A network pharmacological approach to evaluate Jia-Wei-Xiao-Yao-san formula’s mechanistic pathways and its implication in the symptomatology of polycystic ovarian syndrome

Polycystic ovary syndrome (PCOS) is a disorder characterized mainly by a disruption of androgen secretion or endocrine feedback mechanism dysfunction occurring subtlety during adolescence and progressively impairing the ovarian folliculogenesis which affects preponderantly women of reproductively active age. Most of the reproductive active period of women is hampered by this condition, thereof reducing their fertility and causing metabolic disturbances. Traditional Chinese Medicine principles have been historically settled to develop Chinese Herbal Medicine formulas designed to treat various ailments including reproductive disorders. This study addresses the mechanisms of action of Jia-Wei-Xiao-Yao-San formula by examining the functional predicted PCOS-related targets networks first enriched by STITCH chemical interactions and then analyzed by STRING protein interactions database. Using the highest confidence interaction score as a screening binding parameter, we obtained a total of 274 PCOS-related targets interacting with 58 bioactive compounds from the formula and 22 PCOS-related drugs interacting with a total of 133 PCOS-related targets. Our analysis identified a total of 84 common PCOS-related targets shared by both the formula and the PCOS-related drugs and demonstrate the predicted PCOS-related protein-protein interaction network resulting in various KEGG pathways. These findings indicated the formula functionality role preponderantly in cholesterol metabolism, ovarian steroidogenesis, peroxisome proliferator-activated receptors, and adipocytokine signaling pathway. Numerous compounds identified here are known to have high binding interactions with PCOS-related targets. Our methodological approach demonstrates that both the drugs-PCOS-related targets network support Jia-Wei- Xiao-Yao-San formula as an appropriate Traditional Chinese Medicine to treat at least the symptoms associated with PCOS manifestations.