Oligomeric Proanthocyanidin Complex from Avocado Seed as A Promising α-glucosidase Inhibitor: Characteristics and Mechanisms

Abstract

Although considered an abundant source of agricultural by-products, avocado (Persea americana Mill.) seed, with several biological activities and bioactive components, might become a promising resource for phytopharmaceutical development. In this study, through bioassay-guided isolation of the main α-glucosidase inhibitors in avocado seed, we discovered the major α-glucosidase inhibitor to be avocado seed oligomeric proanthocyanidin complex (ASOPC). Thiolysis and UPLC-DAD-HRESIMS showed the presence of A- and B-type procyanidins, and B-type propelargonidin with (epi)afzelechin as extension unit. Mean degree of polymerization (mDP) of ASOPC was calculated as 7.3 ± 1. Furthermore, ASOPC appeared to be a strong, reversible, competitive inhibitor of α-glucosidase, with IC₅₀ value of 0.1 µg/mL, which was significantly lower than Acarbose (IC₅₀ = 75.6 µg/mL), indicated that ASOPC is a potential natural α-glucosidase inhibitor. These findings would contribute to the direction of utilizing avocado seed bioactive components with the possibility to be used as natural anti-diabetic agents.

Key words

Avocado seed - Persea americana - Lauraceae - diabetes mellitus - α-glucosidase inhibitory activity - proanthocyanidins

• References

• 1 Food and Agriculture Organization of the United Nations (FAO). FAOSTAT Database. Rome. Accessed January 15, 2022 at: https://www.fao.org/faostat/en/%23home
• 2 Figueroa JG, Borrás-Linares I, Del Pino-García R, Curiel JA, Lozano-Sánchez J, Segura-Carretero A. Functional ingredient from avocado peel: Microwave-assisted extraction, characterization and potential applications for the food industry. Food Chem 2021; 352: 129300
• 3 Dabas D, Shegog R, Ziegler G, Lambert J. Avocado (Persea americana) seed as a source of bioactive phytochemicals. Curr Pharm Des 2013; 19: 6133-6140
• 4 Barbosa E, Chel L, Gonzalez E, Betancur D. Chemical and technological properties of avocado (Persea americana Mill.) seed fibrous residues. Food Bioprod Process 2016; 100 A: 457-463
• 5 Imafidon KE, Amaechina FC. Effects of aqueous seed extract of Persea americana Mill. (avocado) on blood pressure and lipid profile in hypertensive rats. Adv Biol Res 2010; 4: 116-121
• 6 Raymond Chia TW, Dykes GA. Antimicrobial activity of crude epicarp and seed extracts from mature avocado fruit (Persea americana) of three cultivars. Pharm Biol 2010; 48: 753-756
• 7 Kristanti CD, Simanjuntak FPJ, Dewi NKPA, Tianri SV, Hendra P. Anti-inflammatory and analgesic activities of avocado seed (Persea americana Mill.). J Pharm Sci Community 2017; 14: 104-111
• 8 Owolabi OJ, Anaka ON, Egboh AJ. Effect of Persea americana Mill seeds on rat uterus. J Sci Pr Pharm December 2014; 1: 1-6
• 9 Asaolu MF, Asaolu SS, Oyeyemi AO, Aluko BT. Hypolipemic effects of methanolic extract of Persea americana seeds in hypercholesterolemic rats. J Med Med Sci 2010; 1: 126-128
• 10 del Refugio Ramos-Jerz M, Villanueva S, Deters AM. Influence of avocado seed fractions (Persea americana Mill.) obtained by HSCCC on human skin keratinocytes and fibroblasts: Differences of effects in regard of tested cell types. Planta Med 2007; 73: P-485
• 11 Nayak BS, Raju SS, Chalapathi Rao AV. Wound healing activity of Persea americana (avocado) fruit: a preclinical study on rats. J Wound Care 2008; 17: 123-126
• 12 Kasole R, Martin HD, Kimiywe J. Traditional medicine and its role in the management of diabetes mellitus: “patients” and “herbalists” perspectives. Evid Based Complement Alternat Med 2019; 2019: 2835691
• 13 Edem DO. Hypoglycemic effects of ethanolic extracts of alligator pear seed (Persea americana Mill) in rats. Eur J Sci Res 2009; 33: 669-678
• 14 Temitope IA, Ganiyu O, Akinyemi AJ, Ajani RA, Bakare O. Avocado pear fruits and leaves aqueous extracts inhibit α-amylase, α-glucosidase and SNP induced lipid peroxidation – an insight into mechanisms involve in management of type 2 diabetes. Int J Appl Nat Sci 2014; 3: 21-34
• 15 Oboh G, Isaac AT, Akinyemi AJ, Ajani RA. Inhibition of key enzymes linked to type 2 diabetes and sodium nitroprusside induced lipid peroxidation in ratsʼ pancreas by phenolic extracts of avocado pear leaves and fruit. Int J Biomed Sci 2014; 10: 210-218
• 16 Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M. Acarbose for prevention of type 2 diabetes mellitus: The STOP-NIDDM randomised trial. Lancet 2002; 359: 2072-2077
• 17 Van De Laar FA, Lucassen PL, Akkermans RP, Van De Lisdonk EH, Rutten GE, Van Weel C. Alpha-glucosidase inhibitors for patients with type 2 diabetes: Results from a Cochrane systematic review and meta-analysis. Diabetes Care 2005; 28: 154-163
• 18 DeFronzo RA. Pharmacologic therapy for type 2 diabetes mellitus. Ann Intern Med 1999; 131: 281-303
• 19 Kumar S, Narwal S, Kumar V, Prakash O. α-glucosidase inhibitors from plants: A natural approach to treat diabetes. Pharmacogn Rev 2011; 5: 19-29
• 20 Salehi B, Ata A, Anil Kumar NV, Sharopov F, Ramírez-Alarcón K, Ruiz-Ortega A, Abdulmajid Ayatollahi S, Tsouh Fokou PV, Kobarfard F, Amiruddin Zakaria Z, Iriti M, Taheri Y, Martorell M, Sureda A, Setzer WN, Durazzo A, Lucarini M, Santini A, Capasso R, Ostrander EA. Atta-ur-Rahman, Choudhary MI, Cho WC, Sharifi-Rad J. Antidiabetic potential of medicinal plants and their active components. Biomolecules 2019; 9: 551
• 21 Mwakalukwa R, Amen Y, Nagata M, Shimizu K. Postprandial hyperglycemia lowering effect of the isolated compounds from olive mill wastes – An inhibitory activity and kinetics studies on α-glucosidase and α-amylase enzymes. ACS Omega 2020; 5: 20070-20079
• 22 Uvarani C, Jaivel N, Sankaran M, Chandraprakash K, Ata A, Mohan PS. Axially chiral biscarbazoles and biological evaluation of the constituents from Murraya koenigii . Fitoterapia 2014; 94: 10-20
• 23 Ou-Yang C, Chai W, Xu X, Song S, Wei Q, Huang Q, Zou Z. Inhibitory potential of proanthocyanidins from the fruit pulp of Clausena lansium (Lour.) Skeels against α-glucosidase and non-enzymatic glycation: Activity and mechanism. Process Biochem 2020; 91: 364-373
• 24 Fu Y, Qiao L, Cao Y, Zhou X, Liu Y, Ye X. Structural elucidation and antioxidant activities of proanthocyanidins from Chinese bayberry (Myrica rubra Sieb. et Zucc.) leaves. PLoS One 2014; 9: e96162
• 25 Orejola J, Matsuo Y, Saito Y, Tanaka T. Characterization of proanthocyanidin oligomers of Ephedra sinica . Molecules 2017; 22: 1308
• 26 Lai HY, Lim YY, Kim KH. Isolation and characterisation of a proanthocyanidin with antioxidative, antibacterial and anti-cancer properties from fern Blechnum orientale . Pharmacogn Mag 2017; 13: 31-37
• 27 Wei M, Chai WM, Yang Q, Wang R, Peng Y. Novel Insights into the inhibitory effect and mechanism of proanthocyanidins from Pyracantha fortuneana fruit on α-glucosidase. J Food Sci 2017; 82: 2260-2268
• 28 Ling ZQ, Xie BJ, Yang EL. Isolation, characterization, and determination of antioxidative activity of oligomeric procyanidins from the seedpod of Nelumbo nucifera Gaertn. J Agric Food Chem 2005; 53: 2441-2445
• 29 Zang X, Shang M, Xu F, Liang J, Wang X, Mikage M, Cai S. A-type proanthocyanidins from the stems of Ephedra sinica (Ephedraceae) and their antimicrobial activities. Molecules 2013; 18: 5172-5189
• 30 Santos SAO, Vilela C, Camacho JF, Cordeiro N, Gouveia M, Freire CSR, Silvestre AJD. Profiling of lipophilic and phenolic phytochemicals of four cultivars from cherimoya (Annona cherimola Mill.). Food Chem 2016; 211: 845-852
• 31 López-Cobo A, Gómez-Caravaca AM, Pasini F, Caboni MF, Segura-Carretero A, Fernández-Gutiérrez A. HPLC-DAD-ESI-QTOF-MS and HPLC-FLD-MS as valuable tools for the determination of phenolic and other polar compounds in the edible part and by-products of avocado. LWT – Food Sci Technol 2016; 73: 505-513
• 32 Figueroa JG, Borrás-Linares I, Lozano-Sánchez J, Segura-Carretero A. Comprehensive characterization of phenolic and other polar compounds in the seed and seed coat of avocado by HPLC-DAD-ESI-QTOF-MS. Food Res Int 2018; 105: 752-763
• 33 Chai WM, Wei MK, Wang R, Deng RG, Zou ZR, Peng YY. Avocado proanthocyanidins as a source of tyrosinase inhibitors: Structure characterization, inhibitory activity, and mechanism. J Agric Food Chem 2015; 63: 7381-7387
• 34 Zhang Y, Santosa RW, Zhang M, Huo J, Huang D. Characterization and bioactivity of proanthocyanidins during Malay cherry (Lepisanthes alata) fruit ripening. Food Biosci 2020; 36: 100617
• 35 Hsu CY, Lin GM, Lin HY, Chang ST. Characteristics of proanthocyanidins in leaves of Chamaecyparis obtusa var. formosana as strong α-glucosidase inhibitors. J Sci Food Agric 2018; 98: 3806-3814
• 36 Fang HL, Liu ML, Li SY, Song WQ, Ouyang H, Xiao ZP, Zhu HL. Identification, potency evaluation, and mechanism clarification of α-glucosidase inhibitors from tender leaves of Lithocarpus polystachyus Rehd. Food Chem 2022; 371: 131128
• 37 Chai W, Ou-Yang C, Ma Z, Song S, Huang Q, Wei Q, Peng Y. Anti-α-glucosidase and antityrosinase activity of condensed tannins from the bark of Clausena lansium (Lour.) Skeels with antiproliferative and apoptotic properties in B16 mouse melanoma cells. Process Biochem 2019; 86: 205-214
• 38 Zhang D, Liu X, Yang Z, Shi J, Zhao L, Battino M, Xiao J, Deng X, Wu Y, Wang C, Shi B, Zou X. Interactions between phenols and alkylamides of Sichuan pepper (Zanthoxylum Genus) in α-glucosidase inhibition: A structural mechanism analysis. J Agric Food Chem 2021; 69: 5583-5598
• 39 Li K, Yao F, Du J, Deng X, Li C. Persimmon tannin decreased the glycemic response through decreasing the digestibility of starch and inhibiting α-amylase, α-glucosidase, and intestinal glucose uptake. J Agric Food Chem 2018; 66: 1629-1637
• 40 Kawakami W, Oshima A, Yanase E. Structural characterization of proanthocyanidins from adzuki seed coat. Food Chem 2018; 239: 1110-1116
• 41 Gu L, Kelm M, Hammerstone JF, Beecher G, Cunningham D, Vannozzi S, Prior RL. Fractionation of polymeric procyanidins from lowbush blueberry and quantification of procyanidins in selected foods with an optimized normal-phase HPLC−MS fluorescent detection method. J Agric Food Chem 2002; 50: 4852-4860
• 42 Xie HX, Zhang J, Li Y, Zhang JH, Liu SK, Zhang J, Zheng H, Hao GZ, Zhu KK, Jiang CS. Novel tetrahydrobenzo[b]thiophen-2-yl)urea derivatives as novel α-glucosidase inhibitors: Synthesis, kinetics study, molecular docking, and in vivo anti-hyperglycemic evaluation. Bioorg Chem 2021; 115: 105236
• 43 Moghimi S, Salarinejad S, Toolabi M, Firoozpour L, Esmaeil Sadat Ebrahimi S, Safari F, Madani-Qamsari F, Mojtabavi S, Faramarzi MA, Karima S, Pakrad R, Foroumadi A. Synthesis, in-vitro evaluation, molecular docking, and kinetic studies of pyridazine-triazole hybrid system as novel α-glucosidase inhibitors. Bioorg Chem 2021; 109: 104670