Amplification of Wound Healing by Propolis and Honey Ointment in Healthy and Diabetic Rat Models; Histopathological and Morphometric Findings

Document Type : Original Articles

Authors

1 Toxin Research Center, AJA University of Medical Sciences, Tehran, Iran

2 Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

3 Department of Clinical Sciences, Faculty of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran

4 Biotechnology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Abstract

Skin wound healing, especially in diabetic patients, has been a major medical challenge for decades. In the meantime, the use of traditional medicine has always been questioned. Propolis) resin and wax (is one of the most likely solutions to this problem. The present study aimed to establish an animal model for healing skin wounds and diabetic ulcers. To this aim, rats were randomly allocated into two healthy and diabetic groups (50 mg/kg streptozotocin resulted in diabetes with high BSL to 300 mg/dL), which were divided into four subgroups. The 7 mm full-thickness skin wounds were created on the abdomen region in 80 male Wistar rats using paunch. In the subgroups, the wounds were cleaned with normal 0.9% saline as the control subgroup and dressed with Eucerit, 1.5% honey+eucerit, and 3% propolis +1.5% honey+eucerit, once daily for 14 days in other subgroups, respectively. On days 1, 3, 5, and 7 after the intervention, wound and area contractions were calculated using digital photographs measurement. The histopathological and semi-quantitative studies were performed on days 7 and 14 after wounds creation. The microscopic findings demonstrated that the granulation tissue, fibroblasts, re-epithelization, and angiogenesis increased (P≤0.05) in the subgroups treated by propolis and honey combination in healthy and diabetic rats within 7 and 14 days post-injury. Also, less inflammation and a significant reduction in wound contraction were observed in the same subgroups on days 3, 5, and 7 compared to other subgroups (P≤0.05). The results indicated that significant healing quality and acceleration were affected by propolis and honey compared to other subgroups on days 3 and 5 (P≤0.05).

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Main Subjects

References

  1. Velnar T, Bailey T, Smrkolj V. The wound healing process: an overview of the cellular and molecular mechanisms. Int J Med Res. 2009;37(5):1528-42.
  2. Abu-seida A, Saleh M. A Gigantic Cutaneous Fibroadenoma in a Dog. Asian J Anim Sci. 2016; 10: 113-9.
  3. Rangaswamy P, Rubby SA, Prasanth K. Prospective study of platelet derived growth factor in wound healing of diabetic foot ulcers in Indian population. Int J Surg. 2016; 4: 194-9.
  4. D′Souza M, D′Souza J, Karkada S. Foot care education and platelet derived growth factor on wound healing in foot ulcers among adults. Int J Nutr Pharmacol Neurol Dis. 2016;6:111.
  5. Tzeng Y-S, Deng S-C, Wang C-H, Tsai J-C, Chen T-M, Burnouf T. Treatment of Nonhealing Diabetic Lower Extremity Ulcers with Skin Graft and Autologous Platelet Gel: A Case Series. BioMed Res Int. 2013; 2013: 837620.
  6. Kavitha KV, Tiwari S, Purandare VB, Khedkar S, Bhosale SS, Unnikrishnan AG. Choice of wound care in diabetic foot ulcer: A practical approach. World J Diabetes. 2014; 5: 546-56.
  7. Holland LC, Norris JM. Medical grade honey in the management of chronic venous leg ulcers. Int J Surg. 2015;20:17-20.
  8. Loo AE, Wong YT, Ho R, Wasser M, Du T, Ng WT, Halliwell B. Effects of hydrogen peroxide on wound healing in mice in relation to oxidative damage. PloS One. 2012;7(11):49215.
  9. Yaghoobi R, Kazerouni A. Evidence for clinical use of honey in wound healing as an anti-bacterial, anti-inflammatory anti-oxidant and anti-viral agent: A review. Jundishapur J Nat Pharm Prod. 2013;8(3):100.
  10. Raynaud A, Ghezali L, Gloaguen V, Liagre B, Quero F, Petit JM. Honey-induced macrophage stimulation: AP-1 and NF-κB activation and cytokine production are unrelated to LPS content of honey. Int Immunopharmacol. 2013;17(3):874-9.
  11. Wagh VD. Propolis: a wonder bees product and its pharmacological potentials. Adv Pharmacol Sci. 2013;2013.
  12. Berretta AA, Nascimento AP, Bueno PC, Leite MM. Propolis standardized extract (EPP-AF®), an innovative chemically and biologically reproducible pharmaceutical compound for treating wounds. Int J Biol Sci. 2012;8(4):512.
  13. Lima LD, Andrade SP, Campos PP, Barcelos LS, Soriani FM, Moura SA. Brazilian green propolis modulates inflammation, angiogenesis and fibrogenesis in intraperitoneal implant in mice. BMC Complement Med Ther. 2014 Dec;14(1):1-9.
  14. Park YK, Ikegaki M. Preparation of water and ethanolic extracts of propolis and evaluation of the preparations. Biosci Biotechnol Biochem. 1998;62(11):2230-2.
  15. Gál P, Kilík R, Mokry M, Vidinský B, Vasilenko T, Mozev , et al. Simple method of open skin wound healing model in corticosteroid-treated and diabetic rats: standardization of semi-quantitative and quantitative histological assessments. Vet Med. 2008; 53: 652-9.
  16. Petroll WM, Ma L, Jester JV, Cavanagh HD, Bean J. Organization of Junctional Proteins in Proliferating Cat Corneal Endothelium During Wound Healing. Cornea. 2001; 20.
  17. Barba KR, Samy A, Lai C, Perlman JI, Bouchard CS. Effect of topical anti-inflammatory drugs on corneal and limbal wound healing. J Cataract Refract Surg. 2000; 26.
  18. Latvala T, Puolakkainen P, Vesaluoma M, Tervo T. Distribution of SPARC Protein (Osteonectin) in Normal and Wounded Feline Cornea. Exp Eye Res. 1996; 63: 579-84.
  19. Wong CJ, Peiffer RL, Oglesbee S, Osborne C. Feline ocular epithelial response to growth factors in vitro. Am J Vet Res. 1996; 57: 1748-52.
  20. Bohling MW, Henderson RA, Swaim SF, Kincaid SA, Wright JC. Cutaneous wound healing in the cat: a macroscopic description and comparison with cutaneous wound healing in the dog. Vet Surg. 2004; 33: 579-87.
  21. Pierce GF. Inflammation in nonhealing diabetic wounds: the space-time continuum does matter. Am J Clin Pathol. 2001; 159: 399-403.
  22. Alba-Loureiro TC, Hirabara SM, Mendonça JR, Curi R, Pithon-Curi TC. Diabetes causes marked changes in function and metabolism of rat neutrophils. J Endocrinol. 2006; 188: 295-303. 
  1. Ebadi P, Fazeli M. Evaluation of the potential in vitro effects of propolis and honey on wound healing in human dermal fibroblast cells. S Afr J Bot. 2021; 137: 414-22.
  2. Wahdan HA. Causes of the antimicrobial activity of honey. J Infect Dis. 1998; 26: 26-31.
  3. Sutta J, Hanko J, Janda J, Tkac J. Experimental and clinical experiences in the treatment of wounds in domestic animals by local application of an alcoholic solution of propolis. Folia Vet. 1974; 18:143-7.
  4. McLennan SV, Bonner J, Milne S, Lo L, Charlton A, Kurup S, et al. The anti-inflammatory agent Propolis improves wound healing in a rodent model of experimental diabetes. Wound Repair Regen. 2008; 16: 706-13.
  5. Takzaree N, Hadjiakhondi A, Hassanzadeh G, Rouini MR, Manayi A. Synergistic Effect of Honey and Propolis on Cutaneous Wound Healing in Rats. Acta Med Iran. 2016; 54: 233-9.
  6. Juanes CC, Souza SM, Braga VNL, Barreto FS, Aguiar GR, Pimentel KDG, et al. Red propolis and L-lysine on angiogenesis and tumor growth in a new model of hamster cheek pouch inoculated with Walker 256 tumor cells. Einstein. 2019; 17: eAO4576.
  7. Nindra B, Sungkar A, Yarsa KY, Wasita B. Indonesian Propolis Extract Acts as Antioxidant in Angiogenesis Based on Microvascular Density and Vascular Endothelial Growth Factor Assay: An Experimental Study in Skin Graft Murine Model. Asian J Surg. 2021; 14-22.
  8. Molan P. Honey as a topical antibacterial agent for treatment of infected wounds. World Wide Wounds. 2001:1, 10.
  9. Olczyk P, Komosinska-Vassev K, Winsz-Szczotka K, Stojko J, Klimek K, Kozma EM. Propolis induces chondroitin/dermatan sulphate and hyaluronic Acid accumulation in the skin of burned wound. Evid Based Complement Alternat Med. 2013; 2013: 290675.
  10. Chaudhary A, Bag S, Banerjee P, Chatterjee J. Wound healing efficacy of Jamun honey in diabetic mice model through reepithelialization, collagen deposition and angiogenesi. J Tradit Complement Med. 2020; 10: 529-43.
Archives of Razi Institute
Volume 77, Issue 5 - Serial Number 5
September and October 2022
Pages 1673-1681

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