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Current Bioactive Compounds

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ISSN (Print): 1573-4072
ISSN (Online): 1875-6646

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Research Article

Withania somnifera: The Wonder Plant with Withanolide E and J Inhibit Inflammatory Mediator AP-1 Factor

Author(s): Srushti Sandu Chavadapur, Shivaleela Biradar, Rajappa Joga and Babu Lamani*

Volume 19, Issue 2, 2023

Published on: 06 September, 2022

Article ID: e010622205495 Pages: 16

DOI: 10.2174/1573407218666220601121738

Price: $65

Abstract

Background: Inflammation is a natural biological response of the body tissues to harmful stimuli, such as damaged cells, irritants or pathogens, and it is a protective response involving blood vessels, immune cells and molecular mediators. Activator Protein-1 (AP-1) is a dimer composed of both homo and hetero dimers with jun and fos subfamilies. The heterodimer cfos-cjun complex is upregulated in several inflammatory diseases such as asthma, rheumatoid arthritis, psoriasis etc. Since ancient times, several plants have been used as anti-inflammatory sources. Withania somnifera is a vital plant having well-documented anti-inflammatory properties. In this study, the phytochemicals of Withania somnifera are used to study the inhibitory effect on the inflammatory mediator AP-1 factor.

Objective: Determining the inhibitory effect of Withania somnifera phytochemicals against AP-1 factor (cfos-cjun complex).

Methods: In the present study, the phytochemicals of Withania somnifera were retrieved from the IMPPAT database. All the retrieved molecules were employed to screen in-silico pharmacological properties using in-silico tools such as SwissADME and ProTox II. Further, molecular interactions of receptors and ligands were carried out by the Autodock 4.1 tool.

Results: A total of 90 phytochemicals of Withania somnifera were subjected to the IMPPAT database. Among those, 21 Phytochemicals showed the appropriate drug similarity characteristics. The Autodock 4.1 tool was used to analyse the binding effect of these 21 phytochemicals. Withanolide E and Withanolide J molecules showed excellent inhibitory action compared to others. The interaction pattern showed that SER and ARG amino acids participate in the formation of drug hydrogen bonds.

Conclusion: Among the 90 phytochemicals of Withania somnifera, only two molecules showed potential ligand binding ability. Further, in-vitro studies may validate the findings.

Keywords: 1 (Activator Protein-1), Withania somnifera, Autodock, IMPPAT, Inflammation, Phytochemicals, Autodock 4.1.

Graphical Abstract

[1]
Ferrero-Miliani, L.; Nielsen, O.H.; Andersen, P.S.; Girardin, S.E. Chronic inflammation: Importance of NOD2 and NALP3 in interleukin-1β generation. Clin. Exp. Immunol., 2007, 147(2), 227-235.
[http://dx.doi.org/10.1111/j.1365-2249.2006.03261.x] [PMID: 17223962]
[2]
Chinnasamy, P.; Arumugam, R. In-silico prediction of anticarcinogenic bioactivities of traditional anti-inflammatory plants used by tribal healers in Sathyamangalam wildlife Sanctuary, India. Egyptian J. Basic Appl. Sci., 2018, 5(4), 265-279.
[http://dx.doi.org/10.1016/j.ejbas.2018.10.002]
[3]
Palanki, M.S. Inhibitors of AP-1 and NF- B mediated transcriptional activation: Therapeutic potential in autoimmune diseases and structural diversity. Curr. Med. Chem., 2002, 9(2), 219-227.
[http://dx.doi.org/10.2174/0929867023371265] [PMID: 11860356]
[4]
Ye, N.; Ding, Y.; Wild, C.; Shen, Q.; Zhou, J. Small molecule inhibitors targeting activator protein 1 (AP-1). J. Med. Chem., 2014, 57(16), 6930-6948.
[http://dx.doi.org/10.1021/jm5004733] [PMID: 24831826]
[5]
Chen, L.; Deng, H.; Cui, H.; Fang, J.; Zuo, Z.; Deng, J.; Li, Y.; Wang, X.; Zhao, L. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget, 2017, 9(6), 7204-7218.
[http://dx.doi.org/10.18632/oncotarget.23208] [PMID: 29467962]
[6]
Kumar, D.; Arya, V.; Kaur, R.; Bhat, Z.A.; Gupta, V.K.; Kumar, V. A review of immunomodulators in the Indian traditional health care system. J. Microbiol. Immunol. Infect., 2012, 45(3), 165-184.
[http://dx.doi.org/10.1016/j.jmii.2011.09.030] [PMID: 22154993]
[7]
Ishola, I.O.; Agbaje, E.O.; Adeyemi, O.O.; Shukla, R. Analgesic and anti-inflammatory effects of the methanol root extracts of some selected Nigerian medicinal plants. Pharm. Biol., 2014, 52(9), 1208-1216.
[http://dx.doi.org/10.3109/13880209.2014.880487] [PMID: 24697560]
[8]
Gavande, K.; Jain, K.; Mehta, R. Few medicinal activities of Ashwagandha (Withania somnifera). Int. J. Pharm Life Sci., 2014, 5(6)
[9]
Begum, V.H.; Sadique, J. Long term effect of herbal drug Withania somnifera on adjuvant induced arthritis in rats. Indian J. Exp. Biol., 1988, 26(11), 877-882.
[PMID: 3248848]
[10]
Drwal, M.N.; Banerjee, P.; Dunkel, M.; Wettig, M.R.; Preissner, R. ProTox: A web server for the in silico prediction of rodent oral toxicity. Nucleic Acids Res., 2014, 42, W53-8.
[http://dx.doi.org/10.1093/nar/gku401] [PMID: 24838562]
[11]
Glover, J.N.; Harrison, S.C. Crystal structure of the heterodimeric bZIP transcription factor c-Fos-c-Jun bound to DNA. Nature, 1995, 373(6511), 257-261.
[http://dx.doi.org/10.1038/373257a0] [PMID: 7816143]
[12]
Mohanraj, K.; Karthikeyan, B.S.; Vivek-Ananth, R.P.; Chand, R.B.; Aparna, S.R.; Mangalapandi, P.; Samal, A. IMPPAT: A curated database of Indian medicinal plants, phytochemistry and therapeutics. Sci. Rep., 2018, 8(1), 1-7.
[http://dx.doi.org/10.1038/s41598-018-22631-z] [PMID: 29311619]
[13]
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(1), 42717.
[http://dx.doi.org/10.1038/srep42717] [PMID: 28256516]
[14]
Banerjee, P.; Eckert, A.O.; Schrey, A.K.; Preissner, R. ProTox-II: A webserver for the prediction of toxicity of chemicals. Nucleic Acids Res., 2018, 46(W1), W257-W263.
[http://dx.doi.org/10.1093/nar/gky318] [PMID: 29718510]
[15]
Morris, G.M.; Goodsell, D.S.; Halliday, R.S.; Huey, R.; Hart, W.E.; Belew, R.K.; Olson, A.J. Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function. J. Comput. Chem., 1998, 19(14), 1639-1662.
[http://dx.doi.org/10.1002/(SICI)1096-987X(19981115)19:14<1639:AID-JCC10>3.0.CO;2-B]
[16]
Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev., 2001, 46(1-3), 3-26.
[http://dx.doi.org/10.1016/S0169-409X(00)00129-0] [PMID: 11259830]
[17]
McNeil, M. Arabinogalactan in mycobacteria: Structure, biosynthesis, and genetics.Genetics of bacterial polysaccharides; CRC Press: Boca Raton, FL, 1999, pp. 207-223.
[18]
Alam, S.; Khan, F. Virtual screening, Docking, ADMET and System Pharmacology studies on Garcinia caged Xanthone derivatives for Anticancer activity. Sci. Rep., 2018, 8(1), 5524.
[http://dx.doi.org/10.1038/s41598-018-23768-7] [PMID: 29615704]
[19]
Potts, R.O.; Guy, R.H. Predicting skin permeability. Pharm. Res., 1992, 9(5), 663-669.
[http://dx.doi.org/10.1023/A:1015810312465] [PMID: 1608900]
[20]
Testa, B.; Krämer, S.D. The biochemistry of drug metabolism--an introduction: Part 3. Reactions of hydrolysis and their enzymes. Chem. Biodivers., 2007, 4(9), 2031-2122.
[http://dx.doi.org/10.1002/cbdv.200790169] [PMID: 17886859]
[21]
Saeidnia, S.; Manayi, A.; Abdollahi, M. The pros and cons of the in-silico pharmaco-toxicology in drug discovery and development. Int. J. Pharmacol., 2013, 9(3), 176-181.
[http://dx.doi.org/10.3923/ijp.2013.176.181]
[22]
van Waterschoot, R.A.; Schinkel, A.H. A critical analysis of the interplay between cytochrome P450 3A and P-glycoprotein: Recent insights from knockout and transgenic mice. Pharmacol. Rev., 2011, 63(2), 390-410.
[http://dx.doi.org/10.1124/pr.110.002584] [PMID: 21490128]
[23]
Sharma, S.; Dahanukar, S.; Karandikar, S.M. Effects of long-term administration of the roots of ashwagandha and shatavari in rats. Indian Drugs, 1985, 29, 133-139.

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