HHQG ameliorates acute liver injury (ALI) by inhibiting NLRP3 activation through RASD1-mediated regulation of the PKCδ-NF-κB signaling pathway

Résumé fourni par la source

Acute liver injury (ALI) is a prevalent hepatic condition that poses significant risks to both life and overall health. Traditional Mongolian medicine utilizes Honghua Qinggan Thirteen-Flavor Pills (HHQG) as a primary formula for dispelling liver heat, illustrating both an extensive application in clinical settings and notable therapeutic effectiveness for treating liver ailments such as hepatitis and liver failure. Nevertheless, the molecular mechanisms underpinning the hepatoprotective properties of HHQG remain inadequately understood.We employed a CCl 4 -induced mouse model of liver injury alongside network pharmacology analysis, molecular docking studies, and cellular assays to dissect the effects and mechanisms of action of HHQG. Our findings demonstrated that HHQG significantly improved CCl 4 -induced liver injury in mice, reducing pathological damage and inflammatory factors. Network pharmacology identified 184 overlapping targets, 6 key genes, and 5 key active components in HHQG. Molecular docking confirmed the binding affinity of these components to RASD1. Gene expression analysis in liver tissue revealed a positive correlation between mRNA expression of RASD1 and NLRP3. Cell experiments demonstrated the role of RASD1 in regulating NLRP3 inflammasome and inflammatory factors. Pretreatment of HHQG attenuated LPS-induced inflammatory response and the activation of PKCδ-NF-κB signaling pathway. In the CCl 4 -induced liver injury model, HHQG significantly reduced NLRP3, RASD1, and PKCδ-NF-κB expression.This study revealed that HHQG effectively mitigates CCl 4 -induced liver injury by inhibiting the activation of NLRP3 inflammasome by regulating the PKCδ-NF-κB signaling pathway via RASD1. These findings provide novel theoretical support for the rational application of HHQG as a potential hepatoprotective agent.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.