Lycopus lucidus Extract Improves Experimental Polycystic Ovary Syndrome with Gut Microbiota and Metabolome Remodeling

This study investigated the therapeutic effects of ZeLan extract on polycystic ovary syndrome (PCOS) and evaluated its association with gut microbiota-metabolome remodeling. Twenty-four female Sprague-Dawley rats were randomly divided into Control, PCOS Model induced by dehydroepiandrosterone (DHEA), and ZeLan treatment groups (n = 8 each). After 28 days of intervention, serum hormone levels were measured by ELISA; gut microbiota composition was analyzed using 16S rRNA gene sequencing, and serum metabolic profiles were characterized by UHPLC-Q-TOF-MS. Spearman correlation analysis with multiple-testing control was performed to explore microbiota-metabolome associations. ZeLan significantly improved PCOS-associated phenotypes, reducing body weight, testosterone (0.92 vs. 1.85 ng/mL, P < 0.05), LH/FSH ratio, and insulin levels compared with the Model group. Sequencing showed that ZeLan partially restored microbial alpha diversity (Shannon index: 5.79 vs. 4.19) and decreased the Firmicutes-to-Bacteroidetes ratio. ZeLan was associated with enrichment of Lactobacillus and Ruminococcus and lower abundance of Bacteroides, Prevotella, and Escherichia. Metabolomics identified 52 altered metabolite features, with key changes involving steroid hormones, bile acids such as lithocholic acid, and short-chain fatty acids such as butyric acid. These findings suggest that ZeLan ameliorates PCOS-related endocrine and metabolic disturbances and is associated with remodeling of gut microbial and serum metabolic profiles.