OBJECTIVE To systematically identify the main chemical constituents of the Tibetan medicine Guanxinning Granules and to elucidate its mechanism of action in the treatment of coronary artery disease.

METHODS UHPLC-Q-Exactive Orbitrap MS was used to identify the main chemical constituents of the Tibetan medicine Guanxinning Granules. Bioinformatics methods were applied to collect compounds and disease targets, and the interaction analysis of predicted target proteins was performed using the STRING database, and the main pathways of action and targets were predicted by GO and KEGG enrichment analyses. AutodockTools1.5.6 software was used to perform molecular docking of the main components and core targets, and ELISA experiments were used to verify the key targets.

RESULTS Seventy-three compounds were identified in Guanxinning Granules, mainly phenols(23), flavonoids(15), terpenoids(11), organic acids(10) and alkaloids(6). Forty-four active compounds were screened, with 476 targets of action, 63 of which intersected with targets related to coronary artery disease. Network pharmacological analysis showed that the formula mainly acted on the AGE-RAGE signalling pathway, endocrine resistance, fluid shear stress in lipid and atherosclerosis, diabetes complications, endocrine resistance, and fluid shear stress by modulating proteins such as ACE, SERPINE1, AKT1, ESR1, HIF1A, IFNG, NFKB1, NR3C1, and PPARG, as well as atherosclerosis signalling pathways to exert therapeutic effects on coronary artery disease. Molecular docking showed good affinity between the main active ingredients and the targets. ELISA experiments showed that Guanxinning Granules could reduce ACE in rat serum(P<0.05) and elevate SERPINE1 in rat serum(P<0.01).

CONCLUSIONS The present study comprehensively identified the chemical constituents of Guanxinning Granules and preliminarily elucidated the mechanism of action in the treatment of coronary artery disease, which provided a basic theoretical basis for further clinical application, pharmacological and quality control studies of this preparation.