Nimbolide Reduces Inflammation and Oxidative Stress to Inhibit Disease Progression in Septic Acute Kidney Injury Mice

The study investigates the protective role of Nimbolide, a natural limonoid, against sepsis-associated acute kidney injury (SA-AKI) and its underlying molecular mechanisms. A murine sepsis model was established via cecal ligation and perforation. Renal histopathological changes were evaluated by hematoxylin and eosin staining, and renal function was assessed based on serum creatinine (Scr) and blood urea nitrogen (BUN) levels. The levels of inflammatory cytokines (interleukin-6 [IL-6], interleukin-1β [IL-1β], tumor necrosis factor-α [TNF-α]) in serum and renal homogenates were quantified by ELISA. Oxidative stress markers (malondialdehyde [MDA], superoxide dismutase [SOD], glutathione [GSH]) in renal tissue were measured using commercial assay kits. Renal cell apoptosis was detected by transferase dUTP nick end labeling (TUNEL) assay. Also, the protein expression and phosphorylation levels of nuclear factor kappa B (NF-κB) p65 and STAT3 in renal tissues were analyzed by Western blotting. Nimbolide treatment markedly attenuated tubular vacuolization and inflammatory cell infiltration, and improved renal function, as demonstrated by reduced serum Scr and BUN levels. Nimbolide also suppressed the levels of the pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) in both serum and renal tissue. Furthermore, Nimbolide decreased MDA levels, increased SOD activity and GSH content, and inhibited renal apoptosis. Mechanistically, these protective effects were associated with the inhibition of NF-κB p65 and STAT3 phosphorylation in the kidneys. Nimbolide protects against SA-AKI by inhibiting activation of the NF-κB/STAT3 pathway, thereby attenuating inflammation, oxidative stress, and apoptosis.