Bioactive Compounds Analysis of Averrhoa bilimbi L. as Inhibitor of Cyclooxygenase-2 Enzyme Using in silico Approach
Abstract
Averrhoa bilimbi L. is generally used as a food flavor enhancer and traditional medicine to treat inflammation, cancer sores, cough, fever, gout, rectal bleeding, and hemorrhoids. In vivo and in vitro studies on Averrhoa bilimbi L. have shown anti-inflammatory activity, but the active compounds that play a role in anti-inflammatory activity have not been reported. This study aimed to analyze sixtyfour (64) bioactive compounds in the Averrhoa bilimbi L. plant as cyclooxygenase-2 (COX-2) enzyme inhibitors using in silico approach and predict the pharmacokinetic and toxicological profiles of each compound. The cyclooxygenase-2 enzyme is an enzyme that plays a role in the inflammatory process by converting arachidonic acid into prostaglandin. Increased prostaglandins will cause inflammation. The research method used molecular docking with the application of YASARA, PLANTS, Marvinsketch, Pymol, visualization with PLIP and prediction of ADMET with pkCSM. Control compound used celecoxib. The results showed that there were 13 test compounds that were predicted to have better COX-2 inhibitor activity than celecoxib with good pharmacokinetic properties. Erucic acid has the best pharmacokinetic and toxicity profile. Erucic acid has the potential to be developed as a cyclooxygenase-2 enzyme inhibitor drug.
References
2. Deputy Minister of State for Research and Technology for the Empowerment and Promotion of Science and Technology Indonesia. Starfruit (Averrhoa carambola). Bappenas 1–12. 2009.
3. Anggraini T, Febrianti F, Aisman & Ismanto SD. Black tea with Averrhoa bilimbi L. extract: a healthy beverage. Agric. Agric. Sci. Procedia. 2016;9:241–25.
4. Patil AG, Koli SP & Patil DA. Pharmcognostical standardization and HPTLC fingerprint of Averrhoa bilimbi (L.) fruits. Journal of Pharmacy Research. 2013;6:145–50.
5. The Ministry of Health Republic Indonesia. Indonesian medicinal herbs from medicinal plants in Indonesia. 2017.
6. Hasim H, Arifin YY, Andrianto D. & Faridah DN. Ethanol extract of belimbing wuluh leaf (Averrhoa bilimbi) as Antioxidant and Anti-inflammatory. J. Apl. Teknol. Pangan. 2019;8:86-93.
7. Suluvoy JK, KM S, Guruvayoorappan GC. Berlin B G. Protective effect of Averrhoa bilimbi L. fruit extract on ulcerative colitis in wistar rats via regulation of inflammatory mediators and cytokines. Biomedicine and Pharmacotherapy. 2017; 91:1113–21.
8. Miraj AJ. et al. Evaluation of the analgesic and anti-inflammatory activities of methanolic extracts of the leaves of Averrhoa bilimbi leaves. Discov. Phytomedicine. 2019;6:12-5.
9. Baratawidjaja, Karnen G, Rengganis I. Basics of Immunology, 11th Edition (2nd Publication). Publishing Agency of the Faculty of Medicine, University of Indonesia. 2016.
10. Baghaki S. et al. COX2 inhibition in the treatment of COVID-19: Review of literature to propose repositioning
of celecoxib for randomized controlled studies. International Journal of Infectious Diseases. 2020;101:29–32. Availabe from: https://doi.org/10.1016/j.ijid.2020.09.1466.
11. Ahmed QU. et al. Antiradical and Xanthine oxidase inhibitory activity evaluations of Averrhoa bilimbi L. Leaves and tentative identification of bioactive constituents through LC-QTOF-MS/MS and molecular docking approach. Antioxidants . 2018;7:1–16.
12. Abraham CM. A study on phytochemical constituents of Averrhoa. Indian Journal of Applied Research. 2016;6:29–31.
13. Suluvoy JK. & Berlin Grace, V. M. Original article: Phytochemical profile and free radical nitric oxide (NO) scavenging activity of Averrhoa bilimbi L. fruit extract. 3 Biotech. 2017;7:1–11.
14. Kurup SB, SM. Protective potential of Averrhoa bilimbi fruits in ameliorating the hepatic key enzymes in streptozotocin-induced diabetic rats. Biomedicine and Pharmacotherapy. 2017;85:725–32.
15. Protein 6COX, 3LN1. Available from: https://www.rcsb. org/structure/6COX Accessed on 26 October 2020.
16. 2D Structure of Averrhoa bilimbi L. Bioactive Compounds and Control Compounds [Internet]. Available from: http://www.pubchem.ncbi.nlm.nih.gov/. Retrieved 26 October 2020.
17. Yuniarti N, Ikawati Z. & Istyastono, E. P. The importance of ARG513 as a hydrogen bond anchor to discover COX-2 inhibitors in a virtual screening campaign. Bioinformation. 2011;6:164–6.
18. Sudha KN, et al. Virtual screening for novel COX-2 inhibitors using the ZINC database. Bioinformation. 2008;2:325–9.
19. Purnomo H. Computational chemistry molecular docking plants molecular tethering plants (protein-ligand-ant-system) (Ants Science). Pustaka Pelajar, 2011.
20. Rachmania RA. Validation of virtual screening protocol and interaction analysis of natural material-based cancer cell antiproliferation inhibitors against cyclin-dependent kinase 4 (cdk 4) receptor. Media Farm. J. Ilmu Farm. 2019;16:21–40.
21. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Advanced Drug Delivery Reviews. 2012;64:4–17.
22. Pranowo HD, Hetadi A K R. Introduction to Computational Chemistry. Lubuk Agung Bandung, 2011.
23. Salentin S, Schreiber S, Haupt VJ, Adasme MF, Schroeder M. PLIP: Fully automated protein-ligand interaction profiler. Nucleic Acids Research. 2015;43:443–7.
24. Siswandono & Sukardjo, B. Medicinal Chemistry. Airlangga University Press, 2008.
25. Pires DEV, Blundell TL, Ascher DB. pkCSM : predicting small-molecule pharmacokinetic properties using graph-based signatures. Journal of Medicinal Chemistry. 2015;58:4066–72.
26. Hardjono S. Prediksi sifat farmakokinetik, toxicity and cytotoxic activity of n-benzoyl-n'-(4-fluorophenyl) thiourea derivatives as anticancer drug candidates through molecular modeling. Jurnal Ilmu Kefarmasian Indonesia. 2017;14:246–55.
27. Li JJ. Pharmacokinetics (ADME). in Medicinal Chemistry for Practitioners. John Wiley & Sons, Inc, 2020:133–224.
28. The Indonesian Food and Drug Authority. Guidelines for In Vivo Non-Clinical Toxicity Tests. Indonesia, 2014.
29. Calder PC. Fatty acids: Long-chain fatty acids and inflammation. Proceedings of the Nutrition Society. 2012;71:284–9.
30. Liang X, et al. Erucic acid from Isatis indigotica Fort. suppresses influenza a virus replication and inflammation in vitro and in vivo through modulation of NF-κB and p38 MAPK pathway. Journal of Pharmaceutical Analysis. 2020;10:130–46.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
Licencing
All articles in Jurnal Ilmu Kefarmasian Indonesia are an open-access article, distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License which permits unrestricted non-commercial used, distribution and reproduction in any medium.
This licence applies to Author(s) and Public Reader means that the users mays :
- SHARE:
copy and redistribute the article in any medium or format - ADAPT:
remix, transform, and build upon the article (eg.: to produce a new research work and, possibly, a new publication) - ALIKE:
If you remix, transform, or build upon the article, you must distribute your contributions under the same license as the original. - NO ADDITIONAL RESTRICTIONS:
You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
It does however mean that when you use it you must:
- ATTRIBUTION: You must give appropriate credit to both the Author(s) and the journal, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.
You may not:
- NONCOMMERCIAL: You may not use the article for commercial purposes.
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.