Skip to main content

Advertisement

Log in

Anti-inflammatory and antiresorptive effects of Calendula officinalis on inflammatory bone loss in rats

  • Original Article
  • Published:
Clinical Oral Investigations Aims and scope Submit manuscript

Abstract

Objective

The aim of this work was to evaluate the anti-inflammatory and antiresorptive effects of Calendula officinalis (CLO) on alveolar bone loss (ABL) in rats.

Material and methods

Male Wistar rats were subjected to ABL by ligature with nylon thread around the second upper left molar. The contralateral hemimaxillae were used as control. Rats received saline solution (SAL) or CLO (10, 30, or 90 mg/kg) 30 min before ligature and daily until the 11th day. The maxillae were removed and prepared for macroscopic, radiographic, micro-tomographic, histopathologic, histometric analysis, and immunohistochemical localization of receptor activator of nuclear factor kappa-B ligand (RANKL) and osteoprotegerin (OPG). The gingival tissues were used to quantify the myeloperoxidase (MPO) activity, tumor necrosis factor-alpha (TNF-α), and interleukin-1β (IL-1β) concentrations by ELISA. Blood samples were collected for leukogram and to evaluate the bone-specific alkaline phosphatase (BALP) activity and serum levels of aspartate and alanine transaminases (AST/ALT).

Results

The bone loss induced by 11 days of ligature induced bone loss, reduced levels of BALP, leukocyte infiltration, increased MPO activity, gingival concentrations of TNF-α and IL-1β, and RANKL while reduced OPG immunoexpressions in the periodontal tissue and leukocytosis. Of the CLO, 90 mg/kg reduced bone loss, neutrophilia, the levels of pro-inflammatory mediators, and RANKL expression, while it increased OPG immunopositive cells and BALP serum levels, when compared to SAL. CLO did not affect either kidney or liver function, indicated by serum AST/ALT levels.

Conclusion

The present data suggests that CLO reduced inflammatory bone resorption in experimental periodontitis, which may be mediated by its anti-inflammatory properties and its effects on bone metabolism.

Clinical relevance

CLO can be a potential therapeutical adjuvant in the treatment of periodontitis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Pihlstrom BL, Michalowicz BS, Johnson NW (2005) Periodontal disease. Lancet 366:1809–1820

    Article  PubMed  Google Scholar 

  2. Giannobile WV (2008) Host-response therapeutics for periodontal diseases. J Periodontol 79(8 Suppl):1592–1600

    Article  PubMed  PubMed Central  Google Scholar 

  3. Silva N, Abusleme L, Bravo D et al (2015) Host response mechanisms in periodontal diseases. J Appl Oral Sci 23:329–255

    Article  PubMed  PubMed Central  Google Scholar 

  4. Kayal RA (2013) The role of osteoimmunology in periodontal disease. Biomed Res Int 2013:1–12

    Article  Google Scholar 

  5. Souza PP, Lerner UH The role of cytokines in inflammatory bone loss. Immunol Investig 42:555–622

  6. Norlindh T (1946) Studies in the Calenduleae II. Phytogeography and interrelation. Botaniska Notiser 4:471–506

    Google Scholar 

  7. Ukiya M, Akihisa T, Yasukawa K, Tokuda H, Suzuki T, Kimura Y (2006) Anti-inflammatory, anti-tumorpromoting, and cytotoxic activities of constituents of marigold (Calendula officinalis) flowers. J Nat Prod 69:1692–1696

    Article  PubMed  Google Scholar 

  8. Saini P, Al-Shibani N, Sun J et al (2012) Effects of Calendula officinalis on human gingival fibroblasts. Homeopathy 101:92–98

    Article  PubMed  Google Scholar 

  9. Khairnar MS, Pawar B, Marawar PP, Mani A (2013) Evaluation of Calendula officinalis as an anti-plaque and anti-gingivitis agent. J Indian Soc Periodontol 17:741–747

    Article  PubMed  PubMed Central  Google Scholar 

  10. Bezerra MM, de Lima V, Alencar VB et al (2000) Selective cyclooxygenase-2 inhibition prevents alveolar bone loss in experimental periodontitis in rats. J Periodontol 71:1009–1014

    Article  PubMed  Google Scholar 

  11. Preethi KC, Kuttan R (2009) Wound healing activity of flower extract of Calendula officinalis. J Basic Clin Physiol Pharmacol 20:73–79a

    Article  PubMed  Google Scholar 

  12. Goes P, Lima AP, Melo IM, Rêgo RO, Lima V (2010) Effect of Atorvastatin in radiographic density on alveolar bone loss in wistar rats. Braz Dent J 21:193–198

    Article  PubMed  Google Scholar 

  13. Lisboa MR, Gondim DV, Ervolino E et al (2015) Effects of electroacupuncture on experimental periodontitis in rats. J Periodontol 86:801–811

    Article  PubMed  Google Scholar 

  14. Leitão RF, Ribeiro RA, Chaves HV, Rocha FA, Lima V, Brito GA (2005) Nitric oxide synthase inhibition prevents alveolar bone resorption in experimental periodontitis in rats. J Periodontol 76:956–963

    Article  PubMed  Google Scholar 

  15. Goes P, Melo IM, Silva LM et al (2014) Low-dose combination of alendronate and atorvastatin reduces ligature-induced alveolar bone loss in rats. J Periodontal Res 49:45–54

    Article  PubMed  Google Scholar 

  16. Moss DW, Whitby LG (1975) A simplified heat-inactivation method for investigating alkaline phosphatase isoenzymes in serum. Clin Chim Acta 61:63–71

    Article  PubMed  Google Scholar 

  17. Goes P, Melo IM, Dutra CS, Lima AP, Lima V (2012) Effect of alendronate on bone-specific alkaline phosphatase on periodontal bone loss in rats. Arch Oral Biol 57:1537–1544

    Article  PubMed  Google Scholar 

  18. Sousa LH, Linhares EV, Alexandre JT et al (2016) Effects of atorvastatin on periodontitis of rats subjected to glucocorticoid-induced osteoporosis. J Periodontol 87:1206–1216

    Article  PubMed  Google Scholar 

  19. Dalcico R, de Menezes AM, Deocleciano OB et al (2013) Protective mechanisms of simvastatin in experimental periodontal disease. J Periodontol 84:1145–1157

    Article  PubMed  Google Scholar 

  20. de Barros Silva PG, de Oliveira CC, Brizeno L et al (2016) Immune cellular profile of bisphosphonaterelated osteonecrosis of the jaw. Oral Dis 22:649–657

    Article  PubMed  Google Scholar 

  21. Arora D, Rani A, Sharma A (2013) A review on phytochemistry and ethnopharmacological aspects of genus Calendula. Pharmacogn Rev 7:179–187

    Article  PubMed  PubMed Central  Google Scholar 

  22. Tanideh N, Tavakoli P, Saghiri MA et al (2013) Healing acceleration in hamsters of oral mucositis induced by 5-fluorouracil with topical Calendula officinalis. Oral Surg Oral Med Oral Pathol Oral Radiol 115:332–338

    Article  PubMed  Google Scholar 

  23. Garnero P (2008) Biomarkers for osteoporosis management: utility in diagnosis, fracture risk prediction and therapy monitoring. Mol Diagn Ther 12:157–170

    Article  PubMed  Google Scholar 

  24. Forte L, Torricelli P, Boanini E et al (2016) Antioxidant and bone repair properties of quercetinfunctionalized hydroxyapatite: an in vitro osteoblast-osteoclast-endothelial cell co-culture study. Acta Biomater 32:298–308

    Article  PubMed  Google Scholar 

  25. Zhou Y, Wu Y, Jiang X et al (2016) The effect of quercetin on the osteogenesic differentiation and angiogenic factor expression of bone marrow-derived mesenchymal stem cells. PLoS One 10:e0129605

    Article  Google Scholar 

  26. Srivastava S, Bankar R, Roy P (2013) Assessment of the role of flavonoids for inducing osteoblast differentiation in isolated mouse bone marrow derived mesenchymal stem cells. Phytomedicine 20:683–690

    Article  PubMed  Google Scholar 

  27. Wang XC, Zhao NJ, Guo C, Chen JT, Song JL, Gao L (2014) Quercetin reversed lipopolysaccharide-induced inhibition of osteoblast differentiation through the mitogen-activated protein kinase pathway in MC3T3-E1 cells. Mol Med Rep 10:3320–3326

    Article  PubMed  Google Scholar 

  28. Araújo AA, Souza TO, Moura LM et al (2013) Effect of telmisartan on levels of IL-1, TNF-α, downregulated COX-2, MMP-2, MMP-9 and RANKL/RANK in an experimental periodontitis model. J Clin Periodontol 40:1104–1111

    Article  PubMed  PubMed Central  Google Scholar 

  29. Araújo AA, Varela H, Brito GA et al (2014) Azilsartan increases levels of IL-10, down-regulates MMP-2, MMP-9, RANKL/RANK, Cathepsin K and up-regulates OPG in an experimental periodontitis model. PloS One 9:e96750

    Article  PubMed  PubMed Central  Google Scholar 

  30. Gonçalves DC, Evangelista RC, da Silva RR et al (2014) Infliximab attenuates inflammatory osteolysis in a model of periodontitis in Wistar rats. Exp Biol Med 239:442–453

    Article  Google Scholar 

  31. Preethi KC, Kuttan G, Kuttan R (2009) Anti-inflammatory activity of flower extract of Calendula officinalis Linn. and its possible mechanism of action. Indian J Exp Biol 47:113–120b

    PubMed  Google Scholar 

  32. Schwingel TE, Klein CP, Nicoletti NF et al (2014) Effects of the compounds resveratrol, rutin, quercetin, and quercetin nanoemulsion on oxaliplatin-induced hepatotoxicity and neurotoxicity in mice. Naunyn Schmiedebergs Arch Pharmacol 387:837–848

    Article  PubMed  Google Scholar 

  33. Napimoga MH, Clemente-Napimoga JT, Macedo CG et al (2013) Quercetin inhibits inflammatory bone resorption in a mouse periodontitis model. J Nat Prod 76:2316–2321

    Article  PubMed  Google Scholar 

  34. Hajishengallis G, Chavakis T, Hajishengallis E, Lambris JD (2015) Neutrophil homeostasis and inflammation: novel paradigms from studying periodontitis. J Leukoc Biol 98:539–548

    Article  PubMed  Google Scholar 

  35. Hienz SA, Paliwal S, Ivanovski S (2015) Mechanisms of bone resorption in periodontitis. J Immunol Res 2015:615486

    Article  PubMed  PubMed Central  Google Scholar 

  36. Walsh MC, Choi Y (2014) Biology of the RANKL-RANK-OPG system in immunity, bone, and beyond. Front Immunol 5:511

    Article  PubMed  PubMed Central  Google Scholar 

  37. de Araújo RF Jr, Reinaldo MP, Brito GA (2014) Olmesartan decreased levels of IL-1β and TNF-α, downregulated MMP-2, MMP-9, COX-2, RANK/RANKL and up-regulated SOCs-1 in an intestinal mucositis model. PLoS One 9:e114923

    Article  PubMed  PubMed Central  Google Scholar 

  38. U.S Food and Drug Administration. Generally Recognized as Safe (GRAS) Available at: http://www.fda.gov/food/ingredientspackaginglabeling/gras/default.htm

Download references

Funding

This work was supported by CNPq (grant # 480481/2013-0) and FUNCAP (grant # PJP-0072-00092.01.00/12), Brazilian agencies.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Paula Goes.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

The protocol was approved by the Committee on the Ethics of Animal Experiments of the Federal University of Ceará (Permit Number: 49/2012).

Informed consent

For this type of study, formal consent is not required.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Alexandre, J.T.M., Sousa, L.H.T., Lisboa, M.R.P. et al. Anti-inflammatory and antiresorptive effects of Calendula officinalis on inflammatory bone loss in rats. Clin Oral Invest 22, 2175–2185 (2018). https://doi.org/10.1007/s00784-017-2308-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00784-017-2308-7

Keywords

Navigation