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

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.