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

Authors

  • Saja Majeed Shareef
  • Sarmed Hashim Kathem

DOI:

https://doi.org/10.47750/pnr.2022.13.04.018

Keywords:

Acute kidney injury, Lipopolysaccharides, Gentiopicroside.

Abstract

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-κB, AP-1, IRF3 and proinfammtory markers IL-1β and iNOS. Furthermore, TNF-α 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-α, and IL-1β. 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 KIM1 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

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Published

2022-10-07

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Section

Articles

How to Cite

Gentiopicroside ameliorates lipopolysaccharide-induced acute kidney injury by inhibiting TLR4/NF-κB signaling in mice model. (2022). Journal of Pharmaceutical Negative Results, 13(4), 135-145. https://doi.org/10.47750/pnr.2022.13.04.018