Nanocurcumin modulates mir-223-3p and nf-κb levels in the pancreas of rat model of polycystic ovary syndrome to attenuate autophagy flare, insulin resistance and improve ß cell mass

Abstract

Purpose: Polycystic ovary syndrome (PCOS) is a prevalent female endocrine disorder. 50– 70% of PCOS patients suffer from glucose intolerance, insulin and β cell impairments. Updated studies reveal the crucial regulatory role of inflammation modulators in various diseases, by manipulating autophagy and oxidative stress. However, the data available about autophagy in PCOS pancreas, especially in relation to inflammation key players are little. This study investigated pancreatic autophagy status in PCOS rat model, with miR-223-3p and NF-κB levels as pivotal regulators of oxidative stress-autophagy axis, insulin, and β cell integrity. We then analyzed nanocurcumin effects as a putative anti-inflammatory nutraceu-tical on the disrupted parameters. Methods: Nanocurcumin was characterized using transmission electron microscopy (TEM) and Fourier-transform IR (FT-IR) spectroscopy. Adult virgin Wistar rats were selected, and PCOS was induced using letrozole (1mg/kg). Nanocurcumin was ingested following letro-zole. Sex hormones and insulin resistance were determined. miR-223-3p expression was determined using real-time PCR. Immunohistochemistry and Western blotting determined β cells, NF-κB, and autophagy markers p62 and LC3II. Results: PCOS group showed significant disruptions in sex hormones and a double fold increase in glucose and insulin levels, exhibiting insulin resistance. Immunostaining con-firmed around 46% deterioration of ß cell mass. Real-time PCR showed significant down-regulation of miR-223-3p. Immunohistochemistry and Western blotting revealed a drastic upsurge of NF-κB, and autophagy markers p62 and LC3II, confirming bioinformatics target analysis. Interestingly, compared to PCOS group, nanocurcumin (200mg/kg) significantly upregulated miR-223-3p expression by 30%. It subsided NF-κB and autophagy eruption to restore ß cell mass and attenuate insulin resistance. Conclusion: To the best of our knowledge, this study is the first to highlight the vital contribution of miR-223-3p and NF-κB levels in aggravating PCOS pancreatic autophagy and consequent impairments. It spots nanocurcumin potential as an inflammation and autophagy modulator, for possible better management of PCOS complications.