Antifibrotic Effect of Ethanolic Extract of Nerium indicum Mill. Standardized 5α-Oleandrin on Keloid Fibroblasts Cells

https://doi.org/10.22146/mot.35116

Mae Sri Hartati Wahyuningsih(1*), Fara Silvia Yuliani(2), Dwiki Yuliya Rahmawati(3), Annisa Nurul Pratiwi(4)

(1) Department of Pharmacology and Therapy, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada
(2) Department of Pharmacology and Therapy, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada
(3) Program S1 Pendidikan Dokter,Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada
(4) Program S1 Pendidikan Dokter,Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada
(*) Corresponding Author

Abstract


Keloid is a skin lesion caused by an abnormal proliferation of fibroblasts and the deposition of collagen in the wound healing process. Therapy for keloids is relatively limited and mostly has side effects. Recent studies show that 5α-oleandrin from N. indicum Mill. (N. indicum) has anti-keloid effect by inhibiting (proliferation, migration activity and TGF-β1 expression) keloid fibroblast. Further studies with N. indicum extract standardized 5α-oleandrin should be conducted to develop it as an anti-keloid agent by performing at proliferative effects, collagen accumulation, and keloid fibroblast migration. The antifibrotic activity of N. indicum extract on the proliferation of keloid fibroblasts was measured by MTT assay, whereas collagen deposits were observed by Sirius Red method. Observation of keloid fibroblast migration by scratch assay is according to Liang et al. (2009). Ethanol extract of N. indicum standardized 5α-oleandrin can inhibit the proliferation of keloid fibroblas with IC50 0.458 μg/mL, also inhibited collagen deposits with IC50 0.055 μg/mL at incubation for 72 hours. In incubation 48 hours after treatment with ethanol extract of 1.0 μg/mL occurred inhibition of migration significantly compared with control.

Keywords


Keloid; Nerium indicum Mill; proliferation; collagen; cell migration

Full Text:

PDF


References

Arno, A.I., Gauglitz, G.G., Barret, J.P., Jeschke, M.G., 2015, Up-to-date Approach to Manage Keloids and Hyperthrophic Scars: A Useful Guide. Burns: Journal of the International Society for Burns Injuries, 40(7): 1255-1266.

Bayat, A., Arscott, G., Ollier, W.E.R., McGrouther, D.A,, Ferguson, M.W.J., 2005, Keloid disease: Clinical relevance of single versus multiple site scars. British Association of Plastic Surgeons, 58:28-37.

Brown, J. and Bayat, A., 2009, Genetic susceptibility to raised dermal scarring. British Journal of Dermatology, 161(1): 8-18.

Chike-Obi, C J., Cole, P.D., Brisset, A.E., 2009, Keloids: Pathogenesis, Clinical Features, and Management. Seminar in Plastic Surgery, 23(3):178-184.

Dahlan, I., 2015, Pengembangan 5α-oleandrin isolasi dari daun Nerium indicum Mill. sebagai obat anti keloid Kajian in vitro pada Sel Fibroblas Keloid, Disertasi, . Fakultas Kedokteran Universitas Gadjah Mada, Yogyakarta.

Dahlan, I, Wirohadidjojo, Y.W., Wahyuningsih, M.S.H., Aryandono, T., Soebono, H., 2018, 5α-Oleandrin has better Anti-fibrotic effects than Mitomycin-C in Keloid Fibroblast Cultures, BMC Complementary and Alternative Medicine, Inpress.

Desmouliere, A., Darby, I.A., Laverdet, B., Bonté, F., 2014, Fibroblasts and myofibroblasts in wound healing. Clin. Cosmet. Investig. Dermatol.12: 301-311

Gauglitz, G.G., Korting, H.C., Pavicic, T., Rucicka, T., Jeschke, M.G., 2011, Hypertrophic scarring and keloids: pathomechanisms and current and emerging treatment strategies. Mol Med;17(1–2):113–25.

Goldsmith, L.A., Katz, S., Gilchrest, B.A., Paller,A.S., Leffell,D.J., 2007. Fitzpatrick's Dermatology In General Medicine, Seventh Edition. 1st ed. McGraw-Hill Publishing, pp.553-554

Hanahan, D., Wienberg, R.A., 2000, The Hallmarks of Cancer Cell, 100, 57-70.

Liang, Y., Niederstrasser, H., Edwards, M., Charles, E., Jackson, John, A., 2009, Distinct roles for CARMIL isoforms in cell migration. Mol Biol Cell. 20(24): 5290-5305.

Muhammad, F., Yuliani, F.S., Wahyuningsih, M.S.H., 2017, Aktivitas Antifibrotik Ekstrak Klorofom Nerium indicum dalam Menghambat Proliferasi Fibroblas Keloid dengan MTT Assay, Prosiding Seminar Nasional “Peran Herbal untuk mencegah Proses Degenerasi, Auditorium Fakultas Kedokteran UGM, 22 April 2017, ISBN: 978-602-50277-0-3: p.46-50.

Naitoh, M., Kubota, H., Ikeda, M., 2005, Gene expression in human keloids is altered from dermal to chondrocytic and osteogenic lineage, Genes to Cells 10, 1081–1091

Naitoh, M., Hosokawa, N., Kubota, H., Tanaka, T., Shirane, H., Sawada, M., Nishimura, Y., Nagata, K., 2001, Upregulation of HSP47 and Collagen Type III in the Dermal Fibrotic Disease, Keloid, Biochemical and Biophysical Research Communications, 280 (5): 1316-22

Pratiwi, A.N., 2017, Aktivitas Antifibrotik Ekstrak Etanol Nerium indicum Mill dalam Menghambat Sintesis Kolagen Keloid dengan Metode Pewarnaan Sirius Red, Skripsi. Fakultas Kedokteran Universitas Gadjah Mada, Yogyakarta.

Prayong, P., Barusrux, S., Weerapreeyakul, N., 2008, Cytotoxic activity screening of some indigenous Thai plants. Fitoterapia, 79: 598-601

Rahmawati, D.Y., 2017, Aktivitas Antifibrotik Ekstrak Etanol Nerium indicum dalam Menghambat Proliferasi Fibroblas Keloid dengan MTT Assay, Skripsi. Fakultas Kedokteran Universitas Gadjah Mada, Yogyakarta.

Seo, B.F., Lee, J.Y., Jung, S.N., 2013, Models of abnormal scarring. http:///BioMed. Researchinternational.com/article/423147

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

Wahyuningsih, M.S.H., Wahyuono, S., Wayan, T., 2000, Isolasi dan Identifikasi Senyawa Bioaktif dari daun Nerium indicum Mill, Indonesian Journal of Pharmacy, 11(2): 86-95

Wahyuningsih, M.S.H., Mubarika, S., R.L.H. Bolhuis,. K. Nooter., Ganjar, I.G., Wahyuono, S., 2004, Cytotoxicity of oleandrin isolated from the leaves of Nerium indicum Mill on several human cancer cell lines. Indonesian Journal of Pharmacy, 15(2): 96-103

Wahyuningsih, M.S.H., Mubarika, S., Ganjar, I.G., Hamann, M.T., Wahyuono, S., 2006, Identification of Cardenolide compounds as selective anticancer isolated from Nerium indicum Mill. Leaves and its cytotoxic effect, Journal of Traditional Medicine, 11(37): 13-19.

Wahyuningsih, M.S.H., Mubarika, S., Bolhuis, R.L.H., Nooter, K., Oostrum, R.G., Wahyuono, S., Gandjar, I.G., 2008, Selectivity of Compounds Isolated from the Leaves of Nerium indicum Mill. on Various Human Cancer Cell Lines, The Medical Journal of Malaysia, Suppl. A, 63: 24-25.

Wahyuningsih, M.S.H., Mubarika, S., Ganjar, I.G., Wahyuono, S., Takeya, T., 2017, 5α-oleandrin reduce Bcl-2 protein and increase Bax protein expression on Hela cervical cancer cell, Univ Med, 36(2): 102-109

Yang, L., Pang, Y., Moses, H.L., 2010, TGF-β and immune cells: an important regulatory axis in the tumor microenvironment and progression. Trends Immunol. 31: 220-227.



DOI: https://doi.org/10.22146/mot.35116

Article Metrics

Abstract views : 3467 | views : 4572

Refbacks

  • There are currently no refbacks.


Bookmark and Share


Copyright (c) 2018 Majalah Obat Tradisional

Creative Commons License
This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

©Majalah Obat Tradisional (Traditional Medicine Journal)
 ISSN 2406-9086
Faculty of Pharmacy
Universitas Gadjah Mada