Molecular Docking of Soybean (Glycine max) Seed and Ginger (Zingiber officinale) Rhizome Components as Anti-Diabetic Through Inhibition of Dipeptidyl Peptidase 4 (DPP-4) and Alpha-Glucosidase Enzymes doi.org/10.26538/tjnpr/v5i10.7
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Abstract
Dipeptidyl Peptidase-4 (DPP-4) and alpha-glucosidase (α-glucosidase) are enzymes involved in carbohydrate metabolism. Inhibition of these enzymes contribute to blood glucose level suppression. Soybean (Glycine max) seeds and ginger (Zingiber officinale) rhizome are herbs that have anti-diabetic activity. The mechanism of action, however, has not been thoroughly explored. This study aims to evaluate the anti-diabetic potentials of the chemical components in soybean seeds and ginger rhizome through inhibition activity of DPP-4 and α-glucosidase in silico. Soybean seed and ginger rhizome were extracted using the maceration method with ethanol solvent. Ethanol extract of soybean seeds and ginger rhizome were analysed using Liquid Chromatography-Mass Spectrometry (LC-MS/MS). The potency of active compounds from the plants on DPP-4 and α-glucosidase were evaluated by in silico study using web-based software (Docking server). Soybean seed were found to contain phytosterols, mainly beta sitosterol, campesterol, stigmasterol, and lanosterol. Meanwhile, ginger rhizome was found to contain 6-gingerdiol, 10-gingerol and 12-shogaol. Molecular docking study showed that stigmasterol and 12-shogaol strongly inhibits DPP-4 activity while stigmasterol and 6-Gingerdiol strongly inhibited α-glucosidase. This shows that both soybean seed and ginger rhizome potentially act as an anti-diabetic by inhibiting DPP-4 and α-glucosidase; however, soybean seed is more potent due to its ability to inhibit both of the tested enzymes.
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Deacon C. Dipeptidyl peptidase 4 inhibitors in the treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2020; 16(11): 642-653.
Singh S, Wright E, Kwan A, Thompson J, Syed I, Korol EE, Waser NA, Yu MB, Juneja R. Glucagon-like peptide-1 receptor agonists compared with basal insulins for the treatment of type 2 diabetes mellitus: a systematic review and meta-analysis. Diabetes, Obes Metab. 2016; 19(2):228-238.
Gallwitz B. Clinical Use of DPP-4 Inhibitors. Front Endocrinol (Lausanne). 2019; 10(1):1-8.
Pereira A, Banegas-Luna A, 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.
Zeng L, Zhang G, Lin S, Gong D. Inhibitory Mechanism of Apigenin on α-Glucosidase and Synergy Analysis of Flavonoids. J Agric Food Chem. 2016; 64(37): 6939-6949.
Soelistijo, SA. Consensus of the Management and Prevention of Type 2 Diabetes Mellitus in Indonesia (1st Ed.). Jakarta: PB Perkeni; 2015. p6-65
Pang G, Li F, Yan Y, Zhang Y, Kong L, Zhu P, Wang KF, Zhang F, Liu B, Lu CL. Herbal medicine in the treatment of patients with type 2 diabetes mellitus. Chin Med J (Engl). 2019; 132(1):78-85.
World Health Organization (WHO). WHO Traditional Medicine Strategy 2014-2023 [Internet]. World Health Organization (WHO). Geneva; 2013. Available from: http://apps.who.int/iris/bitstream/10665/92455/1/9789241506090_eng.pdf?ua=1 (Accessed 04.09.2021
Mustofa M, Mukhtar D, Susmiarsih T, Royhan A. Effect of Soybean (Glycine max (L) Merril) on Blood Glucose Levels and Expression of Pancreatic B Cell Insulin in Diabetic Rats. J Kedokt Yars.β 2010; 18(2):094-103.
Pabich M and Materska M. Biological Effect of Soy Isoflavones in the Prevention of Civilization Diseases. Nutr. 2019; 11(7): 1660.
Bischoff-Kont I and Fürst R. Benefits of Ginger and Its Constituent 6-Shogaol in Inhibiting Inflammatory Processes. Pharmaceuticals (Basel). 2021; 14(6):571p.
Tiwari V, Mishra B, Dixit A, Antony J, Tiwari R, Sharma N. Opportunity, Challenge and scope of natural products in medicinal chemistry. Kerala: Res Signpost; 2011; 103-121 p.
Yulianingtyas Y and Kusmartono B. Optimization of Volume of solvent and Maceration Time of Flavonoid Extraction of Belimbing Wuluh Leaves (Averrhoa Bilimbi L.). J Tek Kim. 2016; 10:58-64.
Nicklaus M. Online SMILES Translator [Internet]. Cactus.nci.nih.gov. 2020 [cited 4 September 2021]. Available from: https://cactus.nci.nih.gov/translate
Seo CS and Shin HK. Liquid chromatography tandem mass spectrometry for the simultaneous quantification of eleven phytochemical constituents in traditional Korean medicine, sogunjung decoction. Processes. 2021; 9(1):1-10.
O'Boyle N, Banck M, James C, Morley C, Vandermeersch T, Hutchison G. Open Babel: An open chemical toolbox. J Cheminfo. 2011; 3(1):33.
Putra AMJ. Once Again About Docking [Internet]. LIPI. 2014. Available from: http://u.lipi.go.id/1391883188. Accessed 04.09.2021.
Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, Heer FT, de Beer TAP, Rempfer C, Bordoli L, Lepore R, Schwede T. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 2018; 46(W1):W296-303.
Khalaf I, Corciovă A, Vlase I, Ivănescu B and Lazăr D. LC/MS Analysis of Sterolic Compounds from Glycyrrhiza Glabra. Stud Univ Babes-Bolyai Chem. 2011; 3(1):97-102.
Fikri F, Saptarini N, Levita J. The Inhibitory Activity on the Rate of Prostaglandin Production by Zingiber officinale var. Rubrum. Pharmacol Clin Pharm Res. 2016; 1(1):33-41.
Bilbao A. Proteomics Mass Spectrometry Data Analysis Tools. Encyclopedia of Bioinformatics and Computational Biology: ABC of Bioinformatics. Elsevier Ltd; 2018. 84-95p.
Skubic C, Vovk I, Rozman D, Križman M. Simplified LC-MS Method for Analysis of Sterols in Biological Samples. Molecules. 2020; 25(18):2-10
Zhu H, Chen J, He Z, Hao W, Liu J, Kwek E Ma KY, Bi Y. Plasma Cholesterol-Lowering Activity of Soybean Germ Phytosterols. Nutrients. 2019; 11(11):2-18.
Trautwein E, Vermeer M, Hiemstra H, Ras R. LDL-Cholesterol Lowering of Plant Sterols and Stanols-Which Factors Influence Their Efficacy? Nutrients. 2018; 10(9):1262.
Nguyen H, Neelakadan A, Quach T, Valliyodan B, Kumar R, Zhang Z and Nguyen HT. Molecular characterization of Glycine max squalene synthase genes in seed phytosterol biosynthesis. Plant Physiol Biochem. 2013; 73(1):23-32.
Daszynski D, Santhoshkumar P, Phadte A, Sharma K, Zhong H, Lou MF and Kador PF. Failure of Oxysterols Such as Lanosterol to Restore Lens Clarity from Cataracts. Sci Rep. 2019; 9(1):8459.
Wei C, Tsai Y, Korinek M, Hung P, El-Shazly M, Cheng YB, Wu YC, Hsieh TJ, Chang FR. 6-Paradol and 6-Shogaol, the Pungent Compounds of Ginger, Promote Glucose Utilization in Adipocytes and Myotubes, and 6-Paradol Reduces Blood Glucose in High-Fat Diet-Fed Mice. Int J Mol Sci. 2017; 18(1):168.
Mahmudati N. Ginger (Zingiber officinale) extract decrease TNF expression of rat induced by High Fat Diet (HFD). Proc Biol Educ Conf, FKIP UNS-2016. 2016; 13(1):653-5.
Lipinski C, Lombardo F, Dominy B, Feeney P. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2012; 64(1):4-17.
Purnomo Y, Soeatmadji DW, Sumitro SB, Widodo MA, Antidiabetic potential of Urena lobata leaf extract through inhibition of Dipeptidyl Peptidase-IV activity. Asian Pac J Trop Biomed. 2015; 5(8): 645-649.
Utomo D, Widodo N, Rifa’i M. Identifications small molecules nhibitor of p53-mortalin complex for cancer drug using virtual screening. Bioinformation. 2012; 8(9):426-429.
Riyanti S, Suganda AG and Sukandar EY. Dipeptidyl PeptidaseIV Inhibitory Activity of Some Indonesian Medicinal Plants. Asian J Pharm Clin Res. 2016; 9(2): 375-377.
Bikadi Z and Hazai E. Application of the PM6 semi-empirical method to modeling proteins enhances docking accuracy of AutoDock. J Cheminfo. 2009; 1(1): 15.
Purnomo Y, Makdasari J, Fatahillah FI. Inhibitory activity of Urena lobate leaf extract on alpha-amylase and alpha glucosidase: in vitro and in silico approach. J Basic Clin Physiol Pharmacol . 2021; 32(4):889-894.
Rosiarto B, Puspaningtyas A, Holidah D. Study of Antioxidant Activity of Compound 1-(p-chlorobenzoyloxymethyl)-5-fluorouracil with Molecular Docking Method and DPPH. Med Rep. 2014; 2(1):95-99.