Salvianolic Acid B Inhibits Oxidative Stress in Glomerular Mesangial Cells Alleviating Diabetic Nephropathy by Regulating SIRT3/FOXO1 Signaling

Abstract

Introduction: Oxidative stress is pivotal in advancing diabetic nephropathy (DN). Salvianolic acid B (SAB), derived from Radix Salviae miltiorrhizae, exhibits renoprotective effects. However, the mechanisms underlying its action in DN are not fully elucidated. This study explores SAB’s protective effect on DN, focusing on its antioxidative properties in glomerular mesangial cells. Methods: The renoprotective effects of various SAB dosages on DN rats were assessed by evaluating kidney tissue pathological alterations through hematoxylin and eosin, periodic acid-Schiff, Masson, TUNEL staining, and kidney function through biochemical detection. Cell counting kit-8 and lactate dehydrogenase cytotoxicity assays were utilized to evaluate the viability of high glucose (HG)-induced HBZY-1 cells treated with various SAB dosages. Oxidative stress and inflammation levels were measured using enzyme-linked immunosorbent assay kits. The Sirtuin 3 (SIRT3)/Forkhead box transcription factor O1 (FOXO1) pathway was examined through Western blot and immunohistochemistry. Results: SAB mitigated kidney histopathological alterations and function and cell apoptosis in DN rats at various dosages. It enhanced the activity of glutathione peroxidase and superoxide dismutase while decreasing reactive oxygen species and malondialdehyde levels both in vivo and in vitro. SAB also suppressed the levels of pro-inflammatory cytokines (IL-1β, IL-6, MCP-1, and TNF-α) and the expression of collagen IV and fibronectin in HG-induced HBZY-1 cells. Furthermore, SAB activated the SIRT3/FOXO1 signaling pathway. Conclusion: Our findings suggest that SAB may alleviate oxidative stress in DN both in vivo and in vitro, potentially through the activation of the SIRT3/FOXO1-mediated signaling pathway. This study provides initial insights into the possible antioxidative and renoprotective effects of SAB, indicating its potential utility as a therapeutic agent for DN.