The effect of Centella asiatica to the vascular endothelial growth factor and vascular endothelial growth factor receptor-2 on the rotenone induced zebrafish larvae (Danio rerio) stunting model

Dyah Woro Kartiko Kusumo Wardani; Mulyohadi Ali; Husnul Khotimah; Nurdiana; Wibi Riawan; Dianita Primihastuti; Fitra Arsy Nur Cory'ah; Linda Ika Puspita Ariati; Vanda Primaditya; Yuningsih; Zakiah

doi:10.30574/gscbps.2018.5.2.0117

Authors

Dyah Woro Kartiko Kusumo Wardani Master of Midwifery Program, Faculty of Medicine Universitas Brawijaya, Malang, Indonesia.
Mulyohadi Ali Department of Pharmacology, Faculty of Medicine, Universitas Brawijaya, Indonesia.
Husnul Khotimah Department of Pharmacology, Faculty of Medicine, Universitas Brawijaya, Indonesia.
Nurdiana Department of Pharmacology, Faculty of Medicine, Universitas Brawijaya, Indonesia.
Wibi Riawan Departement of Biochemistry-Biomolecular Faculty of Medicine, Universitas Brawijaya, Indonesia.
Dianita Primihastuti Institute of Health Science William Booth Surabaya, Surabaya, Indonesia.
Fitra Arsy Nur Cory'ah Midwifery Academy Poltekes Kemenkes Mataram, West Nusa Tenggara, Indonesia.
Linda Ika Puspita Ariati Midwifery Academy of Jember, Jember, East Java, Indonesia.
Vanda Primaditya Midwifery academy of Berlian Nusantara, Magetan, Indonesia.
Yuningsih Midwifery Academy Dr. Soebandi, Jember, East Java, Indonesia.
Zakiah University of Darul Ulum Jombang High Islamic Boarding School, Jombang, East Java, Indonesia.

DOI:

https://doi.org/10.30574/gscbps.2018.5.2.0117

Keywords:

VEGF, VEGFR-2, Stunting, Zebrafish, Centella asiatica

Abstract

Stunting is a condition of obstructed body length growth in the first two year of life. Rotenone as a pesticide specimen which trigger stunting condition, inhibits the mitochondrial complex I causing an increased level of ROS that affects angiogenesis and vasculogenesis process that involve VEGF with VEGFR-2. Centella asiatica serves as antioxidant which inhibits ROS production and revitalize blood vessels. The purpose of this research is to discover the effect of Centella asiatica ethanolic extract to the enhancement of body length through the expression of the VEGF and VEGFR-2 on the rotenone-induced zebrafish larvae stunting model. The result in this study proved that 12.5 ppb rotenone could induce stunting growth in 6 dpf (days post fertilization) zebrafish larvae (Danio rerio). The administration of Centella asiatica ethanolic extract improved the body length, along with the increasing of VEGF [2.5 mg/ml] and VEGFR-2 [5 mg/ml]. The correlation test showed a positive and strong relevance the levels of Centella asiatica and the expression of VEGF and VEGFR-2. It can be concluded that Centella asiatica ethanolic extract could inhibit stunting and improved the body length through increasing the expression of VEGF and VEGFR-2 in stunting model zebrafish larvae.

Metrics

Metrics Loading ...

References

UNICEF. Division of Communication. (2009). Tracking progress on child and maternal nutrition: a survival and development priority. UNICEF.

World Health Organization. (2015). Nutrition landscape information system (NLIS). Country profile indicators: interpretation guide. NutrLandscInfSyst NLIS Geneva WHO, 20(1), 1–4.

Kementrian Kesehatan, RI. (2016). INFODATIN. Indonesian Ministry of Health's Data and Information Center. Short Toddler Situation. Jakarta. 2442–7659.

Anugraheni HS. (2012). Risk factor for stunting among 12-36 month children at Patisubdistrictin Patidistrict. Nutrition Science Study Program, Faculty of Medicine, Diponegoro University, Semarang.

Purwandini K andKartasurya MI. (2013). The effect of micronutrient sprinkle on motor development among stunted children aged 12-36 months. Journal of Nutrition College, 2(1), 147-163.

Khasanah DP, Hadi H and Paramashanti BA. (2016). Time of complementary feeding introduction was associated with stunting in children 6-23 month old in Sedayu, Bantul. Indonesian Journal of Nutrition and Dietetics, 4(2), 105-111.

Li N, Ragheb, K, Lawler G, Sturgis J, Rajwa B, Melendez JA and Robinson JP. (2003). Mitochondrial complex I inhibitor rotenone induces apoptosis through enhancing mitochondrial reactive oxygen species production. Journal of Biological Chemistry, 278(10), 8516-8525.

Fontanesi F. (2001). Mitochondria: structure and role in respiration. eLS, 1-13.

Shibuya M. (2011). Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: a crucial target for anti-and pro-angiogenic therapies. Genes & cancer, 2(12), 1097-1105.

Carlson BM. (2014). Human Embryology and Developmental Biology 5th Edition. Sanders Elsevier. Philadelphia.

Widayati E. (2017). Biological Oxidation, Free Radicals, and Antioxidant. MajalahIlmiah Sultan Agung, 50(128), 26-32.

Zainol MK, Abd-Hamid A, Yusof S and Muse R. (2003). Antioxidative activity and total phenolic compounds of leaf, root and petiole of four accessions of Centella asiatica (L.) Urban. Food Chemistry, 81(4), 575-581.

Bian D, Liu M, Li Y, Xia Y, Gong Z and Dai Y. (2012). Madecassoside, a triterpenoid saponin isolated from Centella asiatica herbs, protects endothelial cells against oxidative stress. Journal of biochemical and molecular toxicology, 26(10), 399-406.

Salamah N and Farahana L. (2014). Antioxidant activity assay of ethanolic extract of Centella asiatica (L.) Urbherb using phosphomolybdate method.Pharmaciana, 4(1), 23-30.

Chandrika UG and Kumara PAP. (2015). Chapter Four-Gotu Kola (Centella asiatica): Nutritional properties and plausible health benefits. Advances in food and nutrition research, 76, 125-157.

Hashim P, Sidek H, Helan MHM, Sabery A, Palanisamy UD and Ilham M. (2011). Triterpene composition and bioakctivities of Centella asiatica. Molecules, 16(2), 1310-1322.

Barbazuk WB, Korf I, Kadavi C, Heyen J, Tate S, Wun E, Bedell JA, McPherson JD and Johnson SL. (2000). The syntenic relationship of the zebrafish and human genomes. Genome research, 10(9), 1351-1358.

Eisen JS. (1996).Zebrafish make a big splash. Cell 87, 969–977.

Wixon J. (2000). Featured organism: Danio rerio, the zebrafish. Yeast, 17(3), 225-231.

Goldsmith P and Solari R. (2003). The role of zebrafish in drug discovery-Drug Discovery World. Spring, 5(45), 56–68.

Reed B and Jennings M. (2011). Guidance on the housing and care of Zebrafish. Research Animals Department, Science Group, RSPCA 62 p. 1–27.

Sorribes A. (2013). The ontogeny of sleep-wake cycles in zebrafish: a comparison to humans. Frontiers in Neural Circuits, 7, 178.

Kong YX, van Bergen N, Bui BV, Chrysostomou V, Vingrys AJ, Trounce IA and Crowston JG. (2012). Impact of aging and diet restriction on retinal function during and after acute intraocular pressure injury. Neurobiology of aging, 33(6), 1126-e15.

Han G, Casson RJ, Chidlow G and Wood JP. (2014). The mitochondrial complex I inhibitor rotenone induces endoplasmic reticulum stress and activation of GSK-3β in cultured rat retinal cells. Investigative ophthalmology and visual science, 55(9), 5616-5628.

Ott KC. (2006). Rotenone. A brief review of its chemistry, environmental fate, and the toxicity of rotenone formulations.

Singer TP and Ramsay RR. (1994). The reaction sites of rotenone and ubiquinone with mitochondrial NADH dehydrogenase. Biochimica et Biophysica Acta (BBA)-Bioenergetics, 1187(2), 198-202.

Uauy R. (2013). Improving linear growth without excess body fat gain in women and children. Food and nutrition bulletin, 34(2), 257-260.

Melo KM, Oliveira R, Grisolia CK, Domingues I, Pieczarka JC, de Souza Filho J and Nagamachi CY. (2015). Short-term exposure to low doses of rotenone induces developmental, biochemical, behavioral, and histological changes in fish. Environmental Science and Pollution Research, 22(18), 13926-13938.

Cook LW, Paradise CJ and Lom B. (2005). The pesticide malathion reduces survival and growth in developing zebrafish. Environmental toxicology and chemistry, 24(7), 1745-1750.

Ridlayanti A, Khotimah K and Ali M. (2016). Protection of Centella asiatica extract through BDNF expresion on zebrafish (Danio rerio) larvae induced by rotenone. [Thesis]. Universitas Brwijaya Malang.

Wijayanti R, Khotimah K and Ali M. (2016). Protection of Gotu kola extract (Centella asiatica) through the expression of Hsp60 and Bax on rotenone-induced zebrafish larvae stunting model (Danio rerio) [Thesis]. Universitas Brawijaya Malang.

Olsson A, DimbergA, Kreuger J and Lena CW. (2006). VEGF receptor signalling — in control of vascular function. Nature Reviews-Molecular Cell Biology, 7, 359-371.

Carmeliet P andCollen D. (1999). Role of vascular endothelial growth factor and vascular endothelial growth factor receptors in vascular development. In Vascular Growth Factors and Angiogenesis. Springer Berlin Heidelberg, 133-158.

Moller B, Lindblom B and Olovsson M. (2002). Ekspression of the vascular endhotelial growth factor B and C and their receptors in human endometrium during the mestrual cycle. Acta Obstetrica et Gynecologica Scandinvica, 81(9), 817-824.

Olszewska-Pazdrak B, Hein TW, Olszewska P and Carney DH. (2009). Chronic hypoxia attenuates VEGF signaling and angiogenic responses by down regulation of KDR in human endothelial cells. American Journal of Physiology-Cell Physiology, 296(5), C1162-C1170.

Sadler TW. (2013). Medical Embryology. 12th Edition. Jakarta: Medical Book Publisher.

Sanhueza C, Wehinger S, Bennett JC, Valenzuela M, Owen GI and Quest AF. (2015). The twisted survivin connection to angiogenesis. Molecular cancer, 14(1), 198.

Lyttle D, Frase K, Fleming S, Mercer A, Robinson A. (1994). Homologs of vascular endothelial growth factor are encoded by the poxvirus orf virus. J. Virol., 68, 84-92.

Takahashi T, Yamaguchi S, Chida K and Shibya M. (2001). A single auto- phosphorylation site on KDR/Flk-1 is essential for VEGF-A-dependent activation of PLC-gamma and DNA synthesis in vascular endothelial cells. EMBO 20, 2768-2778.

Kim YW and Byzova TV. (2014). Oxidative stress in angiogenesis and vascular disease. Blood, 123(5), 625-631.

Yupi Supartini. (2004). Textbook Basic Concepts of Child Nursing. EGC. Jakarta.

Prentice A, Schoenmakers I, Laskey MA, de Bono S, Ginty F and Goldberg GR. (2006). Symposium on ‘Nutrition and health in children and adolescents’ Session 1: Nutrition in growth and development Nutrition and bone growth and development. Proceedings of the Nutrition Society, 65(4), 348-360.

Hanum S, W MA and Rahayu M. (2016). The effect of Centella asiatica’s extract towards the expression of tyrosine hydroxylase (TH) and locomotor activity in zebrafish (Danio rerio), 29(2), 99-103.

Winarto IW and Surbakti IM. (2003). Khasiat and Manfaat Pegagan: Tanaman Penambah Daya Ingat. Agro Media.

Khotimah H, Yuliyani T, Nuraenah E, Zahara E and Umi Kalsum N. (2018). Centella asiatica increased the body length through the modulation of antioxidant in rotenone-induced zebrafish larvae. Biomedical and Pharmacology Journal, 11(2), 827-833.