Exploring the key ingredients and mechanisms of Banxia Xiexin decoction for the treatment of polycystic ovary syndrome based on network pharmacology and experimental validation.

PURPOSE

This study aimed to investigate the key bioactive constituents and polypharmacological mechanisms of Banxia Xiexin Decoction (BXD) against polycystic ovary syndrome (PCOS) through integrated network pharmacology and experimental validation.

METHODS

Network pharmacology was used to determine the key ingredients, potential targets and signaling pathways. 3-week-old female mice were injected subcutaneously with DHEA (6mg/100g body weight) daily to construct a PCOS model and administered different doses BXD and its key ingredients for intervention. Ovarian pathology, vaginal smears, oxidative stress-related indicators, and hub genes were tested to evaluate its therapeutic effects.

RESULTS

We identified 3 key ingredients and 99 potential targets for BXD treatment of PCOS. Biological functions of these targets were mainly enriched in oxidative stress, hormone response and apoptosis. KEGG analysis showed they were mainly involved in signaling pathways such as PI3K-AKT, MAPK, HIF-1 and IL17. By PPI and algorithmic analysis, we identified 8 hub genes, 5 of which (JUN, MAPK1, MAPK3, FOS, TP53) were related to oxidative stress. Further analysis indicated that quercetin, glycyrrhetinic acid A and naringenin are the three key ingredients of BXD, and they have superior binding effects on the hub genes. Animal experiments demonstrated that BXD and its three key ingredients significantly ameliorated the PCOS symptoms, oxidative stress-related indicators and the expression of hub genes.

CONCLUSIONS

Five oxidative stress-related hub targets of BXD for PCOS were identified, including FOS, JUN, MAPK3, TP53 and HSP90AA1, while three key ingredients of BXD, quercetin, glycyrrhetinic acid A and naringenin, were uncovered.