Inhibitory effect of bushen huoxue formula against dehydroepiandrosterone-induced inflammation in granulosa cells through TLR4/NF-κB signaling pathway

Pak J Pharm Sci. 2022 May;35(3):701-710.

Abstract

Androgen exposure may be an important factor in promoting the development of polycystic ovary syndrome (PCOS) and disease progression. Bushen Huoxue Formula (BHF), a traditional Chinese medicine, is prescribed in clinical settings as a PCOS remedy, albeit with unclear pharmacological effects on granulosa cells. The present research explores potentially advantageous BHF impacts and whereby BHF alleviates dehydroepiandrosterone (DHEA)-induced inflammation and endocrine disruption. Six chemical components in BHF were identified and fingerprint analysis showed good reproducibility. Using a human granulosa cell line (KGN), BHF effects on cell viability, secretion of steroidogenic and inflammatory factors were evaluated and TLR4/NF-κB pathway expression was examined. Our results demonstrate that BHF treatment of KGN cells in a DHEA-induced inflammatory state led to increased cell viability, decreased testosterone and estradiol production, and decreased CYP19A1 and HSD3B2 mRNA expression. Further experiments revealed that BHF inhibited the expression of pro-inflammatory cytokines and considerably hindered up-regulation in protein levels of TLR4, MyD88, and TRAF6, while inhibiting the activation of NF-κB and phosphorylation of IκBα. Collectively, BHF administration protected granulosa cells from DHEA-induced injuries through down-regulating pro-inflammatory cytokines and blocking the pathway of TLR4/NF-κB. Therefore, BHF hold promise as a therapeutic formulation for preventing androgen induced PCOS.

MeSH terms

  • Androgens / metabolism
  • Androgens / pharmacology
  • Androgens / therapeutic use
  • Cytokines / metabolism
  • Dehydroepiandrosterone / metabolism
  • Dehydroepiandrosterone / pharmacology
  • Dehydroepiandrosterone / therapeutic use
  • Drugs, Chinese Herbal
  • Female
  • Granulosa Cells / metabolism
  • Humans
  • Inflammation / metabolism
  • NF-kappa B* / metabolism
  • Polycystic Ovary Syndrome* / chemically induced
  • Polycystic Ovary Syndrome* / drug therapy
  • Polycystic Ovary Syndrome* / metabolism
  • Reproducibility of Results
  • Signal Transduction
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism

Substances

  • Androgens
  • Cytokines
  • Drugs, Chinese Herbal
  • NF-kappa B
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • bushen huoxue
  • Dehydroepiandrosterone