Yinling Qushi Granule as a therapeutic agent for metabolic syndrome: pharmacological, molecular targets, and pharmacokinetic insights.

Metabolic Syndrome (MetS) is a globally prevalent condition with unclear underlying mechanisms. Current treatments primarily focus on alleviating individual symptoms, lacking long-term therapeutic strategies that target the disease's endotypes. In this study, we found that Yinling Qushi Granule (YLQSG), a formulated prescription for treating Dampness Syndrome (DS) in Traditional Chinese Medicine (TCM), effectively attenuated hypertension associated with MetS. After 12 weeks of YLQSG treatment, MetS patients showed significant reduction in systolic and diastolic blood pressure, body mass index (BMI) and glycated hemoglobin (HbA1c). Chemical analysis has identified a total of 96 components of YLQSG, alongside with 27 serum absorbed prototypes and 13 metabolites. In vivo metabolic profiling revealed critical Phase I metabolism including dehydration, demethylation, and oxidation. By integrating network pharmacology and molecular docking, we proposed 11 triterpenoids from the sovereign herb Poria cocos (Schw.) Wolf as active constituents of YLQSG. These triterpenoids showed potent binding affinities with AGTR1 and 11β-HSD1, two crucial druggable targets in the renin-angiotensin-aldosterone system. Pharmacokinetics of these 11 lanosterol-type triterpenoids in rat serum indicated their good drug likeness properties. In summary, our findings highlight the potential of YLQSG in treating MetS, particularly hypertension, and identify its active compounds and potential molecular targets, offering a promising alternative strategy for the long-term management of MetS. Trial registrationChiCTR, ChiCTR2200063506. Registered 9 September 2022,  https://www.chictr.org.cn/showproj.html?proj=174653 .