Endoplasmic reticulum as a therapeutic target in type 2 diabetes: Role of phytochemicals

Type 2 diabetes mellitus (T2DM) is a metabolic disorders characterized by insulin resistance and β-cell dysfunction with an increasing worldwide incidence. Several studies have revealed that long-term glucotoxicity results in β-cell failure and death through induction of endoplasmic reticulum (ER) stress. Owing to the chronic progression of T2DM and the low effectiveness of antidiabetic drugs in long-term use, medicinal plants and their secondary metabolites seem to be the promising alternatives. Here we have provided a comprehensive review regarding the role of phytochemicals to alleviate ER stress in T2DM. Ginsenoside compound K, baicalein, quercetin, isopulegol, kaempferol, liquiritigenin, aspalathin, and tyrosol have demonstrated remarkable improvement of T2DM via modulation of ER stress. Arctigenin and total glycosides of peony have been shown to be effective in the treatment of diabetic retinopathy through modulation of ER stress. The effectiveness of grape seed proanthocyanidins and wolfberry is also shown in the relief of diabetic neuropathy and retinopathy. Resveratrol is involved in the prevention of atherosclerosis via ER stress modulation. Taken together, the data described herein revealed the capability of herbal constituents to prevent different complications of T2DM via a decrease in ER stress which open new doors to the treatment of diabetes.