Inhibition of α-glucosidase by trilobatin and its mechanism: kinetics, interaction mechanism and molecular docking

He, Ming; Zhai, Yuhan; Zhang, Yuqing; Xu, Shuo; Yu, Shaoxuan; Wei, Yingxin; Xiao, Haifang; Song, Yuanda

doi:10.1039/d1fo03636j

Cited by 31 publications

(25 citation statements)

References 50 publications

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“…The Lineweaver-Burk plots revealed that the LS extract inhibited α-glucosidase by a non-competitive mechanism with a K i value of 1.32 µg/mL, which is in accordance with a previous kinetic analysis, indicating that trilobatin reversibly inhibited α-glucosidase in a non-competitive manner (He et al. 2022 ). This effect was stronger than that of acarbose, as positive control.…”

Section: Discussionsupporting

confidence: 90%

Antihyperglycemic effects of Lysiphyllum strychnifolium leaf extract in vitro and in vivo

Goli

Sato

et al. 2023

Pharmaceutical Biology

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Context Lysiphyllum strychnifolium (Craib) A. Schmitz (LS) (Fabaceae) has traditionally been used to treat diabetes mellitus. Objective This study demonstrates the antidiabetic and antioxidant effects of aqueous extract of LS leaves in vivo and in vitro . Materials and methods The effects of aqueous LS leaf extract on glucose uptake, sodium-dependent glucose cotransporter 1 (SGLT1) and glucose transporter 2 (GLUT2) mRNA expression in Caco-2 cells, α-glucosidase, and lipid peroxidation were evaluated in vitro . The antidiabetic effects were evaluated using an oral glucose tolerance test (OGTT) and a 28-day consecutive administration to streptozotocin (STZ)-nicotinamide (NA)-induced type 2 diabetic mice. Results The extract significantly inhibited glucose uptake (IC 50 : 236.2 ± 36.05 µg/mL) and downregulated SGLT1 and GLUT2 mRNA expression by approximately 90% in Caco-2 cells. Furthermore, it non-competitively inhibited α-glucosidase in a concentration-dependent manner with the IC 50 and K i of 6.52 ± 0.42 and 1.32 µg/mL, respectively. The extract at 1000 mg/kg significantly reduced fasting blood glucose levels in both the OGTT and 28-day consecutive administration models as compared with untreated STZ-NA-induced diabetic mice ( p < 0.05). Significant improvements of serum insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and GLUT4 levels were observed. Furthermore, the extract markedly decreased oxidative stress markers by 37–53% reduction of superoxide dismutase 1 (SOD1) in muscle and malondialdehyde (MDA) in muscle and pancreas, which correlated with the reduction of MDA production in vitro (IC 50 : 24.80 ± 7.24 µg/mL). Conclusion The LS extract has potent antihyperglycemic activity to be used as alternative medicine to treat diabetes mellitus.

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Section: Discussionsupporting

confidence: 90%

Antihyperglycemic effects of Lysiphyllum strychnifolium leaf extract in vitro and in vivo

Goli

Sato

et al. 2023

Pharmaceutical Biology

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“…It has been reported that trilobatin is a strong α-glucosidase inhibitor, which may be beneficial to improve the blood glucose level in DM. 40 However, the fundamental measure to reduce blood glucose fluctuation is to improve the islet function. 41 In our included studies, it has been most commonly reported that DST ameliorates blood glucose and insulin resistance in DM animals, which is also shown in our meta-analysis.…”

Section: Discussionmentioning

confidence: 99%

Effects of natural dihydrochalcones in sweet tea (Lithocarpus polystachyus) on diabetes: a systematical review and meta-analysis of animal studies

et al. 2022

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“…The double reciprocal fitting curve of the preparation is: (R 2 = 0.9989), the Michaelis constant Km is 0.514, and the maximum rate of enzymatic reaction Vmax is 0.08. In addition, it can be seen from the Figure 6 that the inhibition curves of different horizontal intercepts and slopes intersect at one point with the longitudinal axis, indicating that the inhibitor concentration increases, Km increases, and Vmax remains unchanged, which is the most significant feature of competitive inhibition [ 32 ]. It was also shown that MAP-2 can bind to the active site of α-glucosidase in a reversible manner, thereby inhibiting the decomposition of glycosides into glucose and reducing postprandial blood glucose.…”

Section: Resultsmentioning

confidence: 99%

“…Lactase, also known as β-galactosidase, is one of the important functions of enzymes of the intestinal tract, mainly composed of small intestinal villus and intestinal bacteria secrete of brush border, and closely associated with diarrhea, abdominal distention [ 33 ], and studies have shown that, when the body lacks lactase, the symptoms of lactose intolerance occurs [ 34 ], such as severe diarrhea, abdominal distension [ 32 ], and severe cases can produce dehydration, acidosis and growth disorder, etc. [ 35 ].…”

Section: Resultsmentioning

confidence: 99%

Optimization of Extraction Process of Polysaccharides MAP-2 from Opuntia Milpa Alta by Response Surface Methodology and Evaluation of Its Potential as α-Glucosidase Inhibitor

Yang

Zhou

et al. 2022

Foods

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The α-glucosidase inhibitors play an important role in blood glucose control in patients with type 2 diabetes. At present, the development of new α-glucosidase inhibitors is an urgent clinical need. Our previous studies have found that the polysaccharide MAP-2 in the cactus Opuntia Milpa Alta has significantly better activity than acarbose (one of the most widely used first-line α-glucosidase inhibitors in clinical practice), but its optimal extraction process parameters and inhibition kinetic characteristics are not clear, and whether it has the potential to become a new α-glucosidase inhibitors is also unclear. In this study, based on previous research, we used the combination of single factor experiments and the response surface method (RSM) to identify the optimal extraction conditions for MAP-2 as follows: solid-liquid ratio 1:4, extraction temperature 90 °C, extraction time 1 h. Under these conditions, the extraction yield of MAP-2 was 3.47 ± 0.062%. When the concentration of MAP-2 was 16 mg/mL, the inhibition rate of α-glucosidase was 91.13 ± 0.62%. In addition, the results of inhibition kinetics showed that the inhibition rate of MAP-2 on α-glucosidase was the highest at pH 7.4 for 30 min, and showed a good dose-effect relationship, which was a reversible competitive inhibition. Meanwhile, we also compared the activities of MAP-2 and acarbose on the side effects of acarbose related enzymes. Compared with acarbose, MAP-2 not only had a better activation effect on lactase, but also inhibited the activity of hyaluronidase, and the activation and inhibition rate were positively correlated with the concentration. However, under the same conditions, the effect of acarbose on hyaluronidase was opposite to that of MAP-2. At low concentration, acarbose had a certain activation effect on lactase, but gradually attained an inhibitory effect with the increase in concentration. In contrast, MAP-2 not only activates lactase activity, improves diarrhea, abdominal distension, and abdominal pain, but also inhibits hyaluronidase activity, to solve the side effects of allergic reactions, suggesting that MAP-2 has the potential to become a novel and effective inhibitor of α-glucosidase with fewer side effects.

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Inhibition of α-glucosidase by trilobatin and its mechanism: kinetics, interaction mechanism and molecular docking

Abstract: α-Glucosidase is related to the increase of postprandial blood glucose in vivo. Inhibition of α-glucosidase is supposed to be an effective approach to treat type 2 diabetes mellitus (T2DM). Trilobatin,...

Cited by 31 publications

References 50 publications

Antihyperglycemic effects of Lysiphyllum strychnifolium leaf extract in vitro and in vivo

Antihyperglycemic effects of Lysiphyllum strychnifolium leaf extract in vitro and in vivo

Effects of natural dihydrochalcones in sweet tea (Lithocarpus polystachyus) on diabetes: a systematical review and meta-analysis of animal studies

Optimization of Extraction Process of Polysaccharides MAP-2 from Opuntia Milpa Alta by Response Surface Methodology and Evaluation of Its Potential as α-Glucosidase Inhibitor

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