Study on the Mechanism of the Chinese Herbal Pair Banxia-Chenpi in Ameliorating Polycystic Ovary Syndrome Based on the CYP17A1 Gene.

Abstract

Ethnopharmacological relevance: As a typical Traditional Chinese Medicine (TCM) couplet medicine, Arum Ternatum Thunb. (Pinellia ternata (Thunb.) Makino, known as Banxia in Chinese) and Citrus Reticulata (pericarps of Citrus reticulata Blanco, known as Chenpi in Chinese) has been widely used in clinical practice for their properties of drying dampness, resolving phlegm, relieving oppression and masses. According to the TCM theories, the imbalance in fluid metabolism could lead to the accumulation of the excess dampness and phlegm, resulting in the pathological phenotype as 'damp-phlegm syndrome'. It can further lead to polycystic ovary syndrome (PCOS) when this accumulation of the excess fluid presents in uterus, affecting women's fertility and endocrine function. Recent studies have indicated that Banxia-Chenpi herbal pair (BXCP) exhibits significant therapeutic effects on damp-phlegm syndrome, yet the precise mechanisms underlying its anti-PCOS actions remain to be fully elucidated.

Aim of the study: The objective was to investigate the signaling pathway involved in steroid biosynthesis, particularly the cytochrome P450 family 17, subfamily A, member 1 (CYP17A1), and to evaluate the effects and mechanisms of BXCP in ameliorating PCOS through both in vivo and in vitro experiments.

Materials and methods: A systematic evaluation was conducted to assess BXCP's effects on serum biochemical indicators and ovarian tissue pathology in a PCOS rat model (induced by high-fat diet + letrozole) and a DHT-induced human granulosa cells (KGN) model. Core targets were screened using absorbed components analysis, bioinformatics, metabolomics, and network analysis. RT-qPCR and Western blot techniques were employed to confirm the expression of CYP17A1 and related signaling molecule expression during BXCP's amelioration of PCOS, both in vivo and in vitro.

Results: BXCP significantly ameliorated PCOS in vivo by mitigating weight gain, regulating estrus cycles, and normalizing sex hormone levels in rats. It upregulated metabolites related to steroid biosynthesis, including cortolone and progesterone, with CYP19A1, AKR1C3, and HSD17B1 as key regulators of CYP17A1. The main BXCP components, Naringenin and Nobiletin, increased CYP17A1 and CYP19A1 protein expression while decreased AKR1C3 and HSD17B1.

Conclusion: In conclusion, BXCP ameliorates PCOS by activating the CYP17A1-centered steroid biosynthesis pathway. These findings provide new insights into BXCP's clinical potentials in the management of patients with PCOS, highlighting the importance of TCM in modern medicine.