Alpha Glucosidase Inhibitory Activities of Plants with Focus on Common Vegetables

Abstract

Type-2 diabetes mellitus is one of the most prevalent metabolic diseases in the world, and is characterized by hyperglycemia (i.e., high levels of glucose in the blood). Alpha-glucosidases are enzymes in the digestive tract that hydrolyze carbohydrates into glucose. One strategy that has been developed to treat type-2 diabetes is inhibition of the activity of alpha-glucosidases using synthetic drugs. However, these inhibitors are usually associated with gastrointestinal side effects. Therefore, the development of inhibitors from natural products offers an alternative option for the control of hyperglycemia. In recent years, various studies have been conducted to identify alpha-glucosidases inhibitors from natural sources such as plants, and many candidates have transpired to be secondary metabolites including alkaloids, flavonoids, phenols, and terpenoids. In this review, we focus on the alpha-glucosidases inhibitors found in common vegetable crops and the major classes of phytochemicals responsible for the inhibitory activity, and also as potential/natural drug candidates for the treatment of type-2 diabetes mellitus. In addition, possible breeding strategies for production of improved vegetable crops with higher content of the inhibitors are also described.

Keywords: alpha-glucosidase; alpha-glucosidase inhibitor; breeding; diabetes; secondary metabolites; vegetables.

Figure 1

Molecular structure of representative commercialized glucosidase inhibitor drugs.

Figure 2

Basic modes of action of α-glucosidase inhibitors (AGIs). (A) Absorption of glucose produced from carbohydrates by hydrolytic glucosidase activity of α-glucosidase (AG) in the small intestine. (B–D) Competitive, non-competitive (allosteric), and uncompetitive inhibition of the AG activity by AGIs, respectively.

Figure 3

Schematic diagram of the procedure through which AGI activity is measured in plant extracts using different substrates; pNPG (A) and maltose/sucrose (B). pNPG, p-nitrophenyl-α-d-glucopyranoside, AG, α-glucosidase; PE, plant extract; AGI, α-glucosidase inhibitor.

Figure 4

A flowchart depicting breeding strategies for developing varieties with high AGI content. Genome editing (GE) can be used for creating targeted gene modifications as a method of mutation breeding. Anther/microspore culture technology can also contribute to reduce the time required to develop pure lines. Novel genes can be introgressed into the cultivated species through interspecific hybridization with the wild species.