An Immunoinformatic of Epigallocatechin-3-O-gallate as Adjuvant Therapy of Periodontitis: An in-silico Study

Authors

  • Mohammed A. Aljunaid Doctoral program of Dental Medicine, Faculty of Dental Medicine, Universitas Airlangga, Surabaya- Indonesia
  • Rini D. Ridwan Oral Biology Department, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
  • Sidarningsih Sidarningsih Oral Biology Department, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
  • Yuliati Yuliati Oral Biology Department, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
  • Fianza Rezkita Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
  • Andari Sarasati Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
  • Viol Kharisma Graduate Student of Biology, Faculty of Mathematics and Natural Science, Universitas Brawijaya, Indonesia
  • Alexander P. Nugraha Orthodontics Department, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia
  • Huda R. Qaid Doctoral program of Dental Medicine, Faculty of Dental Medicine, Universitas Airlangga, Surabaya- Indonesia
  • Maria J. Anggakusuma Residence in Periodontic Program, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.
  • Shuhdi G. Alaghbari Lecturer in Department of Dental Medicine, Faculty of Medicine, Taiz University, Taiz-Yemen

DOI:

https://doi.org/10.26538/tjnpr/v8i3.19

Keywords:

Periodontitis, Medicine, Molecular docking, in silico, EGCG, Bone regeneration

Abstract

Periodontitis results in irreversible bone resorption. Epigallocatechin-3-O-gallate (EGCG) is one of the prominent compounds in green tea and is recognized for its therapeutic efficacy. EGCG supports bone formation and possesses antioxidant and anti-inflammatory properties. EGCG inhibits bone resorption by encouraging osteoclast apoptosis, preventing formation, and supporting the development of mineralized bone nodules. This study investigates the efficacy of EGCG in immunoinformatic as a potential treatment for periodontitis. The 3D chemical structures were obtained from the PubChem database. PyRx v.0.8 software was used to conduct molecular docking simulations. The results showed an inhibitory effect on the protein samples Nuclear Factor Associate T cell-1 (NFATc1), Sclerostin, Tartate Resistant Acid Phosphatase (TRAP), Receptor Activator of kappa beta and ligand (RANK-RANKL), Runt-related transcription factor2 (RUNX2), Osterix, and Osteocalcin. The docking analysis of target proteins RUNX2, Osterix, and Osteocalcin showed that EGCG exhibited the most negative binding energy, -7.0 kcal/mol, in the RUNX2 domain, potentially enhancing osteonectin activity. The findings indicate that the EGCG inhibits osteoclastic activity by binding and suppressing NFATc1, RANK-RANKL, Sclerostin, and TRAP. Consequently, EGCG substantially enhances osteogenic processes by promoting RUNX2, Osterix, and Osteocalcin in silico.

Author Biographies

Mohammed A. Aljunaid, Doctoral program of Dental Medicine, Faculty of Dental Medicine, Universitas Airlangga, Surabaya- Indonesia

Lecturer in Department of Dental Medicine, Faculty of Medicine, Taiz University, Taiz-Yemen

Huda R. Qaid, Doctoral program of Dental Medicine, Faculty of Dental Medicine, Universitas Airlangga, Surabaya- Indonesia

Faculty of Oral and Dental Medicine, Alsaeed University, Taiz, Yemen.

Shuhdi G. Alaghbari, Lecturer in Department of Dental Medicine, Faculty of Medicine, Taiz University, Taiz-Yemen



References

Jameson JL, de Kretser DM, Grossman AB, Potts JT, De Groot JL, Giudice LC, Melmed S, Weir GC. Endocrinology: Adult and Pediatric. (2nd ed.). Elsevier Inc.; 2015.

Hienz SA, Paliwal S, Ivanovski S. Mechanisms of Bone Resorption in Periodontitis. J Immunol Res. 2015;2015:615486. doi:10.1155/2015/615486

Tsuchida S, Nakayama T. Recent Clinical Treatment and Basic Research on the Alveolar Bone. Biomedicines. 2023;11(3). doi:10.3390/BIOMEDICINES11030843

Nazir M, Al-Ansari A, Al-Khalifa K, Alhareky M, Gaffar B, Almas K. Global Prevalence of Periodontal Disease and Lack of Its Surveillance. Sci. World J. 2020;2020:8. doi:10.1155/2020/2146160

Elburki MS. The Etiology and Pathogenesis of Periodontal Disease. BAOJ Dentistry. 2018;4(2). https://www.researchgate.net/publication/326543693

Wright CD, McNeil DW, Edwards CB, Crout RJ, Neiswanger K, Shaffer JR, Marazita ML. Periodontal status and quality of life: Impact of fear of pain and dental fear. Pain Res Manag. 2017;2017:9. doi:10.1155/2017/5491923

Kon M, Ishikawa T, Ohashi Y, Yamada H, Ogasawara M. Epigallocatechin gallate stimulated histamine production and downregulated histamine H1 receptor in oral cancer cell lines expressing histidine decarboxylase. J Oral Biosci. 2022;64(1):120-130. doi:10.1016/J.JOB.2022.01.003

Sitasari PI, Narmada IB, Hamid T, Triwardhani A, Nugraha AP, Rahmawati D. East Java green tea methanolic extractcan enhance RUNX2 and Osterixexpression during orthodontic tooth movement in vivo. J Pharm Pharmacogn Res. 2020;8(4):290-298. Accessed January 23, 2024.

https://scholar.unair.ac.id/en/publications/east-java-greentea-methanolic-extractcan-enhance-runx2-and-oster

Chu C, Deng J, Man Y, Qu Y. Green Tea Extracts Epigallocatechin-3-gallate for Different Treatments. Biomed Res Int. 2017;2017. doi:10.1155/2017/5615647

Bafor EE, Eze C, Omoruyi O, Elvis-Offiah BU, Viegelmann C, Edrada-Ebel R. Green tea inhibits uterine contractility in Ex vivo (Non-pregnant) mice models. Trop J Nat Prod Res. 2018;2(6):254-261. doi:10.26538/TJNPR/V2I6.1

Luqman A, Kharisma VD, Ruiz RA, Götz F. In Silico and in Vitro Study of Trace Amines (TA) and Dopamine (DOP) Interaction with Human Alpha 1-Adrenergic Receptor and the Bacterial Adrenergic Receptor QseC. Cell Physiol Biochem. 2020;54(5):888-898. doi:10.33594/000000276

Putra WE, Kharisma VD, Susanto H. The exploration of medicinal plants’ phytochemical compounds as potential inhibitor against human α-3 nicotinic acetylcholine receptors: The insight from computational study. AIP Conf Proc. 2020;2231. doi:10.1063/5.0002480

Kharisma VD, Widyananda MH, Ansori ANM, Nege AS, Naw SW, Nugraha AP. Tea catechin as antiviral agent via apoptosis agonist and triple inhibitor mechanism against HIV-1 infection: A bioinformatics approach. J Pharm Pharmacogn Res. 2021;9(4):435-445. Accessed January 23, 2024. https://scholar.unair.ac.id/en/publications/lacatequina-del-t%C3%A9-como-agente-antiviral-atrav%C3%A9s-de-un-agonista

Hartati FK, Djauhari AB, Viol Dhea K. Evaluation of pharmacokinetic properties, toxicity, and bioactive cytotoxic activity of black rice (Oryza sativa l.) as candidates for diabetes mellitus drugs by in silico. Biointerface Res Appl Chem. 2021;11(4):12301-12311. doi:10.33263/BRIAC114.1230112311

Legeay S, Rodier M, Fillon L, Faure S, Clere N. Epigallocatechin Gallate: A Review of Its Beneficial Properties to Prevent Metabolic Syndrome. Nutrients. 2015;7(7):5443. doi:10.3390/NU7075230

Huang HT, Cheng TL, Lin SY, Ho CJ, Chyu JY, Yang R Sen, Chen CH, Shen CL. Osteoprotective Roles of Green Tea Catechins. Antioxidants. 2020;9(11):1136. doi:10.3390/ANTIOX9111136

Kim JH, Kim N. Regulation of NFATc1 in Osteoclast Differentiation. J Bone Metab. 2014;21(4):233. doi:10.11005/JBM.2014.21.4.233

Fabre S, Funck-Brentano T, Cohen-Solal M. Anti-Sclerostin Antibodies in Osteoporosis and Other Bone Diseases. J Clin Med. 2020;9(11):1-16. doi:10.3390/JCM9113439

Komori T. Molecular Mechanism of Runx2-Dependent Bone Development. Mol Cells. 2020;43(2):168. doi:10.14348/MOLCELLS.2019.0244

Lin SY, Kang L, Wang CZ, Huang HH, Cheng TL, Huang HT, Lee MJ, Lin YS, Ho ML, Wang GJ, Chen CH. (−)- Epigallocatechin-3-Gallate (EGCG) Enhances Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells. Molecules. 2018;23(12). doi:10.3390/MOLECULES23123221

Eerola SK, Santio NM, Rinne S, Kouvonen P, Corthals GL, Scaravilli M, Scala G, Serra A, Greco D, Ruusuvuori P, Latonen L, Rainio EM, Visakorpi T, Koskinen PJ. Phosphorylation of NFATC1 at PIM1 target sites is essential for its ability to promote prostate cancer cell migration and invasion. Cell Commun Signal. 2019;17(1). doi:10.1186/S12964-019-0463-Y

Liang Q, Wang Y, Lu Y, Zhu Q, Xie W, Tang N, Huang L, An T, Zhang D, Yan A, Liu S, Ye L, Zhu C. RANK promotes colorectal cancer migration and invasion by activating the Ca2+-calcineurin/NFATC1-ACP5 axis. Cell Death Dis. 2021;12(4). doi:10.1038/S41419-021-03642-7

Trevillyan JM, Chiou XG, Chen YW, Ballaron SJ, Sheets MP, Smith ML, Wiedeman PE, Warrior U, Wilkins J, Gubbins EJ, Gagne GD, Fagerland J, Carter GW, Luly JR, Mollison KW, Djuric SW. Potent inhibition of NFAT activation and T cell cytokine production by novel low molecular weight pyrazole compounds. J Biol Chem. 2001;276(51):48118-48126. doi:10.1074/JBC.M107919200

Cohen P. The origins of protein phosphorylation. Nat Cell Biol. 2002;4(5):E127-E130. doi:10.1038/ncb0502-e127

Chen Y, Zhao X, Wu H. Transcriptional Programming in Arteriosclerotic Disease: A Multifaceted Function of the Runx2 (Runt-Related Transcription Factor 2). Arterioscler Thromb Vasc Biol. 2021;41(1):20-34. doi:10.1161/ATVBAHA.120.313791

Kim WJ, Shin HL, Kim BS, Kim HJ, Ryoo HM. RUNX2- modifying enzymes: therapeutic targets for bone diseases.Exp Mol Med. 2020;52(8):1178-1184. doi:10.1038/s12276-020-0471-4

Wu M, Brown AC. Applications of Catechins in the Treatment of Bacterial Infections. Pathogens. 2021;10(5). doi:10.3390/PATHOGENS10050546

Asahi Y, Noiri Y, Miura J, Maezono H, Yamaguchi M, Yamamoto R, Azakami H, Hayashi M, Ebisu S. Effects of the tea catechin epigallocatechin gallate on Porphyromonas gingivalis biofilms. J Appl Microbiol. 2014;116(5):1164- 1171. doi:10.1111/JAM.12458

Shen CL, Yeh JK, Cao JJ, Wang JS. Green Tea and Bone metabolism. Nutr Res. 2009;29(7):437. doi:10.1016/J.NUTRES.2009.06.008

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Published

2024-03-30

How to Cite

Aljunaid, M. A., Ridwan, R. D., Sidarningsih, S., Yuliati, Y., Rezkita, F., Sarasati, A., … Alaghbari, S. G. (2024). An Immunoinformatic of Epigallocatechin-3-O-gallate as Adjuvant Therapy of Periodontitis: An in-silico Study. Tropical Journal of Natural Product Research (TJNPR), 8(3), 6604–6608. https://doi.org/10.26538/tjnpr/v8i3.19