Renoprotective Effects of a Herbal Formulation Against Lipopolysaccharide-Induced Acute Kidney Injury Through Anti-Inflammatory and Antioxidant Activities

Abstract

Sepsis-associated acute kidney injury (AKI) is a severe inflammatory complication with limited therapeutic options. This study investigated the protective effects of Taiwan Chingguan Yihau (NRICM101), a herbal formulation, against lipopolysaccharide (LPS)-induced AKI. Male C57BL/6 mice were injected with LPS to induce AKI in vivo, followed by therapeutic administration of NRICM101. NRK-52E renal epithelial cells were stimulated with LPS to induce inflammatory responses and oxidative stress in vitro. Key bioactive compounds were identified via HPLC and analyzed using molecular docking. NRICM101 significantly alleviated renal dysfunction, as indicated by blood urea nitrogen (BUN) and serum creatinine (Scr) levels, and reduced histopathological damage in mice. It effectively suppressed the production of pro-inflammatory cytokines, attenuated intracellular and mitochondrial ROS, and preserved mitochondrial membrane potential. Mechanistically, NRICM101 markedly downregulated the expression of phosphorylated p65 (p-p65), NOD-like receptor protein 3 (NLRP3), and cleaved caspase-1, indicating modulation of nuclear factor kappa-B (NF-κB)/NLRP3 inflammasome signaling associated with renal pyroptosis. Molecular docking predicted potential interactions of NRICM101-derived bioactive constituents with the toll-like receptor 4 (TLR4)/MD-2 complex. Collectively, our findings suggest that NRICM101 ameliorates LPS-induced acute renal injury through anti-inflammatory and antioxidant effects associated with modulation of NF-κB/NLRP3-related signaling.