Morus alba L. (Sangzhi) alkaloids reduce polycystic ovary syndrome by improving hypothalamic-pituitary-ovarian axis function

  • Phytomedicine. 2026 Jul:156:158243. doi: 10.1016/j.phymed.2026.158243.
Yuanyuan Liu  1 ,  Ruoyan Wu  2 ,  Huijuan Li  3 ,  Danfeng Pu  2 ,  Xingang Wang  3 ,  Shan Chen  3 ,  Chenjie Jiang  2 ,  Wangmin Hu  3 ,  Liyun Wang  4 ,  Xinhua Ye  5 ,  Wenlong Huang  6 ,  Xueqin Wang  7 ,  Yun Hu  2 ,  Shiqin Yuan  2 ,  Yumeng Han  2 ,  Jun Ye  8 ,  Qing He  9 ,  Lan Xu  10 ,  Yuling Liu  11
Affiliations
  • 1. Beijing Wehand-Bio Pharmaceutical Co. Ltd, Beijing, China; School of Pharmaceutical Sciences, Tsinghua University, Beijing, China.
  • 2. Provincial Clinical Key Specialty, Department of Endocrinology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, China.
  • 3. Beijing Wehand-Bio Pharmaceutical Co. Ltd, Beijing, China.
  • 4. Municipal Clinical Key Specialty, Department of Endocrinology, The Affiliated Yixing Hospital of Jiangsu University, Yixing, Jiangsu, China.
  • 5. Provincial Clinical Key Specialty, Department of Endocrinology, The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu, China.
  • 6. Municipal Clinical Key Specialty, Department of Endocrinology, Jiangyin People's Hospital Affiliated to Nantong University, Jiangyin, Jiangsu, China.
  • 7. Provincial Clinical Key Specialty, Department of Endocrinology, Affiliated Hospital 2 of Nantong University and First People's Hospital of Nantong City, Nantong, Jiangsu, China.
  • 8. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Beijing Key Laboratory of Key Technologies for Natural Drug Delivery and Novel Formulations, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
  • 9. National Drug Clinical Trial Institution, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, China. Electronic address: [email protected].
  • 10. Provincial Clinical Key Specialty, Department of Endocrinology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu, China. Electronic address: [email protected].
  • 11. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China; Beijing Key Laboratory of Key Technologies for Natural Drug Delivery and Novel Formulations, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China. Electronic address: [email protected].
PMID: 42107446 DOI: 10.1016/j.phymed.2026.158243
Abstract

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.

Keywords
Hyperandrogenism; Hypothalamic-pituitary-ovarian axis; Insulin resistance; Morus alba L. (Sangzhi) alkaloids; Polycystic ovary syndrome.
Products