Inhibition of α-glucosidase and α-amylase by herbal compounds for the treatment of type 2 diabetes: A validation of in silico reverse docking with in vitro enzyme assays.
Acarbose
/ therapeutic use
Alkaloids
/ therapeutic use
Apigenin
/ therapeutic use
Benzodioxoles
/ therapeutic use
Chemical Phenomena
Computer Simulation
Diabetes Mellitus, Type 2
/ drug therapy
Dose-Response Relationship, Drug
Flavanones
/ therapeutic use
Glycoside Hydrolase Inhibitors
/ therapeutic use
Hep G2 Cells
Humans
Hypoglycemic Agents
/ therapeutic use
Molecular Docking Simulation
/ methods
Piperidines
/ therapeutic use
Plants, Medicinal
/ chemistry
Polyunsaturated Alkamides
/ therapeutic use
Spices
alpha-Amylases
/ antagonists & inhibitors
alpha-Glucosidases
2型糖尿病
herbal compounds
in vitro cytotoxicity
reverse molecular docking
type 2 diabetes
α-amylase
α-glucosidase
α-淀粉酶
α-葡萄糖苷酶
体外细胞毒性
反向分子对接
草药化合物
Journal
Journal of diabetes
ISSN: 1753-0407
Titre abrégé: J Diabetes
Pays: Australia
ID NLM: 101504326
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
revised:
25
01
2021
received:
31
07
2020
accepted:
03
02
2021
pubmed:
8
2
2021
medline:
15
1
2022
entrez:
7
2
2021
Statut:
ppublish
Résumé
α-Amylase and α-glucosidase are important therapeutic targets for the management of type 2 diabetes mellitus. The inhibition of these enzymes decreases postprandial hyperglycemia. In the present study, compounds found in commercially available herbs and spices were tested for their ability to inhibit α-amylase and α-glucosidase. These compounds were acetyleugenol, apigenin, cinnamic acid, eriodictyol, myrcene, piperine, and rosmarinic acid. The enzyme inhibitory nature of the compounds was evaluated using in silico docking analysis with Maestro software and was further confirmed by in vitro α-amylase and α-glucosidase biochemical assays. The relationships between the in silico and in vitro results were well correlated; a more negative docking score was associated with a higher in vitro inhibitory activity. There was no significant (P > .05) difference between the inhibition constant (K Several of the herbal compounds studied could regulate postprandial hyperglycemia. Using herbal plants has several advantages including low cost, natural origin, and easy cultivation. These compounds can easily be consumed as teas or as herbs and spices to flavor food. 背景: α-淀粉酶和α-葡萄糖苷酶是2型糖尿病治疗的重要靶点。抑制这些酶可以降低餐后高血糖。在本研究中, 测试了在市售草药和香料中发现的化合物对α-淀粉酶和α-葡萄糖苷酶的抑制能力。这些化合物是乙酰亮酚、芹菜素、肉桂酸、芥子醇、月桂烯、胡椒碱和迷迭香酸。 方法: 用Maestro软件进行电子对接分析, 并通过体外α-淀粉酶和α-葡萄糖苷酶生化测定进一步证实化合物的抑酶活性。 结果: 体内和体外结果之间有很好的相关性；对接得分越低, 体外抑制活性越高。广泛应用的α-葡萄糖苷酶和α-淀粉酶抑制剂阿卡波糖与芹菜素、芥子醇和胡椒碱的抑制常数(Ki)值无显著性差异(P>0.05)。对于α-淀粉酶, 阿卡波糖的Ki值与芹菜素、肉桂酸、迷迭香酸无显著差异(P>0.05)。另外采用了硫代罗丹明B(SRB)比色法检测中药复方对C2C12和HepG2细胞活力的影响。乙酰亮酚、肉桂酸、月桂烯、胡椒碱和迷迭香酸的IC50值与阿卡波糖相似(P>0.05)。 结论: 所研究的几种中草药化合物具有调节餐后高血糖的作用。使用中草药植物具有成本低、来源天然、易于栽培等优点。这些化合物可以很容易地作为茶或草药和香料食用并为食物调味。.
Sections du résumé
BACKGROUND
BACKGROUND
α-Amylase and α-glucosidase are important therapeutic targets for the management of type 2 diabetes mellitus. The inhibition of these enzymes decreases postprandial hyperglycemia. In the present study, compounds found in commercially available herbs and spices were tested for their ability to inhibit α-amylase and α-glucosidase. These compounds were acetyleugenol, apigenin, cinnamic acid, eriodictyol, myrcene, piperine, and rosmarinic acid.
METHODS
METHODS
The enzyme inhibitory nature of the compounds was evaluated using in silico docking analysis with Maestro software and was further confirmed by in vitro α-amylase and α-glucosidase biochemical assays.
RESULTS
RESULTS
The relationships between the in silico and in vitro results were well correlated; a more negative docking score was associated with a higher in vitro inhibitory activity. There was no significant (P > .05) difference between the inhibition constant (K
CONCLUSIONS
CONCLUSIONS
Several of the herbal compounds studied could regulate postprandial hyperglycemia. Using herbal plants has several advantages including low cost, natural origin, and easy cultivation. These compounds can easily be consumed as teas or as herbs and spices to flavor food.
背景: α-淀粉酶和α-葡萄糖苷酶是2型糖尿病治疗的重要靶点。抑制这些酶可以降低餐后高血糖。在本研究中, 测试了在市售草药和香料中发现的化合物对α-淀粉酶和α-葡萄糖苷酶的抑制能力。这些化合物是乙酰亮酚、芹菜素、肉桂酸、芥子醇、月桂烯、胡椒碱和迷迭香酸。 方法: 用Maestro软件进行电子对接分析, 并通过体外α-淀粉酶和α-葡萄糖苷酶生化测定进一步证实化合物的抑酶活性。 结果: 体内和体外结果之间有很好的相关性；对接得分越低, 体外抑制活性越高。广泛应用的α-葡萄糖苷酶和α-淀粉酶抑制剂阿卡波糖与芹菜素、芥子醇和胡椒碱的抑制常数(Ki)值无显著性差异(P>0.05)。对于α-淀粉酶, 阿卡波糖的Ki值与芹菜素、肉桂酸、迷迭香酸无显著差异(P>0.05)。另外采用了硫代罗丹明B(SRB)比色法检测中药复方对C2C12和HepG2细胞活力的影响。乙酰亮酚、肉桂酸、月桂烯、胡椒碱和迷迭香酸的IC50值与阿卡波糖相似(P>0.05)。 结论: 所研究的几种中草药化合物具有调节餐后高血糖的作用。使用中草药植物具有成本低、来源天然、易于栽培等优点。这些化合物可以很容易地作为茶或草药和香料食用并为食物调味。.
Autres résumés
Type: Publisher
(chi)
背景: α-淀粉酶和α-葡萄糖苷酶是2型糖尿病治疗的重要靶点。抑制这些酶可以降低餐后高血糖。在本研究中, 测试了在市售草药和香料中发现的化合物对α-淀粉酶和α-葡萄糖苷酶的抑制能力。这些化合物是乙酰亮酚、芹菜素、肉桂酸、芥子醇、月桂烯、胡椒碱和迷迭香酸。 方法: 用Maestro软件进行电子对接分析, 并通过体外α-淀粉酶和α-葡萄糖苷酶生化测定进一步证实化合物的抑酶活性。 结果: 体内和体外结果之间有很好的相关性；对接得分越低, 体外抑制活性越高。广泛应用的α-葡萄糖苷酶和α-淀粉酶抑制剂阿卡波糖与芹菜素、芥子醇和胡椒碱的抑制常数(Ki)值无显著性差异(P>0.05)。对于α-淀粉酶, 阿卡波糖的Ki值与芹菜素、肉桂酸、迷迭香酸无显著差异(P>0.05)。另外采用了硫代罗丹明B(SRB)比色法检测中药复方对C2C12和HepG2细胞活力的影响。乙酰亮酚、肉桂酸、月桂烯、胡椒碱和迷迭香酸的IC50值与阿卡波糖相似(P>0.05)。 结论: 所研究的几种中草药化合物具有调节餐后高血糖的作用。使用中草药植物具有成本低、来源天然、易于栽培等优点。这些化合物可以很容易地作为茶或草药和香料食用并为食物调味。.
Identifiants
pubmed: 33550683
doi: 10.1111/1753-0407.13163
doi:
Substances chimiques
Alkaloids
0
Benzodioxoles
0
Flavanones
0
Glycoside Hydrolase Inhibitors
0
Hypoglycemic Agents
0
Piperidines
0
Polyunsaturated Alkamides
0
Apigenin
7V515PI7F6
alpha-Amylases
EC 3.2.1.1
alpha-Glucosidases
EC 3.2.1.20
eriodictyol
Q520486B8Y
Acarbose
T58MSI464G
piperine
U71XL721QK
Types de publication
Journal Article
Validation Study
Langues
eng
Sous-ensembles de citation
IM
Pagination
779-791Subventions
Organisme : University of Pretoria
Informations de copyright
© 2021 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.
Références
Goldenberg R. Definition, classification and diagnosis of diabetes, prediabetes and metabolic syndrome. Can J Diabetes. 2013;37(Suppl 1):S8-S11.
American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2009;33(Supplement 1):S62-S69.
International Diabetes Federation. In: Karuranga S, Malanda B, Saeedi P, Salpea P, eds. IDF Diabetes Atlas. 9. Brussels, Belgium: International Diabetes Federation. https://idf.org/e-library/epidemiology-research/diabetes-atlas.html. Accessed: March 23, 2020; 2019.
Olokoba AB, Obateru OA, Olokoba LB. Type 2 diabetes mellitus- a review of current trends. Oman Med J. 2012;27(4):269-273.
Wilke T, Boettger B, Berg B, et al. Epidemiology of urinary tract infections in type 2 diabetes mellitus patients: an analysis based on a large sample of 456,586 German T2DM patients. J Diabetes Complications. 2015;29(8):1015-1023.
Papatheodorou K, Banach M, Bekiari E, Rizzo M, Edmonds M. Complications of diabetes 2017. J Diabetes Res. 2018;2018:3086167.
Harding JL, Pavkov ME, Magliano DJ, Shaw JE, Gregg EW. Global trends in diabetes complications: a review of current evidence. Diabetologia. 2019;62(1):3-16.
Rivera-Chavez J, Gonzalez-Andrade M, Gonzalez Mdel C, Glenn AE, Mata R, Thielavins A. J and K: alpha-glucosidase inhibitors from MEXU 27095, an endophytic fungus from Hintonia latiflora. Phytochemistry. 2013;94:198-205.
Proenca C, Freitas M, Ribeiro D, et al. Alpha-glucosidase inhibition by flavonoids: an in vitro and in silico structure-activity relationship study. J Enzyme Inhib Med Chem. 2017;32(1):1216-1228.
He K, Shi JC, Mao XM. Safety and efficacy of acarbose in the treatment of diabetes in Chinese patients. Ther Clin Risk Manag. 2014;10:505-511.
Proença C, Freitas M, Ribeiro D, et al. Evaluation of a flavonoids library for inhibition of pancreatic α-amylase towards a structure-activity relationship. J Enzyme Inhib Med Chem. 2019;34(1):577-588.
Powers AC, Niswender KD, Evans-Molina C. In: Jameson J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Loscalzo J, eds. Diabetes Mellitus: Diagnosis, Classification, and Pathophysiology. Harrison's Principles of Internal Medicine. 20th. New York: McGraw-Hill; 2018. https://accesspharmacy.mhmedical.com/content.aspx?bookid=2129§ionid=19228 8322. Accessed: April 17, 2020.
Brayer GD, Sidhu G, Maurus R, et al. Subsite mapping of the human pancreatic R-amylase active site through structural, kinetic, and mutagenesis techniques. Biochemistry. 2000;39(16):4778-4791.
Israili ZH. Advances in the treatment of type 2 diabetes mellitus. Am J Ther. 2011;18(2):117-152.
Ali MS, Jahangir M, ul Hussan SS, Choudhary MI. Inhibition of a-glucosidase by oleanolic acid and its synthetic derivatives. Phytochemistry. 2002;60:295-299.
Rouzbehan S, Moein S, Homaei A, Moein MR. Kinetics of α-glucosidase inhibition by different fractions of three species of Labiatae extracts: a new diabetes treatment model. Pharm Biol. 2017;55(1):1483-1488.
Stoilova I, Trifonova D, Marchev A, Stanchev V, Angelova G, Krastanov A. Phytochemical constituents and in vitro anti-diabetic properties of Ziziphus jujubа (Rhamnaceae) fruits. Int J Pharmacogn Phytochem Res. 2017;9(2):150-158.
Adisakwattana S, Chantarasinlapin P, Thammarat H, Yibchok-Anun S. A series of cinnamic acid derivatives and their inhibitory activity on intestinal α-glucosidase. J Enzyme Inhib Med Chem. 2009;24(5):1194-1200.
Asowata-Ayodele AM, Afolayan AJ, Otunola GA. Ethnobotanical survey of culinary herbs and spices used in the traditional medicinal system of Nkonkobe municipality, eastern cape, South Africa. S Afr J Bot. 2016;104:69-75.
Pereira ASP, Banegas-Luna AJ, Peña-García J, Pérez-Sánchez H, Apostolides Z. Evaluation of the anti-diabetic activity of some common herbs and spices: providing new insights with inverse virtual screening. Molecules. 2019;24(22):4030.
National Center for Biotechnology Information. PubChem Compound Summary for CID 7136, Acetyleugenol. In. PubChem Compound Summary for CID 7136, Acetyleugenol; October 2, 2020: National Library of Medicine; 2020. https://pubchem.ncbi.nlm.nih.gov/compound/Acetyleugenol. Accessed: October 2, 2020.
Shan B, Cai YZ, Sun M, Corke H. Antioxidant capacity of 26 spice extracts and characterization of their phenolic constituents. J Agric Food Chem. 2005;53(20):7749-7759.
Shukla R, Pandey V. Role of flavonoids in management of inflammatory disorders. In: Vadnere GP, Lodhi S, eds. Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory. 2nd. Cambridge, Massachusetts: Academic Press; 2019. https://www.sciencedirect.com/book/9780128138205/bioactive-food-as-dietary-interventions-for-arthritis-and-related-inflammatory-diseases. Accessed October 2, 2020.
Shankar E, Goel A, Gupta K, Gupta S. Plant flavone apigenin: an emerging anticancer agent. Curr Pharmacol Rep. 2017;3(6):423-446.
Das AB, Goud VV, Das C. Phenolic compounds as functional ingredients in beverages. Value-Added Ingredients and Enrichments of Beverages. India: Elsevier; 2019. 285-323. https://www.sciencedirect.com/book/9780128166871/value-added-ingredients-and-enrichments-of-beverages. Accessed: September 29, 2020.
Lee J, Lee DG, Park JY, Chae S, Lee S. Analysis of the trans-Cinnamic acid content in Cinnamomum spp and commercial cinnamon powder using HPLC. J Agr Chem Environ. 2015;04(04):102-108.
Lin LZ, Mukhopadhyay S, Robbins RJ, Harnly JM. Identification and quantification of flavonoids of Mexican oregano (Lippia graveolens) by LC-DAD-ESI/MS analysis. J Food Compost Anal. 2007;20(5):361-369.
Clarke S. Families of compounds that occur in essential oils. Essential Chemistry for Aromatherapy. London: Churchill Livingstone; 2008. https://www.sciencedirect.com/book/9780443104039/essential-chemistry-for-aromatherapy. Accessed: April 27, 2020.
Duke JA. Handbook of Phytochemical Constituents of GRAS Herbs and Other Economic Plants. Boca Raton, FL: CRC Press; 1992. https://phytochem.nal.usda.gov/phytochem/search/list. Accessed: October 2, 2020.
Izawa K, Amino Y, Masanori K. Human-environment interactions - taste. Comprehensive Natural Products II. Vol 4. Japan: Elsevier; 2010:631-671. https://www.sciencedirect.com/referencework/9780080453828/comprehensive-natural-products-ii. Accessed May 2, 2020.
Neveu V, Perez-Jiménez J, Vos F, et al. Phenol-explorer: an online comprehensive database on polyphenol contents in foods. Database. 2010. https://doi.org/10.1093/database/bap024. http://phenol-explorer.eu (free access).
The Metabolomics Innovation Centre: FooDB (Version 1.0). Database, Canada: The Metabolomics Innovation Centre. 2017. https://foodb.ca (free access),
Peter KV. Handbook of Herbs and Spices. 2nd ed. Cambridge: Woodhead Publishing; 2012. https://www.sciencedirect.com/book/9780857090393/handbook-of-herbs-and-spices. Accessed: April 12, 2020.
Balachandran P, Parthasarathy V, Kumar ATV. Isolation of compounds from Sargassum wightii by GCMS and the molecular docking against anti-inflammatory marker COX2. Int Lett Chem Phys Astron. 2016;63:1-12.
Subramaniyan V, Palani M, Srinivasan P, Kumar Singh S. Novel ligand-based docking; molecular dynamic simulations; and absorption, distribution, metabolism, and excretion approach to analyzing potential acetylcholinesterase inhibitors for Alzheimer's disease. Jf Pharm Anal. 2017;8(6):413-420.
Protein Preparation. Protein Preparation. Glide 6.7 User Manual. Schrödinger Press; 2015. http://gohom.win/ManualHom/Schrodinger/Schrodinger_2015-2_docs/glide/glide_user_manual.pdf. Accessed: October 27, 2019.
Dizdaroglu Y, Albay C, Arslan T, et al. Design, synthesis and molecular modeling studies of some pyrazole derivatives as carbonic anhydrase inhibitors. J Enzyme Inhib Med Chem. 2019;35(1):289-297.
Banerjee K, Gupta U, Gupta S, et al. Molecular docking of glucosamine-6-phosphate synthase in Rhizopus oryzae. Biomed Inform. 2011;7(6):285-290.
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.
Vichai V, Kirtikara K. Sulforhodamine B colorimetric assay for cytotoxicity screening. Nat Protoc. 2006;1(3):1112-1116.
Ademiluyi AO, Oboh G. Soybean phenolic-rich extracts inhibit key-enzymes linked to type 2 diabetes (alpha-amylase and alpha-glucosidase) and hypertension (angiotensin I converting enzyme) in vitro. Exp Toxicol Pathol. 2013;65(3):305-309.
Luyen NT, Binh PT, Tham PT, et al. Wedtrilosides A and B, two new diterpenoid glycosides from the leaves of Wedelia trilobata (L.) Hitch. with α-amylase and α-glucosidase inhibitory activities. Bioorg Chem. 2019;85:319-324.
Friesner RA, Banks JL, Murphy RB, et al. Glide: a new approach for rapid, accurate docking and scoring. 1. Method and assessment of docking accuracy. J Med Chem. 2004;47(7):1739-1749.
Sharma R, Kothapalli R, Van Dongen AM, Swaminathan K. Chemoinformatic identification of novel inhibitors against Mycobacterium tuberculosis L-aspartate alpha-decarboxylase. PLoS One. 2012;7(3):1-7.
Ntie-Kang F. An in silico evaluation of the ADMET profile of the StreptomeDB database. SpringerPlus. 2013;2(353):1-11.
QikProp 3. 5 User Manual [Schrodinger Press]. 2012. https://www.schrodinger.com. Accessed: April 27, 2020.
Jain PP, Degani MS, Raju A, Ray M, Rajan MGR. Rational drug design based synthesis of novel arylquinolines as anti-tuberculosis agents. Bioorg Med Chem Lett. 2013;23:6097-6105.
Rohini K, Shanthi V. Discovery of potent Neuraminidae inhibitors using a combination of pharmacophore-based virtual screening and molecular simulation approach. Appl Biochem Biotechnol. 2018;184:1421-1440.
Rahimzadeh M, Jahanshahi S, Moein S, Moein MR. Evaluation of alpha- amylase inhibition by Urtica dioica and Juglans regia extracts. Iran J Basic Med Sci. 2014;17:465-469.
Poovitha S, Parani M. In vitro and in vivo α-amylase and α-glucosidase inhibiting activities of the protein extracts from two varieties of bitter gourd (Momordica charantia L.). BMC Complement Altern Med. 2016;16(S1):185.
Son HU, Lee SH. Comparison of alpha-glucosidase inhibition by Cudrania tricuspidata according to harvesting time. Biomed Rep. 2013;1(4):624-628.
Etxeberria U, de la Garza AL, Campión J, Martínez JA, Milagro FI. Antidiabetic effects of natural plant extracts via inhibition of carbohydrate hydrolysis enzymes with emphasis on pancreatic alpha amylase. Expert Opin Ther Targets. 2012;16(3):269-297.
Galati G, O'Brien PJ. Potential toxicity of flavonoids and other dietary phenolics: significance for their chemopreventive and anticancer properties. Free Radic Biol Med. 2004;37(3):287-303.
Neiro EL, Machado-Santelli M. Cinnamic acid induces apoptotic cell death and cytoskeleton disruption in human melanoma cells. J Exp Clin Cancer Res. 2013;32(1):31.
Şahin S, Tezcan G, Demir C, Tunca B, ÇeÇener G, Egeli Ü. Cytotoxic activity of Rosmarinic acid isolated from Prunella vulgaris L. and Prunella grandiflora L. in different tumor cells. Trak Univ J Nat Sci. 2017;18(1):9-13.
Orlando JB, Silva BO, Pires-Cunha CL, Hiruma-Lima CA, Gaivao IOM, Maistro EL. Genotoxic effects induced by beta-myrcene following metabolism by liver HepG2/C3A human cells. J Toxicol Environ Health A. 2019;82(3):176-185.
Han Y, Chin Tan TM, Lim LY. In vitro and in vivo evaluation of the effects of piperine on P-gp function and expression. Toxicol Appl Pharmacol. 2008;230(3):283-289.
Paarakh PM, Sreeram DC, SS D, Ganapathy SP. In vitro cytotoxic and in silico activity of piperine isolated from Piper nigrum fruits Linn. In Silico Pharmacol. 2015;3(1):9.
Mclver LA, Tripp J. Acarbose [StatPearls Publishing] 2020. https://www.ncbi.nlm.nih.gov/books/NBK493214/. Accessed: April 27, 2020.
Balfour JA, McTavish D. Acarbose: an update of its pharmacology and therapeutic use in diabetes mellitus. Drugs. 1993;46(6):1025-1054.
Coniff RF, Shapiro JA, Robbins D, et al. Reduction of glycosylated hemoglobin and postprandial hyperglycemia by acarbose in patients with NIDDM: a placebo-controlled dose-comparison study. Diabetes Care. 1995;18(6):817-824.
Pirički AP, Moslavac T, Vugrinec M. Acceptability of parsley tea by adolescents. Glasnik Zastite Bilja. 2010;33(1):46-53.
Mani F, Braga CP, Novelli ELB, Sforcin JM. Influence of clove tea (Syzygium aromaticum) on body weight and biochemical parameters of rats subjected to ethanol consumption and abstinence. Med Chem. 2012;2(4):81-85.
Pȩkal A, Dróżdż P, Biesaga M, Pyrzynska K. Screening of the antioxidant properties and polyphenol composition of aromatised green tea infusions. J Sci Food Agric. 2012;92(11):2244-2249.