Antioxidant and anti-inflammatory effect of ligustilide on sepsis-induced acute kidney injury via TLR4/NF-κB and Nrf2/HO-1 signaling

Purpose: To investigate the protective effect of ligustilide on sepsis-induced acute kidney injury (AKI) and the signaling pathways involved.Methods: Sepsis-induced AKI was established by cecal ligation and puncture (CLP) in mice. Histopathological renal damage was examined using hematoxylin and eosin (H & E) staining while creatinine and cytokines were measured using commercial kits. Protein levels were determined by Western blotting.Results: Vacuoles, dilations, degeneration, and necrosis were observed in CLP mouse kidneys, but these alterations were countered by 20 mg/kg of ligustilide. Serum creatinine, blood urea nitrogen (BUN), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 were significantly increased in CLP mice compared with control. Furthermore, the serum levels of these indicators in serum were lowered by ligustilide (p < 0.01). The expression levels of Toll-like receptor 4 (TLR4) TLR4 and phosphorylated nuclear factor (NF)-κB in CLP mice were also downregulated by ligustilide. Malondialdehyde (MDA) and myeloperoxidase (MPO) levels increased in CLP mice, but were attenuated by ligustilide (p < 0.01). Superoxide dismutase (SOD) and glutathione (GSH) levels decreased in CLP mice but were increased by ligustilide (p < 0.01). Increased expression of Nrf2 and heme oxygenase-1 (HO-1) were observed in CLP mice, and were further enhancced by ligustilide.Conclusion: Ligustilide exerts antioxidant and anti-inflammatory effects on sepsis-induced AKI via TLR4/NF-κB and Nrf2/HO-1 signaling pathways. Keywords: Ligustilide, Sepsis, Acute kidney injury, TLR4/NF-κB signaling pathway, Nrf2/HO-1 signaling pathway