Vitisin A Inhibits MAPK and NF-κB Signaling Pathways and Improves Renal Function in LPS-Induced Acute Kidney Injury Mice.

Abstract

Although natural flavonoids have shown potential in acute kidney injury (AKI) treatment, evidence regarding the renal protective effects of Vitisin A remains limited. We aimed to investigate the protective effects of Vitisin A on renal function and its underlying molecular mechanisms in lipopolysaccharide (LPS)-induced AKI. Renal function was assessed by measuring serum creatinine (Scr), blood urea nitrogen (BUN), and uric acid (UA) in LPS-induced AKI animal models. The expression of renal tubular injury markers (e.g., KIM-1, NGAL) was analyzed using qPCR and Western blot (WB) analysis. Oxidative stress, inflammation, and apoptosis were evaluated by detecting pro-oxidant and antioxidant proteins (e.g., NOX4, MDA, GSH), inflammatory cytokines (e.g., TNF-α, IL-6), and apoptotic proteins (e.g., Bcl-2, Bax). We also examined the activation of NF-κB and MAPK signaling pathways in LPS group and LPS+ Vitisin A group. LPS treatment impaired renal function, increased the expression of renal tubular injury markers, and induced severe oxidative stress and inflammation in renal tissues. Vitisin A treatment markedly improved renal function, alleviated tubular injury, and reduced the elevated expression of NOX4, and MDA while restoring antioxidant protein levels. Furthermore, Vitisin A attenuated renal inflammation and apoptosis. Mechanistically, Vitisin A inhibited the activation of NF-κB and MAPK pathways, as evidenced by reduced phosphorylation of p65, IκBα, ERK, JNK, and p38 in LPS-induced AKI mice. Our study demonstrated that Vitisin A improved renal function, reduced tubular injury, and attenuated inflammation, oxidative stress, and apoptosis in LPS-induced AKI mice, accompanied by suppression of MAPK and NF-κB signaling. Our findings provided experimental evidence supporting Vitisin A as a potential therapeutic agent for AKI. However, further research is needed to evaluate its long-term efficacy and safety for clinical translation.