Harnessing phytochemicals to combat diabetes: Insights into molecular pathways and therapeutic advances

Diabetes mellitus (DM) is a multifactorial metabolic disorder characterized by insulin resistance, pancreatic beta-cell dysfunction, oxidative stress, and chronic inflammation. It is influenced by various molecular pathways, including phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt), glycolysis, hexosamine, diacylglycerol/protein kinase C (DAG/PKC), polyol, and advanced glycation end-products (AGEs). These pathways regulate glucose metabolism, insulin signaling, lipid homeostasis, and inflammatory responses. Single-target therapies often fail to provide comprehensive treatment, making a multi-pathway approach more effective. Several natural compounds exhibit multi-target effects, such as quercetin and anthocyanin, which enhance the PI3K/Akt pathway and inhibit AGEs formation. Epigallocatechin-3-gallate (EGCG) suppresses the hexosamine and polyol pathways, reducing insulin resistance and vascular complications. Luteolin and myricitrin regulate DAG/PKC signaling, minimizing inflammation and endothelial dysfunction. A multi-pathway strategy using natural compounds offers promising therapeutic potential for effective and sustainable DM management.