COMBINED EFFECT OF TOPICAL APPLICATION OF VIRGIN COCONUT OIL (VCO) AND BLACK CUMIN OIL (NIGELLA SATIVA) ON THE UPREGULATION OF VEGF GENE EXPRESSION AND WOUND HEALING IN DIABETIC ULCERATED RATS.
DOI:
https://doi.org/10.22159/ijap.2024.v16s1.07Keywords:
Black cumin oil, Diabetic ulcer, VCO, VEGF, WoundAbstract
Objective: Traditional therapies are increasingly explored as alternative methods for the management of diabetic ulcer. VCO and black cumin oil has attracted attention for its potential therapeutic benefits in promoting skin wound healing.
Methods: The rats were induced with one dose diabetes mellitus through the of intraperitoneal injection of streptozotocin 55 mg/kg body weight. Furthermore, fasting blood glucose (FBG) levels were monitored weekly for assessment. The wound was created using a 10-mm diameter punch biopsy. An experimental methodology was used, comprising the division of 30 rats into six groups, namely control, VCO, black cumin oil, and combinations of VCO and black cumin oil labeled as C1, C2, and C3. The formulated treatments were topically applied to wound for 7 and 14 d. At the end of the treatment, the samples were sacrificed and wound was excised, followed by molecular biological analysis and histopathological examination.
Results: On day 7, VEGF gene expression showed the highest increase in the C3 group, with an average of 1.85±0.10. Meanwhile, the highest increase on day 14 was observed in the C3 group, with an average of 1.69±0.11. C3 group treated wounds healed much faster, as indicated by a decreased time of complete epithelization and higher levels of various skin components.
Conclusion: The combination of VCO and black cumin oil could be used as an agent to accelerate wound healing in diabetic conditions, as indicated by the increased expression of VEGF gene.
Downloads
References
Boulton AJM, Armstrong DG, Kirsner RS, Attinger CE, Lavery LA, Lipsky BA. FFPM, RCPS (Glasg), Joseph L. Mill F. Diagnosis and management of diabetic foot complications. Am Diabetes Association; 2018.
Goldberg SR, Diegelmann RF. Wound healing primer. Surg Clin North Am. 2010;90(6):1133-46. doi: 10.1016/j.suc.2010.08.003, PMID 21074032.
Burgess JL, Wyant WA, Abdo Abujamra BA, Kirsner RS, Jozic I. Diabetic wound-healing science. Medicina (Kaunas). 2021;57(10):1-24. doi: 10.3390/medicina57101072, PMID 34684109.
Zarei F, Negahdari B, Eatemadi A. Diabetic ulcer regeneration: stem cells, biomaterials, growth factors. Artif Cells Nanomed Biotechnol. 2018;46(1):26-32. doi: 10.1080/21691401.2017.1304407, PMID 28355923.
Boyko EJ, Zelnick LR, Braffett BH, Pop-Busui R, Cowie CC, Lorenzi GM. Risk of foot ulcer and lower-extremity amputation among participants in the diabetes control and complications trial/epidemiology of diabetes interventions and complications study. Diabetes Care. 2022;45(2):357-64. doi: 10.2337/dc21-1816, PMID 35007329.
Hunt D. Diabetes: foot ulcers and amputations Search date Nov 2007 Diabetes: foot ulcers and amputations; 2009. p. 1-16.
Pereira RF, Bartolo PJ. Traditional therapies for skin wound healing. Adv Wound Care. 2016;5(5):208-29. doi: 10.1089/wound.2013.0506.
Durasevic S, Jasnic N, Prokic M, Grigorov I, Martinovic V, Dordevic J. The protective role of virgin coconut oil on the alloxan-induced oxidative stress in the liver, kidneys and heart of diabetic rats. Food Funct. 2019;10(4):2114-24. doi: 10.1039/c9fo00107g, PMID 30919867.
Silalahi J, Yuandani Y, Meliala DIPB, Margata L, Satria D. The activity of hydrolyzed virgin coconut oil to increase proliferation and cyclooxygenase-2 expression towards on nih 3T3 cell line in wound healing process. Open Access Maced J Med Sci. 2019;7(19):3164-8. doi: 10.3889/oamjms.2019.804, PMID 31949510.
Ibrahim AH, Li H, Al-Rawi SS, Majid ASA, Al-Habib OA, Xia X. Angiogenic and wound healing potency of fermented virgin coconut oil: in vitro and in vivo studies. Am J Transl Res. 2017;9(11):4936-44. PMID 29218091.
Nevin KG, Rajamohan T. Effect of topical application of virgin coconut oil on skin components and antioxidant status during dermal wound healing in young rats. Skin Pharmacol Physiol. 2010;23(6):290-7. doi: 10.1159/000313516. PMID 20523108.
Ika D, Meliala P, Silalahi J, Yuandani Y, Margata L, Satria D. The role of coconut oil to increase expression of MMP-9, PDGF. Herb Pharm Clin Sci. 2019;7(22):3733-6.
Cascella M, Bimonte S, Barbieri A, Del Vecchio V, Muzio MR, Vitale A. Dissecting the potential roles of Nigella sativa and its constituent thymoquinone on the prevention and on the progression of Alzheimer’s disease. Front Aging Neurosci. 2018;10(16):16. doi: 10.3389/fnagi.2018.00016, PMID 29479315.
Shadli S, Alam M, Haque A, Rokeya B, Ali L. Streptozotocin-induced TYPE 2 diabetic model rats; 2014.
Rujirachotiwat A, Suttamanatwong S. Curcumin upregulates transforming growth factor-β1, its receptors, and vascular endothelial growth factor expressions in an in vitro human gingival fibroblast wound healing model. BMC Oral Health. 2021;21(1):535. doi: 10.1186/s12903-021-01890-9, PMID 34657625.
Johnson KE, Wilgus TA. Vascular endothelial growth factor and angiogenesis in the regulation of cutaneous wound repair. Adv Wound Care. 2014 Mar;3(10):647-61. doi: 10.1089/wound.2013.0517, PMID 25302139.
Shams F, Moravvej H, Hosseinzadeh S, Mostafavi E, Bayat H, Kazemi B. Overexpression of VEGF in dermal fibroblast cells accelerates the angiogenesis and wound healing function: in vitro and in vivo studies. Sci Rep. 2022;12(1):18529. doi: 10.1038/s41598-022-23304-8, PMID 36323953.
Bao P, Kodra A, Tomic-canic M, Golinko MS, Ehrlich HP, Brem H. The role of vascular endothelial growth factor in wound healing. J Surg Res. 2009;153(2):347-58. doi: 10.1016/j.jss.2008.04.023, PMID 19027922.
Belvedere R, Novizio N, Morello S, Petrella A. The combination of mesoglycan and VEGF promotes skin wound repair by enhancing the activation of endothelial cells and fibroblasts and their cross-talk. Sci Rep. 2022:1-11.
Elgohary HM, Al Jaouni SK, Selim SA. Effect of ultrasound-enhanced Nigella sativa seeds oil on wound healing: an animal model. J Taibah Univ Med Sci. 2018;13(5):438-43. doi: 10.1016/j.jtumed.2018.02.008, PMID 31435359.
Qu K, Cha H, Ru Y, Que H, Xing M. Buxuhuayu decoction accelerates angiogenesis by activating the PI3K-Akt-eNOS signalling pathway in a streptozotocin-induced diabetic ulcer rat model. J Ethnopharmacol. 2021;273:113824. doi: 10.1016/j.jep.2021.113824, PMID 33581257.
Kumar B, Sanapalli R, Yele V, Kumar M, Thaggikuppe P, Venkata V. Preclinical models of diabetic wound healing: a critical review. Biomed Pharmacother. 2021;142(1):111946.
Yuan A, Yu C, Luh K, Chen W, Lin F, Kuo S. Quantification of VEGF mRNA expression in non-small cell lung cancer using a real-time quantitative reverse transcription-PCR assay and a comparison. Laboratoory Investig. 2020;80(11):1671-80.
Alhakamy NA, Caruso G, Eid BG, Fahmy UA, Ahmed OAA, Abdel-Naim AB. Ceftriaxone and melittin synergistically promote wound healing in diabetic rats. Pharmaceutics. 2021;13(10):1-19. doi: 10.3390/pharmaceutics13101622, PMID 34683915.
Liu J, Sun F, Wang X, Bi Q. miR-27b promotes angiogenesis and skin repair in scalded rats through regulating VEGF-C expression. Lasers Med Sci. 2020;35(7):1577-88. doi: 10.1007/s10103-020-02991-7, PMID 32170506.
McMinn R. Skin and subcutaneous tissues. New York and London: Academic Press; 1996. p. 1-40.
Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25(4):402-8. doi: 10.1006/meth.2001.1262, PMID 11846609.
Hannan MdA, Ataur Rahman Md, Al Mamun Sohag A, Uddin MdJ, Mahmudul Hasan Sikder MSR, Timalsina B, Munni YA, Sarker PP. Rev black cumin (Nigella sativa L.): a comprehensive review on phytochemistry, health benefits, molecular pharmacology, and safety. Nutrients. 2021;13(6):1-60.
Shibuya M. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: a crucial target for anti- and pro-angiogenic therapies. Genes Cancer. 2011;2(12):1097-105. doi: 10.1177/1947601911423031, PMID 22866201.
Iwata Y, Akamatsu H, Hasegawa S, Takahashi M, Yagami A, Nakata S. The epidermal integrin beta-1 and p75NTR positive cells proliferating and migrating during wound healing produce various growth factors, while the expression of p75NTR is decreased in patients with chronic skin ulcers. J Dermatol Sci. 2013;71(2):122-9. doi: 10.1016/j.jdermsci.2013.04.006, PMID 23642664.
Mallick R, Duttaroy AK. Modulation of endothelium function by fatty acids Mol Cell Biochem. 2022;477(1):15-38. doi: 10.1007/s11010-021-04260-9. PMID 34529222.
Yasmina K, Mahmoud HMAA. Cancer: thymoquinone antioxidant/pro-oxidant effect as the potential anticancer remedy. Biomed Pharmacother. 2019;115(1):1-14.
Sallehuddin N, Nordin A, Bt Hj Idrus R, Fauzi MB. Nigella sativa and its active compound, thymoquinone, accelerate wound healing in an in vivo animal model: a comprehensive review. Int J Environ Res Public Health. 2020;17(11). doi: 10.3390/ijerph17114160, PMID 32545210.
Andriana N, Lister INE, Fachrial E, Ginting CN, Lie S. Effectiveness test of wound healing based virgin coconut oil toward commercial products on rabbits. MECnIT 2020-international conference on mechanical, electronics, computer, and industrial technology. 2020. p. 104-7. doi: 10.1109/MECnIT48290.2020.9166656.
Javadi SMR, Hashemi M, Mohammadi Y, MamMohammadi A, Sharifi A, Makarchian HR. Synergistic effect of honey and Nigella sativa on wound healing in rats. Acta Cir Bras. 2018;33(6):518-23. doi: 10.1590/s0102-865020180060000006, PMID 30020313.
Published
How to Cite
Issue
Section
Copyright (c) 2024 ELIZA ARMAN, ALMAHDY A., PUTRI DAFRIANI, DEDY ALMASDY
This work is licensed under a Creative Commons Attribution 4.0 International License.