Nanocurcumin alleviates insulin resistance and pancreatic deficits in polycystic ovary syndrome rats: Insights on PI3K/AkT/mTOR and TNF-α modulations

Life Sci. 2020 Sep 1:256:118003. doi: 10.1016/j.lfs.2020.118003. Epub 2020 Jun 23.

Abstract

Introduction and aims: Polycystic ovary syndrome (PCOS) is a widespread endocrine disorder affecting females. Mechanisms underlying PCOS complicated pathology remain largely unknown, making current treatment only symptomatic. Increasing reports suggest impaired PI3K/AKT/mTOR pathway and tumor necrosis factor-α (TNF-α) levels are involved in cellular proliferation and metabolism-related disorders. However, rare data explored their role in PCOS. Hence, this study investigated TNF-α and pancreatic PI3K/AKT/mTOR levels in PCOS animal model and evaluated their effects on developed pancreatic deficits. Secondly; we explored the impact of nanocurcumin as powerful anti-inflammatory supplement against these developed pancreatic pathologies.

Methods: PCOS was induced in rats using letrozole. Nanocurcumin was formulated to increase solubility and bioavailability of curcumin. Transmission electron microscopy (TEM), zeta potential and Infra-red spectroscopy (FT-IR) were used for characterization. Nanocurcumin was orally ingested for 15 days.

Findings: PCOS group exhibited significant disturbance in sex hormones, oxidative stress markers, and TNF-α levels as determined by immunoassay. Western blotting revealed significant reduction of PI3K/AKT/mTOR levels leading to impaired insulin sensitivity, decreased β cells function and mass as confirmed by HOMA assessments and immunohistochemistry. Nanocurcumin significantly improved oxidative markers, glucose indices and TNF-α levels. It reinstated PI3K/AKT/mTOR levels, alleviated insulin resistance, and retained islets integrity consequently restoring normal sex hormonal levels.

Significance: To the best of our knowledge, the study is the first to report pancreatic role of PI3K/AKT/mTOR and TNF-α in PCOS and the first to demonstrate nanocurcumin promising potential against PCOS-related pancreatic molecular and histological pathologies that can indeed offer better control of the disease.

Keywords: Inflammation; Nanocurcumin; Pancreas; Polycystic ovary syndrome; TNF-α.

MeSH terms

  • Animals
  • Curcumin / administration & dosage
  • Curcumin / pharmacology*
  • Disease Models, Animal
  • Female
  • Insulin Resistance*
  • Nanoparticles*
  • Pancreas / drug effects*
  • Pancreas / pathology
  • Phosphatidylinositol 3-Kinase / metabolism
  • Polycystic Ovary Syndrome / drug therapy*
  • Polycystic Ovary Syndrome / physiopathology
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Wistar
  • TOR Serine-Threonine Kinases / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Tumor Necrosis Factor-alpha
  • mTOR protein, rat
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Curcumin