Identification of α-Glucosidase inhibition directed phytochemical studies on medicinally important plants

Abstract

α-Glucosidase is a membrane-bound intestinal enzyme responsible for hydrolyzing glycosidic bonds in carbohydrates, releasing free glucose into the bloodstream. This process contributes to postprandial hyperglycemia, a major factor in type 2 diabetes mellitus, which affect millions of people worldwide. α-Glucosidase appears to be overexpressed and speeds up the digestion of carbohydrates. Inhibiting the activity of α-glucosidase can slow carbohydrate digestion, thereby helping to regulate blood glucose levels and manage diabetes. This can be accomplished using α-glucosidase inhibitors. Acarbose and miglitol are two drugs that are effectively used in clinical settings to treat type 2 diabetes. However, these medications can have several side effects. Therefore, it is worthwhile to explore new α-glucosidase inhibitors that may offer the potential for fewer or even no side effects. Given the significance of α-glucosidase inhibitors with fewer side effects, this research project was designed to identify bioactive natural products from edible medicinal plants with potential health benefits. Through a systematic screening of crude plant extracts, we identified five edible herbs, Momordica charantia, Zingiber officinale, Salvia officinalis, Artemisia absinthium, and Olea europaea exhibiting various levels of α-glucosidase inhibitory activity. Among these, Z. officinale (ginger) emerged as a potent source, leading to the isolation and structural elucidation of three bioactive natural compounds designated as compounds 1-3. Notably, compound 2 demonstrated significant α-glucosidase inhibition activity comparable to that of acarbose. Given that Z. officinale is widely used as a flavoring in cuisine, particularly in Southeast Asian countries, we hypothesized that compound 2 may have fewer side effects than acarbose. This thesis describes: (i) bioactivity data for M. charantia, Z. officinale, S. officinalis, A. absinthium, and O. europaea; (ii) bioassay-directed phytochemical studies on Z. officinale; (iii) structure elucidation of compounds 1-3 with the aid of NMR spectroscopy; and (iv) α-glucosidase inhibitory activity data for compounds 1-3.