Gentiopicroside ameliorates lipopolysaccharide-induced acute kidney injury by inhibiting TLR4/NF-?B signaling in mice model

Background: Inflammation is a major factor in the development of acute renal damage and the Toll-like receptor 4 (TLR4) signaling pathway is a major contributor to inflammation in the kidney. Lipopolysaccharide (LPS), a specific ligand for TLR4, has been shown to induce acute kidney injury in human and animal models. Gentiopicroside (GENT) is a natural secoiridoid glycoside with various biological activities.Aim of study: This study aimed to investigate the renoprotective effect of gentiopicroside on LPS-induced AKI in mice model.Method: Real-Time Quantitative qPCR method was used to measure mRNA level of the promising kidney biomarkerKIM-1, TLR-4, transcription factors NF-KB, AP-1, IRF3 and proinfammtory markers IL-113 and iNOS. Furthermore, TNF-alpha was measured by ELISA analysis and biochemical analysis and histological analysis were used to detect renal function.Results: The results showed that gentiopicroside significantly (p<0.05) inhibited LPS-induced TNF-alpha, and IL-113. Furthermore, medium -and high-dose gentiopicroside significantly suppressed the Toll-like receptor 4 (TLR4) / myeloid differential protein-88 (MyD88) / nuclear factor-kappa (NF-B) signaling pathway. Urea and creatinine levels were also reduced with gentiopicroside. Kidney injury molecule-1 KIM -1 expression which was the early indicator for AKI was also inhibited by gentiopicroside compared to LPS group. Conclusion: Our data suggest that gentiopicroside protects against LPS-induced AKI via suppressing the TLR4-MYD88 dependant and independent signaling pathway as well as improving renal function and structural kidney damage. As a result, gentiopicroside may have therapeutic potential for LPS-induced SA-AKI.