Pharmacological evaluation of some biologically active compounds on Metabolic disease induced depression

Abstract

Metabolic diseases and depression are the most common diseases worldwide that exhibit a complex two-way relationship with shared biological mechanisms. A high prevalence of depression is observed in diabetic or obese people in comparison to a normal person. The predominating common factors that play a prime role in mediating this two-way relationship include insulin resistance (IR), inflammation, HPA axis dysfunction, oxidative stress, leptin and ghrelin resistance and thereby lowering SIRT1 expression. SIRT1 is a NAD+-dependent histone deacetylase which plays a crucial role in metabolic diseases by regulating glucose and lipid metabolism, IR, inflammation, and oxidative stress. It also regulates depression by mediating neurogenesis, decreasing inflammation, and regulating the neurotransmitter levels. Considering the beneficial effects of SIRT1, it was hypothesized to be a novel therapeutic target for metabolic disease-induced depression. SIRT1 activators Resveratrol (RES), Pterostilbene (PTE), and Curcumin (CUR) were selected for comparative in-silico and in-vitro analysis for their anti-inflammatory potential. In-silico docking studies were carried out for IL-6, TNF-and#945;, NF-and#954;B, and SIRT1 expression, while the in-vitro THP-1 cell lines were studied for IL-6, TNF-and#945;. PTE showed a favorable docking profile with cytokines and SIRT1 and was found to be more effective than RES and CUR in lowering the concentrations of IL-6 and TNF-and#945; in THP-1 cell lines. Thus, PTE appeared to be a better choice for further in-vivo research for metabolic disease induced depression in laboratory animals. A diabetes induced depression (DID) like behavior (STZ-NA) study was performed in male Wistar rats, and obesity induced depression like behavior (using cafeteria diet) was induced in adolescent Swiss albino mice. newline