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Research Article

阿鲁酰蔗糖酯：α-葡萄糖苷酶和 α-淀粉酶的有效和选择性抑制剂

卷 29, 期 9, 2022

发表于: 27 August, 2021

页: [1606 - 1621] 页: 16

弟呕挨: 10.2174/0929867328666210827102456

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摘要

简介：阿魏酰蔗糖酯（FSEs）是一类广泛分布于植物中的苯丙素蔗糖酯（PSEs）。它们被研究为潜在的选择性 α 葡萄糖苷酶抑制剂 (AGI)，以消除与当前商业 AGI 相关的副作用。后者可有效降低糖尿病患者的血糖水平，但会引起严重的胃肠道副作用。 方法：使用计算机、体外和体内实验的系统结构-活性关系 (SAR) 研究来实现这一目标。评估 FSE 对淀粉和寡糖消化酶 α-葡糖苷酶和 α-淀粉酶的体外抑制作用，然后进行计算机对接研究以确定结合模式。在 STZ 小鼠模型中研究了主要候选 FSE 12。 结果：与 AGI 金标准阿卡波糖相比，所有活性 FSE 均显示出对 α-葡萄糖苷酶的较高抑制百分比和对 α-淀粉酶的较低抑制作用。这表明 FSE 对 α-葡糖苷酶的选择性高于 α-淀粉酶，建议将其用于消除胃肠道副作用。从体外研究来看，蔗糖核心上阿魏酰基取代基的位置和数量、芳香族“OH”基团和二异亚丙基桥是 α-葡糖苷酶和 α-淀粉酶抑制百分比的关键决定因素。特别是，二异亚丙基桥对于实现抑制选择性至关重要。 FSE 的分子对接研究证实了体外结果。分子对接研究进一步表明，游离芳族“OH”基团的存在和蔗糖核心第 3 位的取代对两种酶的抑制都至关重要。从体外和分子对接研究中，FSE 12 被选为体内验证的主要候选者。与对照（仅淀粉）小鼠相比，在 STZ 治疗的小鼠中，FSE 12 与淀粉的口服共同给药消除了餐后葡萄糖的增加并显着降低了血糖波动。 结论：我们的研究揭示了 FSE 作为选择性 AGI 治疗糖尿病的潜力，并假设减少了与商业 AGI 相关的副作用。

关键词: 糖尿病、阿魏酰蔗糖酯、苯丙素蔗糖酯、天然产物、α-葡萄糖苷酶抑制、α-淀粉酶抑制、葡萄糖偏移。

« Previous Next »
[1]
IDF Diabetes Atlas, International diabetes federation: Brussels, 2019. Available from: https://www.diabetesatlas.org/Accessed 8th June 2020]
[2]
Kruger, D.F. Exploring the pharmacotherapeutic options for treating type 2 diabetes. Diabetes Educ., 2008, 34(3)(Suppl. 3), 60S-65S.
[http://dx.doi.org/10.1177/0145721708319234] [PMID: 18525066]
[3]
World Health Organisation-fact sheet- diabetes, Available from: https://www.who.int/news-room/fact-sheets/detail/diabetes [Accessed 8th June 2020]
[4]
Akkati, S.; Sam, K.G.; Tungha, G. Emergence of promising therapies in diabetes mellitus. J. Clin. Pharmacol., 2011, 51(6), 796-804.
[http://dx.doi.org/10.1177/0091270010376972] [PMID: 20705952]
[5]
Levetan, C. Oral antidiabetic agents in type 2 diabetes. Curr. Med. Res. Opin., 2007, 23(4), 945-952.
[http://dx.doi.org/10.1185/030079907X178766] [PMID: 17407651]
[6]
Kumar, R.V.; Sinha, V.R. Newer insights into the drug delivery approaches of α-glucosidase inhibitors. Expert Opin. Drug Deliv., 2012, 9(4), 403-416.
[http://dx.doi.org/10.1517/17425247.2012.663080] [PMID: 22364261]
[7]
Hanefeld, M.; Schaper, F. The role of alpha-glucosidase inhibitors (acarbose). Pharmacotherapy of diabetes: New Developments, 2007, 143-152.
[8]
Zhang, W.; Kim, D.; Philip, E.; Miyan, Z.; Barykina, I.; Schmidt, B.; Stein, H. A multinational, observational study to investigate the efficacy, safety and tolerability of acarbose as add-on or monotherapy in a range of patients: The Gluco VIP study. Clin. Drug Investig., 2013, 33(4), 263-274.
[http://dx.doi.org/10.1007/s40261-013-0063-3] [PMID: 23435929]
[9]
Derosa, G.; Maffioli, P. α-Glucosidase inhibitors and their use in clinical practice. Arch. Med. Sci., 2012, 8(5), 899-906.
[http://dx.doi.org/10.5114/aoms.2012.31621] [PMID: 23185202]
[10]
Kelley, D.E.; Bidot, P.; Freedman, Z.; Haag, B.; Podlecki, D.; Rendell, M.; Schimel, D.; Weiss, S.; Taylor, T.; Krol, A.; Magner, J. Efficacy and safety of acarbose in insulin-treated patients with type 2 diabetes. Diabetes Care, 1998, 21(12), 2056-2061.
[http://dx.doi.org/10.2337/diacare.21.12.2056] [PMID: 9839094]
[11]
Cardullo, N.; Muccilli, V.; Pulvirenti, L.; Cornu, A.; Pouységu, L.; Deffieux, D.; Quideau, S.; Tringali, C. C-glucosidic ellagitannins and galloylated glucoses as potential functional food ingredients with anti-diabetic properties: A study of α-glucosidase and α-amylase inhibition. Food Chem., 2020, 313126099
[http://dx.doi.org/10.1016/j.foodchem.2019.126099] [PMID: 31927321]
[12]
Costamagna, M.S.; Zampini, I.C.; Alberto, M.R.; Cuello, S.; Torres, S.; Pérez, J.; Quispe, C.; Schmeda-Hirschmann, G.; Isla, M.I. Polyphenols rich fraction from Geoffroea decorticans fruits flour affects key enzymes involved in metabolic syndrome, oxidative stress and inflammatory process. Food Chem., 2016, 190, 392-402.
[http://dx.doi.org/10.1016/j.foodchem.2015.05.068] [PMID: 26212988]
[13]
Ranilla, L.G.; Kwon, Y-I.; Apostolidis, E.; Shetty, K. Phenolic compounds, antioxidant activity and in vitro inhibitory potential against key enzymes relevant for hyperglycemia and hypertension of commonly used medicinal plants, herbs and spices in Latin America. Bioresour. Technol., 2010, 101(12), 4676-4689.
[http://dx.doi.org/10.1016/j.biortech.2010.01.093] [PMID: 20185303]
[14]
Guo, Z-H.; Huang, J.; Wan, G-S.; Huo, X-L.; Gao, H-Y. New inhibitors of α-glucosidase in Salacia hainanensis Chun et How. J. Nat. Med., 2013, 67(4), 844-849.
[http://dx.doi.org/10.1007/s11418-013-0744-5] [PMID: 23361306]
[15]
Phan, M.A.T.; Wang, J.; Tang, J.; Lee, Y.Z.; Ng, K. Evaluation of α-glucosidase inhibition potential of some flavonoids from epimedium brevicornum. Lebensm. Wiss. Technol., 2013, 53(2), 492-498.
[http://dx.doi.org/10.1016/j.lwt.2013.04.002]
[16]
Panda, P.; Appalashetti, M.; Judeh, Z.M.A. Phenylpropanoid sucrose esters: Plant-derived natural products as potential leads for new therapeutics. Curr. Med. Chem., 2011, 18(21), 3234-3251.
[http://dx.doi.org/10.2174/092986711796391589] [PMID: 21671860]
[17]
Fan, P.; Terrier, L.; Hay, A-E.; Marston, A.; Hostettmann, K. Antioxidant and enzyme inhibition activities and chemical profiles of Polygonum sachalinensis F.Schmidt ex Maxim (Polygonaceae). Fitoterapia, 2010, 81(2), 124-131.
[http://dx.doi.org/10.1016/j.fitote.2009.08.019] [PMID: 19698767]
[18]
Liu, T.; Yip, Y.M.; Song, L.; Feng, S.; Liu, Y.; Lai, F.; Zhang, D.; Huang, D. Inhibiting enzymatic starch digestion by the phenolic compound diboside A: A mechanistic and in silico study. Food Res. Int., 2013, 54(1), 595-600.
[http://dx.doi.org/10.1016/j.foodres.2013.07.062]
[19]
Panda, P.; Appalashetti, M.; Natarajan, M.; Chan-Park, M.B.; Venkatraman, S.S.; Judeh, Z.M. Synthesis and antitumor activity of lapathoside D and its analogs. Eur. J. Med. Chem., 2012, 53, 1-12.
[http://dx.doi.org/10.1016/j.ejmech.2012.02.032] [PMID: 22542106]
[20]
Panda, P.; Appalashetti, M.; Natarajan, M.; Mary, C-P.; Venkatraman, S.S.; Judeh, Z.M. Synthesis and antiproliferative activity of helonioside A, 3¢,4¢,6¢-tri-O-feruloylsucrose, lapathoside C and their analogs. Eur. J. Med. Chem., 2012, 58, 418-430.
[http://dx.doi.org/10.1016/j.ejmech.2012.10.034] [PMID: 23153813]
[21]
Panda, P. Synthesis and anticancer activity of phenylpropanoid sucrose esters. Doctoral dissertation, Nanyang Technological University: Singapore, 2011.
[22]
Yan, J.; Zhang, G.; Pan, J.; Wang, Y. α-Glucosidase inhibition by luteolin: Kinetics, interaction and molecular docking. Int. J. Biol. Macromol., 2014, 64, 213-223.
[http://dx.doi.org/10.1016/j.ijbiomac.2013.12.007] [PMID: 24333230]
[23]
Steed, J.W.; Atwood, J.L. Supramolecular chemistry; John Wiley & Sons Ltd.: London, 2009.
[http://dx.doi.org/10.1002/9780470740880]
[24]
Hornak, V.; Abel, R.; Okur, A.; Strockbine, B.; Roitberg, A.; Simmerling, C. Comparison of multiple amber force fields and development of improved protein backbone parameters. Proteins Struct. Funct. Bioinform., 2006, 65, 712-725.
[25]
Case, D.A.; Darden, T.A.; Cheatham, T.E., III; Simmerling, C.L.; Wang, J.; Duke, R.E.; Luo, R.; Merz, K.M.; Pearlman, D.A.; Crowley, M.; Walker, R.C.; Zhang, W.; Wang, B.; Hayik, S.; Roitberg, A.; Seabra, G.; Wong, K.F.; Paesani, F.; Wu, X.; Brozell, S.; Tsui, V.; Gohlke, H.; P. A.K. Amber, L, 2006.
[26]
Ryckaert, J-P.; Ciccotti, G.; Berendsen, H.J.C. Numerical integration of the cartesian equations of motion of a system with constraints: Molecular dynamics of n-alkanes. J. Comput. Phys., 1977, 23, 327-341.
[http://dx.doi.org/10.1016/0021-9991(77)90098-5]
[27]
Naïm, M.; Bhat, S.; Rankin, K.N.; Dennis, S.; Chowdhury, S.F.; Siddiqi, I.; Drabik, P.; Sulea, T.; Bayly, C.I.; Jakalian, A.; Purisima, E.O. Solvated interaction energy (SIE) for scoring protein-ligand binding affinities. 1. Exploring the parameter space. J. Chem. Inf. Model., 2007, 47(1), 122-133.
[http://dx.doi.org/10.1021/ci600406v] [PMID: 17238257]
[28]
Cui, Q.; Sulea, T.; Schrag, J.D.; Munger, C.; Hung, M.N.; Naïm, M.; Cygler, M.; Purisima, E.O. Molecular dynamics-solvated interaction energy studies of protein-protein interactions: The MP1-p14 scaffolding complex. J. Mol. Biol., 2008, 379(4), 787-802.
[http://dx.doi.org/10.1016/j.jmb.2008.04.035] [PMID: 18479705]
[29]
Wu, K.K.; Huan, Y. Streptozotocin-induced diabetic models in mice and rats. Curr. Protocols Pharmacol., 2008, 40(SUPPL.), 1-14.
[http://dx.doi.org/10.1002/0471141755.ph0547s40]
[30]
Brosius, F. ow-dose streptozotocin induction protocol (mouse) summary: Reagents and materials: Reagent preparation: Protocol. 2003, 4-6.
[31]
Park, M.H.; Ju, J.W.; Park, M.J.; Han, J.S. Daidzein inhibits carbohydrate digestive enzymes in vitro and alleviates postprandial hyperglycemia in diabetic mice. Eur. J. Pharmacol., 2013, 712(1-3), 48-52.
[http://dx.doi.org/10.1016/j.ejphar.2013.04.047] [PMID: 23669248]

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