• RINDIT PAMBAYUN Departement of Food and Science, Faculty of Agriculture, Sriwijaya University, Palembang, Indonesia
  • RAFIKA PUTRI Student of Dentistry Study Program, Faculty of Medicine, Sriwijaya University, Palembang, Indonesia
  • BUDI SANTOSO Departement of Food and Science, Faculty of Agriculture, Sriwijaya University, Palembang, Indonesia
  • TRI WARDANI WIDOWATI Departement of Food and Science, Faculty of Agriculture, Sriwijaya University, Palembang, Indonesia
  • SITI RUSDIANA PUSPA DEWI Departement of Oral Medicine, Dentistry Study Program, Faculty of Medicine, Sriwijaya University, Palembang, Indonesia


Objective: True experimental in vivo with pre-test and post-test control group design was conducted at Animal House of Medical Faculty of Sriwijaya University Palembang and Biomedical Science Laboratory of Palembang, South Sumatera.

Methods: Thirty rats were divided into five groups; three groups were treated with betel quid ointments at concentration of 5%, 10% and 20%, one group was positive control (hyaluronic acid) and last group was negative control (placebo). One-mm diameter of wound was made on lower lip mucosa of rats with cylinder diamond bur. Wound was induced with carrageenan. The number of neutrophils was counted on the first day and third day after treatment by using hematoanalyzer.

Results: There was a significant decrease of the number of neutrophils for respective groups (p<0.05). Betel quid ointment of 10% and 20% concentration had similar effect to 0.2% hyaluronic acid (p>0.05).

Conclusion: Betel quid has an anti-inflammatory effect on the mucosal wound of rats in a dose-dependent manner.

Keywords: Anti-inflammatory, Betel quid, Mucosal wound


1. Aramwit P, Towiwat P, Srichana T. An investigation of the anti-inflammatory potential of silk sericin. Adv Sci Lett 2013;19:3615-9.
2. Kumar V, Abbas AK, Aster JC. editors. Robbins basic pathology. Canada: Elsevier Saunders; 2013.
3. Puncard NA, Whelan CJ, Adcock I. Journal of inflammation. J Inflamm (Lond) 2004;1:1-4.
4. Gerdle B, Bijar G, Nazdar G, Emmanuael B, Torsten G. Signs of ongoing inflammation in female patients with chronic widespread pain: a multivariate, explorative, cross-sectional study of blood samples. Medicine 2017;96:e6130.
5. Hurlbutt, Michelle, Thomsen L. editors. Denstifying recurrent oral ulcerations. New York: PenWell; 2007.
6. Cawson RK, Odel EW. Cawson’s essentials of oral pathology and oral medicine. China: Churchill Livingstone Elsevier; 2008.
7. Kruger P, Saffarzadeh M, Weber ANR, Rieber N, Radsak M, Bernuth HV, et al. Neutrophils: between host defence, immune modulation, and tissue injury. Plos Pathol 2015;11:1004651.
8. Lacy P. Mechanisms of degranulation in neutrophils. Allergy Asthma Clin Immunol 2006;2:98-108.
9. Leoni G, Neumann PA, Sumagin R, Denning TL, Nusraf A. Wound repair: role of immune-epithelial interactions. Mucosal Immunol 2015;8:959-68.
10. Wright HL, Moost RJ, Bucknall RC, Edwards SW. Neutrophil function in inflammation and inflammatory disease. Rheumatol (Oxford) 2010;49:1618-31.
11. Rosales C, Demaurex N, Lowell CA, E Uribe Querol E. Neutrophils: their role innate and adptive immunity. J Immunol Res 2016. Doi:10.1155/2016/1469780
12. Rahat MA, Coffelt SB, Granot Z, Muthana M, Amedei A. Macrophages and neutrophils: regulation of the inflammatory microenvironment in autoimmunity and cancer. Mediators Inflammation 2016. Doi:10.1155/2016/5894347
13. Koh TJ, DiPietro LA. Inflammation and wound healing: the role of the macrophage. Expert Rev Mol Med 2011:13:e23.
14. Kapoor P, Sachdeva S, Sachdeva S. Topical hyaluronic acid in the management of oral ulcer. Indian. J Derm 2011;56:300-2.
15. Sapna N, Vandana KL. Evaluation of hyaluronan gel (Gengigel) as a topical applicant in the treatment of gingivitis. J Investig Clin Dent 2011;2:162-70.
16. Bitterman Deutsch O, Kogan L, Nasser F. Delayed immune mediated adverse effects of hyaluronic acid fillers: report of five cases and review of the literature. Dermatol Reports 2015;7:5851.
17. Marcelina, Samad R. Salivary profile of betel quid tobacco chewers in district of rembon, tana toraja. J Dentomaxillofac Sci 2013;12:103-13.
18. Alam B, Akter F, Parvin N, Pia RS, Akter S, Chowdhury J, et al. Antioxidant, analgesic, and anti-inflammatory activities of the methanolic extract of Piper betle leaves. Avicenna J Phytomed 2013;3:112-25.
19. Dwivendi V, Tripathi S. Review study on potential activity of piper betle. J Pharmacog Phytochem 2014;3:93.
20. Bhandare AM, Kshirsagar AG, Vyawahare NS, Thorve VS. Potential analgesic, anti-inflammatory and antioxiant activities of hydroalcoholic extract of Areca catechu L. Nut Food Chem Toxicol 2010;48:3412-7.
21. Bhandare A, Kshirsagar A, Vyawahare N, Sharma P, Mohite R. Evaluation of anti-migraine potention of Areca catechu to prevent nitroglycerin-induced delayed inflammation in rat meninges: possible involvement of NOS inhibition. J Ethnopharmacol 2011;136:267-70.
22. Pithayanukul P, Nithitanakool S, Bavovada R. Hepatoprotective potention of extracts from seeds of Areca catechu and nutgalls of Quercus infectoria. Molecules 2009;14:4987-5000.
23. Bak MJ, Truong VL, Kang HS, Jun M, Jeong WK. Anti-inflammatory effect of procyanidins from wild grape (Vitis amurensis). Oxid Med Cell Longev 2013.
24. Katoh M, Oizumi Y, Mohri Y, Hirota M, Makabe H. Synthesis of procyanidin B1, B2, and B4 and their ainti-inflammatory activity: the effect of 4-alkoxy group of catechin and/or epicathecin electrophiles for condensation. Lett Org Chem 2012;9:233-8.
25. Wibowo IS, Dewi SRP, Yasmin U, Octaria F. FDI-IDA continuing education. Editors. The effecttiveness of gambir extract (Uncaria gambir Roxb.) as an anti-inflammatory agents in wistar male rats. Proceeding of FDI-PDGI Continuing Education. Bandung, Indonesia; 2016. p. 11-2.
26. Anggraini T, Tai A, Yoshino T, Itani T. Antioxidative activity and catechin content of four kind of Uncaria gambir extracts from West Sumatra, Indonesia. Afr J Biochem Res 2011;5:33-8.
27. Mbaveng AT, Zhao Q, Kuete V. Harmful and protective effects of phenolic compounds from African medicinal plants. Toxicol Survey African Med Plants 2014;1:577-609.
28. Trekli M, Bettle D, Guesdon F. Ati-inflammatory actions of green tea catechins and ligands of peroxisome proliferator-activated receptors. Int J Exp Pathol 2004;85:A75.
29. Mustofa M, Saujanya KP, Jain D, Sajjanshetty S, Arun A, Uppin L, et al. Role of calcium hydroxide in endodontics: a review. Global J Med Public Health 2012;1:66-8.
30. De Freites RP, Greatti VR, Alcalde MP, Cavenago BC, Vivan RR, Duarte MAH, et al. Effect of the association of nonsteroidal anti-inflammatory and antibiotic drugs on antibiofilm activity and pH of calcium hydroxide pastes. J Endo 2017;43:131-4.
31. Dixit S, Dixit A, Kumar P. Unusual gingival enlargement: a rare case report. Case Reports Dentistry 2014.
32. Arts JMW, Kramer K, Arndt SS, Ohi F. Effects of transfer from breeding to research facility on the welfare of rats. Animals (Basel) 2014;4:712-28.
33. Wowor VN, Supit A, Marbun DR. Profile of chewing betel in Manado. Unsrat Press 2016;2:1-5.
34. Toprani R, Patel D. Betel leaf: revisiting the benefits of an ancient Indian herb. South Asian J Cancer 2013;2:140-1.
35. Reddy PS, Gupta RJ, Reddy SM. Analgesic and anti-inflammatory activity of hydroalcoholic extract of Piper betle leaves in experimental animals. Int J Basic Clin Pharm 2016;5:979-85.
36. Sarpangala KB, Ashwin D, Sarpangala M. Punarnava-a natural remedy by ayurveda. Int J Ayurveda Pharm Res 2016;4:78-83.
37. Yimam M, Lee YC, Kim TW, Moore B, Jiao P, Hong M, et al. Analgesic and anti-inflammatory effect of UP3005, a botanical composition containing two standardized extracts of Uncaria gambir and Morus alba. Pharmacogn Res 2015;7:S39-46.
38. Louwakul P, Lertchirakarn V. Incorporation of anti-inflammatory agent into calcium hydroxide pulp capping material: an in vitro study physical and mechanical properries. Dent Mater J 2012;31:32-9.
39. Huang X, Ma C. Anti-inflammatory effects of eugenol on lipopolysaccharide-induces inflammatory reaction in acute lung injury via regulating inflammation and redox status. Int Immunopharmacol 2015;26:265-71.
40. Magalhaes CB, Riva DR, DePaula LJ, Brando-Lima A, Koatz VGL, Leal-Cardoso JH, et al. In vivo anti-inflammatory action of eugenol on lipopolysaccharide-induced lung injury. J Appl Physiol 2010;108:845-51.
41. Rintu D, Shinjini M, Kaustab M, Pramathadhip P, Umesh PS, Banarjee ER. Anti-oxidant and anti-inflammatory activities of different varietis of piper leaf extracts (Piper betle L.). J Nutr Food Sci 2015;5:415.
42. Pin KY, Chuah AL, Rashih AA, Mazura MP, Fadzureena J, Vimala S, et al. Antioxidant and anti-inflammatory activities of extracts of betel leaves (Piper betle) from solvents with different polarities. J Tropic Forest Sci 2010;22:448-55.
43. Abooali M, Lall GS, Coughlan K, Lall HS, Gibbs BF, Sumbayev VV. Crucial involvement of xanthine oxidase in the intercellular signaling networks associated with human myeloid cell function. Sci Rep 2014;4:6307.
44. Wisastra R, Dekker FJ. Inflammation, cancer and oxidative lipoxygenase activity are intimately linked. Cancer (Basel) 2014;6:1500-21.
45. Theoduloz C, Delporte C, Valenzuela Barra G, Silva X, Cadiz S, Bustamante F, et al. Topical antiinflammatory activity of new hybrid molecules of terpenes and synthetic drugs. Molecules 2015;20:11219-35.
46. Lee KP, Sudjarwo GW, Kim JS, Dirgantara S, Maeng WJ, Hong H. The anti-inflammatory effect of Indonesian Areca catechu leaf extract in vitro and in vivo. Nutr Res Prac 2014;8:267-71.
47. Khan S, Mehmood MH, Ali ANA, Ahmed FS, Dar A, Gilani AH. Studies on anti-inflammatory and analgesic activities of betel nut in rodents. J Ethnopharm 2011;135:654-61.
48. Rismana E, Ningsih S, Fachrudin F. In vitro study of xanthine oxidase inhibitory of gambir (Uncaria gambir) hunter roxb extracts. Pharm J 2017;9:862-5.
49. Morel A, Miller E, Bijak M, Saluk J. The increased level of COX-dependent arachidonic acid metabolism in blood platelets from secondary progressive multiple sclerosis patients. Mol Cell Biochem 2016;420:85-94.
50. Mota MAL, Landim JSP, Targino TSS, Silva SFR, Silva SL, Pereira MRP. Evaluation of the anti-inflammatory and analgesic effects of green tea (Camellia sinensis) in mice. Acta Cirurgica Brasileira 2015;30:242-6.
51. Mohammadi Z, Shalavi S, Yazdizadeh M. Antimicrobial activity of calcium hydroxide in endodontics: a review. Chonnam Med J 2012;48:133-40.
52. Subramaniam P, Konde S, Prashanth P. An in vitro evaluation of pH variations in calcium hydroxide liners. J Indian Soc Pedodontics Preventive Dentistry 2006; 24:144-5.
53. De Freitas RP, Greatti VR, Alcalde MP, Cavenago BC, Vivan RR. Effect of the association of nonsteroidal anti-inflammatory and antibiotik drugs on antibiofilm activity and pH of calcium hydroxide pastes. J Endo 2017;43:131-4.
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