneal dialysis (PD)–induced peritoneal fibrosis and explore the underlying mechanisms.

Methods: Liquid chromatography–mass spectrometry confirmed the presence of Apigenin in SBD III. Human peritoneal mesothelial cells (HMrSV5) were stimulated with PD solution (PDS) to induce fibrosis, and treatment with SBD III and Apigenin was administered.

Results: PDS decreased cell viability and increased the migration and invasion capabilities of HMrSV5 cells. It also reduced E-cadherin expression, while increasing the expression of α-SMA, fibronectin, collagen I, and TGF-β1. SBD III and Apigenin effectively counteracted these effects. Additionally, SBD III and Apigenin inhibited the PDS-induced upregulation and phosphorylation of transforming growth factor-β-activated kinase 1 (TAK1), p38, and nuclear factor-κB (NF-κB), similar to the effects of 5z-7-oxozeaenol. Chronic kidney disease (CKD) was induced in mice by 5/6 nephrectomy, followed by PDS treatment. The therapeutic effects of SBD III and Apigenin were evaluated. CKD mice exhibited reduced body weight and kidney weight indices, along with elevated blood urea nitrogen, urinary creatinine, and urinary protein levels. Fibrosis was observed in the kidneys and peritoneum. PDS treatment also significantly alleviated these effects. Notably, therapeutic effects were further augmented when SBD III and Apigenin were administered.

Conclusion: SBD III and Apigenin ameliorated PDS-induced peritoneal fibrosis by inhibiting epithelial–mesenchymal transition via the TAK1/p38MAPK/NF-κB pathway, indicating promising pharmaceutical candidates for CKD.