Acarbose and voglibose the classic glucosidase inhibitors we

Acarbose and voglibose, the classic α-glucosidase inhibitors, were clinically used to inhibit α-glucosidase activity for the treatment of type 2 diabetes. However, the intake of these drugs may cause some undesirable gastrointestinal side effects and weight gain (Xu et al., 2015). The synthetic drug aminoguanidine (AG) was used as an anti-glycation agent, which inhibited non-enzymatic glycation by trapping reactive carbonyl intermediates and blocking the formation of Schiff Oligomycin A or AGEs (Jariyapamornkoon, Yibchok-anun, & Adisakwattana, 2013). However, AG can cause non-specific and potentially toxic effects (Shen, Xu, & Sheng, 2017). Consequently, recent studies have been focused on the effective and safe natural antidiabetic compounds, mainly phytochemicals from edible plants or medicinal plants for the prevention of diabetes and its complications. Flavonoids, as a group of natural inhibitors extensively distributed in various foods and beverages of plant origin including vegetables, fruits, tea, nuts and herbs, have attracted attention due to their antioxidant, antibacterial and anti-inflammatory activities (Peng, Zhang, Liao, & Gong, 2016). More attentions are focused on flavonoids for their ability of reducing the incidence of chronic diseases, such as neurodegenerative diseases, cardiovascular diseases, type 2 diabetes mellitus, etc. (Del Rio et al., 2013, Zeng et al., 2016). Galangin (3,5,7-trihydroxyflavone), a flavonoid compound, is abundant in propolis and the root of Alpinia officinarum Hance (a traditional Chinese medicine) (Aloud et al., 2017). It has been reported to exert multiple bioactivities, including antiviral, anti-obesity, antioxidant and anti-inflammatory properties (Aloud et al., 2017). Moreover, Huh et al. (2013) reported that after gavage, galangin had no acute and chronic toxicities to rats at the dose levels of 5.0 g/kg and 2000 mg/kg, respectively. Aloud et al. (2017) also found that rats did not exhibit any toxic symptoms after the oral treatment of galangin at the concentrations of lowering plasma glucose. Although galangin was reported to inhibit the formation of AGEs (Liu, Xie, Song, Shang, & Chen, 2012), little has been known about the effect of galangin on the formation of intermediate products (such as fructosamine and α-dicarbonyl compounds) resulting from non-enzymatic glycation in early and middle stages. So far, no systematic study of the anti-glycation activity of galangin has been reported. Moreover, the inhibition mechanism of galangin on α-glucosidase activity is still unclear. Therefore, the present study was aimed to explore the mechanism by which galangin interacts with α-glucosidase, and systematically investigate the inhibitory effects of galangin on non-enzymatic glycation in vitro using bovine serum albumin (BSA)-fructose system as the model by UV–vis absorption, fluorescence and circular dichroism (CD) spectroscopy combined with molecular docking analysis. We hope that this study would provide a deeper understanding in the interaction of galangin with α-glucosidase and useful information on the inhibition of galangin against glycation.
Materials and methods
Results and discussion
Conclusions In summary, galgangin was an effective α-glucosidase and non-enzymatic glycation inhibitor. Galangin reversibly inhibited α-glucosidase with an IC50 value of (27.5 ± 0.5) μM in a mixed-type manner through a monophasic process. The α-glucosidase-galangin complex was formed and the binding process was mainly driven by hydrophobic interaction and hydrogen bonding. α-Glucosidase had one binding site for galangin with the binding constant of (2.06 ± 0.04) × 104 L mol−1 at 25 °C. The molecular docking showed that galangin bound to the catalytic active site of α-glucosidase to induce an unfolding of the constitutive polypeptides of the enzyme, hindering the entrance of substrate to inhibit the catalytic activity of α-glucosidase. Moreover, galangin moderately inhibited the formation of fructosamine and α-dicarbonyl compounds at the studied concentrations, and strongly suppressed the generation of AGEs. This study has provided new insights into the screening of effective α-glucosidase and glycation inhibitors, although it still needs more experiments in vitro and vivo to elucidate.