Panax ginseng sponin alleviate the polycystic ovary syndrome through gut microbiota and metabolites

Polycystic ovary syndrome (PCOS) is a reproductive endocrine disorder in women of childbearing age. The etiology of PCOS is unclear, and thus treatment is limited. Panax ginseng saponin (PNS), a unique Chinese medicinal herb, possess multiple pharmacological functions, especially for metabolic disorders, and showed potential therapeutic effect on ovarian dysfunction. While there are no reports on PCOS treatment with PNS. In this study, the effect of PNS on PCOS was investigated through the measure of typical symptoms and complications indicators based on constructed PCOS rat model. And alteration in structure composition and diversity of the gut microbiota derived from PCOS rats treated with PNS were analyzed by 16S rRNA sequencing. Furthermore, fecal metabolites were determined to elucidate the potential function of the microbiota on PCOS via untargeted metabolomics. And the association between the microbiota and metabolites was further performed using spearman correlation analysis. The results of this study indicated that PNS treatment can significantly improve the polycystic symptoms and estrus cycle of ovary, the sex hormone (testosterone, LH and FSH) in compared with PCOS control group, and insulin resistance and inflammation were also alleviated. Moreover, analyses of gut microbiota showed that microbiota diversity and composition of PCOS group decreased compared with the control, while PNS can restore these indicators. AmongXX Firmicutes, Prevotella and Ruminococcus were domaint bacterial genus in PCOS group; Bacteroidetes and Lactobacillus were most prominent genus in PNS group, enriching and restoring to level of the control group. Additionally, KEGG enrichment of differential metabolites demonstrated that arginine and proline metabolism, arachidonic acid metabolism and steroid hormone biosynthesis were top 4 pathway. The application of PNS significantly improved the levels of inflammatory substances and the release of steroid hormones. Furthermore, correlation analysis exhibited Alistipes correlated with gamma aminobutyric acid (GABA), Progesterone,19(R)-HETE. Dorea is positively correlated with L-arginine, 8-Isoprostane, Isosakuranetin and L-Serin. Additionally, KEGG enrichment of differential metabolites demonstrated that arginine and proline metabolism, arachidonic acid metabolism and steroid hormone biosynthesis were top 4 pathway. The application of PNS significantly improved the levels of inflammatory substances and the release of steroid hormones. Furthermore, correlation analysis exhibited Alistipes correlated with gamma aminobutyric acid (GABA), Progesterone,19(R)-HETE. Dorea is positively correlated with L-arginine, 8-Isoprostane, Isosakuranetin and L-Serin. In conclusion, Our study indicated that PNS can ameliorate PCOS and reveal preliminarily the potential mechanisms through gut microbiota and the several specific key metabolites; which can provide a new strategy for Chinese medicine including PNS based on targeting gut microbiota in prevention and treatment of PCOS.