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.
Highlights
Type 2 diabetes mellitus (T2DM) is characterized by elevated blood glucose levels and can lead to serious complications such as nephropathy, neuropathy, retinopathy, and cardiovascular disease [1,2].T2DM remains one of the most common health issues and accounts for 90% of the cases of diabetes, with a mortality incidence of 4.9 million people worldwide [3]
It has been reported that the activity of human pancreatic α-amylase (HPA) in the small intestine correlates to an increase in post-prandial glucose levels, the control of which is, an important aspect in the treatment of T2DM [30]
Saleh et al (2013) observed significant α-glucosidase and α-amylase inhibitory in the n-hexane fractions of ten plant extracts traditionally used in Iran for diabetes [33,34]
Summary
Type 2 diabetes mellitus (T2DM) is characterized by elevated blood glucose levels and can lead to serious complications such as nephropathy, neuropathy, retinopathy, and cardiovascular disease [1,2].T2DM remains one of the most common health issues and accounts for 90% of the cases of diabetes, with a mortality incidence of 4.9 million people worldwide [3]. Pancreatic α-amylase (E.C. 3.2.1.1) is a key enzyme that breaks down dietary carbohydrates such as starch into simple monosaccharides in the digestive system. These are further degraded by α-glucosidases to glucose which, on absorption, enters the bloodstream. Inhibiting α-amylase and α-glucosidase enzymes can suppress carbohydrate digestion, delay glucose uptake and reduce blood sugar levels [4]. Drugs such as acarbose, voglibose, and miglitol inhibit α-glucosidase and α-amylase in practice, they produce undesired side effects such as bloating, abdominal discomfort, diarrhea, and flatulence [5]
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