Qinggan Jiangzhi Cha ameliorates NAFLD by modulating the AGE-RAGE/PRKCA/MAPK3/AP-1 signaling axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Qinggan Jiangzhi Cha (QGJZC), a compound formulation rooted in Traditional Chinese Medicine, is traditionally employed to clear heat, soothe the liver, and reduce lipid accumulation to alleviate hepatic stagnation and indigestion, aligning with modern NAFLD therapeutic strategies targeting lipid metabolism and inflammation.

AIM OF THE STUDY: This study aimed to evaluate the efficacy of QGJZC against NAFLD and to elucidate the underlying mechanisms.

METHODS

Rats with high-fat diet-induced NAFLD were treated with QGJZC. Therapeutic efficacy was assessed by serum biochemical markers, histopathological staining, and inflammatory cytokines. An integrative approach combining serum chemical analysis, network pharmacology, transcriptomics, and molecular validation was employed to elucidate the mechanism.

RESULTS

QGJZC intervention markedly lowered the elevated serum ALT and AST levels in NAFLD model rats, ameliorated lipid metabolism disorders (decreased TG, TC, and LDL-C; increased HDL-C), and dose-dependently alleviated pathological damage such as hepatic steatosis and inflammatory cell infiltration. Serum pharmacochemical analysis identified 109 absorbed components, with flavonoids being predominant. Integrated network pharmacology and transcriptomic analyses linked the therapeutic mechanism to the AGE-RAGE signaling pathway, among others. Experimental validation demonstrated that QGJZC significantly inhibited the expression of key mediators of the hepatic AGE-RAGE signaling axis (AGEs, RAGE, PRKCA), reduced MAPK3 phosphorylation levels, and attenuated downstream AP-1 nuclear translocation and activation.

CONCLUSIONS

This study demonstrates that QGJZC ameliorates metabolic disturbances and hepatic pathological injury in NAFLD rats. Its therapeutic effects are associated with the synergistic actions of multiple absorbed bioactive constituents and may involve regulation of the AGE-RAGE/PRKCA/MAPK3/AP-1 signaling pathway, thereby attenuating hepatic inflammatory responses. These findings provide pharmacological support for the potential clinical use of QGJZC in NAFLD treatment.