EFFECTIVENESS OF PROPOLIS EXTRACT GEL AS ADJUNCTIVE PERIODONTAL THERAPY: OVERVIEW OF FIBROBLASTS AND NEUTROPHILS (IN VIVO STUDY)

Authors

  • JULIA MAHARANI Faculty of Dentistry, Universitas Sumatera Utara, Medan, Indonesia
  • AMINAH DALIMUNTHE Department of Pharmacology, Faculty of Pharmacy, Universitas Sumatera Utara
  • PITU WULANDARI Department of Periodontics, Faculty of Dentistry, Universitas Sumatera Utara, Medan, Indonesia https://orcid.org/0000-0001-8337-2691
  • WITA ANGGRAINI Department of Periodontology, Faculty of Dentistry, Universitas Trisakti
  • SYAFRUDDIN ILYAS Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Sumatera Utara
  • OLIVIA AVRIYANTI HANAFIAH Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Universitas Sumatera Utara

DOI:

https://doi.org/10.22159/ijap.2024.v16s2.05

Keywords:

Propolis, Periodontitis, Fibroblast, Neutrophil

Abstract

Objective: Propolis has therapeutic activities contributed by its active secondary metabolites to fasten the healing of periodontitis. This study was to analyze the effectiveness of propolis extract gel as an adjunctive periodontal therapy.

Methods: The study used 50 periodontitis-induced Wistar rats, were divided into five treatment groups, and were treated by applying propolis gel with concentrations of 50%, 60%, and 70%, metronidazole gel, and placebo gel after mechanical therapy. The number of fibroblasts and neutrophils was obtained by removing the mandibular gingival tissue on the third and seventh days and were observed using a binocular microscope with 400x magnification using hematoxylin-eosin staining.

Results: The group administered with propolis extract gel showed a higher number of fibroblast cells and lower number of neutrophil cells. The 70% propolis gel appeared effective in inducing the fibroblasts and reducing the neutrophils (p<0.05).

Conclusion: Propolis extract gel can accelerate the healing of periodontitis and potentially be used as adjunctive therapy for periodontitis treatment.

Downloads

Download data is not yet available.

References

Kinane DF. Periodontitis modified by systemic factors. Ann Periodontol. 1999;4(1):54-64. doi: 10.1902/annals.1999.4.1.54, PMID 10863375.

Michaud DS, Fu Z, Shi J, Chung M. Periodontal disease, tooth loss, and cancer risk. Epidemiol Rev. 2017;39(1):49-58. doi: 10.1093/epirev/mxx006, PMID 28449041.

Dumitrescu AL. Editorial: periodontal disease-a public health problem. Front Public Health. 2015;3:278. doi: 10.3389/fpubh.2015.00278, PMID 26779473.

Jin L, Herrera D, Meyle J, Renvert S. Global periodontal health: challenges, priorities and perspectives. In: World Oral Health Forum. FDI World Dental Federation; 2017.

Eke PI, Dye BA, Wei L, Thornton Evans GO, Genco RJ. CDC periodontal disease surveillance workgroup: James beck (University of North Carolina, Chapel Hill, USA), gordon douglass (Past President, American Academy of Periodontology), roy page (University of Washin. Prevalence of periodontitis in adults in the united states: 2009 and 2010. J Dent Res. 2012;91(10):914-20. doi: 10.1177/0022034512457373, PMID 22935673.

Papapanou PN. The prevalence of periodontitis in the US: forget what you were told. J Dent Res. 2012;91(10):907-8. doi: 10.1177/0022034512458692, PMID 22935674.

Kementerian Kesehatan RI. Hasil Utama RISKESDAS 2018. Badan Penelitian dan Pengembangan Kesehatan; 2018. Available from: https://www.google.com/search?client=firefox-b-dandq=Kemenkes+RI.+Riset+kesehatan+dasar%2C+riskesdas.+Jakarta%3A+Balitbang+Kemenkes+RI.+2018.

FDI World Dental Federation. FDI policy statement on oral infection/inflammation as a risk factor for systemic diseases. Adopted by the FDI general assembly: 30 August 2013-Istanbul, Turkey. Int Dent J. 2013;63(6):289-90. doi: 10.1111/idj.12080, PMID 24716241.

Kinane DF, Stathopoulou PG, Papapanou PN. Periodontal diseases. Nat Rev Dis Primers. 2017;3:17038. doi: 10.1038/nrdp.2017.38, PMID 28805207.

Pihlstrom BL, Michalowicz BS, Johnson NW. Periodontal diseases. Lancet. 2005;366(9499):1809-20. doi: 10.1016/S0140-6736(05)67728-8, PMID 16298220.

Tonetti MS, Bottenberg P, Conrads G, Eickholz P, Heasman P, Huysmans MC. Dental caries and periodontal diseases in the ageing population: call to action to protect and enhance oral health and well-being as an essential component of healthy aging-consensus report of group 4 of the joint EFP/ORCA workshop on the boundaries between caries and periodontal diseases. J Clin Periodontol. 2017;44Suppl 18:S135-44. doi: 10.1111/jcpe.12681, PMID 28266112.

Tonetti MS, Van Dyke TE. Periodontitis and atherosclerotic cardiovascular disease: consensus report of the Joint EFP/AAP workshop on periodontitis and systemic diseases. J Clinic Periodontology. 2013;40 Suppl 14. doi: 10.1111/jcpe.12089.

Gainet J, M Brion, J Hakim, MA Gougerot, Pocidalo CE. Interleukin-8 production by polymorphonuclear neutrophils in patients with rapidly progressive periodontitis: an amplifying loop of polymorphonuclear neutrophil activation. Lab Investig 78. 1998;755-762:1.

Romanelli R, Mancini S, Laschinger C, Overall CM, Sodek J, McCulloch CA. Activation of neutrophil collagenase in periodontitis. Infect Immun. 1999;67(5):2319-26. doi: 10.1128/IAI.67.5.2319-2326.1999, PMID 10225890.

Delima AJ, Van Dyke TE. Origin and function of the cellular components in gingival crevice fluid. Periodontol 2000. 2003;31:55-76. doi: 10.1034/j.1600-0757.2003.03105.x, PMID 12656996.

Carbone F, Nencioni A, Mach F, Vuilleumier N, Montecucco F. Pathophysiological role of neutrophils in acute myocardial infarction. Thromb Haemost. 2013;110(3):501-14. doi: 10.1160/TH13-03-0211, PMID 23740239.

Frodermann V, Nahrendorf M. Neutrophil-macrophage cross-talk in acute myocardial infarction. Eur Heart J. 2017;38(3):198-200. doi: 10.1093/eurheartj/ehw085, PMID 28158564.

Ma Y, Yabluchanskiy A, Iyer RP, Cannon PL, Flynn ER, Jung M. Temporal neutrophil polarization following myocardial infarction. Cardiovasc Res. 2016;110(1):51-61. doi: 10.1093/cvr/cvw024, PMID 26825554.

Moutsopoulos NM, Konkel J, Sarmadi M, Eskan MA, Wild T, Dutzan N. Defective neutrophil recruitment in leukocyte adhesion deficiency type I disease causes local IL-17-driven inflammatory bone loss. Sci Transl Med. 2014;6(229):229ra40. doi: 10.1126/scitranslmed.3007696, PMID 24670684.

Hajishengallis G. New developments in neutrophil biology and periodontitis. Periodontol 2000. 2020;82(1):78-92. doi: 10.1111/prd.12313, PMID 31850633.

Maekawa T, Krauss JL, Abe T, Jotwani R, Triantafilou M, Triantafilou K. Porphyromonas gingivalis manipulates complement and TLR signaling to uncouple bacterial clearance from inflammation and promote dysbiosis. Cell Host Microbe. 2014;15(6):768-78. doi: 10.1016/j.chom.2014.05.012, PMID 24922578.

Maekawa T, Abe T, Hajishengallis E, Hosur KB, DeAngelis RA, Ricklin D. Genetic and intervention studies implicating complement C3 as a major target for the treatment of periodontitis. J Immunol. 2014;192(12):6020-7. doi: 10.4049/jimmunol.1400569, PMID 24808362.

Klein OD. Role of fibroblast populations in periodontal wound healing and tissue remodeling. Front Physiol. 2019;1:270.

Daseke MJ, Tenkorang MAA, Chalise U, Konfrst SR, Lindsey ML. Cardiac fibroblast activation during myocardial infarction wound healing: fibroblast polarization after MI. Matrix Biol. 2020;91-92:109-16. doi: 10.1016/j.matbio.2020.03.010, PMID 32446909.

Bansal V, Gupta R, Dahiya P, Kumar M, Samlok JK. A clinico-microbiologic study comparing the efficacy of locally delivered chlorhexidine chip and diode LASER as an adjunct to non-surgical periodontal therapy. J Oral Biol Craniofac Res. 2019;9(1):67-72. doi: 10.1016/j.jobcr.2018.09.001, PMID 30294538.

Singh A, Sridhar R, Shrihatti R, Mandloy A. Evaluation of turmeric chip compared with chlorhexidine chip as a local drug delivery agent in the treatment of chronic periodontitis: a split mouth randomized controlled clinical trial. J Altern Complement Med. 2018;24(1):76-84. doi: 10.1089/acm.2017.0059, PMID 28731780.

Newman MG, Takei HH, Klokkevold PR, Carranza FA. Newman and Carranza’s clinical periodontology/[edited by] Michael G. Newman, Henry H. Takei, Perry R. Klokkevold, Fermin A Carranza; 2019. p. 1–994.

Sukumaran SK, Vadakkekuttical RJ, Kanakath H. Comparative evaluation of the effect of curcumin and chlorhexidine on human fibroblast viability and migration: an in vitro study. J Indian Soc Periodontol. 2020;24(2):109-16. doi: 10.4103/jisp.jisp_173_19, PMID 32189837.

Karygianni L, Al-Ahmad A, Argyropoulou A, Hellwig E, Anderson AC, Skaltsounis AL. Natural antimicrobials and oral microorganisms: a systematic review on herbal interventions for the eradication of multispecies oral biofilms. Front Microbiol. 2015;6:1529. doi: 10.3389/fmicb.2015.01529, PMID 26834707.

Iqbal M, Fan TP, Watson D, Alenezi S, Saleh K, Sahlan M. Preliminary studies: the potential anti-angiogenic activities of two Sulawesi Island (Indonesia) propolis and their chemical characterization. Heliyon. 2019;5(7):e01978. doi: 10.1016/j.heliyon.2019.e01978, PMID 31372523.

Zulhendri F, Felitti R, Fearnley J, Ravalia M. The use of propolis in dentistry, oral health, and medicine: a review. J Oral Biosci. 2021;63(1):23-34. doi: 10.1016/j.job.2021.01.001, PMID 33465498.

Stojanovic S, Najman SJ, Bogdanova Popov B, Najman SS. Propolis: chemical composition, biological and pharmacological activity-a review. amm. 2020;59(2):108-13. doi: 10.5633/amm.2020.0215.

Miguel MG, Nunes S, Dandlen SA, Cavaco AM, Antunes MD. Phenols and antioxidant activity of hydro-alcoholic extracts of propolis from Algarve, South of Portugal. Food Chem Toxicol. 2010;48(12):3418-23. doi: 10.1016/j.fct.2010.09.014, PMID 20849908.

Nakao R, Senpuku H, Ohnishi M, Takai H, Ogata Y. Effect of topical administration of propolis in chronic periodontitis. Odontology. 2020;108(4):704-14. doi: 10.1007/s10266-020-00500-4, PMID 32112365.

Sforcin JM, Bankova V. Propolis: is there a potential for the development of new drugs? J Ethnopharmacol. 2011;133(2):253-60. doi: 10.1016/j.jep.2010.10.032, PMID 20970490.

Rafał IG, Kroliczewski BJ, Gorniak I, Bartoszewski R, Kroliczewski AJ. Comprehensive review of antimicrobial activities of plant flavonoids. Phytochem Rev. 2018 ;18(181):241-72.

Chan JKC. The wonderful colors of the hematoxylin–eosin stain in diagnostic surgical pathology. Int J Surg Pathol. 2014;22(1):12-32. doi: 10.1177/1066896913517939, PMID 24406626.

Ji J, Tong X, Huang X, Zhang J, Qin H, Hu Q. Patient-derived human induced pluripotent stem cells from gingival fibroblasts composited with defined nanohydroxyapatite/chitosan/gelatin porous scaffolds as potential bone graft substitutes. Stem Cells Transl Med. 2016;5(1):95-105. doi: 10.5966/sctm.2015-0139, PMID 26586776.

Yu G, Okawa H, Okita K, Kamano Y, Wang F, Saeki M. Gingival fibroblasts as autologous feeders for induced pluripotent stem cells. J Dent Res. 2016;95(1):110-8. doi: 10.1177/0022034515611602, PMID 26467419.

Liu X, Wang J, Dong F, Li H, Hou Y. Induced differentiation of human gingival fibroblasts into VSMC-like cells. Differentiation. 2017;95:1-9. doi: 10.1016/j.diff.2017.01.001, PMID 28107746.

Liu X, Wang J, Dong F, Li H, Hou Y. Human gingival fibroblasts induced and differentiated into vascular endothelial-like cells. Dev Growth Differ. 2016;58(9):702-13. doi: 10.1111/dgd.12327, PMID 27882546.

Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature. 2008;453(7193):314-21. doi: 10.1038/nature07039, PMID 18480812.

Rout UK, Saed GM, Diamond MP. Transforming growth factor-β1 modulates expression of adhesion and cytoskeletal proteins in human peritoneal fibroblasts. Fertil Steril. 2002;78(1):154-61. doi: 10.1016/s0015-0282(02)03176-x, PMID 12095506.

Araujo MAR, Liberio SA, Guerra RNM, Ribeiro MNS, Nascimento FRF. Mechanisms of action underlying the anti-inflammatory and immunomodulatory effects of propolis: a brief review. Rev Bras Farmacogn. 2012;22(1):208-19. doi: 10.1590/S0102-695X2011005000167.

Sabir A, Tabbu CR, Agustiono P, Sosroseno W. Histological analysis of rat dental pulp tissue capped with propolis. J Oral Sci. 2005;47(3):135-8. doi: 10.2334/josnusd.47.135, PMID 16313091.

Sukmawati A, Wijayanti P, Karina V, Lastianny S. 10% propolis as a subgingival irrigation agent after gingival curettage: a comparative study. J Int Oral Health. 2021;13(6):571. doi: 10.4103/JIOH.JIOH_65_21.

Rajoo M. The role of propolis in inflammation and orofacial pain: a review. Annu Res Rev Biol. 2014;4(4):651-64. doi: 10.9734/ARRB/2014/6111.

Suryono JI, Kido J, Hayashi N, Kataoka M, Nagata T. Effect of porphyromonas gingivalis lipopolysaccharide, tumor necrosis factor-α, and interleukin-1β on calprotectin release in human monocytes. J Periodontol. 2003;74(12):1719-24. doi: 10.1902/jop.2003.74.12.1719.

Riyanti E, Hadidjah D, AI. Pemakaian propolis sebagai antibakteri pada pasta gigi. Bandung: Universitas Padjajaran; 2010. Available from: https://scholar.google.co.id/scholar?hl=enandas_sdt=0,5andcluster=6446061316280007568

ElAttar TMA. Prostaglandin E2 in human gingiva in health and disease and its stimulation by female sex steroids. Prostaglandins. 1976;11(2):331-41. doi: 10.1016/0090-6980(76)90155-6, PMID 1265296.

ElAttar TMA, Lin HS, Tira DE. Arachidonic acid metabolism in inflamed gingiva and its inhibition by anti-inflammatory drugs. J Periodontol. 1984;55(9):536-9. doi: 10.1902/jop.1984.55.9.536, PMID 6592327.

Pouliot M, Clish CB, Petasis NA, Van Dyke TE, Serhan CN. Lipoxin A(4) analogues inhibit leukocyte recruitment to porphyromonas gingivalis: a role for cyclooxygenase-2 and lipoxins in periodontal disease. Biochemistry. 2000;39(16):4761-8. doi: 10.1021/bi992551b, PMID 10769133.

Curtis MA, Diaz PI, Van Dyke TE. The role of the microbiota in periodontal disease. Periodontol. 2020;83(1):14-25. doi: 10.1111/prd.12296, PMID 32385883.

Sahib AH, Shafeeq MAA, Mohsen SM. The effectiveness of ethanolic extract of propolis on wound healing in albino rats. Ann Trop Med Public Heal. 2020;23(7):543-54. doi: 10.36295/ASRO.2020.23735.

Marquele Oliveira F, da Silva Barud H, Torres EC, Machado RTA, Caetano GF, Leite MN. Development, characterization and pre-clinical trials of an innovative wound healing dressing based on propolis (EPP-AF®)-containing self-microemulsifying formulation incorporated in biocellulose membranes. Int J Biol Macromol. 2019;136:570-8. doi: 10.1016/j.ijbiomac.2019.05.135, PMID 31226369.

Zulhendri F, Lesmana R, Tandean S, Christoper A, Chandrasekaran K, Irsyam I. Recent update on the anti-inflammatory activities of propolis. Molecules. 2022;27(23). doi: 10.3390/molecules27238473, PMID 36500579.

Saputri Hasmy N, Lovita Pertiwi T, Benyamin B, Ismail AA. Propolis 10%-gel as a topical drug candidate on gingivitis. Int J Med. 2017;5:12-7.

Gjertsen AW, Stothz KA, Neiva KG, Pileggi R. Effect of propolis on proliferation and apoptosis of periodontal ligament fibroblasts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;112(6):843-8. doi: 10.1016/j.tripleo.2011.08.004, PMID 22099860.

Martin MP, Pileggi R. A quantitative analysis of Propolis: a promising new storage media following avulsion. Dent Traumatol. 2004;20(2):85-9. doi: 10.1111/j.1600-4469.2004.00233.x, PMID 15025690.

Duque C, Hussein H, Bortolatto J, Prakki A, Kishen A. Effect of taxifolin and epigallocatechin-3-gallate on biomineralization potential of stem cells from dental apical papilla. Arch Oral Biol. 2022;138:105413. doi: 10.1016/j.archoralbio.2022.105413, PMID 35367790.

Huang XF, Yuan SJ, Yang C. Effects of total flavonoids from drynaria fortunei on the proliferation and osteogenic differentiation of rat dental pulp stem cells. Mol Med Rep. 2012;6(3):547-52. doi: 10.3892/mmr.2012.974, PMID 22751806.

Wang HL, Katranji A. ABC sinus augmentation classification. Int J Periodontics Restorative Dent. 2008;28(4):383-9. PMID 18717377.

Alipour M, Pouya B, Aghazadeh Z, SamadiKafil H, Ghorbani M, Alizadeh S. The antimicrobial, antioxidative, and anti-inflammatory effects of polycaprolactone/gelatin scaffolds containing chrysin for regenerative endodontic purposes. Stem Cells Int. 2021;2021:3828777. doi: 10.1155/2021/3828777, PMID 34630572.

Kawashima N, Okiji T. Odontoblasts: specialized hard-tissue-forming cells in the dentin-pulp complex. Congenit Anom (Kyoto). 2016;56(4):144-53. doi: 10.1111/cga.12169, PMID 27131345.

Niwa T, Yamakoshi Y, Yamazaki H, Karakida T, Chiba R, Hu JC. The dynamics of TGF-β in dental pulp, odontoblasts and dentin. Sci Rep. 2018;8(1):4450. doi: 10.1038/s41598-018-22823-7, PMID 29535349.

Rahayu RP, Pribadi N, Widjiastuti I, Nugrahani NA. Combinations of propolis and Ca(OH)2 in dental pulp capping treatment for the stimulation of reparative dentin formation in a rat model. F1000Research. Vol. 9; 2020.

Eyarefe OD, Ozota CA, Jarikre TA, Emikpe BO. Pathological and immunohistochemical evaluation of wound healing potential of Nigerian bee propolis in albino rats. Comp Clin Pathol. 2019;28(2):455-66. doi: 10.1007/s00580-018-2873-4.

Published

27-05-2024

How to Cite

MAHARANI, J., DALIMUNTHE, A., WULANDARI, P., ANGGRAINI, W., ILYAS, S., & HANAFIAH, O. A. (2024). EFFECTIVENESS OF PROPOLIS EXTRACT GEL AS ADJUNCTIVE PERIODONTAL THERAPY: OVERVIEW OF FIBROBLASTS AND NEUTROPHILS (IN VIVO STUDY). International Journal of Applied Pharmaceutics, 16(2), 15–21. https://doi.org/10.22159/ijap.2024.v16s2.05

Issue

Section

Original Article(s)

Most read articles by the same author(s)