Potent Natural Inhibitors of Alpha-Glucosidase and the Application of Aspergillus spp. in Diabetes type 2 Drugs: a Review
Authors: Hong Son Bui , Van Nga Vu , Thi Diem Hong Le , Thi Quynh Do 
Published: July 2022

Diabetes Mellitus has been becoming a disease of the century, and disease incidence is still rising worldwide. It causes many serious complications, especially in the eye, heart, kidneys, brain, and vascular system, such as diabetic nephropathy, diabetic retinopathy, liver fa­ilure, etc. Moreover, the process of controlling this disease is complicated. Meanwhile, the antidiabetic drugs on the market are facing some problems with a wide range of adverse reactions. Therefore, finding new drugs to treat diabetes has always been a topic that many researchers are interested in, especially drugs derived from nature like microorganisms and medicinal plants. This review is to provide knowledge concerning the effects of α-glucosidase inhibitors, which are oral antidiabetic drugs commonly used for diabetes mellitus type 2. Besides, we show readers the variety of active ingredients originating from nature, particularly the secondary metabolites of Aspergillus spp., which have many applications in the chemical and medicinal industry.

Keywords:

Diabetes, α-glucosidase inhibitors, Aspergillus.

References

[1] W. H. Organization, Classification of Diabetes Mellitus, https://www.who.int/westernpacific/health-topics/diabetes (accessed on: May 11th, 2021).[2] J. Thrasher, Pharmacologic Management of Type 2 Diabetes Mellitus: Available Therapies, Am J Cardiol, Vol. 120, No. 1, 2017, pp. S4-S16, https://doi.org/10.1016/j.amjcard.2017.05.009.[3] W. Hakamata, M. Kurihara, H. Okuda, T. Nishio, T. Oku, Design and Screening Strategies for Alpha-glucosidase Inhibitors Based on Enzymological Information, Curr Top Med Chem, Vol. 9, No. 1, 2009, pp. 3-12, https://doi.org/10.2174/156802609787354306.[4] US, Patent Version Number: US4062950A, Amino Sugar Derivatives, https://patents.google.com/patent/US4062950A/en(accessed on: May 11th, 2021).[5] A. S. Dabhi, N. R. Bhatt, M. J. Shah, Voglibose: an Alpha- glucosidase Inhibitor, J Clin Diagn Res, Vol. 7, No. 12, 2013, pp. 3023-3027, https://doi.org/10.7860/JCDR/2013/6373.3838.[6] P. Durruty, M. Sanzana, L. Sanhueza, Pathogenesis of Type 2 Diabetes Mellitus, Type 2 Diabetes - from Pathophysiology to Modern Management, Intechopen, United Kingdom, 2019, pp. 1-18.[7] L. N. Khue, T. H. Dang, T. H. Quang, N. T. Khue et al., Guidelines for Diagnosis and Treatment of Diabetes Type 2, Ministry of Health, Vietnam, 2021 (in Vietnamese).[8] M. Okuyama, W. Saburi, H. Mori, A. Kimura, Alpha-Glucosidases and Alpha-1,4-Glucan Lyases: Structures, Functions, and Physiological Actions, Cell Mol Life Sci, Vol. 73, 2016, pp. 2727-2751, https://doi.org/10.1007/s00018-016-2247-5.[9] V. L. Yip, S. G. Withers, Nature's Many Mechanisms for The Degradation of Oligosaccharides, Org Biomol Chem, Vol. 19, No. 2, 2004, pp. 2707-2713, https://doi.org/10.1039/B408880H.[10] B. Henrissat, A. Bairoch, New Families in The Classification of Glycosyl Hydrolases Based on Amino Acid Sequence Similarities, Biochem J, Vol. 293, No. 3, 1993, pp. 781-788, https://doi.org/10.1042/bj2930781.[11] B. Henrissat, A Classification of Glycosyl Hydrolases Based on Amino Acid Sequence Similarities, Biochem J, Vol. 280, No. 2, 1991, pp. 309-316, https://doi.org/10.1042/bj2800309.[12] R. Gupta, P. Gigras, H. Mohapatra, V. K. Goswami, B. Chauhan, Microbial A-amylases: A Biotechnological Perspective, Process Biochemistry, Vol. 38, No. 11, 2003, pp. 1599-1616, https://doi.org/10.1016/s0032-9592(03)00053-0.[13] C. V. D. Maarel, B. V. D. Veen, J. C .M. Uitdehaag, H. Leemhuis, L. Dijkhuizen, Properties and Applications of Starch-Converting Enzymes of The A-Amylase Family, Journal of Biotechnology, Vol. 94, No. 2, 2002, pp. 137-155, https://doi.org/10.1016/s0168-1656(01)00407-2.[14] N. R. Kim, D. W. Jeong, D. S. Ko, J. H. Shim, Characterization of Novel Thermophilic Alpha-Glucosidase from Bifidobacterium Longum, Int J Biol Macromol, Vol. 99, 2017, pp. 594-599, https://doi.org/10.1016/j.ijbiomac.2017.03.009.[15] D. R. Rose, M. M. Chaudet, K. Jones, Structural Studies of The Intestinal Alpha-Glucosidases, Maltase-glucoamylase and Sucrase-isomaltase, J Pediatr Gastroenterol Nutr, Vol. 66, No. 3, 2018, pp. S11-S13, https://doi.org/10.1097/MPG.0000000000001953.[16] L. Ren, X. Qin, X. Cao, L. Wang, F. Bai, G. Bai, Y. Shen, Structural Insight into Substrate Specificity of Human Intestinal Maltase-Glucoamylase, Protein Cell, Vol. 2, 2011, pp. 827-836, https://doi.org/10.1007/s13238-011-1105-3.[17] L. Sim, C. Willemsma, S. Mohan, H. Y. Naim, B. M. Pinto, D. R. Rose, Structural Basis for Substrate Selectivity in Human Maltase-Glucoamylase and Sucrase-Isomaltase N-Terminal Domains, J Biol Chem, Vol. 285, No. 23, 2010, pp. 17763-17770, https://doi.org/10.1074/jbc.M109.078980.[18] K. Jones, L. Sim, S. Mohan, J. Kumarasamy,H. Liu, S. Avery, H. Y. Naim, R. Q. Calvillo, B. L. Nichols, B. M. Pinto, D. R. Rose, Mapping The Intestinal Alpha-Glucogenic Enzyme Specificities of Starch Digesting Mal se-Glucoamylase and Sucrase-Isomaltase, Bioorg Med Chem, Vol. 19, 2011, pp. 3929-3934, https://doi.org/10.1016/j.bmc.2011.05.033.[19] P. T. T. Chau, P. T. Nghia, Enzyme and Application, Education Publisher, Vietnam, 2009.[20] Researchgate, Food Protein-Derived Bioactive Peptides in Management of Type 2 Diabetes - Scientific Figure, https://www.researchgate.net/figure/Mechanism-of-action-of-alpha-glucosidase-inhibitors_fig2_279991207 (accessed on: May 10th, 2021).[21] Z. Liu, S. Ma, Recent Advances in Synthetic Alpha-Glucosidase Inhibitors, Chem Med Chem, Vol. 12, No. 11, 2017, pp. 819-829, https://doi.org/10.1002/cmdc.201700216.[22] A. Lee, P. Patrick, J. Wishart, M. Horowitz, J. E. Morley, The Effects of Miglitol on Glucagon-Like Peptide-1 Secretion And Appetite Sensations in Obese Type 2 Diabetics, Diabetes Obes Metab, Vol. 4, No. 5, 2002, pp. 329-335, https://doi.org/10.1046/j.14631326.2002.00219.x.[23] I. Takei, K. Miyamoto, O. Funae, N. Ohashi, S. Meguro, M. Tokui, T. Saruta, Secretion of GIP in Responders to Acarbose in Obese Type 2 (NIDDM) Patients, Journal of Diabetes and Its Complications, Vol. 15, No. 5, 2001, pp. 245-249, https://doi.org/10.1016/s1056-8727(01)00148-9.[24] X. Bian, X. Fan, C. Ke, Y. Luan, G. Zhao, A. Zeng, Synthesis and Alpha-Glucosidase Inhibitory Activity Evaluation of N-Substituted Aminomethyl-Beta-D-Glucopyranosides, Bioorg Med Chem, Vol. 21, No. 17, 2013, pp. 5442-5450, https://doi.org/10.1016/j.bmc.2013.06.002.[25] J. B. Yang, J. Y. Tian, Z. Dai, F. Ye, S. C. Ma, A. G. Wang, α-Glucosidase Inhibitors Extracted from The Roots of Polygonum Multiflorum Thunb, Fitoterapia, Vol. 117, 2017, pp. 65-70, https://doi.org/10.1016/j.fitote.2016.11.009.[26] Z. Yin, W. Zhang, F. Feng, Y. Zhang, W. Kang, α-Glucosidase Inhibitors Isolated from Medicinal Plants, Food Science and Human Wellness, Vol. 3, No.3-4, 2014, pp. 136-174, https://doi.org/10.1016/j.fshw.2014.11.003.[27] P. Qiu, Z. Liu, Y. Chen, R. Cai, G. Chen, Z. She, Secondary Metabolites with Alpha-Glucosidase Inhibitory Activity from The Mangrove Fungus Mycosphaerella sp. SYSU-DZG01, Mar Drugs, Vol. 17, No. 8, 2019, pp. 483-508, https://doi.org/10.3390/md17080483.[28] S. Munasaroh, S. R. Tamat, R. T. Dewi, Isolation and Identification of α-Glucosidase Inhibitor from Aspergillus Terreus F38, Indonesian Journal of Pharmacy, Vol. 29, No. 2, 2018, pp. 74-79, https://doi.org/10.14499/indonesianjpharm29iss2pp74.[29] R. T. Dewi, A. Suparman, H. Mulyani, P. D. N. Lotulung, Identification of A New Compound as α-Glucosidase Inhibitor from Aspergillus Aculeatus, Annales Bogorienses, Vol. 20, No. 1, 2016, pp. 19-23, https://doi.org/10.14203/ann. bogor .2016.v20.n1.19-23.[30] R. T. Dewi, S. Tachibana, A. Darmawan, Effect on α-Glucosidase Inhibition and Antioxidant Activities of Butyrolactone Derivatives from Aspergillus Terreus MC751, Medicinal Chemistry Research, Vol. 23, 2014, pp. 454-460, https://doi.org/10.1007/s00044-013-0659-4.[31] M. G. Kang, S. H. Yi, J. S. Lee, Production and Characterization of A New Alpha-Glucosidase Inhibitory Peptide from Aspergillus Oryzae N159-1, Mycobiology, Vol. 41, No. 3, 2013, pp. 149-154, https://doi.org/10.5941/MYCO.2013.41.3.149.[32] S. Onose, R. Ikeda, K. Nakagawa, T. Kimura, K. Yamagishi, O. Higuchi, T. Miyazawa, Production of The Alpha-Glycosidase Inhibitor 1-Deoxynojirimycin from Bacillus Species, Food Chem, Vol. 138, No. 1, 2013, pp. 516-523, https://doi.org/10.1016/j.foodchem.2012.11.012.[33] Y. P. Zhu, K. Yamaki, T. Yoshihashi, M. Ohnishi Kameyama, X. T. Li, Y. Q. Cheng, Y. Mori, L. T. Li, Purification and Identification of 1-Deoxynojirimycin (DNJ) in Okara Fermented by Bacillus Subtilis B2 from Chinese Traditional Food (Meitaoza), J Agric Food Chem, Vol. 58,No. 7, 2010, pp. 4097-4103, https://doi.org/10.1021/jf9032377.[34] A. Tabussum, N. Riaz, M. Saleem, M. Ashraf, M. Ahmad, U. Alam, B. Jabeen, A. Malik, A. Jabbar, α-Glucosidase Inhibitory Constituents from Chrozophora Plicata, Phytochemistry Letters, Vol. 6, No. 4. 2013, pp. 614-619, https://doi.org/10.1016/j.phytol.2013.08.005.[35] M. Yagi, T. Kouno, Y. Aoyagi, H. Murai, The Structure of Moranoline, A Piperidine Alkaloid from Morus Species, Journal of The Agricultural Chemical Society of Japan, Vol. 50, No. 11, 1976, pp. 571-572, https://doi.org/10.1271/nogeikagaku1924.50.11_571.[36] M. Hemker, A. Stratmann, K. Goeke, W. Schroder, J. Lenz, W. Piepersberg, H. Pape, Identification, Cloning, Expression, and Characterization of The Extracellular Acarbose-Modifying Glycosyltransferase, AcbD, from Actinoplanes Sp. Strain SE50, J Bacteriol, Vol. 183, No. 15, 2001, pp. 4484-4492, https://doi.org/10.1128/JB.183. 15.4484-4492.2001.[37] E. Truscheit, I. Hillebrand, B. Junge, L. Müller, W. Puls, D. Schmidt, Microbial α-Glucosidase Inhibitors: Chemistry, Biochemistry, and Therapeutic Potential, Presented at Drug Concentration Monitoring Microbial alpha-Glucosidase Inhibitors Plasminogen Activators, Springer-Verlag, Berlin, 1988.[38] Y. Kameda, N. Asano, M. Yoshikawa, M. Takeuchi, T. Yamaguchi, K. Matsui, S. Horii, H. Fukase, Valiolamine, A New Alpha-Glucosidase Inhibiting Aminocyclitol Produced by Streptomyces Hygroscopicus, J Antibiot (Tokyo), Vol. 37, No. 11, 1984, pp. 1301-1307, https://doi.org/10.7164/antibiotics.37.1301.[39] D. T. Tuyen, V. V. Hanh, V. T. T. Hang, D. K. Trinh, D. T. Quyen, Extraction and Purification of DNJ (1-Deoxynojirimycin) Inhibiting α-Glucosidase from B. Subtilis VN9 Strain Isolated from Vietnam, National Biotechnology Conference, 2013.[40] D. T. Tuyen, Optimization and Purification of α-Glucosidase Inhibitor from Bacillus Subtilis YT20 Isolated in Vietnam, Vietnam Journal of Science and Technology, Vol. 59, No. 2, 2021, pp. 179-188, https://doi.org/10.15625/2525-2518/ 59/2/14928.[41] S. E. Baker, J. W. Bennett, An Overview of the Genus Aspergillus, Aspergillus: Molecular Biology and Genomics, The Aspergilli, Taylor & Francis, United Kingdom, 2008, pp. 3-13.[42] H. C. Gugnani, Ecology and Taxonomy of Pathogenic Aspergilli, Front Biosci, Vol. 8, No. 6, 2003, pp. s346- s357, https://doi.org/10.2741/1002.[43] C. G. Shaw, The Genus Aspergillus, Science, Vol. 150, No. 3697, 1965, pp. 736-737, https://doi.org/10.1126/science.150.3697.736-a.[44] M. T. Hedayati, A. C. Pasqualotto, P. A. Warn, P. Bowyer, D. W. Denning, Aspergillus Flavus: Human Pathogen, Allergen and Mycotoxin Producer, Microbiology, Vol. 153, No. 6, 2007, pp. 1677-1692, https://doi.org/10.1099/mic.0.2007/007641-0.[45] T. R. Dagenais, N. P. Keller, Pathogenesis of Aspergillus Fumigatus in Invasive Aspergillosis, Clin Microbiol Rev, Vol. 22, No. 3, 2009, pp. 447-465, https://doi.org/10.1128/CMR.00055-08.[46] S. Amaike, N. P. Keller, Aspergillus Flavus, Annu Rev Phytopathol, Vol. 49, 2011, pp. 107-133, https://doi.org/10.1146/annurev-phyto-072910-095221.[47] J. Houbraken, R. P. De Vries, R. A. Samson, Modern Taxonomy of Biotechnologically Important Aspergillus and Penicillium Species, Adv Appl Microbiol, Vol. 86, 2014, pp. 199-249, https://doi.org/10.1016/B978-0-12-800262-9.00004-4.[48] E. Ichishima, Development of Enzyme Technology for Aspergillus Oryzae, A. Sojae, and A. Luchuensis, The National Microorganisms of Japan, Biosci Biotechnol Biochem, Vol. 80, No. 9, 2016, pp. 1681-1692, https://doi.org/10.1080/09168451.2016.1177445.[49] E. Schuster, N. Dunn-Coleman, J. C. Frisvad, P. W. Van Dijck, on The Safety of Aspergillus Niger-A Review, Appl Microbiol Biotechnol, Vol. 59, No. 4-5, 2002, pp. 426-435, https://doi.org/10.1007/s00253-002-1032-6.[50] J. H. Yu, N. Keller, Regulation of Secondary Metabolism in Filamentous Fungi, Annu Rev Phytopathol, Vol. 43, 2005, pp. 437-458, https://doi.org/10.1146/annurev.phyto.43.040204.140214.[51] J. F. Sanchez, A. D. Somoza, N. P. Keller, C. C. Wang, Advances in Aspergillus Secondary Metabolite Research in The Post-Genomic Era, Nat Prod Rep, Vol. 29, No. 3, 2012, pp. 351-371, https://doi.org/10.1039/c2np00084a.[52] J. W. Bennett, M. Klich, Mycotoxins, Clin Microbiol Rev, Vol. 16, 2003, pp. 497-516, https://doi.org/10.1128/cmr.16.3.497-516.2003.[53] Q. Zhou, J. K. Liao, Statins and cardiovascular Diseases: from Cholesterol Lowering to Pleiotropy, Curr Pharm Des, Vol. 15, No. 5, 2009, pp. 467-478, https://doi.org/10.2174/138161209787315684.[54] A. W. Alberts, Discovery, Biochemistry and Biology of Lovastatin, Am J Cardiol, Vol. 62, No. 15, 1988, pp. 10J-15J, https://doi.org/10.1016/0002-9149(88)90002-1.[55] H. Tomoda, Y. K. Kim, H. Nishida, R. Masuma, S. Omura, Pyripyropenes, Novel Inhibitors of Acyl-Coa: Cholesterol Acyltransferase Produced by Aspergillus Fumigatu- Production, Isolation, and Biological Properties, J Antibiot (Tokyo), Vol. 47, No. 2, 1994, pp. 148-153, https://doi.org/10.7164/antibiotics.47.148.[56] F. Pelaez, Biological Activities of Fungal Metabolites, Marcel Dekker, United Stated of America, 2004.[57] E. L. Dulaney, Penicillin Production by The Aspergillus Nidulans Group, Mycologia, Vol. 39, No. 5, 2018, pp. 582-586, https://doi.org/10.1080/00275514.1947.12017637.[58] T. T. Bladt, J. C. Frisvad, P. B. Knudsen, T. O. Larsen, Anticancer and Antifungal Compounds from Aspergillus, Penicillium and Other Filamentous Fungi, Molecules, Vol. 18, No. 9, 2013, pp. 11338-11376, https://doi.org/10.3390/molecules180911338.[59] Y. Wu, Y. Chen, X. Huang, Y. Pan, Z. Liu, T. Yan, W. Cao, Z. She, alpha-Glucosidase Inhibitors: Diphenyl Ethers and Phenolic Bisabolane Sesquiterpenoids from The Mangrove Endophytic Fungus Aspergillus Flavus QQSG-3, Mar Drugs, Vol. 16, No. 9, 2018, pp. 307-316, https://doi.org/10.3390/md16090307.