Critical Assessment of In Vitro Screening of α-Glucosidase Inhibitors from Plants with Acarbose as a Reference Standard

Abstract

Postprandial hyperglycemia is treated with the oral antidiabetic drug acarbose, an intestinal α-glucosidase inhibitor. Side effects of acarbose motivated a growing number of screening studies to identify novel α-glucosidase inhibitors derived from plant extracts and other natural sources. As “gold standard”, acarbose is frequently included as the reference standard to assess the potency of these candidate α-glucosidase inhibitors, with many outperforming acarbose by several orders of magnitude. The results are subsequently used to identify suitable compounds/products with strong potential for in vivo efficacy. However, most α-glucosidase inhibitor screening studies use enzyme preparations obtained from nonmammalian sources (typically Saccharomyces cerevisiae), despite strong evidence that inhibition data obtained using nonmammalian α-glucosidase may hold limited value in terms of identifying α-glucosidase inhibitors with actual in vivo hypoglycemic potential. The aim was to critically discuss the screening of novel α-glucosidase inhibitors from plant sources, emphasizing inconsistencies and pitfalls, specifically where acarbose was included as the reference standard. An assessment of the available literature emphasized the cruciality of stating the biological source of α-glucosidase in such screening studies to allow for unambiguous and rational interpretation of the data. The review also highlights the lack of a universally adopted screening assay for novel α-glucosidase inhibitors and the commercial availability of a standardized preparation of mammalian α-glucosidase.

Key words

α-glucosidase inhibitor - acarbose - antidiabetic - in vitro screening - α-glucosidase inhibition reference standard - mammalian α-glucosidase

Publication History

Received: 26 March 2021

Accepted after revision: 22 July 2021

Article published online:
18 October 2021

• References

• 1 Di Stefano E, Oliviero T, Udenigwe CC. Functional significance and structure-activity relationship of food-derived α-glucosidase inhibitors. Curr Opin Food Sci 2018; 20: 7-12
• 2 Assefa ST, Yang EY, Chae SY, Song M, Lee J, Cho MC, Jang S. Alpha glucosidase inhibitory activities of plants with focus on common vegetables. Plants 2019; 9: 2
• 3 Yin Z, Zhang W, Feng F, Zhang Y, Kang W. α-Glucosidase inhibitors isolated from medicinal plants. Food Sci Hum Wellness 2014; 3: 136174
• 4 Ghani U. Re-exploring promising α-glucosidase inhibitors for potential development into oral antidiabetic drugs: Finding needle in the haystack. Eur J Med Chem 2015; 103: 133-162
• 5 Kumar V, Prakash O, Kumar S, Narwal S. α-glucosidase inhibitors from plants: a natural approach to treat diabetes. Pharmacogn Rev 2011; 5: 19-29
• 6 Xiao J, Kai G, Yamamoto K, Chen X. Advance in dietary polyphenols as α-glucosidases inhibitors: a review on structure-activity relationship aspect. Crit Rev Food Sci Nutr 2013; 53: 818-836
• 7 Proença C, Ribeiro D, Freitas M, Fernandes E. Flavonoids as potential agents in the management of type 2 diabetes through the modulation of α-amylase and α-glucosidase activity: a review. Crit Rev Food Sci Nutr 2021;
• 8 Frommer W, Puls W, Schmidt DD. Herstellung von Saccharase-Inhibitoren. German Patent Application DE2209834B2, 1972: 1-9
• 9 Smith DL, Orlandella RM, Allison DB, Norian LA. Diabetes medications as potential calorie restriction mimetics–a focus on the alpha-glucosidase inhibitor acarbose. GeroScience 2021; 43: 1123-1133
• 10 Tundis R, Loizzo MR, Menichini F. Natural products as α-amylase and α-glucosidase inhibitors and their hypoglycaemic potential in the treatment of diabetes: an update. Mini-Reviews Med Chem 2010; 10: 315-331
• 11 IDF. International Diabetes Federation Facts Sheet. IDF Diabetes Atlas 9th Ed 2019. Accessed June 21, 2021 at: https://www.diabetesatlas.org/en/
• 12 Baynest HW. Classification, pathophysiology, diagnosis and management of diabetes mellitus. J Diabetes Metab 2015; 06: 1000541
• 13 Most J, Tosti V, Redman LM, Fontana L. Calorie restriction in humans: an update. Ageing Res Rev 2017; 39: 36-45
• 14 Dorling JL, Martin CK, Redman LM. Calorie restriction for enhanced longevity: The role of novel dietary strategies in the present obesogenic environment. Ageing Res Rev 2020; 64: 101038
• 15 Pifferi F, Aujard F. Caloric restriction, longevity and aging: recent contributions from human and non-human primate studies. Prog Neuro-Psychopharmacology Biol Psychiatry 2019; 95: 109702
• 16 Mercken EM, Carboneau BA, Krzysik-Walker SM, De Cabo R. Of mice and men: The benefits of caloric restriction, exercise, and mimetics. Ageing Res Rev 2012; 11: 390-398
• 17 Testa G, Biasi F, Poli G, Chiarpotto E. Calorie restriction and dietary restriction mimetics: a strategy for improving healthy aging and longevity. Curr Pharm Des 2014; 20: 2950-2977
• 18 Ingram DK, Roth GS. Calorie restriction mimetics: can you have your cake and eat it, too?. Ageing Res Rev 2015; 20: 46-62
• 19 Harrison DE, Strong R, Allison DB, Ames BN, Astle CM, Atamna H, Fernandez E, Flurkey K, Javors MA, Nadon NL, Nelson JF, Pletcher S, Simpkins JW, Smith D, Wilkinson JE, Miller RA. Acarbose, 17-α-estradiol, and nordihydroguaiaretic acid extend mouse lifespan preferentially in males. Aging Cell 2014; 13: 273-282
• 20 Farag YMK, Gaballa MR. Diabesity: an overview of a rising epidemic. Nephrol Dial Transplant 2011; 26: 28-35
• 21 Van de Laar FA, Lucassen PL, Akkermans RP, Van de Lisdonk EH, Rutten GE, Van Weel C. α-Glucosidase inhibitors for patients with type 2 diabetes. Diabetes Care 2005; 28: 166-175
• 22 Tucci SA, Boyland EJ, Halford JC. The role of lipid and carbohydrate digestive enzyme inhibitors in the management of obesity: a review of current and emerging therapeutic agents. Diabetes Metab Syndr Obes Targets Ther 2010; 3: 125-143
• 23 Ingram DK, Roth GS. Glycolytic inhibition: an effective strategy for developing calorie restriction mimetics. GeroScience 2021; 43: 1159-1169
• 24 Bailey C. The current drug treatment landscape for diabetes and perspectives for the future. Clin Pharmacol Ther 2015; 98: 170-184
• 25 Shintani H, Shintani T, Ashida H, Sato M. Calorie restriction mimetics: upstream-type compounds for modulating glucose metabolism. Nutrients 2018; 10: 1-17
• 26 Bischoff H. Pharmacology of α-glucosidase inhibition. Eur J Clin Invest 1994; 24: 3-10
• 27 Truscheit E, Frommer W, Junge B, Müller L, Schmidt DD, Wingender W. Chemistry and biochemistry of microbial α‐glucosidase inhibitors. Angew Chemie Int Ed English 1981; 20: 744-761
• 28 Hakamata W, Kurihara M, Okuda H, Nishio T, Oku T. Design and screening strategies for α-glucosidase inhibitors based on enzymological information. Curr Top Med Chem 2009; 9: 3-12
• 29 Hirsh AJ, Yao SYM, Young JD, Cheeseman CI. Inhibition of glucose absorption in the rat jejunum: A novel action of α-D-glucosidase inhibitors. Gastroenterology 1997; 113: 205-211
• 30 DiNicolantonio JJ, Bhutani J, OʼKeefe JH. Acarbose: safe and effective for lowering postprandial hyperglycaemia and improving cardiovascular outcomes. Open Heart 2015; 2: e000327
• 31 Derosa G, Maffioli P. α-Glucosidase inhibitors and their use in clinical practice. Arch Med Sci 2012; 8: 899-906
• 32 Jenkins DJA, Taylor RH, Nineham R, Goff DV, Bloom SR, Sarson D, George K, Alberti MM. Combined use of guar and acarbose in reduction of postprandial glycaemia. Lancet 1979; 314: 924-927
• 33 Thorburn AW, Brand JC, Truswell AS. Slowly digested and absorbed carbohydrate in traditional bushfoods: A protective factor against diabetes?. Am J Clin Nutr 1987; 45: 98-106
• 34 Treem WR. Congenital sucrase-isomaltase deficiency. J Pediatr Gastroenterol Nutr 1995; 121: 1-14
• 35 Vesa TH, Korpela R, Marteau P. Lactose intolerance. J Am Coll Nutr 2000; 19: 165S-175S
• 36 Kumar RV, Sinha VR. Newer insights into the drug delivery approaches of α-glucosidase inhibitors. Expert Opin Drug Deliv 2012; 9: 403-416
• 37 Prabhakar PK, Kumar A, Doble M. Combination therapy: a new strategy to manage diabetes and its complications. Phytomedicine 2014; 21: 123-130
• 38 Fischer S, Hanefeld M, Spengler M, Boehme K, Temelkova-Kurktschiev T. European study on dose-response relationship of acarbose as a first-line drug in non-insulin-dependent diabetes mellitus: efficacy and safety of low and high doses. Acta Diabetol 1998; 35: 34-40
• 39 Rosak C, Mertes G. Critical evaluation of the role of acarbose in the treatment of diabetes: Patient considerations. Diabetes. Metab Syndr Obes Targets Ther 2012; 5: 357-367
• 40 OʼDea K, Turton J. Optimum effectiveness of intestinal α-glucosidase inhibitors: importance of uniform distribution through a meal. Am J Clin Nutr 1985; 41: 511-516
• 41 Toeller M. Nutritional recommendations for diabetic patients and treatment with α-glucosidase inhibitors. Drugs 1992; 44: 13-20
• 42 Puls W, Keup U, Krause HP, Thomas G, Hoffmeister F. Glucosidase inhibition–a new approach to the treatment of diabetes, obesity, and hyperlipoproteinaemia. Naturwissenschaften 1977; 64: 536-537
• 43 Dodane V, Chevalier J, Ripochel P. Na+/D-glucose cotransport and sucrase activity in intestinal brush border membranes of Zucker rats. Effects of chronic acarbose treatment. Nutr Res 1991; 11: 783-796
• 44 Kim MJ, Lee SB, Lee HS, Lee SY, Baek JS, Kim D, Moon TW, Robyt JF, Park KH. Comparative study of the inhibition of α-glucosidase, α-amylase, and cyclomaltodextrin glucanosyltransferase by acarbose, isoacarbose, and acarviosine-glucose. Arch Biochem Biophys 1999; 371: 277-283
• 45 Halliwell B. Antioxidants in human health and disease. Annu Rev Nutr 1996; 16: 33-50
• 46 Pietta PG. Flavonoids as antioxidants. J Nat Prod 2000; 63: 1035-1042
• 47 Ávila-Gálvez MÁ, González-Sarrías A, Espín JC. In vitro research on dietary polyphenols and health: a call of caution and a guide on how to proceed. J Agric Food Chem 2018; 66: 7857-7858
• 48 Hasan M, Uddin Q, Zaiton S, Soad M, Sarwar T. Animal models and natural products to investigate in vivo and in vitro antidiabetic activity. Biomed Pharmacother 2018; 101: 833-841
• 49 Chiba S. Molecular mechanism in α-glucosidase and glucoamylase. Biosci Biotechnol Biochem 1997; 61: 1233-1239
• 50 Jiang J, Kuo CL, Wu L, Franke C, Kallemeijn WW, Florea BI, Van Meel E, Van der Marel GA, Codée JDC, Boot RG, Davies GJ, Overkleeft HS, Aerts JMFG. Detection of active mammalian GH31 α-glucosidases in health and disease using in-class, broad-spectrum activity-based probes. ACS Cent Sci 2016; 2: 351-358
• 51 Saeki T, Okuyama M, Mori H, Kimura A, Chiba S. Localization of α-glucosidase in yeast cells. J Appl Glycosci 1998; 45: 281-283
• 52 Santos CMM, Freitas M, Fernandes E. A comprehensive review on xanthone derivatives as α-glucosidase inhibitors. Eur J Med Chem 2018; 157: 1460-1479
• 53 Acker MG, Auld DS. Considerations for the design and reporting of enzyme assays in high-throughput screening applications. Perspect Sci 2014; 1: 56-73
• 54 Kamiyama O, Sanae F, Ikeda K, Higashi Y, Minami Y, Asano N. In vitro inhibition of α-glucosidases and glycogen phosphorylase by catechin gallates in green tea. Food Chem 2010; 122: 1061-1066
• 55 Hogan S, Zhang L, Li J, Sun S, Canning C, Zhou K. Antioxidant rich grape pomace extract suppresses postprandial hyperglycemia in diabetic mice by specifically inhibiting alpha-glucosidase. Nutr Metab 2010; 7: 1-9
• 56 Everette JD, Walker RB, Islam S. Inhibitory activity of naturally occurring compounds towards rat intestinal α-glucosidase using p-nitrophenyl-α-D-glucopyranoside (PNP-G) as a substrate. Am J Food Technol 2013; 8: 65-73
• 57 Zhang AJ, Rimando AM, Mizuno CS, Mathews ST. α-Glucosidase inhibitory effect of resveratrol and piceatannol. J Nutr Biochem 2017; 47: 86-93
• 58 Shai LJ, Magano SR, Lebelo SL, Mogale AM. Inhibitory effects of five medicinal plants on rat alpha-glucosidase: comparison with their effects on yeast alpha-glucosidase. J Med Plants Res 2011; 5: 2863-2867
• 59 Olomola TO, Mphahlele MJ, Gildenhuys S. Benzofuran-selenadiazole hybrids as novel α-glucosidase and cyclooxygenase-2 inhibitors with antioxidant and cytotoxic properties. Bioorg Chem 2020; 100: 103945
• 60 Brayer GD, Luo Y, Withers SG. The structure of human pancreatic α‐amylase at 1.8 Å resolution and comparisons with related enzymes. Protein Sci 1995; 4: 1730-1742
• 61 Shinde J, Taldone T, Barletta M, Kunaparaju N, Hu B, Kumar S, Placido J, Zito SW. α-Glucosidase inhibitory activity of Syzygium cumini (Linn.) Skeels seed kernel in vitro and in Goto-Kakizaki (GK) rats. Carbohydr Res 2008; 343: 1278-1281
• 62 Kim YM, Wang MH, Rhee HI. A novel α-glucosidase inhibitor from pine bark. Carbohydr Res 2004; 339: 715-717
• 63 Nguyen VB, Nguyen AD, Kuo YH, Wang SL. Biosynthesis of α-glucosidase inhibitors by a newly isolated bacterium, Paenibacillus sp. TKU042 and its effect on reducing plasma glucose in a mouse model. Int J Mol Sci 2017; 18: 700
• 64 Choo CY, Sulong NY, Man F, Wong TW. Vitexin and isovitexin from the leaves of Ficus deltoidea with in-vivo α-glucosidase inhibition. J Ethnopharmacol 2012; 142: 776-781
• 65 Jenkins DJ, Taylor RH, Goff DV, Fielden H, Misiewicz JJ, Sarson DL, Bloom SR, Alberti KG. Scope and specificity of acarbose in slowing carbohydrate absorption in man. Diabetes 1981; 30: 951-954
• 66 Ren L, Qin X, Cao X, Wang L, Bai F, Bai G, Shen Y. Structural insight into substrate specificity of human intestinal maltase-glucoamylase. Protein Cell 2011; 2: 827-836
• 67 Schmidt DD, Frommer W, Junge B, Müller L, Wingender W, Truscheit E, Schäfer D. α-Glucosidase inhibitors–new complex oligosaccharides of microbial origin. Naturwissenschaften 1977; 64: 535-536
• 68 Son H, Lee S. Comparison of α-glucosidase inhibition by Cudrania tricuspidata according to harvesting time. Biomed Reports 2013; 1: 624-628
• 69 Ibrahim MA, Bester MJ, Neitz AW, Gaspar ARM. Rational in silico design of novel α-glucosidase inhibitory peptides and in vitro evaluation of promising candidates. Biomed Pharmacother 2018; 107: 234-242
• 70 Proença C, Freitas M, Ribeiro D, Oliveira EFT, Sousa JLC, Tomé SM, Ramos MJ, Silva AMS, Fernandes PA, Fernandes E. α-Glucosidase inhibition by flavonoids: an in vitro and in silico structure-activity relationship study. J Enzyme Inhib Med Chem 2017; 32: 1216-1228
• 71 Tipton KF, Armstrong RN, Bakker BM, Bairoch A, Cornish-Bowden A, Halling PJ, Hofmeyr J, Leyh TS, Kettner C, Raushel FM, Rohwer J, Schomburg D, Steinbeck C. Standards for reporting enzyme data: The STRENDA Consortium: what it aims to do and why it should be helpful. Perspect Sci 2014; 1: 131-137
• 72 Jones K, Sim L, Mohan S, Kumarasamy J, Liu H, Avery S, Naim HY, Quezada-Calvillo R, Nichols BL, Pinto BM, Rose DR. Mapping the intestinal alpha-glucogenic enzyme specificities of starch digesting maltase-glucoamylase and sucrase-isomaltase. Bioorganic Med Chem 2011; 19: 3929-3934
• 73 Ramsey RR, Tipton KF. Assessment of enzyme inhibition: a review with examples from the development of monoamine oxidase and cholinesterase inhibitory drugs. Molecules 2017; 22: 1192
• 74 Jhong CH, Riyaphan J, Lin SH, Chia YC, Weng CF. Screening alpha-glucosidase and alpha-amylase inhibitors from natural compounds by molecular docking in silico . Biofactors 2015; 41: 242-251
• 75 Shah MA, Khalil R, Ul-Haq Z, Panichayupakaranant P. α-Glucosidase inhibitory effect of rhinacanthins-rich extract from Rhinacanthus nasutus leaf and synergistic effect in combination with acarbose. J Funct Foods 2017; 36: 325-331
• 76 Senthil SL, Chandrasekaran R, Arjun HA, Anantharaman P. In vitro and in silico inhibition properties of fucoidan against α-amylase and α-D-glucosidase with relevance to type 2 diabetes mellitus. Carbohydr Polym 2019; 209: 350-355
• 77 Hyun TK, Eom SH, Kim JS. Molecular docking studies for discovery of plant-derived α-glucosidase inhibitors. Plant Omics 2014; 7: 166-170
• 78 Mohammadi-Khanaposhtani M, Rezaei S, Khalifeh R, Imanparast S, Faramarzi MA, Bahadorikhalili S, Safavi M, Bandarian F, Nasli Esfahani E, Mahdavi M, Larijani B. Design, synthesis, docking study, α-glucosidase inhibition, and cytotoxic activities of acridine linked to thioacetamides as novel agents in treatment of type 2 diabetes. Bioorg Chem 2018; 80: 288-295
• 79 Han L, Fang C, Zhu R, Peng Q, Li D, Wang M. Inhibitory effect of phloretin on α-glucosidase: Kinetics, interaction mechanism and molecular docking. Int J Biol Macromol 2017; 95: 520-527
• 80 Renda G, Sari S, Barut B, Šoral M, Liptaj T, Özel A, Erik İ, Didem Ş. α-Glucosidase inhibitory effects of polyphenols from Geranium asphodeloides: Inhibition kinetics and mechanistic insights through in vitro and in silico studies. Bioorg Chem 2018; 81: 542-552
• 81 Sim L, Quezada-Calvillo R, Sterchi EE, Nichols BL, Rose DR. Human intestinal maltase-glucoamylase: crystal structure of the N-terminal catalytic subunit and basis of inhibition and substrate specificity. J Mol Biol 2008; 375: 782-792
• 82 Elferink H, Bruekers JPJ, Veeneman GH, Boltje TJ. A comprehensive overview of substrate specificity of glycoside hydrolases and transporters in the small intestine. Cell Mol Life Sci 2020; 77: 4799-4826
• 83 Lee BH, Eskandari R, Jones K, Reddy KR, Quezada-Calvillo R, Nichols BL, Rose DR, Hamaker BR, Pinto BM. Modulation of starch digestion for slow glucose release through “toggling” of activities of mucosal α-glucosidases. J Biol Chem 2012; 287: 31929-31938
• 84 Krause HP, Keup U, Puls W. Inhibition of disaccharide digestion in rat intestine by the α-glucosidase inhibitor acarbose (BAY g 5421). Digestion 1982; 23: 232-238
• 85 Lim J, Kim DK, Shin H, Hamaker BR, Lee BH. Different inhibition properties of catechins on the individual subunits of mucosal α-glucosidases as measured by partially-purified rat intestinal extract. Food Funct 2019; 10: 4407-4413
• 86 Matsui T, Yoshimoto C, Osajima K, Oki T, Osajima Y. In vitro survey of α-glucosidase inhibitory food components. Biosci Biotechnol Biochem 1996; 60: 2019-2022
• 87 Oki T, Matsui T, Osajima Y. Inhibitory effect of α-glucosidase inhibitors varies according to its origin. J Agric Food Chem 1999; 47: 550-553
• 88 Kumar TV, Lakshmanasenthil S, Geetharamani D, Marudhupandi T, Suja G, Suganya P. Fucoidan–a α-D-glucosidase inhibitor from Sargassum wightii with relevance to type 2 diabetes mellitus therapy. Int J Biol Macromol 2015; 72: 1044-1047
• 89 Kim JS, Kwon CS, Son KH. Inhibition of alpha-glucosidase and amylase by luteolin, a flavonoid. Biosci Biotechnol Biochem 2000; 64: 2458-2461
• 90 Choi CW, Choi YH, Cha MR, Yoo DS, Kim YS, Yon GH, Hong KS, Kim YH, Ryu SY. Yeast α-glucosidase inhibition by isoflavones from plants of Leguminosae as an in vitro alternative to acarbose. J Agric Food Chem 2010; 58: 9988-9993
• 91 Hu X, Li S, Wang L, Zhu D, Wang Y, Li Y. Anti-diabetic activities of aqueous extract from Actinidia kolomikta root against α-glucosidase. J Pharmacogn Phytochem 2013; 2: 53-57
• 92 Suresh Babu K, Tiwari AK, Srinivas PV, Ali AZ, Raju BC, Rao JM. Yeast and mammalian α-glucosidase inhibitory constituents from Himalayan rhubarb Rheum emodi Wall.ex Meisson. Bioorganic Med Chem Lett 2004; 14: 3841-3845
• 93 Gowri PM, Tiwari AK, Ali AZ, Rao JM. Inhibition of α-glucosidase and amylase by bartogenic acid isolated from Barringtonia racemosa Roxb. seeds. Phytother Res 2007; 21: 796-799
• 94 Nyambe-Silavwe H, Williamson G. Chlorogenic and phenolic acids are only very weak inhibitors of human salivary α-amylase and rat intestinal maltase activities. Food Res Int 2018; 113: 452-455
• 95 Kim YM, Jeong YK, Wang MH, Lee WY, Rhee HI. Inhibitory effect of pine extract on α-glucosidase activity and postprandial hyperglycemia. Nutrition 2005; 21: 756-761
• 96 Matsui T, Tanaka T, Tamura S, Toshima A, Tamaya K, Miyata Y, Tanaka K, Matsumoto K. α-glucosidase inhibitory profile of catechins and theaflavins. J Agric Food Chem 2007; 55: 99-105
• 97 Visvanathan R, Houghton MJ, Williamson G. Maltoheptaoside hydrolysis with chromatographic detection and starch hydrolysis with reducing sugar analysis: Comparison of assays allows assessment of the roles of direct α-amylase inhibition and starch complexation. Food Chem 2021; 343: 128423
• 98 Hwang IG, Kim HY, Woo KS, Hong JT, Hwang BY, Jung JK, Lee J, Jeong HS. Isolation and characterisation of an α-glucosidase inhibitory substance from fructose-tyrosine Maillard reaction products. Food Chem 2011; 127: 122-126
• 99 Ryu HW, Jeong SH, Curtis-Long MJ, Jung S, Lee JW, Woo HS, Cho JK, Park KH. Inhibition effects of mangosenone F from Garcinia mangostana on melanin formation in B16F10 cells. J Agric Food Chem 2012; 60: 8372-8378
• 100 Bosman SC, De Beer D, Beelders T, Willenburg EL, Malherbe CJ, Walczak B, Joubert E. Simultaneous optimisation of extraction of xanthone and benzophenone α-glucosidase inhibitors from Cyclopia genistoides and identification of superior genotypes for propagation. J Funct Foods 2017; 33: 21-31
• 101 Miller N, Malherbe CJ, Joubert E. In vitro α-glucosidase inhibition by honeybush (Cyclopia genistoides) food ingredient extract–potential for dose reduction of acarbose through synergism. Food Funct 2020; 11: 6476-6486
• 102 Lin M, Qirong L, Dandan L, Shan L, Xiaomei W, Yuanyuan Z. Alpha-glucosidase inhibitory activities of essential oils extracted from three Chinese herbal medicines. Chem Eng Trans 2018; 64: 61-66
• 103 Oki T, Matsui T, Matsumoto K. Evaluation of α-glucosidase inhibition by using an immobilized assay system. Biol Pharm Bull 2000; 23: 1084-1087
• 104 Kawada Y, Miura M, Gomyo T. Inhibitory effect of vegetables, fruits and herbs on α-glucosidase in an immobilized enzyme assay system. Food Sci Technol Res 2006; 12: 275-277
• 105 Govindaraju K, Suganya KSU. In vitro antidiabetic assessment of guavanoic acid functionalized gold nanoparticles in regulating glucose transport using L6 rat skeletal muscle cells. RSC Med Chem 2020; 11: 814-822
• 106 Burton-Freeman BM, Sandhu AK, Edirisinghe I. Mangos and their bioactive components: adding variety to the fruit plate for health. Food Funct 2017; 8: 3010-3032
• 107 Sellamuthu PS, Arulselvan P, Kamalraj S, Fakurazi S, Kandasamy M. Protective nature of mangiferin on oxidative stress and antioxidant status in tissues of streptozotocin-induced diabetic rats. ISRN Pharmacol 2013; 2013: 1-10
• 108 Sathialingam M, Saidian M, Zhang S, Flores A, Alexander M, Lakey JR. Evaluation of Cycloferin supplement on health parameters in experimentally induced diabetic rats with and without exogenous insulin. J Diet Suppl 2019; 16: 454-462
• 109 Phoboo S, Pinto MDS, Barbosa ACL, Sarkar D, Bhowmik PC, Jha PK, Shetty K. Phenolic-linked biochemical rationale for the antidiabetic properties of Swertia chirayita (Roxb. ex Flem.) Karst. Phytother Res 2013; 27: 227-235
• 110 Gu C, Yang M, Zhou Z, Khan A, Cao J, Cheng G. Purification and characterization of four benzophenone derivatives from Mangifera indica L. leaves and their antioxidant, immunosuppressive and α-glucosidase inhibitory activities. J Funct Foods 2019; 52: 709-714
• 111 Shi Z, Liu Y, Yuan Y, Song D, Qi M, Yang XJ, Wang P, Li X, Shang J, Yang Z. In vitro and in vivo effects of norathyriol and mangiferin on α-glucosidase. Biochem Res Int 2017; 2017: 1-7
• 112 Sekar V, Chakraborty S, Mani S, Sali VK, Vasanthi HR. Mangiferin from Mangifera indica fruits reduces postprandial glucose level by inhibiting α-glucosidase and α-amylase activity. South African J Bot 2019; 120: 129-134
• 113 Dineshkumar B, Mitra A, Manjunatha M. Studies on the antidiabetic and hypolipidemic potentials of mangiferin (xanthone glucoside) in streptozotocin-induced type 1 and type 2 diabetic model rats. Int J Adv Pharm Sci 2010; 1: 75-85
• 114 Wan LS, Min QX, Wang YL, Yue YD, Chen JC. Xanthone glycoside constituents of Swertia kouitchensis with α-glucosidase inhibitory activity. J Nat Prod 2013; 76: 1248-1253
• 115 Kulkarni VM, Rathod VK. Exploring the potential of Mangifera indica leaves extract versus mangiferin for therapeutic application. Agric Nat Resour 2018; 52: 155-161
• 116 Bosman SC, De Beer D, Beelders T, Willenburg EL, Malherbe CJ, Walczak B, Joubert E. Simultaneous optimisation of extraction of xanthone and benzophenone α-glucosidase inhibitors from Cyclopia genistoides and identification of superior genotypes for propagation. J Funct Foods 2017; 33: 21-31
• 117 Feng J, Yang X, Wang R. Bio-assay guided isolation and identification of alpha-glucosidase inhibitors from the leaves of Aquilaria sinensis . Phytochemistry 2011; 72: 242-247
• 118 Nian S, Li H, Liu E, Li P. Comparison of α-glucosidase inhibitory effect and bioactive constituents of Anemarrhenae Rhizoma and fibrous roots. J Pharm Biomed Anal 2017; 145: 195-202
• 119 Li Y, Peng G, Li Q, Wen S, Huang TH, Roufogalis BD, Yamahara J. Salacia oblonga improves cardiac fibrosis and inhibits postprandial hyperglycemia in obese Zucker rats. Life Sci 2004; 75: 1735-1746
• 120 Vo THT, Nguyen TD, Nguyen QH, Ushakova NA. Extraction of mangiferin from the leaves of the mango tree Mangifera indica and evaluation of its biological activity in terms of blockade of α-glucosidase. Pharm Chem J 2017; 51: 806-810
• 121 Prashanth D, Amit A, Samiulla DS, Asha MK, Padmaja R. α-Glucosidase inhibitory activity of Mangifera indica bark. Fitoterapia 2001; 72: 686-688
• 122 Zhang H, Zhong J, Zhang Q, Qing D, Yan C. Structural elucidation and bioactivities of a novel arabinogalactan from Coreopsis tinctoria . Carbohydr Polym 2019; 219: 219-228
• 123 Mathivha LP, Thibane VS, Mudau FN. Antidiabetic and anti-proliferative activities of herbal teas, Athrixia phylicoides DC and Monsonia burkeana Planch. ex Harv, indigenous to South Africa. Br Food J 2019; 121: 964-974
• 124 Sathya A, Siddhuraju P. Role of phenolics as antioxidants, biomolecule protectors and as antidiabetic factors–evaluation on bark and empty pods of Acacia auriculiformis . Asian Pac J Trop Med 2012; 5: 757-765
• 125 Dehghan H, Sarrafi Y, Salehi P. Antioxidant and antidiabetic activities of 11 herbal plants from Hyrcania region, Iran. J Food Drug Anal 2016; 24: 179-188
• 126 Johnson MH, Lucius A, Meyer T, De Mejia EG. Cultivar evaluation and effect of fermentation on antioxidant capacity and in vitro inhibition of α-amylase and α-glucosidase by highbush blueberry (Vaccinium corombosum). J Agric Food Chem 2011; 59: 8923-8930
• 127 Chen S, Liu Y, Liu Z, Cai R, Lu Y, Huang X, She Z. Isocoumarins and benzofurans from the mangrove endophytic fungus Talaromyces amestolkiae possess α-glucosidase inhibitory and antibacterial activities. RSC Adv 2016; 6: 26412-26420
• 128 Lavelli V, Sri Harsha PSC, Ferranti P, Scarafoni A, Iametti S. Grape skin phenolics as inhibitors of mammalian α-glucosidase and α-amylase–effect of food matrix and processing on efficacy. Food Funct 2016; 7: 1655-1663
• 129 Alvarado-Díaz CS, Gutiérrez-Méndez N, Mendoza-López ML, Rodríguez-Rodríguez MZ, Quintero-Ramos A, Landeros-Martínez LL, Rodríguez-Valdez LM, Rodríguez-Figueroa JC, Pérez-Vega S, Salmeron-Ochoa I, Leal-Ramos MY. Inhibitory effect of saccharides and phenolic compounds from maize silks on intestinal α-glucosidases. J Food Biochem 2019; 43: e12896
• 130 Rodrigues MJ, Custódio L, Lopes A, Oliveira M, Neng NR, Nogueira JMF, Martins A, Rauter AP, Varela J, Barreira L. Unlocking the in vitro anti-inflammatory and antidiabetic potential of Polygonum maritimum . Pharm Biol 2017; 55: 1348-1357
• 131 Ali RB, Atangwho IJ, Kuar N, Ahmad M, Mahmud R, Asmawi MZ. In vitro and in vivo effects of standardized extract and fractions of Phaleria macrocarpa fruits pericarp on lead carbohydrate digesting enzymes. BMC Complement Altern Med 2013; 13: 39
• 132 Mushtaq A, Ali S, Nawaz Tahir M, Ismail H, Mirza B, Saadiq M, Abdul Haleem M, Iqbal M. New bioactive heteroleptic copper(II) carboxylates: Structure, enzymatic and DNA-binding studies. Acta Chim Slov 2017; 64: 397-408
• 133 Hidaka H, Takaya T, Marshall JJ. Studies on amylase inhibitor, BAYe 4609 and BAYg 5421 from Actinoplanes sp. J Japanese Soc Starch Sci 1980; 27: 114-119
• 134 Junge B, Heiker FR, Kurz J, Müller L, Schmidt DD, Wünsche C. Untersuchungen zur Struktur des α-D-Glucosidaseinhibitors Acarbose. Carbohydr Res 1984; 128: 235-268
• 135 Zhang J, Zhao S, Yin P, Yan L, Han J, Shi L, Zhou X, Liu Y, Ma C. α-Glucosidase inhibitory activity of polyphenols from the burs of Castanea mollissima Blume. Molecules 2014; 19: 8373-8386
• 136 Elya B, Basah K, Munʼim A, Yuliastuti W, Bangun A, Septiana EK. Screening of α-glucosidase inhibitory activity from some plants of Apocynaceae, Clusiaceae, Euphorbiaceae, and Rubiaceae. J Biomed Biotechnol 2012; 2012: 1-6
• 137 Thengyai S, Thiantongin P, Sontimuang C, Ovatlarnporn C, Puttarak P. α-Glucosidase and α-amylase inhibitory activities of medicinal plants in Thai antidiabetic recipes and bioactive compounds from Vitex glabrata R. Br. stem bark. J Herb Med 2020; 19: 100302
• 138 Su CH, Lai MN, Ng LT. Inhibitory effects of medicinal mushrooms on α-amylase and α-glucosidase – enzymes related to hyperglycemia. Food Funct 2013; 4: 644-649
• 139 Zhang Z, Kong F, Ni H, Wan J, Hua D, Yan C. Structural characterization, α-glucosidase inhibitory and DPPH· scavenging activities of polysaccharides from guava. Carbohydr Polym 2016; 144: 106-114
• 140 Ni M, Hu X, Gong D, Zhang G. Inhibitory mechanism of vitexin on α-glucosidase and its synergy with acarbose. Food Hydrocoll 2020; 105: 105824
• 141 Cuevas-Juárez E, Yuriar-Arredondo KY. Antioxidant and α-glucosidase inhibitory properties of soluble melanins from the fruits of Vitex mollis Kunth, Randia echinocarpa Sessé et Mociño and Crescentia alata Kunth. J Funct Foods 2014; 9: 78-88
• 142 Figueiredo-González M, Reboredo-Rodríguez P, González-Barreiro C, Carrasco-Pancorbo A, Cancho-Grande B, Simal-Gandara J. The involvement of phenolic-rich extracts from Galician autochthonous extra-virgin olive oils against the α-glucosidase and α-amylase inhibition. Food Res Int 2019; 116: 447-454
• 143 Zhang L, Tu Z, Xie X, Lu Y, Wang Z, Wang H, Sha X. Antihyperglycemic, antioxidant activities of two Acer palmatum cultivars, and identification of phenolics profile by UPLC-QTOF-MS/MS: New natural sources of functional constituents. Ind Crops Prod 2016; 89: 522-532
• 144 Blaskiewicz R. The Big Pharma conspiracy theory. Med Writ 2013; 22: 259-261
• 145 Figueiredo-González M, Grosso C, Valentão P, Andrade PB. α-Glucosidase and α-amylase inhibitors from Myrcia spp.: a stronger alternative to acarbose?. J Pharm Biomed Anal 2016; 118: 322-327
• 146 Zhang X, Li G, Wu D, Yu Y, Hu N, Wang H, Li X, Wu Y. Emerging strategies for the activity assay and inhibitor screening of alpha-glucosidase. Food Funct 2020; 11: 66-82
• 147 Mahajan PM, Desai KM, Lele SS. Production of cell membrane-bound α- and β-glucosidase by Lactobacillus acidophilus . Food Bioprocess Technol 2012; 5: 706-718
• 148 Matsui T, Kobayashi M, Hayashida S. Luteolin, a flavone, does not suppress postprandial glucose absorption through an inhibition of α-glucosidase action. Biosci Biotechnol Biochem 2002; 66: 689-692
• 149 Matsui T, Ueda T, Oki T, Sugita K, Terahara N, Matsumoto K. α-glucosidase inhibitory action of natural acylated anthocyanins. 1. Survey of natural pigments with potent inhibitory activity. J Agric Food Chem 2001; 49: 1948-1951
• 150 Ogunwande IA, Matsui T, Fujise T, Matsumoto K. α-Glucosidase inhibitory profile of Nigerian medicinal plants in immobilized assay system. Food Sci Technol Res 2007; 13: 169-172
• 151 Matsui T, Shimada M, Saito N, Matsumoto K. α-Glucosidase inhibition assay in an enzyme-immobilized amino-microplate. Anal Sci 2009; 25: 559-562
• 152 Cogoli A, Mosimann H, Vock C, Von Balthazar AK, Semenza G. A simplified procedure for the isolation of the sucrase-isomaltase complex from rabbit intestine – its amino‐acid and sugar composition. Eur J Biochem 1972; 30: 7-14
• 153 Demirci S, Sahiner M, Yilmaz S, Karadag E, Sahiner N. Enhanced enzymatic activity and stability by in situ entrapment of α-Glucosidase within super porous p(HEMA) cryogels during synthesis. Biotechnol Reports 2020; 28: e00534
• 154 Cai Y, Wu L, Lin X, Hu X, Wang L. Phenolic profiles and screening of potential α-glucosidase inhibitors from Polygonum aviculare L. leaves using ultra-filtration combined with HPLC-ESI-qTOF-MS/MS and molecular docking analysis. Ind Crops Prod 2020; 154: 112673
• 155 Wang L, Liu Y, Luo Y, Huang K, Wu Z. Quickly screening for potential α-glucosidase inhibitors from guava leaves tea by bioaffinity ultrafiltration coupled with HPLC-ESI-TOF/MS method. J Agric Food Chem 2018; 66: 1576-1582
• 156 Ning Z, Zhai L, Huang T, Peng J, Hu D, Xiao H, Wen B, Lin C, Zhao L, Bian Z. Identification of α-glucosidase inhibitors from Cyclocarya paliurus tea leaves using UF-UPLC-Q/TOF-MS/MS and molecular docking. Food Funct 2019; 10: 1893-1902
• 157 Li C, Zi Y, Xu D, Jiang D, Qu F, Zhao X. A fluorescence strategy for monitoring α-glucosidase activity and screening its inhibitors from Chinese herbal medicines based on Cu nanoclusters with aggregation-induced emission. Anal Bioanal Chem 2021; 413: 2553-2563
• 158 Lankatillake C, Luo S, Flavel M, Lenon GB, Gill H, Huynh T, Dias DA. Screening natural product extracts for potential enzyme inhibitors: protocols, and the standardisation of the usage of blanks in α-amylase, α-glucosidase and lipase assays. Plant Methods 2021; 17: 1-19
• 159 Liu DM, Dong C, Ma RT. A colorimetric method for screening α-glucosidase inhibitors from flavonoids using 3,3′,5,5′-tetramethylbenzidine as a chromogenic probe. Colloids Surfaces B Biointerfaces 2021; 197: 111400
• 160 Zhang BW, Li X, Sun WL, Xing Y, Xiu ZL, Zhuang CL, Dong YS. Dietary flavonoids and acarbose synergistically inhibit α-glucosidase and lower postprandial blood glucose. J Agric Food Chem 2017; 65: 8319-8330
• 161 Ishikawa F, Jinno K, Kinouchi E, Ninomiya K, Marumoto S, Xie W, Muraoka O, Morikawa T, Tanabe G. Diastereoselective synthesis of salacinol-type α-glucosidase inhibitors. J Org Chem 2018; 83: 185-193