Effect of Flaxseed on TGF-Β, IL-6, and MMP9 Genes Expression during Wound Healing Process in Rabbits

Basma Ezzat Mustafa Al-Ahmad; Nazih Shaban  Mustafa; Khairani Idah  Mokhtar; Widya  Lestari; Munirah  Sha’ban; Aliah Ahmad  Nazri; Omar Abdul  Jabbar

doi:10.3889/oamjms.2023.10518

Authors

Basma Ezzat Mustafa Al-Ahmad Fundamental Dental Medical Sciences, Kulliyyah of Dentistry, International Islamic University, Kuala Lumpur, Malaysia https://orcid.org/0000-0001-9953-4536
Nazih Shaban Mustafa Department of Oral Maxillofacial Surgery and Oral Diagnosis, Kulliyyah of Dentistry, International Islamic University,Kuala Lumpur, Malaysia
Khairani Idah Mokhtar Fundamental Dental Medical Sciences, Kulliyyah of Dentistry, International Islamic University, Kuala Lumpur, Malaysia
Widya Lestari Fundamental Dental Medical Sciences, Kulliyyah of Dentistry, International Islamic University, Kuala Lumpur, Malaysia
Munirah Sha’ban Department of Biomedical Sciences, Kuliyyah of Allied Health Science, International Islamic University, Kuala Lumpur, Malaysia
Aliah Ahmad Nazri Department of Biomedical Sciences, Kuliyyah of Allied Health Science, International Islamic University, Kuala Lumpur, Malaysia
Omar Abdul Jabbar Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Al Mashreq University, Baghdad, Iraq

DOI:

https://doi.org/10.3889/oamjms.2023.10518

Keywords:

Flaxseed, Gene expression, Wound healing, Rabbit

Abstract

BACKGROUND: Wound healing is a natural restorative response to tissue injury, and it involves regulated order of cellular and biochemical actions to reinstate tissue after injury, which involves resurfacing reconstitution, and restoration of tensile strength of injured skin. Normal and impaired wound healing post-significant problems related to healthcare and expenditure. Most of the chemical medications which widely used for wound healing might cause unwanted side effects with prolonged use such as hyper scarring, thus studies using natural products are now deemed important. Flaxseed is a natural product that enhances the immune system functioning against different diseases. Nevertheless, limited studies have been done looking into the response triggered by immune cells and the wound-healing-related genes with the use of flaxseed extract onto the wounded skin for the healing process.

AIM: The main objective of this study is to analyze the expression of wound healing-related genes during different stages of the wound healing process induced by flaxseed in vivo.

METHODS: The effect of flaxseed oil in the early stages (day 4 and 7) and late stages (day 14) of wound healing was explored on New Zealand white rabbits by creating a longitudinal full thickness wound on their back. The gene expression profiles of transforming growth factor-beta (TGF-β), IL-6, and metalloproteinase (MMP9) genes which have roles in wound healing through inflammation, proliferation, and remodeling were studied by polymerase chain reaction method.

RESULTS: Flaxseed extract has significant effects in up-regulating anti-inflammatory marker TGF-β in wounds. Flaxseed oil also reduces the expression level of MMP9 on day 14 of wound healing.

CONCLUSIONS: This suggests that flaxseed extract has the potential to promote wound healing through the regulation of TGF-β and MMP9 in vivo.

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References

Theobald S, Brandes N, Gyapong M, El-Saharty S, Proctor E, Diaz T, et al. Implementation research: New imperatives and opportunities in global health. Lancet. 2018;392(10160):2214- 28. https://doi.org/10.1016/S0140-6736(18)32205-0 PMid:30314860 DOI: https://doi.org/10.1016/S0140-6736(18)32205-0

Leburu-Masigo GE, Kgadima NP. Gender-based violence during the Covid-19 pandemic in South Africa: Guidelines for social work practice. Gend Behav. 2020;18(4):16618-28.

World Health Organization. Progress Report on Access to Hepatitis C Treatment: Focus on Overcoming Barriers in Low-and Middle-income Countries. Geneva: World Health Organization; 2018.

Tang X, Wang X, Sun Y, Zhao L, Li D, Zhang J, et al. Magnesium oxide‐assisted dual‐cross‐linking bio‐multifunctional hydrogels for wound repair during full‐thickness skin injuries. Adv Funct Mater. 2021;31(43):2105718. https://doi.org/10.1002/adfm.202105718 DOI: https://doi.org/10.1002/adfm.202105718

Maver T, Kurečič M, Smrke DM, Kleinschek KS, Maver U. Plant-derived medicines with potential use in wound treatment. In: Herbal Medicine. London, United Kingdom: IntechOpen; 2018 https://doi.org/10.5772/intechopen.72813 DOI: https://doi.org/10.5772/intechopen.72813

Tang N, Zhang R, Zheng Y, Wang J, Khatib M, Jiang X, et al. Highly efficient self‐healing multifunctional dressing with antibacterial activity for sutureless wound closure and infected wound monitoring. Adv Mater. 2022;34(3):e2106842. https://doi.org/10.1002/adma.202106842 PMid:34741350 DOI: https://doi.org/10.1002/adma.202270025

Li R, Li DH, Zhang HY, Wang J, Li XK, Xiao J. Growth factors-based therapeutic strategies and their underlying signaling mechanisms for peripheral nerve regeneration. Acta Pharmacol Sin. 2020;41(10):1289-300. https://doi.org/10.1038/s41401-019-0338-1 PMid:32123299 DOI: https://doi.org/10.1038/s41401-019-0338-1

Xia H, Li X, Gao W, Fu X, Fang RH, Zhang L, et al. Tissue repair and regeneration with endogenous stem cells. Nat Rev Mater. 2018;3(7):174-93. https://doi.org/10.1038/s41578-018-0027-6 DOI: https://doi.org/10.1038/s41578-018-0027-6

Ryu HS, Lim NK, Padalhin AR, Abueva C, Park SY, Chung PS, et al. Improved healing and macrophage polarization in oral ulcers treated with photobiomodulation (PBM). Lasers Surg Med. 2022;54(4):600-10. https://doi.org/10.1002/lsm.23510 DOI: https://doi.org/10.1002/lsm.23510

PMid:34913510 10. Tavarini S, De Leo M, Matteo R, Lazzeri L, Braca A, Angelini LG. Flaxseed and camelina meals as potential sources of health-beneficial compounds. Plants (Basel). 2021;10(1):156. https://doi.org/10.3390/plants10010156 PMid:33466939 DOI: https://doi.org/10.3390/plants10010156

Hady AA, Darweesh MF, Motar AA. The antibacterial of essential fatty acid semicarbazide extracted from flaxseed oil against some nosocomial infection Bacteria in Iraq. Int J Curr Pharm Rev Res. 2017;8(1):31-9. https://doi.org/10.25258/ijcprr.v8i01.9086 DOI: https://doi.org/10.25258/ijcprr.v8i01.9086

Balić A, Vlašić D, Žužul K, Marinović B, Mokos ZB. Omega-3 versus omega-6 polyunsaturated fatty acids in the prevention and treatment of inflammatory skin diseases. Int J Mol Sci. 2020;21(3):741. https://doi.org/10.3390/ijms21030741 PMid:31979308 DOI: https://doi.org/10.3390/ijms21030741

Giacomelli L, Moglia A, Losa G, Quaglino P. Clinical use of Capilen, a liposomal cream based on fresh plant extracts enriched with omega fatty acids. Drugs Context. 2020;9:1-9. https://doi.org/10.7573/dic.2019-10-1 PMid:32158486 DOI: https://doi.org/10.7573/dic.2019-10-1

Al-Ahmad BE, Kashmoola MA, Jabbar OA, Mokhtar KI, Mohamad N, Rahim RA, et al. Histopathological changes of the flaxseed extract on skin wound healing in diabetic rabbits. Open Access Maced J Med Sci. 2020;8(A):881-92. https://doi.org/10.3889/oamjms.2020.5145 DOI: https://doi.org/10.3889/oamjms.2020.5145

Gupta P, Toksha B, Rahaman M. A review on biodegradable packaging films from vegetative and food waste. Chem Rec. 2022;22(7):e202100326. https://doi.org/10.1002/tcr.202100326 PMid:35253984 DOI: https://doi.org/10.1002/tcr.202100326

Dai NT, Chang HI, Wang YW, Fu KY, Huang TC, Huang NC, et al. Restoration of skin pigmentation after deep partial or full-thickness burn injury. Adv Drug Deliv Rev. 2018;123:155-64. https://doi.org/10.1016/j.addr.2017.10.010 PMid:29079536 DOI: https://doi.org/10.1016/j.addr.2017.10.010

Livak KJ, Wills QF, Tipping AJ, Datta K, Mittal R, Goldson AJ, et al. Methods for qPCR gene expression profiling applied to 1440 lymphoblastoid single cells. Methods. 2013;59(1):71-9. https://doi.org/10.1016/j.ymeth.2012.10.004 PMid:23079396 DOI: https://doi.org/10.1016/j.ymeth.2012.10.004

Kuan PF, Yang X, Ren X, Che C, Waszczuk M, Kotov R, et al. Mapping the transcriptomics landscape of post-traumatic stress disorder symptom dimensions in world trade center responders. Transl Psychiatry. 2021;24:11(1):310. https://doi.org/10.1038/s41398-021-01431-6 PMid:34031375 DOI: https://doi.org/10.1038/s41398-021-01431-6

De Oliveira Gonzalez AC, Costa TF, de Araújo Andrade Z, Medrado AR. Wound healing-a literature review. An Bras Dermatol. 2016;91(5):614-20. https://doi.org/10.1590/abd1806-4841.20164741 PMid:27828635 DOI: https://doi.org/10.1590/abd1806-4841.20164741

Nayak BS, Ramdath DD, Marshall JR, Isitor GN, Eversley M, Xue S, et al. Wound‐healing activity of the skin of the common grape (Vitis vinifera) variant, cabernet sauvignon. Phytother Res. 2010;24(8):1151-7. https://doi.org/10.1002/ptr.2999 PMid:20066659 DOI: https://doi.org/10.1002/ptr.2999

Mannan A, Garg N, Singh TG, Kang HK. Peroxisome proliferator-activated receptor-gamma (PPAR-ɣ): Molecular effects and its importance as a novel therapeutic target for cerebral ischemic injury. Neurochem Res. 2021;46(11):2800-31. https://doi.org/10.1007/s11064-021-03402-1 PMid:34282491 DOI: https://doi.org/10.1007/s11064-021-03402-1

Hwang SM, Chung G, Kim YH, Park CK. The role of maresins in inflammatory pain: Function of macrophages in wound regeneration. Int J Mol Sci. 2019;20(23):5849. https://doi.org/10.3390/ijms20235849 PMid:31766461 DOI: https://doi.org/10.3390/ijms20235849

Tian W, Liu S, Li B. Potential role of exosomes in cancer metastasis. Biomed Res Int. 2019;2019:4649705. https://doi.org/10.1155/2019/4649705 PMid:31355262 DOI: https://doi.org/10.1155/2019/4649705

Gushiken LF, Beserra FP, Bastos JK, Jackson CJ, Pellizzon CH. Cutaneous wound healing: An update from physiopathology to current therapies. Life (Basel). 2021;11(7):665. https://doi.org/10.3390/life11070665 PMid:34357037 DOI: https://doi.org/10.3390/life11070665

Martinez-Ferrer M, Afshar-Sherif AR, Uwamariya C, de Crombrugghe B, Davidson JM, Bhowmick NA. Dermal transforming growth factor-beta responsiveness mediates wound contraction and epithelial closure. Am J Pathol. 2010;176(1):98-107. https://doi.org/10.2353/ ajpath.2010.090283 PMid:19959810 DOI: https://doi.org/10.2353/ajpath.2010.090283

Beroual K, Agabou A, Abdeldjelil MC, Boutaghane N, Haouam S, Hamdi-Pacha Y. Evaluation of crude flaxseed (Linum usitatissimum L.) oil in burn wound healing in New Zealand rabbits. Afr J Tradit Complement Altern Med. 2017;14(3):280-6. https://doi.org/10.21010/ajtcam.v14i3.29 DOI: https://doi.org/10.21010/ajtcam.v14i3.29

Mondal S, Adhikari N, Banerjee S, Amin SA, Jha T. Matrix metalloproteinase-9 (MMP-9) and its inhibitors in cancer: A minireview. Eur J Med Chem. 2020;194:112260. https://doi.org/10.1016/j.ejmech.2020.112260 PMid:32224379 DOI: https://doi.org/10.1016/j.ejmech.2020.112260

Nielsen SH, Mouton AJ, DeLeon-Pennell KY, Genovese F, Karsdal M, Lindsey ML. Understanding cardiac extracellular matrix remodeling to develop biomarkers of myocardial infarction outcomes. Matrix Biol. 2019;75:43-57. https://doi.org/10.1016/j.matbio.2017.12.001 PMid:29247693 DOI: https://doi.org/10.1016/j.matbio.2017.12.001

Manosalva C, Alarcón P, González K, Soto J, Igor K, Peña F, et al. Free fatty acid receptor 1 signaling contributes to migration, MMP-9 activity, and expression of IL-8 induced by linoleic acid in HaCaT cells. Front Pharmacol. 2020;11:595. https://doi.org/10.3389/fphar.2020.00595 PMid:32431615 DOI: https://doi.org/10.3389/fphar.2020.00595

Jahan I. Elucidating the Role of Hemodynamic Force in Regulating the Attachment of Vascular Smooth Muscle Cells (VSMCS) to Maturing Vessels During Mouse Embryonic Development. Springfield: Missouri State University; 2022. Available from: https://www.bearworks.missouristate.edu/theses/3737