Mogroside V Alleviates Renal Injury in Diabetic Mice via Regulation of the TLR4/NF-κB Pathway and Modulation of ECM Remodeling

Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease, yet effective therapeutic strategies targeting its underlying mechanisms remain limited. Mogroside V (MV), a natural saponin from Siraitia grosvenorii, exhibits anti-inflammatory and antioxidant properties, but its role in DKD is unclear. This study investigated the effects and mechanisms of MV on renal injury in DKD using db/db mice and high-glucose-induced human renal mesangial cells (HRMCs). MV (25–100 mg/kg/d) was orally administered to db/db mice for eight weeks; HRMCs were treated with 0.5–2 μM MV under high-glucose conditions. Renal function, pathological changes, the expression of TLR4/MyD88/NF-κB pathway components, inflammatory cytokines, apoptosis-related factors, and ECM markers were assessed. MV significantly reduced fasting blood glucose, proteinuria, serum creatinine, and urea nitrogen levels, and ameliorated renal pathological injury in db/db mice. Mechanistically, MV downregulated TLR4, MyD88, and p-NF-κBp65 expression, suppressed inflammatory cytokine release (TNF-α, IL-1β, IL-6, MCP-1, IL-18), attenuated apoptosis (increased Bcl-2/Bax ratio, decreased caspase-3), and reduced ECM accumulation (decreased MMP-9, Col IV) both in vivo and in vitro. These findings suggest that MV protects against diabetic kidney disease, potentially by regulating the TLR4/NF-κB signaling pathway and improving extracellular matrix remodeling.