Serkan DÜNDAR, Mehmet GÜL, Abdulsamet TANIK, Gökhan ARTAŞ, Mehmet Emrah POLAT, Akın YİĞİN, Erhan Cahit ÖZCAN

The effect of caffeic acid phenethyl ester and Ankaferd Blood Stopper on the diabetic and nondiabetic gingival wound healing: an experimental study

Background/aim: Healthy wound healing is very important for patient comfort. Diabetes is one of the factors that negatively affect wound healing. Ankaferd Blood Stopper (ABS) and caffeic acid phenethyl ester (CAPE) are antiinflammatory and antimicrobial agents and may have positive effects on wound healing. Materials and methods: In this study, 72 male Wistar albino rats were used. Rats; control, CAPE, ABS, diabetes + control, diabetes + ABS and diabetes + CAPE groups were divided into 6 groups. A healthy 36 rats created diabetes using streptozotocin (STZ). A gingival wound was created using a 4-mm punch biopsy in the gingival tissue under the lower anterior incisors of the rats. Results: The comparison between the nondiabetic groups had a statistically significant positive effect compared to the control group of CAPE and ABS (P ˂ 0.05). In the comparison between ABS and diabetes + ABS groups and in the comparison between CAPE and diabetes + CAPE groups, a decrease in vascularization in diabetes + CAPE groups was observed and it was statistically significant (P ˂ 0.005). Conclusion: ABS and CAPE have been found to have positive effects on gingival wound healing in the nondiabetic group. We think that this situation is caused by its antiinflammatory and antimicrobial properties.Key words: Ankaferd Blood Stopper, caffeic acid phenethyl ester, diabetes, gingival wound healing

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1. Smith PC, Caceres M, Martinez C, Oyarzún A, Martínez J. Gingival wound healing: an essential response disturbed by aging? Journal of dental research 2015; 94 (3): 395-402. doi: 10.1177/0022034514563750
2. Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001; 414 (6865): 813-820. doi: 10.1038/414813a
3. King GL. The role of inflammatory cytokines in diabetes and its complications. Journal of Periodontology 2008; 79 (8): 1527-1534. doi: 10.1902/jop.2008.080246
4. Lalla E, Papapanou PN. Diabetes mellitus and periodontitis: a tale of two common interrelated diseases. Nature Reviews Endocrinology 2011; 7 (12): 738-748. doi: 10.1038/nrendo.2011.106
5. Borgnakke WS, Ylöstalo PV, Taylor GW, Genco RJ. Effect of periodontal disease on diabetes: systematic review of epidemiologic observational evidence. Journal of Periodontology 2013; 84 (4): 135-152. doi: 10.1902/jop.2013.1340013
6. Simpson TC, Weldon JC, Worthington HV, Needleman I, Wild SH et al. Treatment of periodontal disease for glycaemic control in people with diabetes mellitus. Cochrane Database of Systematic Reviews 2015; 2015 (11): CD004714. doi: 10.1002/14651858.CD004714.pub3
7. Lerman OZ, Galiano RD, Armour M, Levine JP, Gurtner GC. Cellular dysfunction in the diabetic fibroblast: impairment in migration, vascular endothelial growth factor production, and response to hypoxia. The American journal of pathology 2003; 162 (1): 303-312. doi: 10.1016/S0002-9440(10)63821-7
8. Falanga V. Wound healing and its impairment in the diabetic foot. The Lancet 2005; 366 (9498): 1736-1743. doi: 10.1016/ S0140-6736(05)67700-8
9. Romana-Souza B, Dos Santos JS, Monte-Alto-Costa A. Caffeic acid phenethyl ester promotes wound healing of mice pressure ulcers affecting NF-κB, NOS2 and NRF2 expression. Life Sciences 2018; 207: 158-165. doi: 10.1016/j.lfs.2018.05.057
10. Goker H, Haznedaroglu IC, Ercetin S, Kirazlı S, Akman U et al. Haemostatic actions of the folkloric medicinal plant extract Ankaferd Blood Stopper. Journal of International Medical Research 2008; 36 (1): 163-170. doi: 10.1177/147323000803600121
11. Fisgin NT, Cayci YT, Coban AY, Ozatli D, Tanyel E et al. Antimicrobial activity of plant extract Ankaferd Blood Stopper®. Fitoterapia 2009; 80 (1): 48-50. doi: 10.1016/j.fitote.2008.09.006
12. Işler SC, Demircan S, Cakarer S, Cebi Z, Keskin C et al. Effects of folk medicinal plant extract Ankaferd Blood Stopper® on early bone healing. Journal of Applied Oral Science 2010; 18 (4): 409-414. doi: 10.1590/s1678-77572010000400015
13. Gül M, Günay A, Tanık A. An evaluation of the effects of caffeic acid phenethyl ester and Ankaferd blood stopper on secondary wound healing of oral mucosal tissue. Turkish Journal of Medical Sciences 2020; 50 (1): 248-257. doi: 10.3906/sag-1908-114
14. Bolzán AD, Bianchi MS. Genotoxicity of streptozotocin. Mutation Research 2002; 512 (2-3): 121-134. doi: 10.1016/s1383- 5742(02)00044-3
15. Andrade Cetto A, Wiedenfeld H, Revilla MC, Sergio IA. Hypoglycemic effect of Equisetum myriochaetum aerial parts on streptozotocin diabetic rats. Journal of Ethnopharmacology 2000; 72: 129-133. doi: 10.1016/s0378-8741(00)00218-x
16. Shu C, Chen C, Zhang DP, Guo H, Zhou H et al. Gastrodin protects against cardiac hypertrophy and fibrosis. Molecular and Cellular Biochemistry 2012; 359 (1-2): 9-16. doi: 10.1007/ s11010-011-0992-1
17. Yıldırım İH, Çakmak EA, Camcı C. Gene expression of ING4 gene in pancreatic cancers and splice forms of ING4 gene. Cellular and Molecular Biology 2018; 64 (13): 6-9.
18. Guo S, Dipietro LA. Factors affecting wound healing. Journal of Dental Research 2010; 89 (3): 219-229. doi: 10.1177/0022034509359125
19. Kido D, Mizutani K, Takeda K, Mikami R, Matsuura T et al. Impact of diabetes on gingival wound healing via oxidative stress. PLoS One 2017; 12 (12): e0189601. doi: 10.1371/journal. pone.0189601
20. Li J, Chen J, Kirsner R. Pathophysiology of acute wound healing. Clinics in Dermatology 2007; 25 (1): 9-18. doi: 10.1016/j. clindermatol.2006.09.007
21. Salles J, De Souza BR, Costa AMA. Caffeic acid phenethyl ester ımproves diabetic mice cutaneous wound healing. The FASEB Journal 2019; 33 (S1): 812.
22. Magro-Filho O, De Carvalho AC. Topical effect of propolis in the repair of sulcoplasties by the modified Kazanjian technique. Cytological and clinical evaluation. The Journal of Nihon University School of Dentistry 1994; 36 (2): 102-111. doi: 10.2334/josnusd1959.36.102
23. Armutcu F, Gürel A, Hoşnuter M, Pabuçcu O, Altnyazar C. Caffeic acid phenethyl ester improves oxidative erythrocyte damage in a rat model of thermal injury. Journal of Burn Care & Rehabilitation 2004; 25 (2): 171-178. doi: 10.1097/01. bcr.0000111765.08625.d4
24. Topal A, Satar NYG, Cangul IT, Oktay MA, Inan K et al. Ankaferd blood stopper accelerates deep second degree burn wound healing in rats. Acta Veterinaria Brno 2018; 87 (3): 261-267. doi: 10.2754/avb201887030261
25. Akalin C, Kuru S, Barlas AM, Kismet K, Kaptanoglu B et al. Beneficial effects of Ankaferd Blood Stopper on dermal wound healing: an experimental study. International Wound Journal 2014; 11 (1): 64-68. doi: 10.1111/j.1742- 19 481X.2012.01063.x
26. Pamuk F, Cetinkaya BO, Keles GC, Balli U, Koyuncuoglu CZ et al. Ankaferd blood stopper enhances healing after osseous grafting in patients with intrabony periodontal defects. Journal of Periodontal Research 2016; 51 (4): 540-547. doi: 10.1111/ jre.12334
27. Keceli HG, Aylikci BU, Koseoglu S, Dolgun A. Evaluation of palatal donor site haemostasis and wound healing after free gingival graft surgery. Journal of Clinical Periodontology 2015; 42 (6): 582-589. doi: 10.1111/jcpe.12404
28. Kiwanuka E, Junker J, Eriksson E. Harnessing growth factors to influence wound healing. Clinics in Plastic Surgery 2012; 39 (3): 239-248. doi: 10.1016/j.cps.2012.04.003
29. Greca FH, Souza Filho ZA, Giovanini A, Camargo Junior CA, Rubin MR et al. Interleukin-6 (IL-6) influence on colonic anastomosis healing in rats. Acta Cirurgica Brasileira 2007; 22 (2): 110-114. doi: 10.1590/s0102-86502007000200006
30. Guo F, Hutchenreuther J, Carter DE, Leask A. TAK1 is required for dermal wound healing and homeostasis. Journal of Investigative Dermatology 2013; 133 (6): 1646-1654. doi: 10.1038/ jid.2013.28
31. Anderson JM, McNally AK. Biocompatibility of implants: lymphocyte/macrophage interactions. Seminars in Immunopathology 2011; 33 (3): 221-233. doi: 10.1007/s00281-011-0244-1
32. Witte MB, Kiyama T, Barbul A. Nitric oxide enhances experimental wound healing in diabetes. British Journal of Surgery 2002; 89: 1594-1601. doi: 10.1046/j.1365-2168.2002.02263.x
33. Lee PC, Salyapongse AN, Bragdon GA, Shears LL 2nd, Watkins SC et al. Impaired wound healing and angiogenesis in eNOS-deficient mice. American Journal of Physiology-Heart and Circulatory Physiology 1999; 277 (4): H1600-H1608. doi: 10.1152/ajpheart.1999.277.4.H1600
34. Malone-Povolny MJ, Maloney SE, Schoenfisch MH. Nitric oxide therapy for diabetic wound healing. Advanced Healthcare Materials 2019; 8 (12). doi: 10.1002/adhm.201801210