Computational Study on the Comparative Differences in the Activity of Inhibitors of Human versus Rat Alpha-Glucosidase

Nakamura, Shinya; Shimada, Kazuko; Tanabe, Genzoh; Muraoka, Osamu; Nakanishi, Isao

doi:10.4236/ojmc.2017.72002

Cited by 3 publications

(4 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, the N-terminal catalytic domain of rat ntMGAM and that of human ntMGAM (hntMGAM) were reported to share 60% amino acid sequence similarity. 48,49 Thus, it is not surprising that the inhibitory potencies of sulfonium salts such as 1 and 2 against rat maltase were comparable to those against human maltase. 10 In contrast, although the full-length amino acid sequence of yeast a-glucosidase only shares 42% similarity with that of human maltase, the catalytic domain (in the range of 5 Å around the substrate binding site) of yeast a-glucosidase exhibits high similarity (83%) to that of human maltase.…”

Section: Resultsmentioning

confidence: 99%

Role of the thiosugar ring in the inhibitory activity of salacinol, a potent natural α-glucosidase inhibitor

Takashima,

Nakamura,

Nagayama

et al. 2024

RSC Adv.

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

Role of the thiosugar ring in the inhibitory activity of salacinol, a potent natural α-glucosidase inhibitor

Takashima,

Nakamura,

Nagayama

et al. 2024

RSC Adv.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Although the inhibitory effects of tea catechins on alpha-glucosidase were validated in rat alpha-glucosidase as undertaken in most studies [ 17 , 18 ], the homology of alpha-glucosidase between rats and humans is only 74% [ 19 ], which affects the inhibitory effect of the compounds [ 20 ]. For this reason, we further investigated the inhibitory activity of GTEs and their catechins on human alpha-glucosidase in differentiated Caco-2 cells.…”

Section: Resultsmentioning

confidence: 99%

“…It has been reported that catechins, especially gallate catechins, strongly inhibit alpha-glucosidase activity in S. cerevisiae or a rat model [ 17 , 18 ]. However, the homology of alpha-glucosidase between rats and humans is only 74% [ 19 ], and the difference in the inhibitory effect of alpha-glucosidase by the compound was observed between rats and humans [ 20 ]. For example, acarbose showed lower inhibitory activity in humans than in rats due to the weak interaction of acarbose with the Nt-MGAM domain [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

“…However, the homology of alpha-glucosidase between rats and humans is only 74% [ 19 ], and the difference in the inhibitory effect of alpha-glucosidase by the compound was observed between rats and humans [ 20 ]. For example, acarbose showed lower inhibitory activity in humans than in rats due to the weak interaction of acarbose with the Nt-MGAM domain [ 20 ]. Therefore, the results of studies in rats may not be fully applicable to humans.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Extraction Efficiency and Alpha-Glucosidase Inhibitory Activities of Green Tea Catechins by Different Infusion Methods

Orita,

Chogahara,

Okuda

et al. 2023

Foods

View full text Add to dashboard Cite

Alpha-glucosidase is an important target for glycemic control with the aim of reducing the risk of type 2 diabetes (T2D). Green tea catechins have been reported to inhibit alpha-glucosidase activity as a potential beverage to control blood glucose levels. However, the effects of the daily infusion style of green tea on tea catechins and their activity remain unclear. In this study, the extraction efficiency of catechins was investigated for 12 green tea extracts (GTEs) infused with 70% ethanol (70% EtOH for 24 h, a favored solvent for catechin extraction), room temperature water infusion (RT H2O for 24 h, an easy way to drink tea), and hot water infusion (Hot H2O for 90 s, a standard way to drink tea). Eight catechins were quantified by HPLC, and the inhibitory effect of GTEs and their catechins on alpha-glucosidase was measured with both rat intestinal enzymes and human Caco-2 cells. The inhibitory mechanism was further analyzed in silico by docking catechins to human alpha-glucosidase using Molecular Operating Environment software. The results showed that total catechins and gallate catechins were efficiently extracted in the order of 70% EtOH, RT H2O, and Hot H2O, and the inhibitory activity against alpha-glucosidase also followed a similar order. Pearson correlation analysis indicated that the alpha-glucosidase inhibitory activity of GTEs was significantly positively correlated with the contents of total catechins, especially gallate catechins. Gallate catechins, such as EGCg and ECg, showed lower IC50 values than free catechins for the enzyme in both rats and humans. In silico simulation revealed that gallate catechins were bound to the different sites with free catechins, and the docking energy of gallate catechins was lower than that of free catechins. Taken together, our data indicated that the daily infusion style of green tea significantly impacted the extraction efficiency and alpha-glucosidase inhibitory activities of catechins, which will give us insight into the use of green tea catechins for glycemic control through efficient infusion.

show abstract

Biochemical and In Silico Aspects of Active Compounds From Nyctanthes arbor‐tristis Flower As Antidiabetic Agent

ALNadhari,

Alsakkaf,

Albarakat

2024

Biotech and App Biochem

View full text Add to dashboard Cite

Targeting alpha‐glucosidase (maltase‐glucoamylase [MGAM] and sucrase‐isomaltase [SI]) under diabetes conditions is important to overcome hyperglycemia. Moreover, it is necessary to mitigate hyperglycemia‐mediated oxidative stress to evade the progression of diabetes‐associated secondary complications. Hence, in the present study, under‐explored Nyctanthes arbor‐tristis flowers (NAFs) were studied for inhibition of alpha‐glucosidase activities. The NAF methanolic extract (NAFME) was prepared. Through liquid chromatography/electrospray ionization tandem mass spectrometry (LC–ESI/MS/MS) analysis, various phytocompounds belonging to different classes—flavonoids, iridoid glycosides, proanthocyanidin, anthocyanin, polyphenol, phenolic acid, fatty acid ester, and carotenoid—were identified. NAFME showed in vitro antioxidant activity. NAFME inhibited maltase, sucrase, glucoamylase, and isomaltase in mixed mode with Ki values of 179.93, 176.38, 126.03, and 201.56 µg/mL, respectively. In silico screening of phytocompounds identified in NAFME indicated that hinokiflavone (HKF), pelargonidin‐3‐O‐glucoside (PG), isorhamnetin‐3‐glucoside‐7‐rhamnoside (IGR), and petunidin‐3‐rutinoside (PR) showed better interactions with different subunits of human alpha‐glucosidase, namely, N‐terminal (Nt‐MGAM and Nt‐SI) and C‐terminal (Ct‐MGAM and Ct‐SI). Molecular dynamics (MD) simulation, binding free energy study (molecular mechanics–generalized Born surface area [MM/GBSA]), and post‐MD simulation studies (principal component analysis [PCA] and dynamic cross‐correlation matrix [DCCM]) provided an in‐depth understanding of these ligands’ interactions with proteins. The overall efficacy of NAFME against oxidative stress and alpha‐glucosidase in vitro is understood. Moreover, in silico analysis has shown the possible potential of HKF, PG, IGR, and PR to act as alpha‐glucosidase inhibitors. Further studies on the antidiabetic potential of NAFME, HKF, PG, IGR, and PR in in vivo conditions are required to fully unveil the applicability of NAFME in the management of T2DM as a complementary medicine.

show abstract

Computational Study on the Comparative Differences in the Activity of Inhibitors of Human versus Rat Alpha-Glucosidase

Cited by 3 publications

References 29 publications

Role of the thiosugar ring in the inhibitory activity of salacinol, a potent natural α-glucosidase inhibitor

Role of the thiosugar ring in the inhibitory activity of salacinol, a potent natural α-glucosidase inhibitor

Extraction Efficiency and Alpha-Glucosidase Inhibitory Activities of Green Tea Catechins by Different Infusion Methods

Biochemical and In Silico Aspects of Active Compounds From Nyctanthes arbor‐tristis Flower As Antidiabetic Agent

Contact Info

Product

Resources

About