EFFECT OF THYMOQUINONE ON WOUND HEALING IN ALLOXAN-INDUCED DIABETIC RATS

  • Ahmadi Yusmin Environmental and Life Sciences Programme, Faculty of Science, Universiti Brunei Darussalam, Jalan Tungku Link, Gadong BE1410,Brunei Darussalam
  • Norhayati Ahmad Environmental and Life Sciences Programme, Faculty of Science, Universiti Brunei Darussalam, Jalan Tungku Link, Gadong BE1410, Brunei Darussalam http://orcid.org/0000-0002-3904-5981

Abstract

 

 Objective: Nigella sativa and its active constituent thymoquinone (TQ) have been extensively documented for its pharmacological values, but its application in wound healing in particular in a diabetic wound healing model is less documented.

Methods: In our study, alloxan-induced diabetic rats were used as a chronic delayed wound model and topical administration of TQ 10% w/v were used to assess the role and function of TQ in wound healing through wound contraction and histological analysis.

Results: Although statistically insignificant, we found out that TQ accelerated wound healing in post-wounding day 3 (inflammatory phase), whereas aggressively decelerating wound healing in post-wounding day 7 (proliferation phase). In addition, our histological analyses of wound granulation tissues at post-wounding day 14 substantiate our claim by showing that TQ treatment had delayed wound healing progression of the diabetic rats.

Conclusions: Our study shows that TQ accelerates wound healing during the inflammatory phase; however, decelerate rapidly during the proliferation phase. We speculate the acceleration of wound healing during the inflammatory phase was due to its well-documented antioxidant, anti-inflammatory, and antimicrobial properties while its deceleration of wound healing during the proliferation phase was due to its well-documented antiangiogenic effect.

Keywords: Wound healing, Thymoquinone, Nigella sativa, Diabetes mellitus.

Author Biographies

Ahmadi Yusmin, Environmental and Life Sciences Programme, Faculty of Science, Universiti Brunei Darussalam, Jalan Tungku Link, Gadong BE1410,Brunei Darussalam
Graduate student, Environmental & Life Sciences, Faculty of Science
Norhayati Ahmad, Environmental and Life Sciences Programme, Faculty of Science, Universiti Brunei Darussalam, Jalan Tungku Link, Gadong BE1410, Brunei Darussalam
SENIOR LECTURER, ENVIRONMENTAL AND LIFE SCIENCES GROUP, Faculty of Sceience,

References

1. Günter CI, Machens HG. New strategies in clinical care of skin wound healing. Eur Surg Res 2012;49:16-23.
2. Eming SA. Etiology and pathophysiology. Ther Skin Dis 2010;735-51. DOI: 10.1007/978-3-540-78814-0_62.
3. Kolluru GK, Bir SC, Kevil CG. Endothelial dysfunction and diabetes: Effects on angiogenesis, vascular remodeling, and wound healing. Int J Vasc Med 2012;2012:918267.
4. Bowling FL, Rashid ST, Boulton AJ. Preventing and treating foot complications associated with diabetes mellitus. Nat Rev Endocrinol 2015;11:606-16.
5. Catrina SB, Zheng X. Disturbed hypoxic responses as a pathogenic mechanism of diabetic foot ulcers. Diabetes Metab Res Rev 2016;32 Suppl 1:179-85.
6. Casella S, Bielli A, Mauriello A, Orlandi A. Molecular pathways regulating macrovascular pathology and vascular smooth muscle cells phenotype in Type 2 diabetes. Int J Mol Sci 2015;16:24353-68. 7. Amin MA, Abdel-Raheem IT. Accelerated wound healing and anti-inflammatory effects of physically cross linked polyvinyl alcohol-chitosan hydrogel containing honey bee venom in diabetic rats. Arch Pharm Res 2014;37:1016-31.
8. Banu A, Noorul Hassan MM, Rajkumar J, Srinivasa S. Spectrum of bacteria associated with diabetic foot ulcer and biofilm formation: A prospective study. Australas Med J 2015;8:280-5.
9. Cordell GA. Phytochemistry and traditional medicine - The revolution continues. Phytochem Lett. DOI: 10.1016/j.phytol.2014.06.002.
10. El-Dakhakhny M. Studies on the chemical constitution of Egyption N. sativa L. Seeds. Planta Med 1963;11(2):465-70.
11. Ab Rahman MR, Abdul Razak F, Mohd Bakri M. Evaluation of wound closure activity of Nigella sativa, Melastoma malabathricum, Pluchea indica, and Piper sarmentosum extracts on scratched monolayer of human gingival fibroblasts. Evid Based Complement Alternat Med 2014;2014:190342.
12. Selçuk CT, Durgun M, Tekin R, Yolbas L, Bozkurt M, Akçay C, et al. Evaluation of the effect of thymoquinone treatment on wound healing in a rat burn model. J Burn Care Res 2013;34:e274-81.
13. McLaughlin PJ, Pothering CA, Immonen JA, Zagon IS. Topical treatment with the opioid antagonist naltrexone facilitates closure of full-thickness wounds in diabetic rats. Exp Biol Med (Maywood) 2011;236:1122-32.
14. Umachigi SP, Jayaveera KN, Kumar CK, Kumar GS, Swamy BM, Kumar DV. Studies on wound healing properties of Quercus infectoria. Trop J Pharm Res 2008;7(1):913-9.
15. Shi HX, Lin C, Lin BB, Wang ZG, Zhang HY, Wu FZ, et al. The anti-scar effects of basic fibroblast growth factor on the wound repair in vitro and in vivo. PLoS One 2013;8:e59966.
16. Eroschenko VP. DiFiore’s Atlas of Histology with Functional Correlations. USA: Lippincott Williams & Wilkins; 2008.
17. Brown DA, Gibran NS. History of wound care. In: Jeschke MG, Kamolz L, Sjöberg F, Wolf SE, editors. Handbook of Burns Volume 1: Acute Burn Care. Vienna: Springer Vienna; 2012. p. 325-8.
18. Jepps OG, Dancik Y, Anissimov YG, Roberts MS. Modeling the human skin barrier--towards a better understanding of dermal absorption. Adv Drug Deliv Rev 2013;65(2):152-68.
19. Hadagali MD. Chua LS. The anti-inflammatory and wound healing properties of honey. Eur Food Res Technol 2015;239(6):1003-14.
20. Woo CC, Kumar AP, Sethi G, Tan KH. Thymoquinone: Potential cure for inflammatory disorders and cancer. Biochem Pharmacol 2012;83:443-51.
21. Kasuya A, Tokura Y. Attempts to accelerate wound healing. J Dermatol Sci 2014;76:169-72.
22. Valizadeh R, Hemmati AA, Houshmand G, Bayat S, Bahadoram M. Wound healing potential of Althaea officinalis flower mucilage in rabbit full thickness wounds. Asian Pac J Trop Biomed 2015;5(11):937-43.
23. Henshaw FR, Boughton P, Lo L, McLennan SV, Twigg SM. Topically applied connective tissue growth factor/CCN2 improves diabetic preclinical cutaneous wound healing: Potential role for CTGF in human diabetic foot ulcer healing. J Diabetes Res 2015;2015:236238.
24. Huang SM, Wu CS, Chao D, Wu CH, Li CC, Chen GS, et al. High-glucose-cultivated peripheral blood mononuclear cells impaired keratinocyte function via reduced IL-22 expression: Implications on impaired diabetic wound healing. Exp Dermatol 2015;24:639-41.
25. Zhang Z, Cao G, Sha L, Wang D, Liu M. The efficacy of sodium aescinate on cutaneous wound healing in diabetic rats. Inflammation 2015;38:1942-8.
26. Kant V, Gopal A, Pathak NN, Kumar P, Tandan SK, Kumar D. Antioxidant and anti-inflammatory potential of curcumin accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats. Int Immunopharmacol 2014;20:322-30.
27. Farahpour M, Emami P, Ghayour S. In vitro antioxidant properties and wound healing activity of hydroethanolic turmeric rhizome extract (Zingiberaceae). Int J Pharm Pharm Sci 2014;6(8);474-8.
28. Alenzi FQ, Altamimi MA, Kujan O, Tarakji B, Tamimi W, Bagader O, et al. Antioxidant properties of Nigella sativa. J Mol Genet Med 2013;7(3):1000077.
29. Bodnar RJ. Anti-angiogenic drugs: Involvement in cutaneous side effects and wound-healing complication. Adv Wound Care (New Rochelle) 2014;3:635-46.
30. Gali-Muhtasib H, Roessner A, Schneider-Stock R. Thymoquinone: A promising anti-cancer drug from natural sources. Int J Biochem Cell Biol 2006;38:1249-53.
31. Almeida BM, Nascimento MF, Pereira-Filho RN, Melo GC, Santos JC, Oliveira CR, et al. Immunohistochemical profile of stromal constituents and lymphoid cells over the course of wound healing in murine model. Acta Cir Bras 2014;29:596-602.
32. Hirapara H, Ghori V, Anovadiya A, Tripathi C. Effect of amlodipine and enalpril on wound healing in diabetic wistar albino rats. Int J Pharm Pharm Sci 2016;8(7);257-61.
33. Bagdas D, Etoz BC, Gul Z, Ziyanok S, Inan S, Turacozen O, et al. In vivo systemic chlorogenic acid therapy under diabetic conditions: Wound healing effects and cytotoxicity/genotoxicity profile. Food Chem Toxicol 2015;81:54-61.
34. Saito H, Yamamoto Y, Yamamoto H. Diabetes alters subsets of endothelial progenitor cells that reside in blood, bone marrow, and spleen. Am J Physiol Cell Physiol 2012;302:C892-901.
35. Moghadamtousi SZ, Rouhollahi E, Hajrezaie M, Karimian H, Abdulla MA, Kadir HA. Annona muricata leaves accelerate wound healing in rats via involvement of Hsp70 and antioxidant defence. Int J Surg 2015;18:110-7.
36. Shabana A, El-Menyar A, Asim M, Al-Azzeh H, Al Thani H. Cardiovascular benefits of black cumin (Nigella sativa). Cardiovasc Toxicol 2013;13(1):9-21.
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How to Cite
Yusmin, A., and N. Ahmad. “EFFECT OF THYMOQUINONE ON WOUND HEALING IN ALLOXAN-INDUCED DIABETIC RATS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 10, no. 9, Sept. 2017, pp. 242-5, doi:10.22159/ajpcr.2017.v10i9.18951.
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