BIOCOMPUTATIONAL AND PHARMACOLOGICAL ANALYSIS OF PHYTOCHEMICALS FROM ZINGIBER OFFICINALE (GINGER), ALLIUM SATIVUM (GARLIC), AND MURRAYAKOENIGII (CURRY LEAF) IN CONTRAST TO TYPE 2-DIABETES

RATUL BHOWMIK; SHUBHAM ROY; SOUNOK SENGUPTA; SAMEER SHARMA

doi:10.22159/ijap.2021v13i5.42294

Authors

RATUL BHOWMIK Department of Pharmaceutical Chemistry, SPER, Jamia Hamdard, New Delhi, India
SHUBHAM ROY Department of Pharmaceutical Chemistry, SPER, Jamia Hamdard, New Delhi, India
SOUNOK SENGUPTA Department of Pharmacology, NSHM Knowledge Campus, Kolkata-Group of Institutions, Kolkata, West Bengal, India
SAMEER SHARMA Department of Bioinformatics, BioNome Private Limited, Bengaluru, India

DOI:

https://doi.org/10.22159/ijap.2021v13i5.42294

Keywords:

Diabetes, Phytochemicals, ADME, Molecular docking

Abstract

Objective: This study was aimed to analyze the inhibitory effect of the flavonoid class of phytochemicals present in ginger (Zingiber Officinale), garlic (Allium sativum), and curry leaf (Murrayakoenigii) against some receptors of type-2 diabetes such as human aldose reductase receptor, mitogen synthase kinase receptor, as well as dipeptidyl peptidase receptor by implementing several in silico analysis techniques.

Methods: The 3D structures of the flavonoid class of phytochemicals of all the three plants were retrieved from the PubChem database in 3D SDF format and were converted to PDB format using PyMol software. These phytochemicals were subjected to in silico tools such as SwissADME, Pre-ADMET, and iMODS web server. The PDB-IDs of the targeted receptors human aldose reductase, dipeptidyl peptidase-IV, and mitogen synthase kinase were retrieved from Protein Data Bank in PDB format. All these receptors were then prepared for docking procedure using Autodock Tools. Now, both the prepared proteins and ligands were subjected to docking analysis using Pyrex (AutodockVina).

Results: Naringenin and kaempferol showed excellent docking results with the aldose reductase receptor. On the other hand, rutin showed the best docking score with dipeptidyl peptidase receptor-IV, whereas, epigallocatechin showed the best docking results with mitogen synthase kinase receptor. The ADME analysis showed that resveratrol had the best gastrointestinal absorption as well as high blood-brain barrier permeability.

Conclusion: Overall, the molecular docking results when analyzed showed a good binding affinity with the targeted receptors of diabetes. The ADME analysis and molecular docking results of the phytochemicals concluded that these compounds can be used as a potential cure for treating diabetes.

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References

Singletary K. Ginger: an overview of health benefits. Nutr Today 2010;45:171-83.

Stoilova I, Krastanov A, Stoyanova A, Denev P, Gargova S. Antioxidant activity of a ginger extract (Zingiber officinale). Food Chem 2007;102:764-70.

Rana SV, Pal R, Vaiphei K, Sharma SK, Ola RP. Garlic in health and disease. Nutr Res Rev 2011;24:60-71.

Zhou Y, Zhuang W, Hu W, Liu G, Wu T, Wu X. Consumption of large amounts of Allium vegetables reduces the risk for gastric cancer in a meta-analysis. Gastroenterology 2011;141:80-9.

Saini SC, Bala G, Reddy S. A review on curry leaves (Murraya koenigii): versatile multi-potential medicinal plant. Am J Phytomed Clin Ther 2015;3:363-8.

Pietta PG. Flavonoids as antioxidants. J Nat Prod 2000;63:1035-42.

Panche AN, Diwan AD, Chandra SR. Flavonoids: an overview. J Nutr Sci 2016;5:e47.

Kim S, Chen J, Cheng T, Gindulyte A, He J, He S, et al. PubChem 2019 update: improved access to chemical data. Nucleic Acids Res 2019;47. DOI:10.1093/nar/gky1033

Kim S, Thiessen PA, Bolton EE, Chen J, Fu G, Gindulyte A, et al. PubChem substance and compound databases. Nucleic Acids Res 2016;44:D1202–D1213.

DeLano WL. The PyMOL molecular graphics system. Version 2.3. Schrodinger LLC; 2020.

Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, et al. The protein data bank. Nucleic Acids Res 2000;28:235-42.

Forli W, Halliday S, Belew R, Olson A. AutoDock Version 4.2. Citeseer; 2012.

Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep 2017;7:42717.

Trott O, Olson AJ. AutoDock vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010;31:455-61.

Dallakyan S, Olson AJ. Small-molecule library screening by docking with PyRx. Methods Mol Biol 2015;1263:1.

DS Visualizer. v4. 0.100. 13345, Accelrys Software Inc; 2013.

Nikoulina SE, Ciaraldi TP, Mudaliar S, Carter L, Johnson K, Henry RR. Inhibition of glycogen synthase kinase 3 improves insulin action and glucose metabolism in human skeletal muscle. Diabetes 2002;51:2190-8.

Deacon CF. Corrigendum: physiology and pharmacology of DPP-4 in glucose homeostasis and the treatment of type 2 diabetes frontiers in endocrinology. Frontiers Endocrinol 2019;10:275.

Rohrborn D, Wronkowitz N, Eckel J. DPP4 in diabetes. Front Immunol 2015;6:1-20.

Alexiou P, Pegklidou K, Chatzopoulou M, Nicolaou I, Demopoulos V. Aldose reductase enzyme and its implication to major health problems of the 21st century. Curr Med Chem 2009;16:734-52.

Schemmel KE, Padiyara RS, D’Souza JJ. Aldose reductase inhibitors in the treatment of diabetic peripheral neuropathy: a review. J Diabetes Its Complications 2010;24:354-60.

Gebhardt R, Beck H. Differential inhibitory effects of garlic-derived organosulfur compounds on cholesterol biosynthesis in primary rat hepatocyte cultures. Lipids 1996;3:1269-76.

Salehi I, Vahidinia A, Bakhtiari A, Mohammadi P, Sukumaran A, Hosseini-Zijoud SM. The effect of fresh garlic on the lipid profile and atherosclerosis development in male rats fed with a high ghee diet. Int J Pharm Pharm Sci 2015;7:486-90.

Chrubasik S, Pittler MH, Roufogalis BD. Zingiberis rhizoma: a comprehensive review on the ginger effect and efficacy profiles. Phytomedicine 2005;12:684-701.

Kemkar K, LS, Sathiyanarayanan A, Mahadik K. 6-Shogaol rich ginger oleoresin loaded mixed micelles enhances in vitro cytotoxicity on mcf-7 cells and in vivo anticancer activity against dal cells. Int J Pharm Pharm Sci 2018;10:160-8.

Bhandari U, Kanojia R, Pillai KK. Effect of ethanolic extract of Zingiber officinale on dyslipidaemia in diabetic rats. J Ethnopharmacol 2005;97:227-30.

Norajit K, Laohakunjit N, Kerdchoechuen O. Antibacterial effect of five zingiberaceae essential oils. Molecules 2007;12:2047-60.

Iyer UM, Mani UV. Studies on the effect of curry leaves supplementation (Murraya koenigi) on lipid profile, glycated proteins and amino acids in non-insulin-dependent diabetic patients. Plant Foods Hum Nutr 1990;40:275-82.