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Plant Science Today (PST)

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Early Access

Evaluation of the alpha-amylase inhibitory activity of Euclea natalensis extracts used in the treatment of diabetes mellitus: An experimental and in silico approach

DOI
https://doi.org/10.14719/pst.2845
Submitted
6 August 2023
Published
22-05-2024
Versions

Abstract

Diabetes, a chronic metabolic disorder with increasing global prevalence, poses a significant public health concern, necessitating the development of safe and effective drugs. This study specifically assessed the inhibitory effects of Euclea natalensis leaf extracts on alpha-amylase through in vitro, in vivo, and in silico methods. The extracts were sequentially obtained using solvents of graded polarity. alpha-amylase inhibition studies were conducted through spectrophotometric methods, while in vivo assessments were performed using a starch tolerance test on rats. Molecular docking was carried out using Autodock 4.2.6, and SwissADME, along with ADMETlab 2.0, were employed to determine the drug-likeness and toxicity properties of the literature-mined compounds. The extracts demonstrated significant in vitro inhibition of alpha-amylase, with the methanol extract exhibiting the highest percentage of inhibition at 27% ± 4.2, followed by hexane and aqueous extracts at 18% ± 2.5 and 18% ± 3.7, respectively. In vivo, the extracts lowered blood glucose levels, with acarbose reducing peak blood glucose levels by 42%, while both the aqueous and methanol extracts reduced it by 19% each after 30 min. The overall glucose-lowering effect, based on the area under the starch tolerance curve, ranked as follows: acarbose > methanol > aqueous > hexane > dichloromethane extract. Molecular docking identified 20(29)-lupene-3 beta-isoferulate C3 as the most promising compound with the lowest binding energy of -11.4 kcal/mol. Molecular dynamics revealed that C3 loses stability as it diverges from the active site. Additionally, while all other compounds passed the Lipinski drug-likeness criteria, 20(29)-lupene-3 beta-isoferulate C3 did not. Therefore, the present study suggests that E. natalensis exhibits antidiabetic properties through the inhibition of alpha-amylase and may serve as a source of potential antidiabetic drug molecules.

References

  1. IDF. IDF diabetes atlas 10th edition [Internet]. Brussels, International Diabetes Federation. 2021; p. 5-7. https://doi.org/https://diabetesatlas.org/atlas/tenth-edition/
  2. ElSayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D et al. Classification and diagnosis of diabetes: Standards of care in diabetes. Diabetes Care. 2023;46(1):19-40. https://doi.org/10.2337/dc23-S002
  3. Elsayed NA, Aleppo G, Aroda VR, Bannuru RR, Brown FM, Bruemmer D et al. Pharmacologic approaches to glycemic treatment: Standards of care in diabetes. Diabetes Care. 2023;46(supp):S140-57. https://doi.org/10.2337/dc23-S009-
  4. Zhou X, Shrestha SS, Shao H, Zhang P. Factors contributing to the rising national cost of glucose lowering medicines for diabetes during 2005–2007 and 2015–2017. Diabetes Care. 2020;43(10):20-29. https://doi.org/10.2337/dc19-2273
  5. Tiongco REG, Arceo ES, Rivera NS, Flake CCD, Policarpio AR. Estimation of salivary glucose, amylase, calcium and phosphorus among non-diabetics and diabetics: Potential identification of non-invasive diagnostic markers. Diabetes Metab Syndr. 2019;13(4):2601-05. https://doi.org/10.1016/j.dsx.2019.07.037
  6. Pérez-Ros P, Navarro-Flores E, Julián-Rochina I, Martínez-Arnau FM, Cauli O. Changes in salivary amylase and glucose in diabetes: A scoping review. Diagnostics. 2021;11(3):453. https://doi.org/10.3390/diagnostics11030453
  7. Standl E, Baumgartl HJ, Füchtenbusch M, Stemplinger J. Effect of acarbose on additional insulin therapy in type 2 diabetic patients with late failure of sulphonylurea therapy. Diabetes Obes Metab. 1999;1(4):215-20. https://doi.org/10.1046/j.1463-1326.1999.00021.x
  8. Kumar Y, Goyal K, Kumar AK. Pharmacotherapeutics of miglitol: An ?-glucosidase inhibitor. J Anal Pharm Res. 2018;7(6);617-19. https://doi.org/10.15406/japlr.2018.07.00292
  9. Matsumoto K, Yano M, Miyake S, Ueki Y, Yamaguchi Y, Akazawa S, Tominaga Y. Effects of voglibose on glycemic excursions, insulin secretion and insulin sensitivity in non-insulin-treated NIDDM patients. Diabetes Care. 1998;21(2):256-60. https://doi.org/10.2337/diacare.21.2.256
  10. Mentreddy SR. Medicinal plant species with potential antidiabetic properties. J Sci Food Agric. 2007;87(5):1074-79. https://doi.org/10.1002/jsfa.2811
  11. Usai R, Majoni S, Rwere F. Natural products for the treatment and management of diabetes mellitus in Zimbabwe-a review. Front Pharmacol. 2022;13:1-21. https://doi.org/10.3389/fphar.2022.980819
  12. Mbuni YM, Wang S, Mwangi BN, Mbari NJ, Musili PM, Walter NO, Hu G, Zhou Y, Wang Q. Medicinal plants and their traditional uses in local communities around Cherangani hills, Western Kenya. Plants. 2020;9(3):331. https://doi.org/10.3390/plants9030331
  13. Renuka R, Jeyanthi GP. Evaluation of in vitro ? - amylase inhibitory kinetics and free radical scavenging activities of Momordica charantia. Int J ChemTech Res. 2017;10(7):315-23.
  14. Li K, Yao F, Xue Q, Fan H, Yang L, Li X, Sun L, Liu Y. Inhibitory effects against ?-glucosidase and ?-amylase of the flavonoids-rich extract from Scutellaria baicalensis shoots and interpretation of structure–activity relationship of its eight flavonoids by a refined assign-score method. Chem Cent J. 2018;12(1):82. https://doi.org/10.1186/s13065-018-0445-y
  15. Ben LJ, Boujbiha MA, Dahane S, Cherifa AB, Khlifi A, Chahdoura H et al. ?-Amylase and ?-glucosidase inhibitor effects and pancreatic response to diabetes mellitus on Wistar rats of Ephedra alata areal part decoction with immunohistochemical analyses. Environ Sci Pollut Res. 2019;26(10):9739-54. https://doi.org/10.1007/s11356-019-04339-3
  16. Bati K, Kwape TE, Chaturvedi P. Anti-diabetic effects of an ethanol extract of Cassia abbreviata stem bark on diabetic rats and possible mechanism of its action. J Pharmacopuncture. 2017;20(1):45-51. https://doi.org/10.3831/KPI.2017.20.008
  17. Maroyi A. Review of ethnomedicinal uses, phytochemistry and pharmacological properties of Euclea natalensis A.DC. Molecules. 2017;22(12):2128. https://doi.org/10.3390/molecules22122128
  18. Lall N, Weiganand O, Hussein AA, Meyer JJM. Antifungal activity of naphthoquinones and triterpenes isolated from the root bark of Euclea natalensis. S Afr J Bot. 2006;72(4):579-83. https://doi.org/10.1016/j.sajb.2006.03.005
  19. Kooy F, Meyer JJM, Lall N, Matumba MG, Ayeleso AO, Nyakudya TT et al. Antimycobacterial activity and possible mode of action of newly isolated neodiospyrin and other naphthoquinones from Euclea natalensis. J Ethnopharmacol. 2012;7:349-52. https://doi.org/10.3390/molecules24040661
  20. Deutschländer MS, Lall N, Van de Venter M, Dewanjee S. The hypoglycemic activity of Euclea undulata Thunb. var. myrtina (Ebenaceae) root bark evaluated in a streptozotocin–nicotinamide induced type 2 diabetes rat model. S Afr J Bot. 2012;80:9-12. https://doi.org/10.1016/j.sajb.2012.02.006
  21. Nkobole N, Houghton PJ, Hussein A, Lall N. Antidiabetic activity of Terminalia sericea constituents. Nat Prod Commun. 2011;6(11):1585-88. https://doi.org/10.1177/1934578x1100601106
  22. Kamtekar S, Keer V, Patil V. Estimation of phenolic content, flavonoid content, antioxidant and alpha amylase inhibitory activity of marketed polyherbal formulation. J Appl Pharm Sci. 2014;4(9):61-65. https://doi.org/10.7324/JAPS.2014.40911
  23. Dou F, Xi M, Wang J, Tian X, Hong L, Tang H, Wen A. ?-Glucosidase and ?-amylase inhibitory activities of saponins from traditional Chinese medicines in the treatment of diabetes mellitus. Pharmazie. 2013;68(4):300-04. https://doi.org/10.1691/ph.2013.2753
  24. Bati K. Evaluation of the antidiabetic effects and possible mechanisms of action of Euclea natalensis extracts [Dissertation]. Botswana International University of Science and Technology; 2021.
  25. Zhao B, Wu F, Han X, Zhou W, Shi Q, Wang H. Protective effects of acarbose against insulitis in multiple low-dose streptozotocin-induced diabetic mice. Life Sci. 2020;263. https://doi.org/10.1016/j.lfs.2020.118490
  26. Rosak C, Mertes G. Critical evaluation of the role of acarbose in the treatment of diabetes: Patient considerations. Diabetes Metab Syndr Obes. 2012;5:357-67. https://doi.org/10.2147/dmso.s28340
  27. Li W, Yuan G, Pan Y, Wang C, Chen H. Network pharmacology studies on the bioactive compounds and action mechanisms of natural products for the treatment of diabetes mellitus: A review. Front Pharmacol. 2017;8(2):1-10. https://doi.org/10.3389/fphar.2017.00074
  28. Striegel L, Kang B, Pilkenton SJ, Rychlik M, Apostolidis E. Effect of black tea and black tea pomace polyphenols on ?-glucosidase and ?-amylase inhibition, relevant to type 2 diabetes prevention. Front Nutr. 2015;2(2):1-6. https://doi.org/10.3389/fnut.2015.00003
  29. Deutschländer MS, Lall N, Van de Venter M, Hussein AA. Hypoglycemic evaluation of a new triterpene and other compounds isolated from Euclea undulata Thunb. var. myrtina (Ebenaceae) root bark. J Ethnopharmacol. 2011;133(3):1091-95. https://doi.org/10.1016/J.JEP.2010.11.038
  30. 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. https://doi.org/10.1186/1472-6882-13-39
  31. Guerrero-Romero F, Simental-Mendía LE, Guerra Rosas MI, Sayago-Monreal VI, Morales Castro J, Gamboa-Gómez CI. Hypoglycemic and antioxidant effects of green tomato (Physalis ixocarpa Brot.) calyxes’ extracts. J Food Biochem. 2021;45(4):e13678. https://doi.org/10.1111/jfbc.13678
  32. Beejmohun V, Peytavy-Izard M, Mignon C, Muscente-Paque D, Deplanque X, Ripoll C, Chapal N. Acute effect of Ceylon cinnamon extract on postprandial glycemia: Alpha-amylase inhibition, starch tolerance test in rats and randomized crossover clinical trial in healthy volunteers. BMC Complement Altern Med. 2012;14(1):351. https://doi.org/10.1186/1472-6882-14-351
  33. Meng XY, Zhang HX, Mezei M, Cui M. Molecular docking: A powerful approach for structure-based drug discovery. Curr Comput Aided Drug Des. 2012;7(2):146-57. https://doi.org/10.2174/157340911795677602
  34. Li J, Fu A, Zhang L. An overview of scoring functions used for protein–ligand interactions in molecular docking. Interdiscip Sci. 2019;11(2):320-28. https://doi.org/10.1007/s12539-019-00327-w
  35. Naqvi AAT, Mohammad T, Hasan GM, Hassan MdI. Advancements in docking and molecular dynamics simulations towards ligand-receptor interactions and structure-function relationships. Curr Top Med Chem. 2019;18(20):1755-68. https://doi.org/10.2174/1568026618666181025114157
  36. Martínez L. Automatic identification of mobile and rigid substructures in molecular dynamics simulations and fractional structural fluctuation analysis. PLoS One. 2015;10(3):e0119264. https://doi.org/10.1371/journal.pone.0119264
  37. Kwofie SK, Broni E, Asiedu SO, Kwarko GB, Dankwa B, Enninful KS et al. Cheminformatics-based identification of potential novel anti-sars-cov-2 natural compounds of African origin. Molecules. 2021;26(2):406. https://doi.org/10.3390/molecules26020406
  38. Zhao Y, Zeng C, Massiah MA. Molecular dynamics simulation reveals insights into the mechanism of unfolding by the A130T/V mutations within the MID1 zinc-binding Bbox1 domain. PLoS One. 2015;10(4):e0124377. https://doi.org/10.1371/journal.pone.0124377
  39. Oyewusi HA, Wu YS, Safi SZ, Wahab RA, Hatta MHM, Batumalaie K. Molecular dynamics simulations reveal the inhibitory mechanism of Withanolide A against ?-glucosidase and ?-amylase. J Biomol Struct Dyn. 2023;41(13):6203-18. https://doi.org/10.1080/07391102.2022.2104375
  40. Akshatha JV, SantoshKumar HS, Prakash HS, Nalini MS. In silico docking studies of ?-amylase inhibitors from the anti-diabetic plant Leucas ciliata Benth. and an endophyte, Streptomyces longisporoflavus. 3Biotech. 2021;11:51. https://doi.org/10.1007/s13205-020-02547-0
  41. Swargiary A, Daimari M. GC–MS analysis of phytocompounds and antihyperglycemic property of Hydrocotyle sibthorpioides Lam. SN Appl Sci. 2021;3:36. https://doi.org/10.1007/s42452-020-04101-2

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