Safety and efficacy of Tithonia diversifolia (Hemsley) A. Gray extract gel on keloid patient

  • Dwi Aris Agung Nugrahaningsih Universitas Gadjah Mada, Indonesia
  • Mae Sri Hartati Wahyuningsih Department of Pharmacology and Therapy, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada; Herbal Medicine Center, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada
  • Karim Zulkarnain Faculty of Pharmacy, Universitas Gadjah Mada
  • Mia Munawaroh Yuniyanti Department of Pharmacology and Therapy, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada; Herbal Medicine Center, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada
  • Rianto Noviady Ramli Department of Plastic Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada
  • Ishandono Dachlan Department of Plastic Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada
Keywords: Tithonia diversifolia, keloid, scar, treatment

Abstract

Keloid is a benign form of dermis tumor formed due to imbalance of collagen deposition and degradation during wound healing. Preclinical studies showed Tithonia diversifolia (Hemsley) A. Gray (T. diversifolia) potency as keloid treatment by inhibiting keloid fibroblast proliferation, collagen deposition, TGFβ1 and VEGF expression. This study aims to examine the safety and efficacy of T. diversifolia extract gel for keloid treatment in keloid patient. Fourteen keloid patients were included in the study with ratio 1:1. The participants received either T. diversifolia extract gel 2% or triamcinolone acetate cream 0.025% for 12 weeks. Evaluation of efficacy was done every 4 weeks until week 12 using Vancouver Scar Score, the patient and observer Scar assessment. Vancouver scar total score was improved in week 12 from baseline in both groups. Improvement from baseline after 12 weeks of treatment also found in patient and observer scar assessment total scale. Those scores on week 12 were similar between those on T. diversifolia extract gel 2% and triamcinolone acetate cream 0.025% treatment. Conclusions: T. diversifolia extract gel 2% is efficacious and safe for keloid treatment.

References

1. Marneros AG, Krieg T. Keloids - Clinical diagnosis, pathogenesis, and treatment options. JDDG - J Ger Soc Dermatology. 2004;2(11):905–13.
2. Chike-Obi C, Cole P, Brissett A. Keloids: Pathogenesis, Clinical Features, and Management. Semin Plast Surg. 2009;23(03):178–84.
3. Davis SA, Feldman SR, McMichael AJ. Management of keloids in the United States, 1990-2009: An analysis of the national ambulatory medical care survey. Dermatologic Surg. 2013;39(7):988–94.
4. Gu JQ, Gills JJ, Park EJ, Mata-Greenwood E, Hawthorne ME, Axelrod F, et al. Sesquiterpenoids from Tithonia diversifolia with potential cancer chemopreventive activity. J Nat Prod. 2002;65(4):532–6.
5. Wahyuningsih M, Soeparto A. Pemurnian isolat aktif (T. diversifolia) dan uji sitotoksiknya terhadap sel hela in vitro. Gadjah Mada University; 2010.
6. Lee MY, Liao MH, Tsai YN, Chiu KH, Wen HC. Identification and anti-human glioblastoma activity of tagitinin C from tithonia diversifolia methanolic extract. J Agric Food Chem. 2011;59(6):2347–55.
7. Liao MH, Tsai YN, Yang CY, Juang CL, Lee MY, Chang LH, et al. Anti-human hepatoma Hep-G2 proliferative, apoptotic, and antimutagenic activity of tagitinin C from Tithonia diversifolia leaves. J Nat Med. 2013;67(1):98–106.
8. Wei R, Zhao Y, Wang J, Yang X, Li S, Wang Y, et al. Tagitinin C induces ferroptosis through PERK-Nrf2-HO-1 signaling pathway in colorectal cancer cells. Int J Biol Sci. 2021;17(11):2703–17.
9. Wahyuningsih M, Wijayanti MA. Isolasi, identifikasi senyawa antikanker dari fraksi aktif Tithonia diversifolia (Hemsley) A Gray, selektivitas dan mekanisme apoptosis secara in vitro. Yogyakarta; 2009.
10. Wahyuningsih MSH, Wirohadidjojo YW, Hidayat R, Sadid A. Antifibrotic effect of standardized ethanol extract of Tithonia diversifolia (Hemsley) A. Gray on keloid fibroblasts. Int J Pharmacogn Phytochem Res. 2015;7(4):642–7.
11. Wicaksana AY, Nugrahaningsih DAA, Wahyuningsih MSH. Effect of tagitinin C isolated from kembang bulan [ Tithonia diversifolia (Hemsley) A. Gray] leaves on VEGF and TNF- α expressions of keloid fibroblast. J Med Sci (Berkala Ilmu Kedokteran). 2020;52(4):292–9.
12. Sullivan T, Smith J, Kermode J, Mclver E CD. Rating the Burn Scar. J Burn Care Rehabil. 1990;11(3):256–60.
13. Draaijers LJ, Tempelman FRH, Botman YAM, Tuinebreijer WE, Middelkoop E, Kreis RW, et al. The Patient and Observer Scar Assessment Scale: A reliable and feasible tool for scar evaluation. Plast Reconstr Surg. 2004;113(7):1960–5.
14. Wang ZC, Zhao WY, Cao Y, Liu YQ, Sun Q, Shi P, et al. The Roles of Inflammation in Keloid and Hypertrophic Scars. Front Immunol. 2020;11(December):1–10.
15. Betarbet U, Blalock TW. Keloids: A Review of Etiology, Prevention, and Treatment. J Clin Aesthet Dermatol. 2020;13(2):33–43.
16. Berman B, Maderal A, Raphael B. Keloids and hypertrophic scars: Pathophysiology, classification, and treatment. Dermatologic Surg. 2017;43:S3–18.
17. Wu Y, Zhang Q, Ann DK, Akhondzadeh A, Duong HS, Messadi D V., et al. Increased vascular endothelial growth factor may account for elevated level of plasminogen activator inhibitor-1 via activating ERK1/2 in keloid fibroblasts. Am J Physiol - Cell Physiol. 2004;286(4 55-4):C905–12.
18. Wilgus TA, Ferreira AM, Oberyszyn TM, Bergdall VK, Dipietro A. Regulation of scar formation by VEGF. Lab Invest. 2008;88(6):579–90.
19. Astuti I, Wahyuningsih MSH. Mixture of Extract Nerium indicum Mill and Tithonia diversifolia (Hemsley) A. Gray. Inhibits the Migration Activity, Expressions of TGF-β1 and VEGF Keloid Fibroblasts. J Pharm Sci Res [Internet]. 2019;11(5):1710–4. Available from: https://search.proquest.com/docview/2237018593?accountid=17242
20. Abe AE, de Oliveira CE, Dalboni TM, Chagas-Paula DA, Rocha BA, de Oliveira RB, et al. Anti-inflammatory sesquiterpene lactones from tithonia diversifolia trigger different effects on human neutrophils. Rev Bras Farmacogn [Internet]. 2015;25(2):111–6. Available from: http://dx.doi.org/10.1016/j.bjp.2015.01.005
21. Broering MF, Nunes R, De Faveri R, De Faveri A, Melato J, Correa TP, et al. Effects of Tithonia diversifolia (Asteraceae) extract on innate inflammatory responses. J Ethnopharmacol [Internet]. 2019;242(June):112041. Available from: https://doi.org/10.1016/j.jep.2019.112041
22. Ranti I, Wahyuningsih MSH, Wirohadidjojo YW. The antifibrotic effect of isolate tagitinin C from tithonia diversifolia (Hemsley) A. gray on keloid fibroblast cell. Pan Afr Med J. 2018;30:1–8.
23. Santi E, Wahyuningsih MSH, Budiyanto A. Effect of tagitinin C isolated from Tithonia diversifoli (Hemsley) A Gray on migration activity and TGF-β1 levels on keloid fibroblast. J Med Sci (Berkala Ilmu Kedokteran). 2019;51(03):188–94.
24. Miura T, Nosaka K, Ishii H, Ishida T. Antidiabetic effect of Nitobegiku, the herb Tithonia diversifolia, in KK-Ay diabetic mice. Biol Pharm Bull. 2005;28(11):2152–4.
25. O Olukunle J, S Okediran B, A Sogebi E, B Jacobs E. Hypoglycaemic and Hypolipidaemic Effects of the Aqueous Leaf Extracts of Tithonia diversifolia. Annu Res Rev Biol. 2014;4(16):2655–62.
Published
2025-01-07
How to Cite
Dwi Aris Agung Nugrahaningsih, Wahyuningsih, M. S. H., Zulkarnain, K., Yuniyanti, M. M., Ramli, R. N., & Dachlan, I. (2025). Safety and efficacy of Tithonia diversifolia (Hemsley) A. Gray extract gel on keloid patient. Indonesian Journal of Pharmacy. https://doi.org/10.22146/ijp.11655
Section
Research Article

Most read articles by the same author(s)