Anti-α-Glucosidase and Antiglycation Activities of α-Mangostin and New Xanthenone Derivatives: Enzymatic Kinetics and Mechanistic Insights through In Vitro Studies

Diabetes mellitus is characterized by chronic hyperglycemia that promotes ROS formation, causing severe oxidative stress. Furthermore, prolonged hyperglycemia leads to glycation reactions with formation of AGEs that contribute to a chronic inflammatory state. This research aims to evaluate the inhibitory activity of α-mangostin and four synthetic xanthenone derivatives against glycation and oxidative processes and on α-glucosidase, an intestinal hydrolase that catalyzes the cleavage of oligosaccharides into glucose molecules, promoting the postprandial glycemic peak. Antiglycation activity was evaluated using the BSA assay, while antioxidant capacity was detected with the ORAC assay. The inhibition of α-glucosidase activity was studied with multispectroscopic methods along with inhibitory kinetic analysis. α-Mangostin and synthetic compounds at 25 µM reduced the production of AGEs, whereas the α-glucosidase activity was inhibited only by the natural compound. α-Mangostin decreased enzymatic activity in a concentration-dependent manner in the micromolar range by a reversible mixed-type antagonism. Circular dichroism revealed a rearrangement of the secondary structure of α-glucosidase with an increase in the contents of α-helix and random coils and a decrease in β-sheet and β-turn components. The data highlighted the anti-α-glucosidase activity of α-mangostin together with its protective effects on protein glycation and oxidation damage.

Charantoside L, A New Cucurbitane-Type Glycoside from Momordica charantia L. with α-Glucosidase Inhibitory Activities

A new cucurbitane-type glycoside (1) and two known compounds (2-3) were isolated from the ethanol extract of the fruits of Momordica charantia L. Their chemical structures were determined as (19 S,23 E)-5 β­,19-epoxy-19-methoxycucurbita-6,23-diene-3 β,25-diol 3 -O-β-D-allopyranoside (1), goyaglycoside d (2), and (19 S,23 E)-5 β,19-epoxy-19-methoxycucurbita-6,23-diene-3 β,25-diol (3) on the basis of the extensive spectroscopic methods, including 1D, 2D NMR, HRESIMS, and in comparison with the reported data. Compounds 1 to 3 were evaluated for α-glucosidase inhibitory effects. Compounds 1 and 2 showed anti α-glucosidase activity with IC50 values of 134.12 ± 11.20 and 163.17 ± 13.71 µM, respectively, compared with the positive control, acarbose, IC50 160.99 ± 14.30 μM. Compounds 2 and 3 were first isolated from plant M. charantia growing in Vietnam.

Inhibitory activity of flavonoids against human sucrase-isomaltase (α-glucosidase) activity in a Caco-2/TC7 cellular model

Flavonoids may be effective inhibitors of SI in Caco-2/TC7 cells when using natural substrates maltose and sucrose. The chemical features that favor the SI inhibition by flavonoids are the presence of –OH groups at C-3, C-3′, C-4′, C-7 and C-8.

Hydroxyethyl Isoflavonoids from the Leaves of Maclura tricuspidata

: Maclura tricuspidata, which belongs to the Moraceae family, is widely distributed in Asia, including Korea. All parts of this plant, such as roots, fruits, and leaves, are rich in diverse bioactive compounds, especially xanthones and isoflavonoids. Investigation of the leaves of M. tricuspidata through various chromatographic techniques yielded fourteen compounds, including five new compounds. The new compounds were determined to comprise an isoflavonoid structure with hydroxyethyl moiety and defined as hydroxyethylisoflavones A-E (10-14) on the basis of 1D and 2D NMR and MS data. These compounds efficiently inhibited α-glucosidase activity.