Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Combination of Cannabidiol with Taurine Synergistically Treated Periodontitis in Rats

  • Se Woong Kim (Laboratory of Pharmacology, School of Pharmacy, Jeonbuk National University) ;
  • Saroj Kumar Shrestha (Laboratory of Pharmacology, School of Pharmacy, Jeonbuk National University) ;
  • Badmaarag-Altai Chuluunbaatar (Laboratory of Pharmacology, School of Pharmacy, Jeonbuk National University) ;
  • Yunjo Soh (Laboratory of Pharmacology, School of Pharmacy, Jeonbuk National University)
  • Received : 2024.06.17
  • Accepted : 2024.10.03
  • Published : 2025.01.01
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Abstract

The active component in cannabis, cannabidiol (CBD), was first isolated from the hemp plant in 1940. Chronic pain, inflammation, migraines, depression, and anxiety have long been treated with CBD. The fundamental mechanisms of CBD's effects on periodontal inflammation have yet to be fully understood. The amino sulfonic acid taurine is a substance that naturally exists in the body and is an inhibitory modulator of inflammation. This study examined the effects of CBD, taurine, and their combination on inflammatory cytokines and periodontitis in vivo. To assess the expression of inflammatory markers of iNOS, COX-2, TNF-α, and IL-1β, as well as TRAP count and resorbed pit areas, CBD and taurine were applied to RAW264.7 cells. The following groups of 45 Sprague-Dawley rats each were created: control (healthy), vehicle (induced periodontitis), low- and high-dose-CBD with taurine which were each treated for an additional 21 days. Rat teeth were obtained and subjected to histomorphometric studies. The combination of the two significantly decreased the expression of inflammatory markers TNF-α and IL-1β and the amount of TRAP+ cells and resorbed pit areas. Among rats with P. gingivalis-induced periodontitis, the alveolar bone resorption levels, periodontal pocket depth, and distance between cementoenamel junction (CEJ) and alveolar bone crest (ABC) were significantly reduced after treatment with CBD and taurine, suggesting that combining CBD with taurine could be a novel therapeutic agent against periodontal disease.

Keywords

Acknowledgement

This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (NRF2021R1I1A3055927 to Soh Y), and by research funds of Jeonbuk National University in 2024. This paper was also supported by a grant from the Technology Innovation Program (20012892) funded by the Ministry of Trade, Industry & Energy (MOTIE, Korea).

References

  1. Araujo, A. A., Morais, H. B., Medeiros, C., Brito, G. A. C., Guedes, P. M. M., Hiyari, S., Pirih, F. Q. and Araujo Junior, R. F. (2019) Gliclazide reduced oxidative stress, inflammation, and bone loss in an experimental periodontal disease model. J. Appl. Oral Sci. 27, e20180211.
  2. Armingohar, Z., Jørgensen, J., Kristoffersen, A., Schenck, K. and Dembic, Z. (2014) Polymorphisms in the interleukin-1 gene locus and chronic periodontitis in patients with atherosclerotic and aortic aneurysmal vascular diseases. Scand. J. Immunol. 79, 338-345.
  3. Asagiri, M. and Takayanagi, H. (2007) The molecular understanding of osteoclast differentiation. Bone 40, 251-264.
  4. Balli, U., Aydogdu, A., Dede, F. O., Turer, C. C. and Guven, B. (2015) Gingival crevicular fluid levels of sclerostin, osteoprotegerin, and receptor activator of nuclear factor-kappaB ligand in periodontitis. J. Periodontol. 86, 1396-404.
  5. Belibasakis, G. N., Reddi, D. and Bostanci, N. (2011) Porphyromonas gingivalis induces RANKL in T-cells. Inflammation 34, 133-138.
  6. Campos, A. C., Moreira, F. A., Gomes, F. V., Del Bel, E. A. and Guimaraes, F. S. (2012) Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders. Philos. Trans. R. Soc. B 367, 3364-3378
  7. Chen, W., Gao, B., Hao, L., Zhu, G., Jules, J., MacDougall, M. J., Wang, J., Han, X., Zhou, X. and Li, Y. P. (2016) The silencing of cathepsin K used in gene therapy for periodontal disease reveals the role of cathepsin K in chronic infection and inflammation. J. Periodontal Res. 51, 647-660.
  8. Eick, S., Radakovic, S., Pfister, W., Nietzsche, S. and Sculean, A. (2012) Efficacy of taurolidine against periodontopathic species—an in vitro study. Clin. Oral Investig. 16, 735-744.
  9. Elisia, I., Pae, H. B., Lam, V., Cederberg, R., Hofs, E. and Krystal, G. (2018) Comparison of RAW264.7, human whole blood and PBMC assays to screen for immunomodulators. J. Immunol. Methods 452, 26-31.
  10. Haririan, H., Andrukhov, O., Bertl, K., Lettner, S., Kierstein, S., Moritz, A. and Rausch-Fan, X. (2014) Microbial analysis of subgingival plaque samples compared to that of whole saliva in patients with periodontitis. J. Periodontol. 85, 819-828.
  11. Herrera, D., Sanz, M., Jepsen, S., Needleman, I. and Roldan, S. (2002) A systematic review on the effect of systemic antimicrobials as an adjunct to scaling and root planing in periodontitis patients. J. Clin. Periodontol. 29 Suppl 3, 136-159; discussion 160-162.
  12. Iffland, K. and Grotenhermen, F. (2017) An update on safety and side effects of cannabidiol: a review of clinical data and relevant animal studies. Cannabis Cannabinoid Res. 2, 139-154.
  13. Kirschneck, C., Wolf, M., Reicheneder, C., Wahlmann, U., Proff, P. and Roemer, P. (2014) Strontium ranelate improved tooth anchorage and reduced root resorption in orthodontic treatment of rats. Eur. J. Pharmacol. 744, 67-75.
  14. Koide, M., Kobayashi, Y., Yamashita, T., Uehara, S., Nakamura, M., Hiraoka, B. Y., Ozaki, Y., Iimura, T., Yasuda, H., Takahashi, N. and Udagawa, N. (2017) Bone formation is coupled to resorption via suppression of sclerostin expression by osteoclasts. J. Bone Miner. Res. 32, 2074-2086.
  15. Lagha, A. B., Andrian, E. and Grenier, D. (2019) Resveratrol attenuates the pathogenic and inflammatory properties of Porphyromonas gingivalis. Mol. Oral Microbiol. 34, 118-130.
  16. Lee, H. A., Song, Y. R., Park, M. H., Chung, H. Y., Na, H. S. and Chung, J. (2020) Catechin ameliorates Porphyromonas gingivalis-induced inflammation via the regulation of TLR2/4 and inflammasome signaling. J. Periodontol. 91, 661-670.
  17. Li, L., Sapkota, M., Kim, S. W. and Soh, Y. (2016) Herbacetin inhibits RANKL-mediated osteoclastogenesis in vitro and prevents inflammatory bone loss in vivo. Eur. J. Pharmacol. 777, 17-25.
  18. Li, L., Yang, M., Shrestha, S. K., Kim, H., Gerwick, W. H. and Soh, Y. (2021) Kalkitoxin reduces osteoclast formation and resorption and protects against inflammatory bone loss. Int. J. Mol. Sci. 22, 2303.
  19. Li, Y., Li, X., Song, G., Chen, K., Yin, G. and Hu, J. (2012) Effects of strontium ranelate on osseointegration of titanium implant in osteoporotic rats. Clin. Oral Implants Res. 23, 1038-1044.
  20. Lim, E., Park, S. and Kim, H. (1998) Effect of taurine supplementation on the lipid peroxide formation and the activities of glutathione-related enzymes in the liver and islet of type I and II diabetic model mice. Adv. Exp. Med. Biol. 442, 99-103.
  21. Lim, K., See, Y. M. and Lee, J. (2017) A systematic review of the effectiveness of medical cannabis for psychiatric, movement and neurodegenerative disorders. Clin. Psychopharmacol. Neurosci. 15, 301-312.
  22. Lim, Y. R. I., Preshaw, P. M., Lim, L. P., Ong, M. M. A., Lin, H. S., Tan, K. S. (2020) Pterostilbene complexed with cyclodextrin exerts anti-microbial and anti-inflammatory effects. Sci. Rep. 10, 9072.
  23. Loos, B. G. and Van Dyke, T. E. (2020) The role of inflammation and genetics in periodontal disease. Periodontology 2000 83, 26-39.
  24. Marins, L. M., Napimoga, M. H., Malta, F. S., Miranda, T. S., Nani, E. P., Franco, B. D. S. T., da Silva, H. D. P. and Duarte, P. M. (2020) Effects of strontium ranelate on ligature-induced periodontitis in estrogen-deficient and estrogen-sufficient rats. J. Periodontal Res. 55, 141-151.
  25. Miranda, T. S., Napimoga, M. H., Feres, M., Marins, L. M., da Cruz, D. F., da Silva, H. D. P. and Duarte, P. M. (2018) Antagonists of Wnt/beta-catenin signaling in the periodontitis associated with type 2 diabetes and smoking. J. Clin. Periodontol. 45, 293-302.
  26. Ono, T., Hayashi, M., Sasaki, F. and Nakashima, T. (2020) RANKL biology: bone metabolism, the immune system, and beyond. Inflamm. Regen. 40, 2.
  27. Özmeriç, N., Özcan, G., Haytaç, C. M., Alaaddinoğlu, E. E., Sargon, M. F. and Şenel, S. (2000) Chitosan film enriched with an antioxidant agent, taurine, in fenestration defects. J. Biomed. Mater. Res. 51, 500-503.
  28. Park, M. Y., Kwon, H.-J. and Sung, M.-K. (2009) Evaluation of aloin and aloe-emodin as anti-inflammatory agents in aloe by using murine macrophages. Biosci. Biotechnol. Biochem. 73, 828-832.
  29. Park, Y. R., Su, X. D., Shrestha, S. K., Yang, S. Y. and Soh, Y. (2022) 2E-Decene-4,6-diyn-1-ol-acetate inhibits osteoclastogenesis through mitogen-activated protein kinase-c-Fos-NFATc1 signaling pathways. Clin. Exp. Pharmacol. Physiol. 49, 341-349.
  30. Rams, T. E., Degener, J. E. and van Winkelhof, A. J. (2014) Antibiotic resistance in human chronic periodontitis microbiota. J. Periodontol. 85, 160-169.
  31. Schuller-Levis, G. B. and Park, E. (2004) Taurine and its chloramine: modulators of immunity. Neurochem. Res. 29, 117-126.
  32. Sheeba, M. and Asha, V. (2009) Cardiospermum halicacabum ethanol extract inhibits LPS-induced COX-2, TNF-α, and iNOS, which is mediated by NF-κB regulation, in RAW264.7 cells. J. Ethnopharmacol. 124, 39-44.
  33. Soufli, I., Toumi, R., Rafa, H. and Touil-Boukoffa, C. (2016) Overview of cytokines and nitric oxide involvement in immuno-pathogenesis of inflammatory bowel diseases. World J. Gastrointest. Pharmacol. Ther. 7, 353-360.
  34. Teitelbaum, S. L. (2000) Bone resorption by osteoclasts. Science 289, 1504-1508.
  35. Wang, H. W., Lai, E. H., Yang, C. N., Lin, S. K., Hong, C. Y., Yang, H., Chang, J. Z. and Kok, S. H. (2020) Intracanal metformin promotes healing of apical periodontitis via suppressing inducible nitric oxide synthase expression and monocyte recruitment. J. Endod. 46, 65-73.
  36. Yakar, N., Guncu, G. N., Akman, A. C., Pinar, A., Karabulut, E. and Nohutcu, R. M. (2019) Evaluation of gingival crevicular fluid and peri-implant crevicular fluid levels of sclerostin, TWEAK, RANKL, and OPG. Cytokine 113, 433-439.
  37. Yang, M., Li, L., Soh, Y. and Heo, S. M. (2019) Effects of omega-3 fatty acids and aspirin on Porphyromonas gingivalis-induced periodontitis in rats. J. Periodontol. 90, 1307-1319.
  38. Yang, M., Shrestha, S. K., Soh, Y. and Heo, S.-M. (2021) Effects of aloe-emodin on alveolar bone in Porphyromonas gingivalis-induced periodontitis rat model: a pilot study. J. Periodontal Implant Sci. 52, 383-393.