Anti-hyperglycemic effect of two terpenoids isolated from Coula edulis on normoglycemic rats and in silico study of their potential inhibitors on α-amylase and dipeptidylpeptidase 4

Authors

  • Manuela Guaelle Kepawou Department of Organic Chemistry, Faculty of Sciences, The University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon
  • Bruno Dupon Ambamba Akamba Department of Biochemistry, Faculty of Science, University of Yaoundé 1, Yaoundé, Cameroon
  • Michael Hermann Kengne Kamdem Drug Discovery and Smart Molecules Research Laboratory, Department of Chemical Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg 2028, South Africa.
  • Cicilien Quentin Nongni Piebeng Department of Biochemistry, Faculty of Science, University of Yaoundé 1, Yaoundé, Cameroon
  • Valery Wilfried Nguemdjo Chimeze Department of Organic Chemistry, Faculty of Sciences, The University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon
  • Ferdinand Lanvin Edoun Ebouel Department of Biochemistry, Faculty of Science, University of Yaoundé 1, Yaoundé, Cameroon
  • Edwin Mpho Mmutlane Center for Natural Product Research (CNPR), Chemical Sciences Department, University of Johannesburg, Doornfontein, Johannesburg 2028, South Africa.
  • Derek Tantoh Ndinteh Center for Natural Product Research (CNPR), Chemical Sciences Department, University of Johannesburg, Doornfontein, Johannesburg 2028, South Africa.
  • Céline Djama Mbazoa Department of Organic Chemistry, Faculty of Sciences, The University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon
  • Judith Laure Ngondi Department of Biochemistry, Faculty of Science, University of Yaoundé 1, Yaoundé, Cameroon
  • Jean Wandji Department of Organic Chemistry, Faculty of Sciences, The University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon

Abstract

Diabetes causes many deaths around the world, making the search for treatments a real challenge. Plant secondary metabolites are promising candidates because they act as scaffolds in biological processes. This study investigates anti-hyperglycaemic effect of two terpenoids isolated from Coula edulis and in silico study of their potential inhibitors on α-amylase and dipeptidypeptidase 4. After extraction and isolation of the two terpenoids, their structures were characterized using 1D and 2D NMR spectroscopic techniques. Subsequently the anti-hyperglycemic effect was achieved following an overload of starch on the one hand and glucose on the other hand in normoglycemic rats. Each isolated terpenoids was tested at a dose of 3 mg/kg.bw, the same for the reference compounds (Acarbose and glibenclamide). Conformational site analysis and docking parameters such as binding energy, inhibition constant, interaction profiles with diabetes target residues (α-amylase and dipeptidypeptidase 4) were determined using AutoDock 4.2 and Discovery Studio visualizer. The results showed that the terpenoids isolated from coula edulis were Taraxerol and 3β-(Z)-coumaroyltaraxerol, each of its two terpenoids considerably decreased the blood sugar levels in rats after overloading of starch and glucose solutions respectively. Their effects were similar to the reference drugs. Furthermore, the in-silico approach showed that these compounds have good docking scores with α-amylase and with DPP4. Taraxerol exhibited a docking score more than three times than the acarbose docking score. Only 3β-(Z)-coumaroyltaraxerol reacts with at least one amino acid of the α-amylase catalytic triad (Asp 300). Both interact with histidine (His 740) of the DPP4 catalytic triad. In view of this results, taraxerol and 3β-(Z)-coumaroyltaraxerol have anti-hyperglycemic effects and are good candidates for the development of new multitarget antidiabetics.

Keywords: Coula edulis, RMN 1D and 2D, tarxerol, 3β-(Z)-coumaroyltaraxerol and Anti-hyperglycemia

Keywords:

Coula edulis, RMN 1D and 2D, tarxerol, 3β-(Z)-coumaroyltaraxerol, Anti-hyperglycemia

DOI

https://doi.org/10.22270/jddt.v14i2.6406

Author Biographies

Manuela Guaelle Kepawou, Department of Organic Chemistry, Faculty of Sciences, The University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon

Department of Organic Chemistry, Faculty of Sciences, The University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon

Bruno Dupon Ambamba Akamba, Department of Biochemistry, Faculty of Science, University of Yaoundé 1, Yaoundé, Cameroon

Center of Nutrition and Functional Foods, P.O. Box 8024 Yaounde, Cameroon

Michael Hermann Kengne Kamdem, Drug Discovery and Smart Molecules Research Laboratory, Department of Chemical Sciences, University of Johannesburg, P.O. Box 17011, Doornfontein, Johannesburg 2028, South Africa.

Center for Natural Product Research (CNPR), Chemical Sciences Department, University of Johannesburg, Doornfontein, Johannesburg 2028, South Africa.

Research Center for Synthesis and catalysis; Department of Chemical Sciences, University of Johannesburg-Kingsway campus, Auckland Park, 2008, South Africa.

Cicilien Quentin Nongni Piebeng, Department of Biochemistry, Faculty of Science, University of Yaoundé 1, Yaoundé, Cameroon

Center of Nutrition and Functional Foods, P.O. Box 8024 Yaounde, Cameroon

Valery Wilfried Nguemdjo Chimeze, Department of Organic Chemistry, Faculty of Sciences, The University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon

Department of Organic Chemistry, Faculty of Sciences, The University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon

Ferdinand Lanvin Edoun Ebouel, Department of Biochemistry, Faculty of Science, University of Yaoundé 1, Yaoundé, Cameroon

Centre for Food, Food Security and Nutrition Research, Institute of Medical Research and Medicinal Plant Studies, P. O. Box 1033, Yaounde, Cameroon

Edwin Mpho Mmutlane, Center for Natural Product Research (CNPR), Chemical Sciences Department, University of Johannesburg, Doornfontein, Johannesburg 2028, South Africa.

Center for Natural Product Research (CNPR), Chemical Sciences Department, University of Johannesburg, Doornfontein, Johannesburg 2028, South Africa.

Derek Tantoh Ndinteh, Center for Natural Product Research (CNPR), Chemical Sciences Department, University of Johannesburg, Doornfontein, Johannesburg 2028, South Africa.

 Research Center for Synthesis and catalysis; Department of Chemical Sciences, University of Johannesburg-Kingsway campus, Auckland Park, 2008, South Africa.

Céline Djama Mbazoa, Department of Organic Chemistry, Faculty of Sciences, The University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon

Department of Organic Chemistry, Faculty of Sciences, The University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon

Judith Laure Ngondi, Department of Biochemistry, Faculty of Science, University of Yaoundé 1, Yaoundé, Cameroon

Center of Nutrition and Functional Foods, P.O. Box 8024 Yaounde, Cameroon

Jean Wandji, Department of Organic Chemistry, Faculty of Sciences, The University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon

Department of Organic Chemistry, Faculty of Sciences, The University of Yaoundé 1, P.O. Box 812, Yaoundé, Cameroon

References

Saeedi P, Petersohn I, Salpea P, Malanda B, Karuranga S, Unwin N, et al. Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9th edition. Diabetes Res Clin Pract. 2019 Nov;157:107843. https://doi.org/10.1016/j.diabres.2019.107843 PMid:31518657

Goyal R, Singhal M, Jialal I. Type 2 Diabetes. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 Oct 29]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK513253/

Monnier L, Colette C, Owens D. Postprandial and basal glucose in type 2 diabetes: assessment and respective impacts. Diabetes Technol Ther. 2011 Jun;13 Suppl 1:S25-32. https://doi.org/10.1089/dia.2010.0239 PMid:21668334

Aryangat AV, Gerich JE. Type 2 diabetes: postprandial hyperglycemia and increased cardiovascular risk. Vasc Health Risk Manag. 2010;6:145-55. Available from: https://www.tandfonline.com/doi/abs/10.2147/vhrm.s8216 https://doi.org/10.2147/VHRM.S8216 PMid:20448799 PMCid:PMC2860446

Hinnen DA. Therapeutic Options for the Management of Postprandial Glucose in Patients With Type 2 Diabetes on Basal Insulin. Clin Diabetes. 2015;33(4):175-80. https://doi.org/10.2337/diaclin.33.4.175 PMid:26487791 PMCid:PMC4608276

Zhang X, Caner S, Kwan E, Li C, Brayer GD, Withers SG. Evaluation of the Significance of Starch Surface Binding Sites on Human Pancreatic α-Amylase. Biochemistry. 2016;55(43):6000-9. https://doi.org/10.1021/acs.biochem.6b00992 PMid:27756128

Janeček Š, Svensson B, MacGregor EA. α-Amylase: an enzyme specificity found in various families of glycoside hydrolases. Cell Mol Life Sci. 2014;71(7):1149-70. https://doi.org/10.1007/s00018-013-1388-z PMid:23807207

Hossain MdA, Pervin R. Chapter 34 - Current Antidiabetic Drugs: Review of Their Efficacy and Safety. In: Bagchi D, Nair S, editors. Nutritional and Therapeutic Interventions for Diabetes and Metabolic Syndrome (Second Edition). Academic Press; 2018; p. 455-73. Available from: https://www.sciencedirect.com/science/article/pii/B9780128120194000349 https://doi.org/10.1016/B978-0-12-812019-4.00034-9 PMid:30522487 PMCid:PMC6282300

Röhrborn D, Wronkowitz N, Eckel J. DPP4 in Diabetes. Front Immunol. 2015;6:386. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4515598/ https://doi.org/10.3389/fimmu.2015.00386 PMid:26284071 PMCid:PMC4515598

Scheen AJ. Dipeptidylpeptidase-4 inhibitors (gliptins): focus on drug-drug interactions. Clin Pharmacokinet. 2010 Sep;49(9):573-88. https://doi.org/10.2165/11532980-000000000-00000 PMid:20690781

Abid S, Bnouham M. A Review on Experimental Models to Test Medicinal Plants on Postprandial Blood Glucose in Diabetes. Curr Diabetes Rev. 2023;19(9):e080422203278. https://doi.org/10.2174/1573399818666220408100830 PMid:35400346

Panigrahy SK, Bhatt R, Kumar A. Targeting type II diabetes with plant terpenes: the new and promising antidiabetic therapeutics. Biologia (Bratisl). 2021 Jan 1;76(1):241-54. https://doi.org/10.2478/s11756-020-00575-y

Abdullahi M, Adeniji SE. In-silico Molecular Docking and ADME/Pharmacokinetic Prediction Studies of Some Novel Carboxamide Derivatives as Anti-tubercular Agents. Chem Afr. 2020;3(4):989-1000. https://doi.org/10.1007/s42250-020-00162-3

Beyegue E, Azantsa B, Mbong Angie MA, Oben J. Inhibition of Digestive Enzymes, Antioxidant and Free Radical Scavenging Capacities of Stem Bark Extracts of Coula edulis Baill (Olacaceae). J Food Res. 2021 Sep 10;10:1. https://doi.org/10.5539/jfr.v10n5p1

Tamokou JDD, Kuiate JR, Gatsing D, Efouet APN, Njouendou AJ. Antidermatophytic and Toxicological Evaluations of Dichloromethane-Methanol Extract, Fractions and Compounds Isolated from Coula edulis. Iran J Med Sci. 2011 Jun;36(2):111-21.

Kuppusamy A, Arumugam M, George S. Combining in silico and in vitro approaches to evaluate the acetylcholinesterase inhibitory profile of some commercially available flavonoids in the management of Alzheimer's disease. Int J Biol Macromol. 2017 Feb;95:199-203. https://doi.org/10.1016/j.ijbiomac.2016.11.062 PMid:27871793

Brayer GD, Luo Y, Withers SG. The structure of human pancreatic alpha-amylase at 1.8 A resolution and comparisons with related enzymes. Protein Sci Publ Protein Soc. 1995 Sep;4(9):1730-42. https://doi.org/10.1002/pro.5560040908 PMid:8528071 PMCid:PMC2143216

Morris GM, Goodsell DS, Halliday RS, Huey R, Hart WE, Belew RK, et al. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J Comput Chem [Internet]. 1998;19(14):1639-62. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1002/%28SICI%291096-987X%2819981115%2919%3A14%3C1639%3A%3AAID-JCC10%3E3.0.CO%3B2-B

Nithyamol Kalappurakkal V, Bhattacharya D, Chakravarty S, Venkata Uppuluri M. Isolation, Synthesis and AChE Inhibitory Potential of Some Novel Cinnamyl Esters of Taraxerol, the Major Metabolite of the Mangrove Bruguiera cylindrica. Chem Biodivers. 2018 Apr;15(4):e1800008. https://doi.org/10.1002/cbdv.201800008 PMid:29418068

Lawal TA, Ononamadu CJ, Okonkwo EK, Adedoyin HJ, Shettima ML, Muhammad IU, et al. In Vitro and In Vivo Hypoglycaemic Effect of Camellia Sinensis on Alpha Glucosidase Activity and Glycaemic Index of White Bread. Appl Food Res. 2022 Jun 1;2(1):100037. https://doi.org/10.1016/j.afres.2021.100037

Wilcox G. Insulin and Insulin Resistance. Clin Biochem Rev. 2005 May;26(2):19-39. https://doi.org/10.1016/S1097-8690(06)73608-3

Pulikkottil AA, Kumar A, Jangid K, Kumar V, Jaitak V. Structure-based Virtual Screening and Molecular Dynamic Simulation Approach for the Identification of Terpenoids as Potential DPP-4 Inhibitors. Curr Comput Aided Drug Des. 2024;20(4):416-29. https://doi.org/10.2174/1573409919666230515160502 PMid:37190809

Deacon CF. Dipeptidyl peptidase 4 inhibitors in the treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2020;16(11):642-53. Available from: https://www.nature.com/articles/s41574-020-0399-8 https://doi.org/10.1038/s41574-020-0399-8 PMid:32929230

Published

15-02-2024
Statistics
Abstract Display: 291
PDF Downloads: 206
PDF Downloads: 13

How to Cite

1.
Kepawou MG, Ambamba Akamba BD, Kamdem MHK, Piebeng CQN, Chimeze VWN, Ebouel FLE, et al. Anti-hyperglycemic effect of two terpenoids isolated from Coula edulis on normoglycemic rats and in silico study of their potential inhibitors on α-amylase and dipeptidylpeptidase 4. J. Drug Delivery Ther. [Internet]. 2024 Feb. 15 [cited 2025 Feb. 13];14(2):147-5. Available from: https://jddtonline.info/index.php/jddt/article/view/6406

How to Cite

1.
Kepawou MG, Ambamba Akamba BD, Kamdem MHK, Piebeng CQN, Chimeze VWN, Ebouel FLE, et al. Anti-hyperglycemic effect of two terpenoids isolated from Coula edulis on normoglycemic rats and in silico study of their potential inhibitors on α-amylase and dipeptidylpeptidase 4. J. Drug Delivery Ther. [Internet]. 2024 Feb. 15 [cited 2025 Feb. 13];14(2):147-5. Available from: https://jddtonline.info/index.php/jddt/article/view/6406

Most read articles by the same author(s)