Open Access
Research (Published online: 14-03-2018)
8. Expression of vascular endothelial growth factor and matrix metalloproteinase-9 in Apis mellifera Lawang propolis extract gel-treated traumatic ulcers in diabetic rats
Diah Savitri Ernawati and Ade Puspa Sari
Veterinary World, 11(3): 304-309

Diah Savitri Ernawati: Department of Oral Medicine, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.
Ade Puspa Sari: Department of Oral Medicine, Faculty of Dental Medicine, Universitas Airlangga, Surabaya, Indonesia.

doi: 10.14202/vetworld.2018.304-309

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Article history: Received: 24-10-2017, Accepted: 29-01-2018, Published online: 14-03-2018

Corresponding author: Diah Savitri Ernawati

E-mail: diah-s-e@fkg.unair.ac.id

Citation: Ernawati DS, Sari AP (2018) Expression of vascular endothelial growth factor and matrix metalloproteinase-9 in Apis mellifera Lawang propolis extract gel-treated traumatic ulcers in diabetic rats, Veterinary World, 11(3): 304-309.
Abstract

Aim: The aim of this study was to determine the effect of Apis mellifera propolis extract gel on vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) expression in the traumatic ulcers of rats afflicted with diabetes mellitus (DM).

Materials and Methods: The study was conducted on 24 male Wistar rats (Rattus norvegicus) induced with DM by injecting 50 mg/kg of Streptozotocin, intraperitoneally, and a traumatic ulcer on their lower lip mucosa. These were divided into eight groups: Four each for control and treatment groups. Each control and treatment group consisted of three rats. The control groups treated with hydroxypropyl methylcellulose 5% gel and treatment groups were administered with propolis extract gel. The expression of VEGF and MMP-9 was observed on days 3, 5, 7, and 9. Furthermore, mice sacrificed and the lower lip labial mucosa tissue of mice has been taken to make the histopathology anatomy preparation by means of immunohistochemical examination with monoclonal antibodies anti-VEGF and anti-MMP-9.

Results: This experiment revealed higher VEGF expression and lower MMP-9 expression in the treatment group as compared to that of the control group. Analysis of Variance showed significant differences (p<0.01) of both VEGF expression and MMP-9 expression between the two groups. A Tukey's analysis did not find strong contrasts in VEGF and MMP-9 expressions between various treatment groups. However, those between treatment and control groups were found to be considerable.

Conclusion: Propolis extract gel increased the expression of VEGF and decreased that of MMP-9 during the healing process of traumatic ulcers on the oral mucosa of diabetes afflicted Wistar rats (R. norvegicus).

Keywords: diabetes mellitus, matrix metalloproteinase-9, ulcer healing process, vascular endothelial growth factor expression.

References

1. Regezi, J., Sciubba, J. and Jordan, R. (2012) Oral Pathology: Clinical-Pathologic Correlations. Vol 1. Elsevier/Saunders, St. Louis, Mo.

2. Woo, S. and Greenberg, M. (2015) Ulcerative, Vesicular and Bullous Lesions. In: Burket's Oral Medicine. 12th ed., Ch. 4. People's Medical Publishing House, Shelton. p86-88.

3. Araujo, M.A., Liberio, S.A., Guerra, R.N., Ribeiro, M.N. and Nascimento, F.R. (2012) Mechanisms of action underlying the anti-inflammatory and immunomodulatory effects of propolis?: A brief review. Rev. Bras. Farm. Braz. J. Pharmacogn., 22: 208-219. [Crossref]

4. Kumar, V., Abdul, K.A. and Jon, C. (2015) Robbins Basic Pathology of Disease. Elsevier Saunders, Philadelphia, PA.

5. Hasan, A. (2010) Healthy and Beauty with Propolis. IPB Press, Bogor.

6. El Gazaerly, H., Elbardisey, D.M., Eltokhy, H.M. and Teaama, D. (2013) Effect of transforming growth factor beta 1 on wound healing in induced diabetic rats. Int. J. Health Sci (Qassim)., 7: 160-172. [Crossref]

7. Delavarian, Z., Pakfetrat, A., Nazari, F., Tonkaboni, A. and Shakeri, M. (2015) Effectiveness of bee propolis on recurrent aphthous stomatitis?: A randomized clinical trial. Res. J. Fish. Hydrobiol., 10: 1-6.

8. Nakajima, Y., Tsuruma, K., Shimazawa, M., Mishima, S. and Hara, H. (2009) Comparison of bee products based on assays of antioxidant capacities. BMC Complement Altern. Med., 9: 4. [Crossref] [PubMed] [PMC]

9. Bankova, V. (2005) Recent trends and important developments in propolis research. Evid. Based Complement Altern. Med., 2: 29-32. [Crossref] [PubMed] [PMC]

10. Freires, I.A., De Alencar, S.M. and Rosalen, P.L. (2016) A pharmacological perspective on the use of Brazilian red propolis and its isolated compounds against human diseases. Eur. J. Med. Chem., 110: 267-279. [Crossref] [PubMed]

11. Sabir, A. (2005) Antibacterial Activity of Propolis Flavonoid Trigona sp toward Streptococcus mutans (in vitro). Maj. Ked. Gigi., 38: 135-141.

12. Samet, N., Laurent, C., Susarla, S.M. and Samet-Rubinsteen, N. (2007) The effect of bee propolis on recurrent aphthous stomatitis: A pilot study. Clin. Oral. Investig., 11: 143-147. [Crossref] [PubMed]

13. Hozzein, W., Badr, G., Al Ghamdi, A., Sayed, A., Al-Waili, N. and Garraud, O. (2015) Topical application of propolis enhances cutaneous wound healing by promoting tgfbeta/smad mediated collagen production in a streptozotocin induced Type I diabetic mouse model. Cell Physiol. Biochem., 37: 940-954. [Crossref] [PubMed]

14. Wagh, V.D. (2013) Propolis: A wonder bees product and its pharmacological potentials. Adv. Pharmacol. Sci., 2013: 308249. [Crossref] [PubMed] [PMC]

15. Ozan, F., Sumer, Z., Polat, Z.A., Er, K., Ozan, U. and Deger, O. (2007) Effect of mouthrinse containing propolis on oral microorganisms and human gingival fibroblasts. Eur. J. Dent., 1: 195-201. [PubMed] [PMC]

16. Burdock, G.A. (1998) Review of the biological properties and toxicity of bee propolis (propolis). Food Chem. Toxicol., 36: 347-363. [Crossref]

17. Da Silva, R.O., Andrade. V.M., Bulle, R.E.S., Azevedo, D.G.A., Santos, L.B.D., da Silva, F.A., de Souza, A.A.A., de Albuquerque, R.L. Jr. (2015) Acute and sub-acute oral toxicity of Brazilian red propolis in rats. J. Ethnopharmacol., 170: 66-71. [Crossref] [PubMed]

18. Larki-Harchegani, A., Hemmati, A.A., Arzi, A., Borujerdnia, M.G., Esmaeilzadeh, S., Zad, K.M.R. (2013) Evaluation of the effects of caffeic acid phenethyl ester on prostaglandin E2 and two key cytokines involved in bleomycin-induced pulmonary fibrosis. Iran. J. Basic. Med. Sci., 16: 850-857. [PubMed] [PMC]

19. Harmely, F. (2014) Formulation of Propolis Gel Extract from Trigona Itama (Cockrell) Beehive and It's Antibacterial Activity Towards Staphylococcus Epidemidis. Recent Developments of Pharmaceutical and Clinical Research IV. 2014: 88-95.

20. Firdaus, R., Marliyati, S.A. and Roosita, K. (2016) Diabetes Mellitus Animal Model Induced by Streptozotocin-Sucrose for Gestational Diabetes Mellitus Approach. MKMI, 12: 29-34.

21. Subramaniam, B.S., Amuthan, A., D'Almeida, P.M. and Arunkumar, H.D. (2013) Efficacy of gamat extract in wound healing in albino wistar rats. Int. J. Pharm. Sci. Rev. Res., 20: 142-145.

22. Nugroho, A.E. (2006) Diabetes Animal: Mechanism and Pathology Diabetogenic Action. Biodiversitas, 7: 378-382. [Crossref]

23. Ridwan, E. (2013) Ethical animal model for Health Research. J. Indones Med. Assos., 63: 112-116.

24. American Diabetes Association. (2016) American Diabetes Association (ADA) Diabetes Guidelines Summary Recommendation from NDEI. Natl. Diabetes Educ. Initiat., 39: 1-46.

25. Gunay, A., Arpag, O.F., Atilgan, S., Yaman, F., Atalay, Y. and Acikan, I.Z. (2014) Effects of caffeic acid phenethyl ester on palatal mucosal defects and tooth extraction sockets. Drug Des. Devel. Ther., 8: 2069-2074. [Crossref] [PubMed] [PMC]

26. Kolluru, G.K., Bir, S.C. and Kevil, C.G. (2012) Endothelial dysfunction and diabetes: Effects on angiogenesis, vascular remodeling, and wound healing. Int. J. Vasc. Med., 2012: 918267. [Crossref] [PubMed] [PMC]

27. Apriasari, M., Dachlan, Y. and Ernawati, D. (2017) Potential of natural substances to heal oral mucosa ulcers. Salemba Med., 20: 30-34.

28. Hammerle, C.H.F. and Giannobile, W.V. (2014) Biology of soft tissue wound healing and regeneration - Consensus report of group 1 of the 10th European workshop on periodontology. J. Clin. Periodontol., 41: S1-S5. [Crossref] [PubMed]

29. Ayuk, S.M., Abrahamse, H. and Houreld, N.N. (2016) The role of matrix metalloproteinases in diabetic wound healing in relation to photobiomodulation. J. Diabetes Res., 2016: 2897656. [Crossref] [PubMed] [PMC]

30. Volmer-Thole, M. and Lobmann, R. (2016) Neuropathy and diabetic foot syndrome. Int. J. Mol. Sci., 17: (6):917. [Crossref]

31. Larjava, H., Wiebe, C., Gallant-Behm, C., Hart, D.A., Heino, J. and Hakkinen, L. (2011) Exploring scarless healing of oral soft tissues. J. Can. Dent. Assoc (Tor)., 77: b18.

32. Yang, P., Pei, Q., Yu, T., Chang, Q., Wang, D., Gao, M., Zhang, X. and Liu, Y. (2016) Compromised wound healing in ischemic Type 2 diabetic rats. PLoS One, 11: e0152068. [Crossref]

33. Brizeno, L., Assreuy, A., Alves, A., Sousa, F., de B Silva, P., de Sousa, S.C., Lascane, N.A., Evangelista, J.S. and Mota, M.R. (2016) Delayed healing of oral mucosa in a diabetic rat model: Implication of TNF-a, IL-1β and FGF-2. Life Sci., 155: 36-47. [Crossref]

34. Guo, S. and Dipietro, L.A. (2010) Factors affecting wound healing. J. Dent. Res., 89: 219-229. [Crossref] [PubMed] [PMC]