{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:59:48Z","timestamp":1785405588355,"version":"3.56.0"},"reference-count":43,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mSystems"],"published-print":{"date-parts":[[2026,7,21]]},"abstract":"ABSTRACT<\/jats:title>\n \n \n \n Polycystic ovary syndrome (PCOS) is a chronic inflammatory disease caused by a combination of genetic, environmental, and gut microbiota factors. Western medicines can improve ovulation rates, but are linked with reduced pregnancy success and side effects.\n Scutellaria baicalensis<\/jats:italic>\n (\n BAL<\/jats:italic>\n ) is a famous anti-inflammatory Chinese herb, which has therapeutic effects for PCOS; however, the mechanism remains unclear. This study integrated network pharmacology, molecular docking, and animal experiments to investigate the mechanisms by which\n BAL<\/jats:italic>\n improves gut microbiota and intestinal inflammation in a rat PCOS model. We identified 36 active components of\n BAL<\/jats:italic>\n , including\n wogonin<\/jats:italic>\n ,\n baicalein<\/jats:italic>\n , and\n oroxylin A<\/jats:italic>\n , along with 145 potential targets, such as\n TNF<\/jats:italic>\n ,\n IL-6<\/jats:italic>\n , and\n AKT1<\/jats:italic>\n , and network analysis revealed that\n TNF<\/jats:italic>\n ,\n IL-6<\/jats:italic>\n , and\n AKT1<\/jats:italic>\n occupied central positions. Enrichment analyses indicated that\n BAL<\/jats:italic>\n may exert its therapeutic effects by modulating the\n NF-\u03baB<\/jats:italic>\n and Toll-like receptor signaling pathways. Molecular docking results demonstrated strong binding affinities between\n BAL<\/jats:italic>\n \u2019s primary active components and the core targets\n TNF<\/jats:italic>\n ,\n AKT1<\/jats:italic>\n , and\n IL-6. BAL<\/jats:italic>\n experiments in PCOS rats showed that it restored gut microbiota balance. These results showed that\n BAL<\/jats:italic>\n inhibits the\n LPS\/TLR4\/NF-\u03baB<\/jats:italic>\n pathway and downregulates PI3K and p-Akt\/Akt protein expression in ovarian tissue.\n BAL<\/jats:italic>\n also improved reproductive metabolic abnormalities, intestinal inflammation, and dysbiosis. Our study suggests that\n BAL<\/jats:italic>\n inhibits the\n LPS\/TLR4\/NF-\u03baB<\/jats:italic>\n pathway via the gut-ovarian axis, regulating gut microbial composition and alleviating inflammatory states. This may be a mechanism for the therapeutic efficacy of\n BAL<\/jats:italic>\n for PCOS and a novel therapeutic strategy for the clinical management of polycystic ovary syndrome.\n <\/jats:p>\n \n IMPORTANCE<\/jats:title>\n \n PCOS affects women of reproductive age. Current clinical treatment strategies still face limitations in efficacy and long-term side effects. This study employs network pharmacology, molecular docking, and experimental validation to elucidate the mechanism by which the traditional Chinese medicine\n BAL<\/jats:italic>\n improves PCOS. We found that\n BAL<\/jats:italic>\n modulates gut microbiota in a PCOS rat model, significantly increasing the probiotic genus\n Phocaeicola<\/jats:italic>\n . This change correlates with reduced serum LPS levels and alleviated ovarian inflammation. Experiments confirm that\n BAL<\/jats:italic>\n alleviates local ovarian inflammation and insulin resistance by inhibiting the\n LPS\/TLR4\/NF-\u03baB<\/jats:italic>\n signaling pathway, thereby improving PCOS pathological manifestations. This study reveals new mechanisms of\n BAL<\/jats:italic>\n in treating PCOS and highlights the potential bridging role of probiotics like\n Phocaeicola<\/jats:italic>\n . It also provides experimental evidence and theoretical support for integrated Chinese and Western medicine treatment strategies based on regulating gut microbiota.\n <\/jats:p>\n <\/jats:sec>\n <\/jats:sec>","DOI":"10.1128\/msystems.01825-25","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T12:01:32Z","timestamp":1781524892000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Targeting the gut-ovarian axis:\n Scutellaria baicalensis<\/i>\n improves polycystic ovary syndrome by modulating gut microbiota composition and inhibiting the\n LPS\/TLR4\/NF-\u03baB<\/i>\n signaling 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