NF-κB pathway as a molecular target for curcumin in diabetes mellitus treatment: Focusing on oxidative stress and inflammation

Abstract

Diabetes mellitus (DM), a chronic metabolic disorder associated with hyperglycemia and other complications, is one of the five priority non communicable diseases of global interest with unprecedented rise in developing countries. Whereas, the current treatment with insulin and oral hypoglycemic agents is aimed at managing the hyperglycemia and associated complications, there is need to explore other critical pathways in the pathogenesis of DM that can act as potential drug targets with better treatment outcomes. This study comprehensively explains the role of cellular and molecular elements, like hyperglycemia-induced oxidative stress, endothelial dysfunction, and Nuclear Factor Kappa B (NF-κB)’s involvement in inflammation and immune regulation, in the onset of DM. With bioactive compounds from natural products gaining popularity as novel drug molecules due to their diverse pharmacological actions, the study also extensively explores the prospective therapeutic benefits of curcumin (CUR), a bioactive compound known for its antioxidant, anti-inflammatory, and hypoglycemic properties, in addressing diabetic complications, predominantly via the modulation of the NF-κB pathway. The findings reveal that CUR administration effectively lowered blood glucose elevation, reinstated diminished serum insulin levels, and enhanced body weight in Streptozotocin -induced diabetic rats. CUR exerts its beneficial effects in management of diabetic complications through regulation of signaling pathways, such as CaMKII, PPAR-γ, NF-κB, and TGF-β1. Moreover, CUR reversed the heightened expression of inflammatory cytokines (TNF-α, IL-1β, IL-6) and chemokines like MCP-1 in diabetic specimens, vindicating its anti-inflammatory potency in counteracting hyperglycemia-induced alterations. CUR diminishes oxidative stress, avert structural kidney damage linked to diabetic nephropathy, and suppress NF-κB activity. Furthermore, CUR exhibited a protective effect against diabetic cardiomyopathy, lung injury, and diabetic gastroparesis. Conclusively, the study posits that CUR could potentially offer therapeutic benefits in relieving diabetic complications through its influence on the NF-κB pathway.