Nano-phytocompound Combats Food Additive-Induced Genotoxicity and Mitochondrial Dysfunction in Diabetic Model: An In Silico Predicted Experimental Study

The study focuses on the therapeutic management of diabetes and associated complications induced by the food additive alloxan (ALX), which is detrimental to pancreatic β cell functioning. To address the problem, a flavonoid compound curcumin (CUR) with anti-diabetic, anti-genotoxic, and anti-inflammatory properties was considered to test its effectiveness in preventing ALX-induced diabetic complications based on evidences from molecular docking study. In silico study of CUR revealed its interactions with proteins PARP-1, p53, Bcl-2, and Cyt c suggesting a possible function of CUR in modulating cellular cascades. Further, to expedite targeted and faster drug delivery, drug bioavailability, and efficient tissue penetration, nanoencapsulation of CUR was opted as a novel drug design tool. AFM, DLS, and FESEM studies confirmed physico-chemical characteristics of newly formed nanocurcumin (NCUR). As validated by in silico docking study, pre-treatment of NCUR in experimental models showed its effective role in restricting genotoxicity and mitochondrial dysfunction by effectively binding with DNA damage repair proteins PARP-1 and p53 and mitochondrial signaling proteins Bcl-2 and Cyt c, respectively. Furthermore, a number of parametric studies have demonstrated NCUR to exert greater efficacy by preventing tissue damage and delaying incidence of diabetes, DNA damage, and chromosomal aberrations. Thus, it can be concluded that pre-treatment of nano-based phyto-drugs offers promising strategy as therapeutic tool for effective regulation of food additive-induced damages and diabetes via balancing the expression of proteins involved therein.