Ekstrak ethanol pegagan (Centella asiatica) meningkatkan osifikasi tulang dan panjang badan larva zebrafish (Danio rerio) model stunting usia 9 hari pasca fertilisasi

Evi Zahara* -  Program Studi D-III Kebidanan Meulaboh, politeknik Kesehatan Kemenkes, Aceh, Indonesia, Indonesia
Een Nuraenah -  Program Studi D-III Kebidanan Politeknik Kesehatan Kemenkes, Jakarta III. Indonesia
Tri Yuliyani -  Dinas Kesehatan Banjar, Kalimantan Selatan, Indonesia
Darwitri Darwitri -  4Program Studi D-III Kebidana politeknik Kesehatan Kemenkes, Tanjungpinang, Indonesia
Husnul Khotimah -  Department Farmakologi, Fakultas Kedokteran Universitas Brawijaya. Malang., Indonesia
Umi Kalsum -  Department Farmakologi, Fakultas Kedokteran. Universitas Brawijaya, Malang, Indonesia., Indonesia
I Wayan Arsana Wiyasa -  5Departement of Obstetric and Gynecology, Saiful Anwar Hospital, Fakultas Kedokteran. Universitas Brawijaya, Malang, Indonesia., Indonesia
Nurlaili Ramli -  6Program Studi D-IV Kebidanan politeknik Kesehatan Kemenkes, Aceh, Indonesia., Indonesia
Agus Hendra Al Rahmad -  Bagian Gizi Masyarakat, Jurusan Gizi Politeknik Kesehatan Kemenkes, Aceh, Indonesia., Indonesia
Mohammad Muljohadi Ali -  Department Farmakologi, Fakultas Kedokteran. Universitas Brawijaya, Malang, Indonesia., Indonesia
DOI : 10.30867/action.v3i2.87

Supp. File(s): common.other common.other

Centella Asiatica (Linn) Urban is known as Gotu Kola. Centella Asiatica (CA) is rich in micro and macronutrients. The aim of this study was to investigate the effect of ethanol extract of CA on bone ossification and body length in zebrafish larva stunting model at 9 dpf. This study used zebrafish at 2 hpf (hour post-fertilization) - 9 dpf (day post-fertilization). The population of 300 larvae divided into 5 groups consisting of control group, rotenone group (exposed by 12.5 ppb of rotenone) and 3 rotenone+CA groups that exposed to CA extract for 4, 5 and 6 days,  respectively. The CA extract was obtained by maceration method with ethanol solvent. The results showed that rotenone 12,5 ppb able to inhibit the growth of larvae >2SD of body length and decrease bone ossification at rotenone group, were significantly different from the control group. Administration of CA extract was increased expression of cartilage at rotenone+CA5 as well rotenone+CA6 group and increase expression of bone at the rotenone+CA5 group and also increase body length rotenone+CA groups significantly different from rotenone group. It can be concluded that the period of CA extract exposure can correct the length of the body reaching 99.6% at 9 dpf and increased bone ossification in a time-dependent manner.


Centella asiatica (Linn) Urban dikenal dengan nama pegagan. Centella Asiatica (CA) kaya akan mikro maupun makro nutrisi yang diperlukan bagi tubuh terutama masa pertumbuhan. Penelitian ini bertujuan mengetahui efek ekstrak etanol CA terhadap osifikasi tulang dan panjang badan larva zebrafish model stunting yang diinduksi rotenone pada 9 hari post fertilisasi. Penelitian ini menggunakan zebrafish mulai 2 hpf (hour post fertilisation) - 9 dpf (day post fertilisation), populasi larva sejumlah 300 yang dibagi 5 kelompok yang terdiri dari kelompok kontrol, kelompok rotenon (dipapar rotenone 12,5 ppb) dan 3 kelompok rotenone+CA yang diberikan pegagan selama 4, 5 dan 6 hari secara berurutan. Ekstrak CA diperoleh melalui  metode maserasi dengan pelarut etanol. Hasil penelitian menunjukkan bahwa rotenone dapat menghambat pertumbuhan panjang larva >2SD dan menurunkan osifikasi tulang pada kelompok rotenon secara signifikan dibanding kontrol. Pemberian ekstrak CA dapat meningkatkan ekspresi tulang rawan kelompok rotenone+CA5 maupun rotenone+CA6 dan meningkatkan ekspresi tulang keras kelompok rotenone+CA5 serta meningkatkan panjang badan kelompok rotenone_CA secara signifikan dibanding kelompok rotenone. Dapat disimpulkan bahwa lamanya pemberian ekstrak CA dapat meningkatkan osifikasi tulang dan meningkatkan panjang badan mencapai 99.6% pada 9 dpf. 

Supplement Files

Keywords : Zebrafish, Centella asiatica; bone ossification; body length; stunting

  1. de Onis M., Dewey K. G., Borghi E., Onyango A. W., Blössner M., Daelmans B. et al. The World Health Organization’s Global target for reducing childhood stunting by 2015: rational and proporsed action. Maternal &child Nutrition 2013; 9 (2): 6-26.
  3. UNICEF. Tracking Progress on Child and Maternal Nutrition: A survival and development priority. UNICEF. 2009; Available from: http://www.unicef.org/publications/ index_51656.html.
  5. Badan Penelitian Dan Pengembangan Kesehatan RI. 2013. Riskesdas 2013. Jakarta; 209
  6. Black RE, Victora CG, Walker SP, Bhutta ZA, Christian P, de Onis M, Ezzati M, Grantham-McGregor S, Katz J, Martorell R, et al. Maternal and child underutrition and overweight in low-income and middle-income countries. Lancet. 2013; 382:427-51.
  7. Berkman DS, Lescano AG, Gilman RH, Lopez SL, Black MM. Effects of stunting, diarrhoeal disease, and parasitic infection during infancy on cog- nition in late childhood: a follow-up study. Lancet. 2002;359(9306):564–71.
  8. Victora CG., Adair L, Fall C, Hallal PC, Martorell R, et al. Maternal and child undernutrition: consequences for adult health and human capital. Lancet. 2008; 371:340–357.
  9. MCA Indonesia. 2013. Stunting dan Masa Depan Indonesia. pp.2-5
  10. Bourke CD, Berkley JA & Prendergast AJ. Immune Dysfunction as a Cause and Consequence of Malnutrition. Trends in Immunology, 2016; 37(6), 386–398.
  11. Tsang KY, Chan D and Cheah KSE. Fate of grouth plate hypertrophic chondrocytes: Death or lineage extension? Develop Growth Differ. 2015; 57(2): 179-192.
  12. Helmi, Z. Buku Ajar Gangguan Muskuloskeletal. Anatomi dan Fisiologi Tulang. Cetakan kedua. Jakarta.: Salemba Medika; 2013.
  13. Primihastuti D, Ali MM & Kalsum U. Pengaruh Ekstrak Etanol Pegagan (Centella asiatica) Terhadap Ossifikasi Tulang dan Osteoklastogenesis pada Model Stunting Larva Zebrafish Model Stunting. Tidak diterbitkan. Universitas Brawijaya. Malang. 2017.
  15. Wauquier, F., Leotoing, L., Coxam, V., Guicheux, J., Wittrant, T. 2009. Oxidative stress in bone remodelling and disease. Trends Mol Med. 15(1):468-77.
  16. Shen CL, Cao JJ, Dagda RY, Tenner T E.Jr, Chyu MC, & Yeh JK. Supplementation with green tea polyphenols improves bone microstructure and quality in aged, orchidectomized rats. Calcified Tissue International. 2011; 88(6), 455-463.
  18. Joshi K & Chaturvedi P. Green Leafy Vegetable: An Overview, 2013; 4 (1), 135-149.
  19. Hashim P. Cetella asiatica in food and beverage application and its potential antioxidant and neuroprotective effect. International Food Research Journal. 2011; 18(4):pp. 1215-1222.
  20. Randriamampionona D, Diallo B, Rakotoniriana F, Rabemanantsoa C, Cheuk K, Corbisier AM, et al. Comparative analysis of active constituents in Centella asiatica samples from Madagascar: Application for ex situ conservation and clonal propagation. Fitoterapia. 2007.78(7): 482-489.
  21. Cory’ah, F.A., Khotimah, H., Nurdiana. 2017. Pengaruh Ekstrak Etanol Pegagan (Centella Asiatica) terhadap Panjang Badan Ekspresi Insulin Like Growth Faktor 1 (IGF-1) dan Insulin Reseptor Substrat (IRS) pada Larva Zebrafish (Danio Rario) Model Sunting Dengan Indksi Rotenon. Tidak diterbitkan, Universitas Brawijaya. Malang. 2017.
  22. Khotimah H, Sumitro SB, & Widodo MA. Zebrafish Parkinson’s Model : Rotenone decrease motility , Apoptosis of Zebrafish Brain. International Journal of PharmTech Research. 2015b; 8(4), 614–621.
  23. Avdesh A, Chen M, Marin-lverson MT, Mondal A, Ong D, Rainey-Smith S, Martins RN. Regular care and maintenance of zebrafish (Danio rerio) laboratory: an introduction. Jornal of Visualized Experiments. 2012; 18(69):e4196.
  24. Spence R, Gerlach G, Lawrence C & Smith C. The Behaviour and Ecology of The Zebrafish Danio Rerio. Biological Reviews. 2008; 13-34.
  25. Shi-ying L, Jing-Feng C, Zhi-guo Z, Xio-hua LV, Ya-jun Y, Jing-jing Z. Salvianolic acid B stimulates osteogenesis in dexamethasone-treated zebrafish larvae. Acta Pharmacological Sinica. 2016; 37: 1370-1380
  26. Saravanan KS, Sindhu KM, Senthikumar KS, Mohanakumar KP. L-De-phenyl protects against rotenone-induced, oxidative stress-mediated dopaminergic neurodegeneration in rats. Neurochem Int. 2006; 49: 28–40.
  27. Martin JA, Martin A, Molinari A, Morgan W, Ramalingam W, Buckwalter JA and McKinley TO. Mitochondria electron transport and couplet in articular cartilage. Osteoartritis and cartilage / OARS, Osteoarthritis Research Society. 2013; 20(4): 323-329.
  28. Hock JM, Krishnan V, Onyia JE, Bidwell JP, Milas J, Stanislaus D. Osteoblast apoptosis and bone turnover. J Bone Miner Res. 2001; 16:975–984.
  29. Alikhani Z, Alikhani M, Boyd CM, Nagao K, Trackman PC, Graves DT. Advanced glycation end products enhance expression of pro-apoptotic genes and stimulate fibroblast apoptosis through cytoplasmic and mitochondrial pathways. J Biol Chem. 2005; 280:12087–12095.
  30. Juranek I and Bezek S. Controversy of free radical hypothesis: Reactive oxygen species-cause or consequence of tissue injury? General Physiology and Biophysics. (2005; 24(3): 263-278.
  31. Lean JM, Davies JT, Fuller K, Jagger CJ, Kirstein B, Partington GA et al. A crucial role for thiol antioxidants in estrogen-deficiency bone loss. J Clin Invest. 2003; 112(6), 915-923.
  32. Baek KH, Oh KW, Lee WY, Lee SS, Kim, MK, KwonHS et al. Association of oxidative stress with postmenopausal osteoporosis and the effects of hydrogen peroxide on osteoclast formation in human bone marrow cell cultures. Calcified Tissue International. 2010; 87(3), 226-235.
  33. Fontani F, Marcucci G, Iantomasi T, Brandi ML, Vincenzini MT. Glutathione, N-acetylcysteine and lipoic acid down-regulate starvation-induced apoptosis, RANKL/OPG ratio and sclerostin in osteocytes: involvement of JNK and ERK1/2 signalling. Calcif Tissue Int. 2015; 96:335–346
  34. Bellido T. Osteocyte-driven bone remodeling. Calcif Tissue Int. 2014;94:25–34.
  35. Domazetovic V, Marcucci G, Lantomasi T, Brandi ML and Vincenzini MT. Oxidative stress in bone remodeling: role of antioxidants. Clinica Case In Mineral Bone Metabolism. 2017; 14(2):209-216.
  36. Winarto, W.R. dan M. Surbakti. Khasiat dan Manfaat Pegagan. Agromedia Pustaka, Jakarta. 2003.
  37. Dou Y, Mujeeb A, Zheng Y, Ge Z. Optimalization of dual effects of Mg-1Ca alloys on the of chondrocytes and osteoblasts in vitro. Progres in Natural Science Material International. 24: 433-440.
  38. Kementrian Kesehatan RI. 2016. Info. Situasi Balita Pendek. 2442–7659.
  39. Sorribes A. The Otogeny of sleep-wake cycles in zebrafish: a comparison to humans. Frontiers in neural Circuits. 2013. 178
  40. Crofton KM. Thyroid Disrupting Chemicals: Mechanisms and Mixtures. International Journal of Andrology. 2008; 31(2): 209-223.
  41. Zubairi SI, Sarmidi MR, Aziz RA. A Study of Rotenone from Derris Roots of Varies Location, Plant Parts and Types of Solvent Used. Advances in Environmental Biology. 2014; 8(2): 445-449
  43. Ott KC. Rotenone. A brief breif riview of its chemistry, environmental fate and the toxicity of rotenone formulation. 2006.
  44. Melo KM, Oliveira R, Grisolia CK, Domingues I, Pieczarka JC, Filho JdS, Nagamachi CY. Short-term exposure to low dose of rotenone induces developmental, biochemical, behavioral, and histological change in fish. Environmental Science and Pollution Research. 2015; 22(18): pp 13926-13938.
  45. Wardani, DW. Pengaruh Ekstrak Etanol Pegagan (Centella asiatica) Terhadap Ekspresi Vascular Endothelial Growth Factor Receptor-2 pada Model Stunting Larva Zebrafish Model Stunting. [Tesis]. Universitas Brawijaya. Malang. 2017.
  46. Sutardi, S. Kandungan Bahan Aktif Tanaman Pegagan dan Khasiatnya untuk Meningkatkan Sistem Imun Tubuh. Jurnal Penelitian Dan Pengembangan Pertanian. 2017; 35(3), 121.
  47. Prentice A, Schoenmakers I, Laskey MA, de Bone S, Ginty F & Goldberg GR. Symposium on ‘Nutrition and health inchildren and adolencents’ session 1: Nutrition in growth and development nutrition and bond growth development. Proceedings of the Nutrition Society. 2006; 64(4): pp. 340-360
  48. Bender DA. Free Radicals an Antioxidant Nutrients. In: Murray K, Bender DA, Botham KM, et al. Eds. Harper’s Illustrated Biochemistry, Ed 28th Mc Graw Hill Lange 2009;482-86.

Open Access Copyright (c) 2018 Evi Zahara, Een Nuraenah, Tri Yuliyani, Darwitri Darwitri, Husnul Khotimah, Umi Kalsum, I Wayan Arsana Wiyasa, Nurlaili Ramli, Agus Hendra Al Rahmad, Mohammad Muljohadi Ali
Creative Commons License
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

AcTion: Aceh Nutrition Journal
Published by: Department of Nutrition at the Health Polytechnic of Aceh, Ministry of Health.
Soekarno-Hatta Street, No. 168. Health Polytechnic of Aceh, Aceh Besar, 23352. Telp/Fax: 0651 46126 / 0651 46121.
Website: https://gizipoltekkesaceh.ac.id/
E-mail: [email protected]

e-issn: 2548-5741, p-issn: 2527-3310

All content is licensed under a: Creative Commons Attribution ShareAlike 4.0 International License

View My Stats

Get a feed by atom here, RRS2 here and OAI Links here