ETHANOLIC EXTRACT OF TITHONIA DIVERSIFOLIA (HEMSLEY) A. GRAY INHIBITS MIGRATION ACTIVITY AND DECREASE THE TRANSFORMING GROWTH FACTOR-BETA1, VEGF EXPRESSION ON KELOID FIBROBLASTS

Authors

  • Mae Sri Hartati Wahyuningsih Department of Pharmacology and Therapy, Faculty of Medicine Public Health and Nursing, Universitas Gadjah Mada, Indonesia, Sekip Utara, Yogyakarta 55281.
  • Dwi Aris Agung Nugrahaningsih Department of Pharmacology and Therapy, Faculty of Medicine Public Health and Nursing, Universitas Gadjah Mada, Indonesia, Sekip Utara, Yogyakarta 55281.
  • Arief Budiyanto Departement of Dermatology and Venerology, Faculty of Medicine Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.

DOI:

https://doi.org/10.22159/ajpcr.2019.v12i1.29850

Keywords:

Keloid fibroblast, Tithonia diversifolia, Migration, Transforming growth factor-beta1, Vascular endothelial growth factor

Abstract

Objectives: Keloid occurred due to abnormal wound healing, characterized by massive fibroblast proliferation and excessive collagen accumulation. Tithonia diversifolia Hemsley A. Gray has been known to show antiproliferative effect against some cancer cells in vitro. However, its potential as anti-keloid has not been explored. This study aims to assess the T. diversifolia ethanolic extract effect on fibroblast migration activity, transforming growth factor-beta1 (TGF-β1), and vascular endothelial growth factor (VEGF) expression of keloid fibroblasts in vitro.

Methods: Fibroblasts were isolated from keloid collected from patient keloid tissue. The migration activity of keloid fibroblasts was assessed using scratch assay. The TGF-β1 and VEGF expression examination was done using ELISA.

Results: Ethanolic extract of T. diversifolia treatment at a concentration of 20 μg/ml, 10 μg/ml, and 5 μg/mL for 24 h on keloid fibroblasts culture showed slower migration activity compare to those on keloid fibroblast culture without treatment (p<0.05). The TGF-β1 and VEGF expression was significantly lower in ethanolic extract of T. diversifolia treatment group compared to those on keloid fibroblast without treatment (p<0.05).

Conclusion: Ethanolic extract of T. diversifolia inhibits fibroblast migration activity and decrease the expression of VEGF and TGF-β1 on keloid fibroblasts in vitro.

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References

Sund B. New Developments in Wound Care. London: PJB Publications; 2000. p. 1255.

Bayat A, McGrouther DA, Ferguson MW. Skin scarring. BMJ 2003;326:88-92.

Seo BF, Lee JY, Jung SN. Models of abnormal scarring. Biomed Res Int 2013; 2013:423147.

Muneuchi G, Suzuki S, Onodera M, Ito O, Hata Y, Igawa HH, et al. Long-term outcome of intralesional injection of triamcinolone acetonide for the treatment of keloid scars in asian patients. Scand J Plast Reconstr Surg Hand Surg 2006;40:111-6.

Wahyuningsih MS, Wirohadidjojo YW, Hidayat R, Sadid A. Antifibrotic effect of standardized ethanol extract of Tithonia diversifolia (Hemsley) A. Gray on keloid fibroblasts. Int J Pharmacog Phytochem Res 2015;7:642-7.

Wahyuningsih MS, Wijayanti MA, Budiyanto A, Hanafi M. Isolation and identification of potential cytotoxic compound from Kembang bulan Tithonia diversifolia (Hemsley) A. Gray leaves. Int J Pharm Pharm Sci 2015;7:298-301.

Ranti I. Antifibrotic Effect of Tagitinin C Isolated from the Leaf of Tithonia diversifolia (Hemsley) A. Gray Thesis. Yogyakarta: Universitas Gadjah Mada; 2014.

Liang Y, Niederstrasser H, Edwards M, Jackson CE, Cooper JA. Distinct roles for CARMIL isoforms in cell migration. Mol Biol Cell 2009;20:5290-305.

Straatman K. Wound healing assay. J Mol Biol Cells 2008;10:1-4.

Fujiwara M, Muragaki Y, Ooshima A. Keloid-derived fibroblasts show increased secretion of factors involved in collagen turnover and depend on matrix metalloproteinase for migration. Br J Dermatol 2005; 153:295-300.

Chen Y, Abraham DJ, Shi-Wen X, Pearson JD, Black CM, Lyons KM, et al. CCN2 (connective tissue growth factor) promotes fibroblast adhesion to fibronectin. Mol Biol Cell 2004;15:5635-46.

Xuan YH, Huang BB, Tian HS, Chi LS, Duan YM, Wang X, et al. High-glucose inhibits human fibroblast cell migration in wound healing via repression of bFGF-regulating JNK phosphorylation. PLoS One 2014;9:e108182.

Nemeth AJ. Keloids and hypertrophic scars. J Dermatol Surg Oncol 1993;19:738-46.

Yang L, Pang Y, Moses HL. TGF-beta and immune cells: An important regulatory axis in the tumor microenvironment and progression. Trends Immunol 2010;31:220-7.

Dachlan I. Effect of 5α-Oleandrin Isolated from Nerium indicum Mill as Antikeloid: Study on Fibroblast keloid in vitro Disertation. Yogyakarta: Universitas Gadjah Mada; 2015.

Park SY, Park JY, Kim CH, Kang SU, Kim JH, Bark KM, et al. Effects of Xanthium stramarium and Psoralea corylifolia extracts combined with UVA1 irradiation on the cell proliferation and TGF-β1 expression of keloid fibroblasts. Ann Dermatol 2013;25:304-9.

CarmelietP, JainRK. Angiogenesisincancerandotherdiseases. Nature2000; 407:249-57.

Chau CH, Clavijo CA, Deng HT, Zhang Q, Kim KJ, Qiu Y, et al. Etk/ Bmx mediates expression of stress-induced adaptive genes VEGF, PAI 1, and iNOS via multiple signaling cascades in different cell systems. Am J Physiol Cell Physiol 2005;289:C444-54.

Wu WS, Wang FS, Yang KD, Huang CC, Kuo YR. Dexamethasone induction of keloid regression through effective suppression of VEGF expression and keloid fibroblast proliferation. J Invest Dermatol 2006; 126:1264-71.

Zhang Q, Wu Y, Ann DK, Messadi DV, Tuan TL, Kelly AP, et al. Mechanisms of hypoxic regulation of plasminogen activator inhibitor-1 gene expression in keloid fibroblasts. J Invest Dermatol 2003; 121:1005 12.

Bosco MC, Puppo M, Blengio F, Fraone T, Cappello P, Giovarelli M, et al. Monocytes and dendritic cells in a hypoxic environment: Spotlights on chemotaxis and migration. Immunobiology 2008;213:733-49.

Distler JH, Jüngel A, Pileckyte M, Zwerina J, Michel BA, Gay RE, et al. Hypoxia-induced increase in the production of extracellular matrix proteins in systemic sclerosis. Arthritis Rheum 2007;56:4203 15.

Gira AK, Brown LF, Washington CV, Cohen C, Arbiser JL. Keloids demonstrate high-level epidermal expression of vascular endothelial growth factor. J Am Acad Dermatol 2004;50:850-3.

Sukardiman R, Khotib J. The increasing of VEGF expression and re-epithelialization on dermal wound healing process after treatment of banana peel extract (Musa acuminata Colla). Int J Pharm Pharm Sci 2014;6:427-30.

Suharjono S, Balqianur T. The role of ethyl acetate fraction of Andrographis paniculata and doxorubicin combination toward the increase of apoptosis and decrease of VEGF protein expression of mice fibrosarcoma cells. Int J Pharm Pharm Sci 2015;7:347-50.

PlateKH, WarnkePC. Vascularendothelialgrowthfactor. J Neurooncol1997; 35:365-72.

Published

07-01-2019

How to Cite

Hartati Wahyuningsih, M. S., D. A. Agung Nugrahaningsih, and A. Budiyanto. “ETHANOLIC EXTRACT OF TITHONIA DIVERSIFOLIA (HEMSLEY) A. GRAY INHIBITS MIGRATION ACTIVITY AND DECREASE THE TRANSFORMING GROWTH FACTOR-BETA1, VEGF EXPRESSION ON KELOID FIBROBLASTS”. Asian Journal of Pharmaceutical and Clinical Research, vol. 12, no. 1, Jan. 2019, pp. 342-5, doi:10.22159/ajpcr.2019.v12i1.29850.

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