Development of ginger exosome based therapeutic nano formulation for the amelioration of type 2 diabetes

Abstract

Metabolic disorders such as Type 2 Diabetes (T2DM) impose a significant global health burden. Plant-derived exosome like nanoparticles (P-ELNs) have emerged as promising therapeutic alternate for various diseases. Our data demonstrated that treatment with Ginger-derived exosome like nanoparticles (G-ELNs) significantly enhanced 2-NBDG uptake and down regulated gluconeogenesis in insulin resistant HepG2 cells. Furthermore, oral administration of G-ELNs in T2DM mice leads to significant decrease in fasting blood glucose levels and consequently improved glucose tolerance. Further, these improvements were attributed to enhanced phosphorylation of Akt-2 at ser 474 which leads to increase in insulin sensitivity and consequently improved glucose and lipid homeostasis. G-ELNs were also found to inhibit STZ-induced pancreatic beta cell apoptosis thus, contributing to amelioration of T2DM. To obtain a thorough understanding of the positive effects of G-ELNs, we employed computational tool which revealed that miRNAs present in G-ELNs can modulate PI3K/Akt-2 pathway and also exhibit strong interactions with various target mRNAs such as PCK-1, G6PC, FAS and SREBP1. The above findings were validated in-vitro where down regulation of the target mRNA was effectively achieved using synthetic mimic of G-ELNs miRNA. Overall, the results indicate that miRNAs present in G-ELNs target key metabolic pathways involved in glucose and lipid metabolism consequently exerting therapeutic effects in T2DM. newline