Anti-gallstone effects of Jieshiqing Capsule and its active component verbascoside and the underlying mechanisms.

ETHNOPHARMACOLOGICAL RELEVANCE: Jieshiqing Capsule (JSQ) is a classic traditional Miao medicine with notable clinical efficacy in clearing damp-heat and promoting bile flow to eliminate gallstones. However, the lack of a quality evaluation standard centered on its sovereign herb, together with unclear molecular mechanisms, greatly limits the modernization and broader application of this formulation.

AIM OF THE STUDY: To systematically characterize the chemical basis of JSQ, elucidate the pharmacological mechanism of its core active component against cholesterol gallstones (CGS), and provide a scientific basis for improving its quality standards.

MATERIALS AND

METHODS

UPLC-Q-TOF-MS and HPLC were used to profile JSQ and quantify verbascoside. A CGS mouse model was established. Clinical transcriptomics, untargeted metabolomics, Western blotting and RT-qPCR were integrated to explore the mechanism.

RESULTS

Among 74 annotated constituents, the primary bioactive verbascoside stably maintained 4.361-7.168 mg/g across 15 batches of JSQ. In vivo experiments confirmed that this component significantly inhibited CGS formation, ameliorated dyslipidemia, and alleviated liver injury. Integrated multi-omics analysis revealed that cytokine-cytokine receptor interaction, bile acid metabolism, and steroid biosynthesis are key pathways. Mechanistic studies demonstrated that verbascoside regulates the AGE/RAGE/NF-κB/FXR axis to exert anti-gallstone effects, downregulating the mRNA and protein expression of IL-6, IL-1β, TNF-α, and RAGE, while upregulating FXR, BSEP, NTCP, SHP, CYP7A1, CYP8B1, and NR1H3.

CONCLUSIONS

Verbascoside from JSQ exerts dual anti-inflammatory and bile acid-remodeling effects via the AGE/RAGE/NF-κB/FXR axis, counteracting cholesterol gallstones. This study provides a material basis for a new quality standard centered on the sovereign herb's active component.