Tao Yuan

The Key Laboratory of Plant Resources and Chemistry of Arid Zone, and State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences

Diabetes mellitus is a chronic disease that occurs when the pancreas is no longer able to make insulin, or when the body cannot make good use of the insulin it produces. Diabetes is one of the most prevalent human diseases in the world. About 387 million people living with diabetes worldwide reported by International Diabetes Federation on 2014, and the figure is expected increase 205 million by 2035. Type 2 diabetes mellitus (also called non-insulin resistant diabetes mellitus) accounts for 90-95% of all diabetes, which is characterized by insulin resistance, relative insulin deficiency, and hyperglycemia. Type 2 diabetes is associated with chronic complications such as circulatory disease, stroke, hypertension, blindness, kidney failure, uremia and gangrene of the lower limbs. At present, the therapies for type 2 diabetes rely mainly on several anti-diabetic drugs including insulin itself, sulfonylureas, biguanides, thiazolidinediones, and alpha-glucosidase inhibitors, etc. However, several synthetic drugs have limited efficacy, limited tolerability and significant side effects. Therefore, the search for natural products to serve as more effective anti-diabetic drugs, with reduced side effects, has attracted more and more scientific interest.

After screening of nine food plant extracts using alpha-glucosidase inhibitory bioassay, two of them, red maple bark and twigs, and pomegranate flowers, were selected for chemical investigation as they showed potent inhibitory activities. Bioassay-guided isolation of red maple bark and twigs led to the discovery of 12 gallotannins, the primary SAR study indicated that both the number and positions of galloyl groups attached to the glucitol are important for inhibition of alpha-glucosidase. 15 phenolics including two novel ellagitannins, were isolated and identified from the pomegranate flowers, in vitro alpha-glucosidase inhibitory activities test showed hydrolysable tannins may account for the reported anti-diabetic properties of pomegranate flowers.

AMP-activated protein kinase (AMPK) is an enzyme that plays a key role in cellular energy homeostasis, and the AMPK pathway performs a central function in the regulation of glucose and lipid metabolism. Moreover, AMPK has been shown to be a target for anti-diabetic drugs, including metformin, and several plant natural products derived from traditional medicines. Six rare naturally occurring indazole-type alkaloids including two new compounds were isolated from a defatted extract of black cumin seeds. Among them, 17-O-(b-D-glucopyranosyl)-4-O-methylnigellidine showed more potent ability to regulate glucose consumption than metformin, and increased AMPK phosphorylation in a concentration-dependent manner. Therefore, the compounds identified from black cumin seeds could serve as lead scaffolds for the synthesis of structural analogues with more potent antihyperglycemic activities.