Baicalin suppress the development of polycystic ovary syndrome via regulating the miR-874-3p/FOXO3 and miR-144/FOXO1 axis

Pharm Biol. 2023 Dec;61(1):878-885. doi: 10.1080/13880209.2023.2208636.

Abstract

Context: Polycystic ovary syndrome (PCOS) is a common and complex disease caused by endocrine and metabolic dysfunction in women of reproductive age. Baicalin is reported to ameliorate PCOS.

Objective: This study determines whether baicalin could affect the progression of PCOS.

Materials and methods: To establish an animal model of PCOS, female Sprague-Dawley (SD) rats were subcutaneously injected with dehydroepiandrosterone (DHEA, 60 mg/kg) for 20 days. Next, normal and PCOS mice were divided into 3 groups: control, PCOS, PCOS + Baicalin (20 mg/kg) groups. In addition, the levels of microRNA-874-3p (miR-874-3p) and microRNA-144 (miR-144) in ovarian tissues were assessed by reverse transcription-quantitative polymerase chain reaction (RT-qPCR).

Results: Compared to the PCOS group, baicalin treatment significantly declined free testosterone (33.71 pg/mL vs. 56.05 pg/mL) and luteinizing hormone (LH; 3971.73 pg/mL vs. 5201.50 pg/mL) levels in rats with PCOS. Additionally, compared to the control group, 100 μM baicalin lessened miR-874-3p and miR-144 levels in human ovarian granulosa cells (KGN cells) by 36.87% and 32.57%, respectively. Furthermore, forkhead box O (FOXO) proteins FOXO1 and FOXO3 are the direct targets of miR-144 and miR-874-3p, respectively. Meanwhile, baicalin induced G0-G1 phase arrest (69.56 ± 3.7% at baicalin with 100 μM vs. 51.24 ± 3.2%, control) in KGN cells correlating with decreased p27 Kip1 (FOXO proteins downstream effector gene) expression by 55.5%; however, miR-874-3p or miR-144 overexpression could abolish this effect.

Conclusions: Baicalin could alleviate the symptoms of PCOS via regulating miR-874-3p/FOXO3 and miR-144/FOXO1 axis, demonstrating its potential utility in PCOS treatment.

Keywords: Endocrine and metabolic dysfunction; Scutellaria baicalensis; miRNA.

MeSH terms

  • Animals
  • Apoptosis
  • Cell Proliferation / genetics
  • Female
  • Forkhead Box Protein O1
  • Forkhead Box Protein O3 / genetics
  • Humans
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Polycystic Ovary Syndrome* / chemically induced
  • Polycystic Ovary Syndrome* / drug therapy
  • Polycystic Ovary Syndrome* / genetics
  • Rats
  • Rats, Sprague-Dawley

Substances

  • MIRN874 microRNA, mouse
  • baicalin
  • MicroRNAs
  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • FOXO3 protein, human
  • Forkhead Box Protein O3
  • MIRN144 microRNA, human
  • MIRN874 microRNA, human
  • Foxo1 protein, mouse
  • MIRN144 microRNA, mouse
  • Foxo1 protein, rat
  • MIRN144 microRNA, rat

Grants and funding

The author(s) reported there is no funding associated with the work featured in this article.