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Vulvovaginal candidiasis (VVC) is a prevalent fungal infection affecting the female reproductive tract. Although conventional therapeutic approaches for VVC are relatively well-established, they still exhibit certain limitations. Pulsatilla decoction, a classic traditional Chinese medicine formula, has demonstrated significant clinical efficacy in the treatment of VVC. However, its precise mechanism of action remains incompletely elucidated. Objective To clarify the therapeutic mechanism of the n-butanol extract of Pulsatilla decoction (BEPD) on VVC through network pharmacology and animal experiments. Methods A mouse model of VVC was established and the therapeutic effect of BEPD on VVC was evaluated. Network pharmacology was employed to screen the potential signaling pathways of BEPD on VVC. Western blotting, immunofluorescence, immunohistochemistry, and real-time fluorescence quantitative PCR were employed to measure the changes in autophagy, apoptosis, and related pathway proteins in the vaginal mucosa of mice. Results Network pharmacology analysis identified PIK3R1 and AKT1 as key targets of Pulsatilla decoction in exerting antifungal activity against VVC. KEGG pathway enrichment analysis indicated that Pulsatilla decoction exerted its therapeutic effects on VVC by regulating the PI3K-Akt signaling pathway. Animal experiments confirmed that compared with the VVC model group, the BEPD treatment down-regulated the expression of PI3K, p-Akt, and p-mTOR, significantly up-regulated the expression of autophagy-related proteins LC3B and ATG5, significantly inhibited the expression of apoptosis-related proteins Bax and Cleaved-Caspase-3, and significantly promoted the expression of anti-apoptosis-related protein Bcl-2. Conclusion BEPD may promote autophagy and inhibit apoptosis of vaginal epithelial cells by inhibiting the PI3K-Akt-mTOR signaling pathway, thereby restoring the homeostasis of the vaginal mucosal epithelial barrier and alleviating VVC.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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