Flavonoids Exhibit Potential Antagonistic Activity Against Platelet-Activating Factor (PAF) Receptor http://www.doi.org/10.26538/tjnpr/v6i10.11

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Published: Oct 1, 2022
Keywords:
Methylglyoxal,, AGEPs,, Advanced glycation end products,, Glutathione,, Magnesium,, Ubiquinone.

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Noraziah Nordin
Department of Basic Medical Sciences 1, Faculty of Medicine & Health Sciences, Universiti Sains Islam Malaysia, 71800, Nilai, Negeri Sembilan, Malaysia
Mohd F. A. Ghani
Department of Basic Medical Sciences 1, Faculty of Medicine & Health Sciences, Universiti Sains Islam Malaysia, 71800, Nilai, Negeri Sembilan, Malaysia
Adib A. Abdullah
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University Malaya, 50603, Kuala Lumpur, Malaysia

Abstract

The platelet-activating factor receptor (PAFR) has been a therapeutic target for platelet- activating factor (PAF)-mediated diseases. The pathophysiological condition is triggered by the interaction of PAF agonist. The discovery of PAF antagonists from natural flavonoids could be promising candidates for treating PAF-mediated diseases. Flavonoids that exist in most edible plants possess good health benefits to the human body. The study aimed to investigate the ability of three flavonoids (apigenin, galangin and fisetin) for molecular docking and dynamic simulations into PAFR protein. The PAFR-flavonoid complex binding affinities and interactions were assessed through molecular docking and dynamic simulations. Results found that all flavonoids significantly have a good binding affinity, ranging from - 9.1 to - 8.9 kcalmol-1. The stability of these flavonoids was also achieved in a 30 ns simulation. Four critical residues were detected in all PAFR-flavonoids complexes (Phe97, Phe98, Thr101 and Leu279) from the analysis of MMGBSA binding free energy. Interactions of van der Waals and electrostatic were seen by individual key residues of PAFR for the free energy contribution of ligands binding. All flavonoids showed promising anti-PAF candidate to be developed in the future.

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How to Cite
Nordin, N., F. A. Ghani, M., & A. Abdullah, A. (2022). Flavonoids Exhibit Potential Antagonistic Activity Against Platelet-Activating Factor (PAF) Receptor: http://www.doi.org/10.26538/tjnpr/v6i10.11. Tropical Journal of Natural Product Research (TJNPR), 6(10), 1626-1631. https://tjnpr.org/index.php/home/article/view/1214
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Vol. 6 No. 10 (2022): Tropical Journal of Natural Product Research
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Articles
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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

References

Shukla SD, Fairbairn RL, Gell DA, Latham RD, Sohal SS, Walters EH, O’Toole RF. An antagonist of the platelet-activating factor receptor inhibits adherence of both nontypeable Haemophilus influenzae and Streptococcus pneumoniae to cultured human bronchial epithelial cells exposed to cigarette smoke Int J Chron Obstruct Pulmon Dis. 2016; 11:1647–1655.

Hyland IK, O'Toole RF, Smith JA, Bissember AC. Progress in the Development of Platelet‐Activating Factor Receptor (PAFr) Antagonists and Applications in the Treatment of Inflammatory Diseases. ChemMedChem. 2018; 13(18):1873-84.

Fukunaga A, Khaskhely NM, Sreevidya CS, Byrne SN, Ullrich SE. Dermal dendritic cells, and not Langerhans cells, play an essential role in inducing an immune response. J Immunol. 2008; 180(5):3057-3064.

Tsoupras AB, Iatrou C, Frangia C, Demopoulos CA. The implication of platelet activating factor in cancer growth and metastasis: potent beneficial role of PAF-inhibitors and antioxidants. Infect Disord Drug Targets. 2009; 9(4):390-399.

Shukla SD. Platelet‐activating factor receptor and signal transduction mechanisms. The FASEB J. 1992; 6(6):2296-2301.

Lordan R, Tsoupras A, Zabetakis I, Demopoulos CA. Forty years since the structural elucidation of platelet-activating factor (PAF): historical, current, and future research perspectives. Molecules. 2019; 24(4414):1-32.

Whittaker M. Overview: PAF Receptor Antagonists: Recent Advances. Expert Opin Ther Pat. 1992; 2(5):583-623.

Raffa D, Maggio B, Raimondi MV, Plescia F, Daidone G. Recent discoveries of anticancer flavonoids. Eur J Med Chem. 2017; 142:213-228.

Hakobyan A, Arabyan E, Avetisyan A, Abroyan L, Hakobyan L, Zakaryan H. Apigenin inhibits African swine fever virus infection in vitro. Arch Virol. 2016; 161(12):3445-3453.

Lani R, Hassandarvish P, Shu MH, Phoon WH, Chu JJ, Higgs S, Vanlandingham D, Bakar SA, Zandi K. Antiviral activity of selected flavonoids against Chikungunya virus. Antivir Res. 2016; 133:50-61.

Madunić J, Madunić IV, Gajski G, Popić J, Garaj-Vrhovac V. Apigenin: A dietary flavonoid with diverse anticancer properties. Cancer Lett. 2018; 413:11-22.

Kumar R and Tiku AB. Galangin induces cell death by modulating the expression of glyoxalase-1 and Nrf-2 in HeLa cells. Chem-Biol Interact. 2018; 279:1-9.

Rengarajan T and Yaacob NS. The flavonoid fisetin as an anticancer agent targeting the growth signaling pathways. Eur J Pharmacol. 2016; 789:8-16.

Karlíčková J, Říha M., Filipský T, Macáková K, Hrdina R, Mladěnka P. Antiplatelet effects of flavonoids mediated by inhibition of arachidonic acid-based pathway. Planta Med. 2016; 82(01/02):76-83.

Lee JH, Kim M, Chang KH, Hong CY, Na CS, Dong MS, Lee D, Lee MY. Antiplatelet effects of Rhus verniciflua Stokes heartwood and its active constituents—fisetin, butein, and sulfuretin—in rats. J Med Food. 2015; 18(1):21-30.

Ginwala R, Bhavsar R, Chigbu DG, Jain P, Khan ZK. Potential role of flavonoids in treating chronic inflammatory diseases with a special focus on the anti-inflammatory activity of apigenin. Antioxidants. 2019; 8(35):1-28.

Lee HN, Shin SA, Choo GS, Kim HJ, Park YS, Kim BS, Kim SK, Cho SD, Nam JS, Choi CS, Che JH. Anti‑inflammatory effect of quercetin and galangin in LPS‑stimulated RAW264. Macrophages and DNCB‑induced atopic dermatitis animal models. Int J Mol Med. 2018; 41(2):888-898.

Pal HC, Pearlman RL, Afaq F. Fisetin and its role in chronic diseases. Anti-inflammatory Nutraceuticals and Chronic Diseases. 2016; 213-244.

Zhang H, Zheng W, Feng X, Yang F, Qin H, Wu S, Hou DX, Chen J. Nrf2–ARE signaling acts as master pathway for the cellular antioxidant activity of fisetin. Molecules. 2019; 24(708):2-16.

Devadoss D, Ramar M, Chinnasamy A. Galangin, a dietary flavonol inhibits tumor initiation during experimental pulmonary tumorigenesis by modulating xenobiotic enzymes and antioxidant status. Arch Pharm Res. 2018; 41(3):265-275.

Telange DR, Patil AT, Pethe AM, Fegade H, Anand S, Dave VS. Formulation and characterization of an apigenin-phospholipid phytosome (APLC) for improved solubility, in vivo bioavailability, and antioxidant potential. Eur J Pharm Sci. 2017; 108:36-49.

Ghani MFA, Hamid NA, Nordin N. Flavonoids Docked into Several Target Proteins Associated with Cancer: A Molecular Docking Study. Trop J Nat Prod Res. 2021; 5(12):2057-2062

Benmehdi H, Lamouri A, Serradji N, Pallois F, Heymans F. Synthesis of New Trisubstituted 4‐Aminopiperidines as PAF‐ Receptor Antagonists. Eur J Org Chem. 2008; 299-307.

Cao C, Tan Q, Xu C, He L, Yang L, Zhou Y, Zhou Y, Qiao A, Lu M, Yi C, Han GW. Structural basis for signal recognition and transduction by platelet-activating-factor receptor. Nat Struct Mol Biol. 2018; 25(6):488-495.

Jaghoori MM, Bleijlevens B, Olabarriaga SD. 1001 Ways to run AutoDock Vina for virtual screening. J Comp-aided Mol Desgn. 2016; 30(3):237-249.

Maier JA, Martinez C, Kasavajhala K, Wickstrom L, Hauser KE, Simmerling C. ff14SB: improving the accuracy of protein side chain and backbone parameters from ff99SB. J Chem Theory Comput. 2015; 11(8):3696-3713.

Wang J, Wolf RM, Caldwell JW, Kollman PA, Case DA. Development and testing of a general amber force field. J Comput Chem. 2004; 25(9):1157-1174.

Jakalian A, Jack DB, Bayly CI. Fast, efficient generation of high‐quality atomic charges. AM1‐BCC model: II. Parameterization and validation. J Comput Chem. 2002; 23(16):1623-1641.

Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML. Comparison of simple potential functions for simulating liquid water. Chem Phys. 1983; 79(2):926-935.

Case DA, Ben-Shalom IY, Brozell SR, Cerutti DS, Cheatham III TE, Cruzeiro VW, Darden TA, Duke RE, Ghoreishi D, Gilson MK, Gohlke H. AMBER. University of California, San Francisco; 2018.

Wang J, Wang W, Kollman PA, Case DA. Antechamber: an accessory software package for molecular mechanical calculations. J Am Chem Soc. 2001; 222:U403.

Liu DC, Nocedal J. On the limited memory BFGS method for large scale optimization. Math Program. 1989; 45(1):503-528.

Nocedal J. Updating quasi-Newton matrices with limited storage. Math Comput. 1980; 35(151):773-782.

Loncharich RJ, Brooks BR, Pastor RW. Langevin dynamics of peptides: The frictional dependence of isomerization rates of N‐ acetylalanyl‐N′‐methylamide. Biopolymers: Original Research on Biomolecules. 1992; 32(5):523-535.

Pastor RW, Brooks BR, Szabo A. An analysis of the accuracy of Langevin and molecular dynamics algorithms. Mol Phys. 1988; 65(6):1409-1419.

Åqvist J, Wennerström P, Nervall M, Bjelic S, Brandsdal BO. Molecular dynamics simulations of water and biomolecules with a Monte Carlo constant pressure algorithm. Chem Phys Lett. 2004; 384(4-6):288-294.

Chow KH, Ferguson DM. Isothermal-isobaric molecular dynamics simulations with Monte Carlo volume sampling. Comput Phys Commun. 1995; 91(1-3):283-289.

Eastman P, Swails J, Chodera JD, McGibbon RT, Zhao Y, Beauchamp KA, Wang LP, Simmonett AC, Harrigan MP, Stern CD, Wiewiora RP. OpenMM 7: Rapid development of high- performance algorithms for molecular dynamics. PLoS Comput Biol. 2017; 13(7):e1005659.

Miyamoto S and Kollman PA. Settle: An analytical version of the SHAKE and RATTLE algorithm for rigid water models. J Comput Chem. 1992; 13(8):952-962.

Ryckaert JP, Ciccotti G, Berendsen HJ. Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes. J Comput Phys. 1977; 23(3):327-341.

Darden T, York D, Pedersen L. Particle mesh Ewald: An N⋅ log (N) method for Ewald sums in large systems. Chem Phys. 1993; 98(12):10089-10092.

Roe DR, Cheatham III TE. PTRAJ and CPPTRAJ: software for processing and analysis of molecular dynamics trajectory data. J Chem Theory Comput. 2013; 9(7):3084-3095.

Miller III BR, McGee Jr TD, Swails JM, Homeyer N, Gohlke H, Roitberg AE. MMPBSA. py: an efficient program for end-state free energy calculations. J Chem Theory Comput. 2012; 8(9):3314-3321.

Cao C, Tan Q, Xu C, He L, Yang L, Zhou Y, Zhou Y, Qiao A, Lu M, Yi C, Han GW. Structural basis for signal recognition and transduction by platelet-activating-factor receptor. Nat Struct Mol Biol. 2018; 25(6):488-495.

Jantan I, Jalil J, Abdul Warif NM. Platelet-activating factor (PAF) antagonistic activities of compounds isolated from Guttiferae species. Pharm Biol. 2001b; 39(4):243-246