1. Hederasaponin C inhibits LPS-induced acute kidney injury in mice by targeting TLR4 and regulating the PIP2/NF-κB/NLRP3 signaling pathway.
- Author
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Han S, Li S, Li J, He J, Wang QQ, Gao X, Yang S, Li J, Yuan R, Zhong G, and Gao H
- Subjects
- Animals, Mice, Anti-Inflammatory Agents pharmacology, Anti-Inflammatory Agents therapeutic use, Lipopolysaccharides pharmacology, Molecular Docking Simulation, NLR Family, Pyrin Domain-Containing 3 Protein drug effects, NLR Family, Pyrin Domain-Containing 3 Protein metabolism, Signal Transduction, Toll-Like Receptor 4 drug effects, Toll-Like Receptor 4 metabolism, Phosphoinositide Phospholipase C, Acute Kidney Injury chemically induced, Acute Kidney Injury drug therapy, NF-kappa B drug effects, NF-kappa B metabolism, Saponins pharmacology, Saponins therapeutic use
- Abstract
Acute kidney injury (AKI) is a common clinical condition associated with increased incidence and mortality rates. Hederasaponin C (HSC) is one of the main active components of Pulsatilla chinensis (Bunge) Regel. HSC possesses various pharmacological activities, including anti-inflammatory activity. However, the protective effect of HSC against lipopolysaccharide (LPS)-induced AKI in mice remains unclear. Therefore, we investigated the protective effect of HSC against LPS-induced renal inflammation and the underlying molecular mechanisms. Herein, using MTT and LDH assays to assess both cell viability and LDH activity; using dual staining techniques to identify different cell death patterns; conducting immunoblotting, QRT-PCR, and immunofluorescence analyses to evaluate levels of protein and mRNA expression; employing immunoblotting, molecular docking, SPR experiments, and CETSA to investigate the interaction between HSC and TLR4; and studying the anti-inflammatory effects of HSC in the LPS-induced AKI. The results indicate that HSC inhibits the expression of TLR4 and the activation of NF-κB and PIP2 signaling pathways, while simultaneously suppressing the activation of the NLRP3 inflammasome. In animal models, HSC ameliorated LPS-induced AKI and diminished inflammatory response and the level of renal injury markers. These findings suggest that HSC has potential as a therapeutic agent to mitigate sepsis-related AKI., (© 2023 The Authors. Phytotherapy Research published by John Wiley & Sons Ltd.)
- Published
- 2023
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