Abstract:

Orthodontic treatment is associated with pain, difficulty in plaque control, caries incidence, and slow movement of teeth. Authors hypothesize that the answer to these questions may lie in phytochemicals which are a huge unexplored area. Due to previous reports on Adhathoda vasica about its anti-inflammatory and antimicrobial properties, its use in orthodontics is explored in the dry lab scenario. This can be considered as a preliminary step to study the herb in great detail for use in orthodontic therapy. Computational algorithms from Auto Dock version 4 were used in the study. Vasicine, Vasinone, Vasicoline and Anisotine were analysed against Glucosyltransferase (GFT) of Streptococcus mutans, Gingipain K - Porphyromonas gingivalis, FIM A of Porphyromonas gingivalis, TNF ALPHA and Prostaglandin H synthases. Compounds exerted promising inhibiting action against Streptococcus mutans, Gingipain K, FimA, TNF-alpha and prostaglandin E2. The said phytochemicals - Vasicine, Vasicinone, Vasicoline and Anisotine can further be explored for proper delivery to saliva, periodontal region and to bone for effective use during and after orthodontic treatment.

References:

[1] Strauss, F. J., Espinoza, I., Stähli, A., Baeza, M., Cortés, R., Morales, A., & Gamonal, J., 2019, Dental caries is associated with severe periodontitis in Chilean adults: A cross-sectional study, BMC Oral Health, 19(1), 278. https://doi.org/10.1186/s12903-019-0975-2.

[2] Manji, F., Dahlen, G., & Fejerskov, O., 2018, Caries and periodontitis: Contesting the conventional wisdom on their aetiology, Caries Research, 52(6), 548–564. https://doi.org/10.1159/000488948.

[3] Worthington, H. V., MacDonald, L., Poklepovic Pericic, T., Sambunjak, D., Johnson, T. M., Imai, P., & Clarkson, J. E., 2019, Home use of interdental cleaning devices, in addition to toothbrushing, for preventing and controlling periodontal diseases and dental caries, Cochrane Database of Systematic Reviews, 4(4), CD012018. https://doi.org/10.1002/14651858.CD012018.pub2.

[4] Tartaglia, G. M., Tadakamadla, S. K., Connelly, S. T., Sforza, C., & Martín, C., 2019, Adverse events associated with home use of mouthrinses: A systematic review, Therapeutic Advances in Drug Safety, 10, 2042098619854881. https://doi.org/10.1177/2042098619854881.

[5] Kazancı, F., Aydoğan, C., & Alkan, Ö., 2016, Patients’ and parents’ concerns and decisions about orthodontic treatment, Korean Journal of Orthodontics, 46(1), 20–26. https://doi.org/10.4041/kjod.2016.46.1.20.

[6] Monk, A. B., Harrison, J. E., Worthington, H. V., & Teague, A., 2017, Pharmacological interventions for pain relief during orthodontic treatment, Cochrane Database of Systematic Reviews, 11(11), CD003976. https://doi.org/10.1002/14651858.CD003976.pub2.

[7] Trott, O., & Olson, A. J., 2010, AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, Journal of Computational Chemistry, 31(2), 455–461. https://doi.org/10.1002/jcc.21334.

[8] Forli, S., Huey, R., Pique, M. E., Sanner, M. F., Goodsell, D. S., & Olson, A. J., 2016, Computational protein-ligand docking and virtual drug screening with the AutoDock suite. Nature Protocols, 11(5), 905–919. https://doi.org/10.1038/nprot.2016.051.

[9] Osterberg, F., Morris, G. M., Sanner, M. F., Olson, A. J., & Goodsell, D. S., 2002, Automated docking to multiple target structures: Incorporation of protein mobility and structural water heterogeneity in AutoDock. Proteins, 46(1), 34–40. https://doi.org/10.1002/prot.10028.

[10] Morris, G. M., Goodsell, D. S., Halliday, R. S., Huey, R., Hart, W. E., Belew, R. K., & Olson, A. J., 1998, Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function, Journal of Computational Chemistry, 19(14), 1639–1662. https://doi.org/10.1002/(SICI)1096 987X(19981115)19:14<1639::AID JCC10>3.0.CO;2-B.

[11] Zhang, Q., Nijampatnam, B., Hua, Z., Nguyen, T., Zou, J., Cai, X., Michalek, S. M., Velu, S. E., & Wu, H., 2017, Structure-based discovery of small molecule inhibitors of cariogenic virulence. Scientific Reports, 7(1), 5974. https://doi.org/10.1038/s41598-017-06168-1.

[12] Solis, F. J., & Wets, R. J.-B., 1981, Minimization by random search techniques. Mathematics of Operations Research, 6(1), 19–30. https://doi.org/10.1287/moor.6.1.19.

[13] Bikadi, Z., & Hazai, E., 2009, Application of the PM6 semi-empirical method to modeling proteins enhances docking accuracy of AutoDock. Journal of Cheminformatics, 1, 15. https://doi.org/10.1186/1758-2946-1-15.

[14] Halgren, T. A., 1998, Merck molecular force field. I. Basis, form, scope, parametrization, and performance of MMFF94, Journal of Computational Chemistry, 17(5–6), 490–519.

[15] Sivaraman, D., Pradeep, P. S., Manoharan, S. S., Ramachandra Bhat, C., Leela, K. V., & Venugopal, V., 2020, Revealing potential binding affinity of FDA approved therapeutics targeting Main protease (3CLpro) in impairing novel coronavirus (SARS-CoV-2) replication that causes COVID-19. Coronaviruses, 1, 1–9.

[16] Morris, G. M., Huey, R., Lindstrom, W., Sanner, M. F., Belew, R. K., Goodsell, D. S., & Olson, A. J., 2009, AutoDock4 and AutoDockTools4: Automated docking with selective receptor flexibility. Journal of Computational Chemistry, 30(16), 2785–2791. https://doi.org/10.1002/jcc.21256.

[17] Ren, Z., Chen, L., Li, J., & Li, Y., 2016, Inhibition of Streptococcus mutans polysaccharide synthesis by molecules targeting glycosyltransferase activity, Journal of Oral Microbiology, 8, 31095. https://doi.org/10.3402/jom.v8.31095.

[18] Guevara, T., Rodríguez-Banqueri, A., Lasica, A. M., Ksiazek, M., Potempa, B. A., Potempa, J., & Gomis-Rüth, F. X., 2019, Structural determinants of inhibition of Porphyromonas gingivalis gingipain K by KYT-36, a potent, selective, and bioavailable peptidase inhibitor, Scientific Reports, 9(1), 4935. https://doi.org/10.1038/s41598-019-41354-3.

[19] Rodrigues, R. S., Silveira, V. R., & Rego, R. O., 2020, Analysis of Porphyromonas gingivalis fimA genotypes in severe periodontitis patients, Brazilian Oral Research, 34, e090. https://doi.org/10.1590/1807-3107bor-2020.vol34.0090.

[20] K versus S., 2014, The effect of scaling and root planing on glycaemic control, periodontal status and gingival crevicular fluid TNF-α levels in an Indian population- to reveal the ambivalent link, Journal of Clinical and Diagnostic Research, 8(11), ZC22–ZC26. https://doi.org/10.7860/JCDR/2014/9490.5115.

[21] Båge, T., 2011, Prostaglandin E synthases in periodontitis-affected gingival tissue and in gingival fibroblasts, Karolinska Institutet.