QingGanJianPi oral solution ameliorates hyperlipidemia by facilitating crosstalk between multiple active metabolites and the PPARα-LXRα axis.

OBJECTIVES

QingGanJianPi oral solution (QGJP), a traditional Chinese patent medicine, exhibits lipid-lowering and hepatoprotective effects. This study aimed to elucidate the mechanisms by which QGJP promotes lipid and cholesterol efflux.

METHODS

Drug efficacy was evaluated in HFD-mice. Serum metabolomics combined with network pharmacology was performed to predict the relative signaling pathways involved. Molecular docking and thermal stability assays were conducted to identify active ingredients interacting with potential targets. The mRNA levels and protein expression were analyzed by qPCR and Western blotting.

KEY FINDING: QGJP significantly reduced serum lipid levels in a dose-dependent manner. It also effectively attenuated high-fat diet-induced body weight gain and fat deposition. Untargeted serum metabolomics combined with network pharmacology revealed activation of the PPARα-LXRα-ABCA1 signaling axis following treatment. Among the circulating metabolites, salvianolic acid A was found to activate PPARα, thereby promoting the interaction between PPARα and LXRα, and enhancing the expression of downstream target genes. Furthermore, emodin upregulates ABCA1 expression mainly through direct activation of LXRα, with limited dependence on PPARα.

CONCLUSIONS

Salvianolic acid A and emodin upregulate ABCA1 expression via multiple mechanisms, including direct activation of LXRα or activation through PPARα, thereby demonstrating the multi-target advantages of traditional Chinese medicine and providing preliminary insights into the synergistic interactions among its complex metabolites.