Alpha-Amylase and Alpha-Glucosidase Enzyme Inhibition and Antioxidant Potential of 3-Oxolupenal and Katononic Acid Isolated from Nuxia oppositifolia

Abstract

Nuxia oppositifolia is traditionally used in diabetes treatment in many Arabian countries; however, scientific evidence is lacking. Hence, the present study explored the antidiabetic and antioxidant activities of the plant extracts and their purified compounds. The methanolic crude extract of N. oppositifolia was partitioned using a two-solvent system. The n-hexane fraction was purified by silica gel column chromatography to yield several compounds including katononic acid and 3-oxolupenal. Antidiabetic activities were assessed by α-amylase and α-glucosidase enzyme inhibition. Antioxidant capacities were examined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) scavenging assays. Further, the interaction between enzymes (α-amylase and α-glucosidase) and ligands (3-oxolupenal and katononic acid) was followed by fluorescence quenching and molecular docking studies. 3-oxolupenal and katononic acid showed IC50 values of 46.2 μg/mL (101.6 µM) and 52.4 μg/mL (119.3 µM), respectively against the amylase inhibition. 3-oxolupenal (62.3 µg/mL or 141.9 μM) exhibited more potent inhibition against α-glucosidases compared to katononic acid (88.6 µg/mL or 194.8 μM). In terms of antioxidant activity, the relatively polar crude extract and n-butanol fraction showed the greatest DPPH and ABTS scavenging activity. However, the antioxidant activities of the purified compounds were in the low to moderate range. Molecular docking studies confirmed that 3-oxolupenal and katononic acid interacted strongly with the active site residues of both α-amylase and α-glucosidase. Fluorescence quenching results also suggest that 3-oxolupenal and katononic acid have a good affinity towards both α-amylase and α-glucosidase enzymes. This study provides preliminary data for the plant’s use in the treatment of type 2 diabetes mellitus.

In Vitro Alpha-Amylase and Alpha-Glucosidase Inhibitory Activity and In Vivo Antidiabetic Activity of Withania frutescens L. Foliar Extract

“…Due to its major role in the breakdown of polysaccharides, alpha-amylase is considered one of the most important enzymes in the digestion process found primarily in the saliva and pancreatic juice [ 26 ]. Targeting this enzyme and inhibiting it is one of the possible solutions to prevent high postprandial blood glucose [ 27 ].…”

Untargeted Metabolomics Analysis Using FTIR and UHPLC-Q-Orbitrap HRMS of Two Curculigo Species and Evaluation of Their Antioxidant and α-Glucosidase Inhibitory Activities

“…Phenolic compounds prevent the enzymatic hydrolysis of carbohydrates by inhibiting α-amylase and α-glucosidase, with a mixed mechanism (competitive and uncompetitive) [ 20 ]. Previous studies using in vitro and in vivo testing [ 21 , 22 , 23 ] demonstrated an antidiabetic activity from the rhizome extracts of C. orchioides and C. latifolia . However, in this work, we found that only the rhizome of C. latifolia showed high antioxidant activity and potent inhibition of α-glucosidase enzyme associated with the high phenolic compounds in plants.…”

Marsectohexol and other pregnane phytochemicals derived from Gongronema latifolium as α-amylase and α-glucosidase inhibitors: in vitro and molecular docking studies

“…Important carbohydrate-hydrolysing enzymes such as α-amylase, and α-glucosidase enzymes play key roles in the breakdown of starch, oligosaccharides and disaccharides into monosaccharides for absorption [4,5]; and thereby serve as key targets for phytomedicines towards suppressing carbohydrate digestion, and delaying glucose uptake in the gut [6]. In practice, several synthetic drugs such as acarbose, voglibose, and miglitol are potent inhibitors of carbohydrate-hydrolysing enzymes; however, these drugs are associated with undesirable effects such as bloating, abdominal discomfort, diarrhea, and flatulence [7]. Utilizing natural antidiabetic agents, which can constrain carbohydrate metabolizing enzymes in human gut, is a promising oral policy for blunting postprandial plasma glucose rise; and alleviating diabetes, obesity, and other metabolic syndromes [8,9].…”