Small molecules from natural sources, targeting signaling pathways in diabetes

Diabetes mellitus (DM) is a metabolic disease caused by genetic or environmental factors. It has rendered a severe menace to the middle-aged and elderly, while there is still lack of efficient drugs against this disease. The pathogenic mechanism for DM is complex, and the complicated networks related to this disease involve distinct signaling pathways. Currently, discovery of potential modulators targeting these pathways has become a potent approach for anti-diabetic drug lead compound development. Compared with synthetic compounds, natural products provide inherent larger-scale structural diversity and have been the major resource of bioactive agents for new drug discovery. To date, more and more active components from plants or marine organisms have been reported to regulate diabetic pathophysiological signaling pathways and exhibit anti-diabetic activity. This review will summarize the regulation of natural small molecules on some key signaling pathways involved in DM. These pathways include insulin signaling pathway, carbohydrate metabolism pathway, the pathways involving insulin secretion and PPAR regulation, endoplasmic reticulum (ER) stress and inflammation related pathways and chromatin modification pathways.