IN SILICO STUDY OF APIGENIN AND APIGETRIN AS INHIBITOR OF 3-HYDROXY-3-METHYL-GLUTAYL-COENZYME A REDUCTASE
DOI:
https://doi.org/10.22159/ajpcr.2017.v10i11.20493Keywords:
Anticholesterol, In silico, Apigenin, Apigetrin, 3-hydroxy-3-methyl-glutayl-coenzyme A reductaseAbstract
Â
 Objective: The objectives of this research were to investigate in silico interaction between apigenin and apigetrin with 3-hydroxy-3-methyl-glutayl-coenzyme A (HMG Co-A) reductase, to find the most favorable binding site as well as to predict the binding mode.
Materials and Methods: Docking calculation was performed by branded Sony Vaio PC Linux Ubuntu 14.04 LTS. The binding process based on the best docking result with HMG Co-A reductase was presented in two-dimensional diagram. Statin, atorvastatin, and R-mevalonate were used as standard.
Results: Binding affinity and inhibition constant of R-mevalonate were Ei=−4.2 kcal/mol, Ki=836.78 μM; apigenin Ei=−7.0 kcal/mol, Ki=7.43 μM; apigetrin Ei=−5.9 kcal/mol, Ki=47.53 μM; simvastatin Ei=−8.2 kcal/mol; Ki=0.98 μM; atorvastatin Ei=−8.4 kcal/mol; Ki=0.7 μM. Apigenin had better binding interaction than apigetrin.
Conclusion: Apigenin could be developed as anticholesterol.
Downloads
References
Guyton AC, Hall JE. Textbook of Medical Physiology. 11th ed. Philadelphia, PA: Elsevier Saunders; 2006.
Ruela-de-Sousa RR, Fuhler GM, Blom N, Ferreira CV, Aoyama H, Peppelenbosch MP. Cytotoxicity of apigenin on leukemia cell lines: Implications for prevention and therapy. Cell Death Dis 2010;1:e19.
Kim B, Jung N, Lee S, Sohng JK, Jung HJ. Apigenin inhibits cancer stem cell-like phenotypes in human glioblastoma cells via suppression of c-met signaling. Phytother Res 2016;30(11):1833-40.
Si D, Wang Y, Zhou YH, Guo Y, Wang J, Zhou H, et al. Mechanism of CYP2C9 inhibition by flavones and flavonols. Drug Metab Dispos 2009;37(3):629-34.
Chakravarthi S, Thani PM, Yang DL, Husin LT, Lee N. Role of immunohistochemistry and apoptosis as investigative tools in assessing the prognosis of patients with prostate tumours. Exp Ther Med 2010;1(1):391-3.
Chong FW, Chakravarthi S, Nagaraja HS, Thanikachalam PM, Lee N. Expression of transforming growth factor-beta and determination of apoptotic index in histopathological sections for assessment of the effects of Apigenin (4’, 5’, 7’- trihydroxyflavone) on cyclosporine a induced renal damage. Malays J Pathol 2009;31(1):35-43.
Zbidah M, Lupescu A, Jilani K, Fajol A, Michael D, Qadri SM, et al. Apigenin-induced suicidal erythrocyte death. J Agric Food Chem 2012;60(1):533-8.
Jung UJ, Cho YY, Choi MS. Apigenin ameliorates dyslipidemia, hepatic steatosis and insulin resistance by modulating metabolic and transcriptional profiles in the liver of high-fat diet-induced obese mice. Nutrients 2016;8(5). pii: E305.
Ali S, Srejith K. Multi targeted action of a plant derived flavonoids glucoside ‘apigetrin’ against important macromolecular targets in cancer an in silico validation. Int J Pharm Bio Sci 2014;5(3):478-90.
Lindgren V, Luskey KL, Russell DW, Francke U. Human genes involved in cholesterol metabolism: Chromosomal mapping of the loci for the low density lipoprotein receptor and 3-hydroxy-3-methylglutaryl-coenzyme A reductase with cDNA probes. Proc Natl Acad Sci U S A 1985;82(24):8567-71.
Roitelman J, Olender EH, Bar-Nun S, Dunn WA Jr, Simoni RD. Immunological evidence for eight spans in the membrane domain of 3-hydroxy-3-methylglutaryl coenzyme A reductase: Implications for enzyme degradation in the endoplasmic reticulum. J Cell Biol 1992;117(5):959-73.
Iyan Sopyan, Achmad Fudholi, Muchtaridi, Ika Puspitasari. A simple effort to enhance solubility and dissolution rate of simvastatin using co-crystalization. Int J Pharm Pharm Sci 2016; 8(8): 342-6.
Jeyashanthini Nalaiya, Sreenivasa Rao Sagineedu, Rajakumari Rajasingam, Zawahil Kassim, Mallikarjuna Rao Pichika. A stability indicating RP-HPLC method for simultaneous determination of simvastatin and niacin in a combined dosage form. Int J Pharm Pharm Sci 2015; 7(2): 262-8.
Cechinel-Filho V. Plant Bioactives and Drug Discovery: Principles, Practice and Perspective. Hoboken, NJ, Canada: John Wiley & Sons; 2012. p.104.
Miean KH, Mohamed S. Flavonoid (myricetin, quercetin, kaempferol, luteolin, and apigenin) content of edible tropical plants. J Agric Food Chem 2001;49(6):3106-12.
Jeong GS, Lee SH, Jeong SN, Kim YC, Kim EC. Anti-inflammatory effects of apigenin on nicotine- and lipopolysaccharide-stimulated human periodontal ligament cells via heme oxygenase-1. Int Immunopharmacol 2009;9(12):1374-80.
Wei H, Tye L, Bresnick E, Birt DF. Inhibitory effect of apigenin, a plant flavonoid, on epidermal ornithine decarboxylase and skin tumor promotion in mice. Cancer Res 1990;50(3):499-502.
Brown MS, Goldstein JL. The SREBP pathway: Regulation of cholesterol metabolism by proteolysis of a membrane-bound transcription factor. Cell 1997;89(3):331-40.
WHO. 19th WHO Model List of Essential Medicines. [Last retrieved on 2015 May 10].
Marcou G, Rognan D. Optimizing fragment and scaffold docking by use of molecular interaction fingerprints. J Chem Inf Model 2007;47:195-207.
Steussy CN, Critchelow CJ, Schmidt T, Min JK, Wrensford LV, Burgner JW 2nd, et al. A novel role for coenzyme A during hydride transfer in 3-hydroxy-3-methylglutaryl-coenzyme A reductase. Biochemistry 2013;52:5195-205.
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(2):455-61.
Published
How to Cite
Issue
Section
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.
