Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Morus alba L. (Sangzhi) alkaloids reduce polycystic ovary syndrome by improving hypothalamic-pituitary-ovarian axis function.
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Liu Yuanyuan, Wu Ruoyan, Li Huijuan, Pu Danfeng, Wang Xingang, Chen Shan, Jiang Chenjie, Hu Wangmin, Wang Liyun, Ye Xinhua, Huang Wenlong, Wang Xueqin, Hu Yun, Yuan Shiqin, Han Yumeng, Ye Jun, He Qing, Xu Lan, Liu Yuling
Аннотация
BACKGROUND: Polycystic ovary syndrome (PCOS) is a neuroendocrine-metabolic disorder with no approved drugs. Hypothalamic-pituitary-ovarian (HPO) axis dysfunction is core pathogenesis, and metabolic heterogeneity complicates treatment. Existing medications rarely ameliorate PCOS comprehensively. Sangzhi alkaloids (SZ-A), an extract from Morus alba L. twigs approved for type 2 diabetes in China, have not been systematically explored for PCOS.
PURPOSE: To clarify the therapeutic effect and the mechanisms of SZ-A in PCOS.
STUDY DESIGN: Animal studies, in vitro experiments and a placebo-controlled clinical trial.
MATERIALS AND METHODS: In vivo: Obese/non-obese PCOS rats received oral SZ-A 67, 100, 150 mg/(kg·d) for 21 days (positive controls: Diane-35, metformin). In vitro: Granulosa cell apoptosis induced by dihydrotestosterone was treated with SZ-A 25, 50, 100, 200 μg/ml.
CLINICAL: 6-month placebo-controlled trial (128 PCOS patients; oral SZ-A 300 mg/d, n = 88; placebo, n = 40). Multi-omics/Western blotting explored HPO pathways.
RESULTS AND DISCUSSION: In rats, SZ-A (67 to 150 mg/(kg·d), 21 days) dose-dependently reduced androgens, regularized estrous cycles, and improved ovarian morphology. In vitro, SZ-A (25 to 200 μg/ml) protected granulosa cells from apoptosis. In patients, 6-month SZ-A (300 mg/d) lowered free androgen index and improved menstrual regularity versus placebo. Mechanistically, SZ-A inhibited hyperandrogenism-induced granulosa cell apoptosis and regulated GnRH secretion and downstream signaling pathways.
CONCLUSION: SZ-A exerts therapeutic effects on PCOS by modulating HPO axis function through multiple pathways.
TRIAL REGISTRATION: ChiCTR2200065097.
PURPOSE: To clarify the therapeutic effect and the mechanisms of SZ-A in PCOS.
STUDY DESIGN: Animal studies, in vitro experiments and a placebo-controlled clinical trial.
MATERIALS AND METHODS: In vivo: Obese/non-obese PCOS rats received oral SZ-A 67, 100, 150 mg/(kg·d) for 21 days (positive controls: Diane-35, metformin). In vitro: Granulosa cell apoptosis induced by dihydrotestosterone was treated with SZ-A 25, 50, 100, 200 μg/ml.
CLINICAL: 6-month placebo-controlled trial (128 PCOS patients; oral SZ-A 300 mg/d, n = 88; placebo, n = 40). Multi-omics/Western blotting explored HPO pathways.
RESULTS AND DISCUSSION: In rats, SZ-A (67 to 150 mg/(kg·d), 21 days) dose-dependently reduced androgens, regularized estrous cycles, and improved ovarian morphology. In vitro, SZ-A (25 to 200 μg/ml) protected granulosa cells from apoptosis. In patients, 6-month SZ-A (300 mg/d) lowered free androgen index and improved menstrual regularity versus placebo. Mechanistically, SZ-A inhibited hyperandrogenism-induced granulosa cell apoptosis and regulated GnRH secretion and downstream signaling pathways.
CONCLUSION: SZ-A exerts therapeutic effects on PCOS by modulating HPO axis function through multiple pathways.
TRIAL REGISTRATION: ChiCTR2200065097.