Bu-shen-zhu-yun decoction inhibits granulosa cell apoptosis in rat polycystic ovary syndrome through estrogen receptor α-mediated PI3K/AKT/mTOR pathway

J Ethnopharmacol. 2022 Apr 24:288:114862. doi: 10.1016/j.jep.2021.114862. Epub 2021 Nov 30.

Abstract

Ethnopharmacological relevance: Bu-shen-zhu-yun decoction (BSZYD) is a traditional chinese herbal prescription is widely used in the treatment of infertility.

Aim of the study: We aimed to elucidate the impact of a traditional herbal prescription BSZYD on polycystic ovary syndrome (PCOS).

Materials and methods: The candidate active compounds in BSZYD and their putative targets were investigated by bioinformatics analysis. A deydroepiandrosterone (DHEA)-induced PCOS rat model was then constructed using female Sprague-Dawley (SD) rats. Serum hormone levels were measured by enzyme-linked immunosorbent assay (ELISA). Pathological changes in ovarian tissues were analyzed with hematoxylin and eosin (H&E) staining. The expressions of estrogen receptor α (ER α)-mediated PI3K/AKT/mTOR pathway were measured by immunofluorescence and western blotting.

Results: Bioinformatics analysis showed that the putative targets of active compound candidates in BSZYD were enriched in PI3K/AKT and estrogen signaling pathways related to regulating ovarian ovulation. Animal experiments showed that BSZYD significantly alleviated pathological changes in the ovary, altered hormone levels of serum and reduced apoptosis rate of granulosa cells. In addition, BSZYD treatment notably upregulated the expressions of proteins in ER α-mediated PI3K/AKT/mTOR pathway and downregulated apoptosis-related proteins in PCOS rats.

Conclusion: BSZYD can restore ovary lesions and ameliorate apoptosis through ER α-mediated PI3K/AKT/mTOR pathway, which might partly contribute to the treatment of PCOS.

Keywords: Apoptosis; Bu-shen-zhu-yun decoction; Estrogen receptor α; PI3K/AKT/mTOR pathway; Polycystic ovary syndrome.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Disease Models, Animal
  • Down-Regulation / drug effects
  • Drugs, Chinese Herbal / pharmacology*
  • Estrogen Receptor alpha / metabolism
  • Female
  • Granulosa Cells / drug effects*
  • Phosphatidylinositol 3-Kinase / metabolism
  • Polycystic Ovary Syndrome / drug therapy*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Drugs, Chinese Herbal
  • Estrogen Receptor alpha
  • mTOR protein, rat
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases