Zingerone ameliorates ovarian impairment by regulating steroidogenesis and apoptosis in the letrozole-treated mouse

Ayushmita Dutta1, Guruswami Gurusubramanian1, Vikas Kumar Roy1

  • 1Department of Zoology, Mizoram University, Aizawl, Mizoram 796004, India.

Endocrinology
|July 6, 2026
PubMed

Insights

Zingerone effectively treats PCOS-like symptoms in mice by improving ovarian function, restoring hormonal balance, and enhancing fertility. This natural compound offers a promising therapeutic avenue for polycystic ovary syndrome (PCOS).

Area of Science:

  • Endocrinology
  • Reproductive Biology
  • Pharmacology

Background:

  • Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology.
  • Current treatments for PCOS often have limitations and side effects, necessitating the exploration of novel therapeutic agents.

Purpose of the Study:

  • To investigate the therapeutic potential of zingerone, a compound found in ginger, in a letrozole-induced mouse model of PCOS.
  • To elucidate the molecular mechanisms underlying zingerone's effects on ovarian function, steroidogenesis, and autophagy in PCOS.

Main Methods:

  • A PCOS-like phenotype was induced in mice using letrozole.
  • Mice were treated with varying doses of zingerone (25 and 50 mg/kg).
  • Ovarian morphology, follicular development, granulosa cell proliferation (PCNA), apoptosis (TUNEL, BCL2), steroidogenic gene expression (StAR, aromatase), androgen receptor (AR) expression, and autophagy markers (p62, Beclin1, LC3B) were assessed.

Main Results:

  • Zingerone treatment significantly improved ovarian morphology, promoting follicular development and corpus luteum formation.
  • Zingerone administration attenuated apoptosis and enhanced granulosa cell proliferation.
  • The compound normalized steroidogenesis by reducing testosterone, down-regulating AR, suppressing StAR, and up-regulating aromatase, leading to increased estrogen biosynthesis.
  • Zingerone restored autophagic flux, indicated by decreased p62 and modulated Beclin1/LC3B.
  • Fertility and litter size were significantly improved in zingerone-treated groups.

Conclusions:

  • Zingerone demonstrates significant therapeutic efficacy in ameliorating PCOS-like symptoms in a mouse model.
  • The multi-target actions of zingerone involve restoring endocrine, cellular, and autophagic homeostasis within the ovary.
  • Zingerone represents a promising natural compound for the management of ovarian dysfunction in PCOS.