Ameliorative potential of rosmarinic acid in a rat model of polycystic ovary syndrome: Targeting MCP-1 and VEGF: A histological, immunohistochemical, and biochemical study

Cell Biochem Funct. 2024 Jun;42(4):e4073. doi: 10.1002/cbf.4073.

Abstract

Polycystic ovary syndrome (PCOS) is a multidisciplinary endocrinopathy that affects women of reproductive age. It is characterized by menstrual complications, hyperandrogenism, insulin resistance, and cardiovascular issues. The current research investigated the efficacy of rosmarinic acid in letrozole-induced PCOS in adult female rats as well as the potential underlying molecular mechanisms. Forty female rats were divided into the control group, the rosmarinic acid group (50 mg/kg per orally, po) for 21 days, PCOS group; PCOS was induced by administration of letrozole (1 mg/kg po) for 21 days, and rosmarinic acid-PCOS group, received rosmarinic acid after PCOS induction. PCOS resulted in a marked elevation in both serum luteinizing hormone (LH) and testosterone levels and LH/follicle-stimulating hormone ratio with a marked reduction in serum estradiol and progesterone levels. A marked rise in tumor necrosis factor-α (TNF-α), interleukin-1β, monocyte chemotactic protein-1, and vascular endothelial growth factor (messenger RNA) in the ovarian tissue was reported. The histological analysis displayed multiple cystic follicles in the ovarian cortex with markedly thin granulosa cell layer, vacuolated granulosa and theca cell layers, and desquamated granulosa cells. Upregulation in the immune expression of TNF-α and caspase-3 was demonstrated in the ovarian cortex. Interestingly, rosmarinic acid ameliorated the biochemical and histopathological changes. In conclusion, rosmarinic acid ameliorates letrozole-induced PCOS through its anti-inflammatory and antiangiogenesis effects.

Keywords: MCP‐1; VEGF; letrozole; ovary; rosmarinic acid.

MeSH terms

  • Animals
  • Chemokine CCL2* / metabolism
  • Cinnamates* / pharmacology
  • Depsides* / pharmacology
  • Disease Models, Animal*
  • Female
  • Immunohistochemistry
  • Letrozole* / pharmacology
  • Luteinizing Hormone / blood
  • Luteinizing Hormone / metabolism
  • Polycystic Ovary Syndrome* / chemically induced
  • Polycystic Ovary Syndrome* / drug therapy
  • Polycystic Ovary Syndrome* / metabolism
  • Polycystic Ovary Syndrome* / pathology
  • Rats
  • Rats, Sprague-Dawley
  • Rosmarinic Acid*
  • Testosterone / blood
  • Vascular Endothelial Growth Factor A* / metabolism

Substances

  • Rosmarinic Acid
  • Cinnamates
  • Depsides
  • Vascular Endothelial Growth Factor A
  • Chemokine CCL2
  • Letrozole
  • Ccl2 protein, rat
  • Luteinizing Hormone
  • vascular endothelial growth factor A, rat
  • Testosterone