CSS, a traditional Chinese multi-herbal formulation, alleviates perimenopausal symptoms in rats by regulating hormone levels and interactions with the FMO3 enzyme.
First, perimenopausal symptoms were induced in rats via ovariectomy. Thereafter, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to establish a profiling of the metabolites found in rat plasma following treatment with CSS. Among these metabolites, high-exposure compounds were identified and further analyzed through molecular docking and network pharmacology to study their interactions with steroid metabolism pathways and particularly with FMO3 enzyme.
The discussion of the results indicated that CSS was successful in regulating abnormal hormone levels. The CSS treatment not only reduced levels of triglycerides and cholesterol but also increased IL-10 levels, which collectively contributed towards alleviating PMS symptoms in the rat model. Through LC-MS/MS, liquiritigenin, isosakuranetin, and hesperetin were identified as high-exposure components, suggesting their potential roles in the mitigation of PMS symptoms as well. Network pharmacology and molecular docking analyses showed these flavonoids interacting with the FMO3 enzyme, which was further validated through Cellular Thermal Shift Assay. Finally, it was noted that CSS decreased FMO3 levels in rat liver and serum.
