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

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.

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.

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.

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.

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.