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 nutraceutical 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 letrozole. 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 confirmed around 46% deterioration of ß cell mass. Real-time PCR showed significant downregulation 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.

Potentiating the Cytotoxic Activity of a Novel Simvastatin-Loaded Cubosome against Breast Cancer Cells: Insights on Dual Cell Death via Ferroptosis and Apoptosis

“… 31 , 39 Moreover, this process enhances the therapeutic activity of promising compounds through improving their solubility and adequate delivery. 22 , 40 …”

“…31,39 Moreover, this process enhances the therapeutic activity of promising compounds through improving their solubility and adequate delivery. 22,40 Therefore, in this study, we formulated SIM in a SIM-CB formula. We tested the cytotoxic activity of free SIM and SIM-CB on MCF-7 cells and investigated ferroptosis as a possible additional mechanism contributing to SIM anticancer actions.…”

The Mitigatory Effect of Shen-Qi Compound on the Diabetic Thoracic Aortic Complications through Inhibiting the Inflammatory Microenvironment by miR-223-3p/RBP-J/IRF8 Axis

“…Although miR-223-3p is reported to serve as a sponger of long noncoding RNAs or circular RNAs in a wide variety of Evidence-Based Complementary and Alternative Medicine disease models, several studies have demonstrated that miR-223-3p can be regulated by the extraction of Chinese herbal medicine. For instance, nanocurcumin dampens insulin resistance and autophagy flare with improved β cell mass via regulating miR-223-3p and NF-κB levels in the pancreas of a rat model of polycystic ovary syndrome [35]. Icariin regulates the miR-223-3p/NLRP3 signaling axis to relieve rheumatoid arthritis [36].…”

Regulation of autophagy by plant‐based polyphenols: A critical review of current advances in glucolipid metabolic diseases and food industry applications

“…Possible explanations for the different actions of emodin in these studies are that the relative prevalence of autophagy differs in discreet tissues (kidney and intestine) in energy metabolic processes, and exogenous factors (for example, nutritional status of foods used in the experimental model including amino acids, fatty acids, and glucose) may cause different changes in autophagy regulation. Additionally, in the rat with polycystic ovary syndrome, nanocurcumin functions to upregulate miR‐223‐3p in pancreatic tissues contributing to ameliorating insulin resistance by suppressing autophagy activity as confirmed by dramatic decline in LC3‐II and p62 proteins (Abuelezz et al., 2021). In summary, the current data provide new mechanistic insights into possible contribution of miRNAs regulated by polyphenols involved in maintaining autophagy.…”