DPP-IV Inhibitory Activity of the Ethanolic Extract of Red Gedi Leaves Abelmoschus manihot L. Medic
DOI:
https://doi.org/10.3889/oamjms.2022.8356Keywords:
Abelmoschus manihot L. Medic, DPP-IV inhibitor, Molecular docking, In vitroAbstract
BACKGROUND: At present, there are many drugs used to manage diabetes including dipeptidyl peptidase-4 (DPP-IV) inhibitors which target insulin secretion. Abelmoschus manihot L. Medic, an endemic species of Minahasa, Indonesia, has been used as an antidiabetic herbal medicine.
AIM: In this study, we studied its metabolites activities, in silico and in vitro, as inhibitor for DPP-IV, thus regulating insulin secretion.
RESULTS: Of 38 identified metabolites, when docked into the catalytic site DPP-IV, 10 showed good binding energy within range of the standard gliptin drugs, that is, hibiscetin, gossypentin, gossypetin - 3-glucoside, myricetin, myricetin 3-glucoside, alpha spinasterol, quercetin, syringaresinol, stigmasterol, and isoquercetin. Three of those ten metabolites showed Ki within standard drugs values, that is, gossypetin, alpha spinasterol, and stigmasterol. The profile of molecular dynamic simulation, total energy and root mean square deviation of those metabolites were all similar with the standard gliptin drugs and predicted good stability of the complexes. The subsequent in vitro assay determining DPP-IV activity of the red Gedi leaves extract demonstrated that indeed the extract inhibited DPP-IV activity with IC50 860.67 μg/mL. Further studies are ongoing to prove the antidiabetic properties of the whole as well as isolated single compounds of the extract in particular gossypetin, alpha spinasterol, and stigmasterol as DPP-IV inhibitors.
CONCLUSION: Our in silico studies showed that the compounds of ethanolic extract of red Gedi leaves potentially serve as DPP-IV inhibitors. Based on computed binding affinity, Ki, total energy, RMSD, and stability, the most potent compounds of the extract to inhibit DPP-IV activity are probably gossypetin, alpha spinasterol, and stigmasterol.Downloads
Metrics
Plum Analytics Artifact Widget Block
References
DeFronzo RA, Ferrannini E, Groop L, Henry RR, Herman WH, Holst JJ, et al. Type 2 diabetes mellitus. Nat Rev Dis Primers. 2015;1(1):15019. https://doi.org/10.1038/nrdp.2015.19 PMid:27189025 DOI: https://doi.org/10.1038/nrdp.2015.19
Khan MA, Hashim MJ, King JK, Govender RD, Mustafa H, Al Kaabi J. Epidemiology of Type 2 diabetes-global burden of disease and forecasted trends. J Epidemiol Glob Health. 2020;10(1):107-11. https://doi.org/10.2991/jegh.k.191028.001 PMid:32175717 DOI: https://doi.org/10.2991/jegh.k.191028.001
Suoth E, Kaempe H, Tampi A. Evaluation of total polyphenol and flavonoids isolation of red gedi leaves (Abelmoschus manihot L.) (Evaluasi Kandungan Total Polifenol dan Isolasi Senyawa Flavonoid Pada Daun Gedi Merah). Chem Progress. 2013;6(2):86-91. https://doi.org/10.35799/cp.6.2.2013.3500
Nurrani L, Kinho J. Utilization of natural plant by the North Sulawesi community as a lowering of diabetic. In: International Conference on Forest and Biodiversity. Manado, Indonesia. Manado, Indonesia: Manado Forestry Research Institute; 2013. p. 443-52.
Tangka J, Barung EN, Lyrawati D, Soeatmadji DW, Nurdiana. Identification of metabolite compounds from ethanolic extract of the red gedi leaves (Abelmoschus manihot L. Medik) by LC-ESI-MS. Res J Pharm Tech. 2021. In Press.
Purnomo Y, Soeatmadji DW, Sumitro SB, Widodo MA. Anti-diabetic potential of Urena lobata leaf extract through inhibition of dipeptidyl peptidase IV activity. Asian Pac J Trop Biomed. 2015;5(8):645-9. https://doi.org/10.1016/j.apjtb.2015.05.014 DOI: https://doi.org/10.1016/j.apjtb.2015.05.014
Fuadi A, Tangka J, Martino YA, Purnomo Y. Potency of ethanolic extract of Abelmoschus manihot (L.) Medik on kidney SOD levels and kidney MDA levels in diabetic rat model. J Bio Komplementer Med. 2020;7(2):1-8.
Fitriyah NY, Tangka J, Amalia Y, Purnomo Y. Effect of ethanolic extract of Abelmoschus manihot (L.) Medik on tissue tnf-alfa levels and aortic lumen diameter of diabetic rat. J Community Med. 2020;8(2):1-7.
Nurasidah R, Tangka J, Elyani H, Purnomo Y. Effect ethanolic extract of Abelmoschus manihot (L.) Medik on renal tumor necrosis factor alpha (TNF-α) levels and glomerular epithelial cell necrosis levels in diabetic rat model. J Bio Komplementer Med. 2020;7(2):1-10.
Sakinah A, Tangka J, Purwanti S, Purnomo Y. Effect of ethanol extract of Abelmoschus manihot (L.) Medik on TNFalfa heart levels and total of cardiomyocyte necrosis in diabetes mellitus rats. J Bio Komplementer Med. 2020;7(2):1-9.
Cole DJ, Horton JT, Nelson L, Kurdekar V. The future of force fields in computer-aided drug design. Future Med Chem. 2019;11(18):2359-63. https://doi.org/10.4155/fmc-2019-0196 DOI: https://doi.org/10.4155/fmc-2019-0196
Hu Z, Jiang J. Assessment of biomolecular force fields for molecular dynamics simulations in a protein crystal. J Comput Chem. 2010;31(2):371-80. https://doi.org/10.1002/jcc.21330 PMid:19479737 DOI: https://doi.org/10.1002/jcc.21330
Tian C, Kasavajhala K, Belfon KA, Raguette L, Huang H, Migues AN, et al. ff19SB: Amino-acid-specific protein backbone parameters trained against quantum mechanics energy surfaces in solution. J Chem Theory Comput. 2020;16(1):528-52. https://doi.org/10.1021/acs.jctc.9b00591 PMid:31714766 DOI: https://doi.org/10.1021/acs.jctc.9b00591
Case DA, Cheatham TE 3rd, Darden T, Gohlke H, Luo R, Merz KM Jr., et al. The Amber biomolecular simulation programs. J Comput Chem. 2005;26(16):1668-88. https://doi.org/10.1002/jcc.20290 PMid:16200636 DOI: https://doi.org/10.1002/jcc.20290
Patel BD, Ghate MD. Recent approaches to medicinal chemistry and therapeutic potential of dipeptidyl peptidase-4 (DPP-4) inhibitors. Eur J Med Chem. 2016;74:574-605. https://doi.org/10.1016/j.ejmech.2013.12.038 PMid:24531198 DOI: https://doi.org/10.1016/j.ejmech.2013.12.038
Verma D, Mitra D, Paul M, Chaudhary P, Kamboj A, Thatoi H, et al. Potential inhibitors of SARS-CoV-2 (COVID 19) proteases PLpro and Mpro/3CLpro molecular docking and simulation studies of three pertinent medicinal plant natural components. Curr Res Pharmacol Drug Discov. 2021;2:100038. https://doi.org/10.1016/j.crphar.2021.100038 PMid:34870149 DOI: https://doi.org/10.1016/j.crphar.2021.100038
Abraham MJ, Spoel D, Lindahl E, Hess B, GROMACS-Development-Team. GROMACS User Manual Version 2016; 2018.
Mavridis L, Mitchell JBO. Predicting the protein targets for athletic performance-enhancing substances. J Cheminform. 2013;5(1):31. https://doi.org/10.1186/1758-2946-5-31 PMid:23800040 DOI: https://doi.org/10.1186/1758-2946-5-31
Arulmozhiraja S, Matsuo N, Ishitsubo E, Okazaki S, Shimano H, Tokiwa H. Comparative binding analysis of dipeptidyl peptidase IV (DPP-4) with antidiabetic drugs-An Ab Initio Fragment Molecular Orbital Study. PLoS One. 2016;11(11):e0166275. https://doi.org/10.1371/journal.pone.0166275 PMid:27832184 DOI: https://doi.org/10.1371/journal.pone.0166275
Nabeno M, Akahoshi F, Kishida H, Miyaguchi I, Tanaka Y, Ishii S, et al. A comparative study of the binding modes of recently launched dipeptidyl peptidase IV inhibitors in the active site. Biochem Biophys Res Commun. 2013;434(2):191-6. https://doi.org/10.1016/j.bbrc.2013.03.010 PMid:23501107 DOI: https://doi.org/10.1016/j.bbrc.2013.03.010
Pine TD, Alam G, Attamimi F. Quality standardisation of gedi (Abelmoschus manihot (L.) Medik) leaf extract and test of antioxidant effect with DPPH method. J Farmasi UIN Alauddin Makassar. 2015;3(3):111-28. https://doi.org/10.24252/jfuinam.v3i3.2214
Downloads
Published
How to Cite
License
Copyright (c) 2022 Juliet Tangka, Elisabeth Natalia Barung, Diana Lyrawati, Djoko Soeatmadji, Nurdiana Nurdiana (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
http://creativecommons.org/licenses/by-nc/4.0
