Kinetics and mechanism of α-glucosidase inhibition by edible brown algae in the management of type 2 diabetes

Abstract

<jats:title>Abstract</jats:title><jats:p>Prevalence of type 2 diabetes mellitus has significantly increased in the last three decades and currently affects about 1 in 10 globally. A common therapeutic target for type 2 diabetes is α- glucosidase, an essential enzyme located at the brush border of the small intestinal epithelium. The inhibition of α-glucosidase results in a reduced digestion of carbohydrates and a decrease of postprandial blood glucose. Although, synthetic inhibitors are available in the market, these are usually associated with significant gastrointestinal side effects. In this study, natural inhibitors derived from edible brown algae are being investigated as an alternative.</jats:p><jats:p>Polysaccharide- and polyphenolic-enriched extracts from <jats:italic>Ascophyllum nodosum</jats:italic> and <jats:italic>Fucus vesiculosus</jats:italic> were characterized and screened for their inhibitory effects against α-glucosidase obtained from rat intestine using maltose, sucrose, and p-nitrophenyl (pNPG) as substrates. Acarbose was used as a synthetic inhibitor. Furthermore, enzyme kinetics and mechanism of inhibition of α- glucosidase were determined using linear and non-linear regression methods (GraphPad Prism ver. 6, GraphPad Software, La Jolla California USA).</jats:p><jats:p>All tested extracts showed a dose-dependent inhibitory effect against α-glucosidase. However, the type of inhibition varied between the extracts. Most importantly, the composition analysis showed that the seaweed extracts had different polysaccharide and phenolic contents, suggesting different mode of actions against α-glucosidase. The relation between chemical composition and inhibitory activity of the compounds are discussed.</jats:p><jats:p>In summary, the current study demonstrates the mechanisms in which different brown seaweed extracts with various composition effectively inhibit α-glucosidase. Therefore, this natural inhibitor can be considered as a potential candidate for the management of type 2 diabetes mellitus.</jats:p>

Bioactive molecules from soybeans (Glycine max) with anti-type 2 diabetes activity: a systematic review

“…The mammalian α-glucosidase is synthesized in the mucosal brush border of the small intestine, and its major physiological function is to catalyze the digestion of disaccharides and starch which make up a huge percentage of the human diet [145]. The enzyme selectively catalyzes the endonucleolytic or exonucleolytic hydrolysis of various sugars producing monosaccharides, oligosaccharides, or glycosaminoglycans, which increases postprandial blood glucose [146][147][148]. This enzyme is considered a crucial clinical target for the treatment of T2D [149].…”

Structural characterization and hypoglycemic effect of polysaccharides of Polygonatum sibiricum

“…In the research on diabetes and related diseases, glycosidase has been identified as the key enzyme that regulates blood glucose levels in the human body. Inhibitors of glucosidase activity in the small intestine villi have been found to delay the breakdown and digestion of complex carbohydrates and disaccharides, thereby reducing the absorption of glucose in the intestinal cavity and mainly lowering postprandial blood sugar (Maha et al., 2020). Additionally, inhibiting amylase can effectively balance blood glucose concentration by slowing down the rise of blood glucose after eating, thus lowering overall blood glucose levels (Rane et al., 2020).…”

Potential α-Glucosidase Inhibitors from the Deep-Sea Sediment-Derived Fungus Aspergillus insulicola

“…The inhibition of α -glucosidase can reduce the cleavage of glucose from disaccharides or oligosaccharides to inhibit postprandial hyperglycemia [ 4 ]. Therefore, α -glucosidase is a common therapeutic target for the treatment of T2DM [ 5 ]. Currently available α -glucosidase inhibitors, such as acarbose, voglibose and miglitol, have been used to treat T2DM patients.…”