The protective effect of vinpocetine against Estradiol-benzoate induced cervical hyperkeratosis in female rats via modulation of SIRT1/Nrf2, and NLRP3 inflammasome

Sci Rep. 2024 Aug 19;14(1):19171. doi: 10.1038/s41598-024-69431-2.

Abstract

The current study was assigned to determine the putative preventive role of vinpocetine (VIN) in cervical hyperkeratosis (CHK) in female rats. Estradiol Benzoate (EB) was utilized in a dose f (60 μg/100 g, i.m) three times/week for 4 weeks to induce cervical hyperkeratosis. VIN was administered alone in a dose of (10 mg/kg/day, orally) for 4 weeks and in the presence of EB. Levels of malondialdehyde (MDA), total nitrites (NOx), reduced glutathione (GSH), interleukin-18 (IL-18), IL-1β, tumor necrosis factor-alpha (TNF-α) were measured in cervical tissue. The expression of NLRP3/GSDMD/Caspase-1, and SIRT1/Nrf2 was determined using ELISA. Cervical histopathological examination was also done. EB significantly raised MDA, NOx, TNF-α, IL-18, IL-1β, and GSDMD and up-regulated NLRP3/Caspase-1 proteins. However, GSH, SIRT1, and Nrf2 levels were reduced in cervical tissue. VIN significantly alleviates all biochemical and histopathological abnormalities. VIN considerably mitigates EB-induced cervical hyperkeratosis via NLRP3-induced pyroptosis and SIRT1/Nrf2 signaling pathway.

Keywords: Estradiol; Hyperkeratosis; NLRP3; Nrf2; Vinpocetine.

MeSH terms

  • Animals
  • Cervix Uteri* / drug effects
  • Cervix Uteri* / metabolism
  • Cervix Uteri* / pathology
  • Estradiol* / analogs & derivatives
  • Estradiol* / pharmacology
  • Female
  • Inflammasomes* / drug effects
  • Inflammasomes* / metabolism
  • NF-E2-Related Factor 2* / metabolism
  • NLR Family, Pyrin Domain-Containing 3 Protein* / metabolism
  • Rats
  • Signal Transduction / drug effects
  • Sirtuin 1* / metabolism
  • Vinca Alkaloids* / pharmacology
  • Vinca Alkaloids* / therapeutic use

Substances

  • Sirtuin 1
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • NF-E2-Related Factor 2
  • Estradiol
  • Inflammasomes
  • vinpocetine
  • Vinca Alkaloids
  • estradiol 3-benzoate
  • Sirt1 protein, rat
  • Nfe2l2 protein, rat
  • Nlrp3 protein, rat