Journal of Ethnopharmacology 122 (2009) 410–415 Contents lists available at ScienceDirect Journal of Ethnopharmacology journal homepage: www.elsevier.com/locate/jethpharm Ethnopharmacological communication Toxicity studies of Tithonia diversifolia A. Gray (Asteraceae) in rats T.O. Elufioye a , O.I. Alatise b , F.A. Fakoya b , J.M. Agbedahunsi c , P.J. Houghton d,∗ a Faculty of Pharmacy, Department of Pharmacognosy, University of Ibadan, Ibadan, Nigeria b Faculty of Basic Medical Sciences, Department of Anatomy and Cell Biology, Obafemi Awolowo University, Ile-Ife, Nigeria c Drug Research and Production Unit, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Nigeria d Pharmacognosy Research Laboratories, Pharmaceutical Sciences Division, Kings College London, 150 Stamford Street, London SE1 9NN, UK article info Article history: Received 2 April 2008 Received in revised form 25 November 2008 Accepted 5 December 2008 Available online 14 December 2008 Keywords: Tithonia diversifolia Toxicity Liver Kidney Antimalarial abstract Objective: To investigate the toxicity of an ethanolic extract of the aerial parts of Tithonia diversifolia, used in Nigeria to treat malaria, in rats. Materials and methods: A 70% ethanol extract was administered orally to adult Wistar rats at various dosages (400–1600 mg/kg) and the animals sacrificed and various organs examined at a range of times from 30 min up to 24 h after administration. Results: The studies showed a dose- and time-dependent toxic effect, which was reversible on the kidney and liver while there was no noticeable adverse effect on the morphology of the heart, spleen and brain. Conclusion: A 70% ethanol extract of the aerial parts of Tithonia diversifolia, which had previously been shown to reduce parasitemia in mice infected with Plasmodium, displayed kidney and liver toxicity at the lowest dose tested. The use of this plant extract against malaria therefore raises concerns over its safety. © 2008 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Malaria remains to be a major public health issue. It is the leading cause of morbidity and mortality in sub-Saharan African especially among the children. Several efforts are geared toward prevention and treatment of the disease. Nevertheless, the disease is still ravaging the life of most African children. A major problem is the resistance of the causative parasite to most of the available remedy. Hence, it will be necessary to discover other remedies before the resistance to current remedies becomes a widespread problem. Tithonia diversifolia A. Gray, commonly known as Mexican sun flower, although introduced to Nigeria, now enjoys a wide reputa- tion there in the management of malaria. The leaf is macerated in alcohol and drank for the treatment of chronic malaria. There is in vitro evidence for its antiplasmodial activity (Goffin et al., 2002) while a study on the antimalarial fraction revealed the presence of a new sesquiterpene lactone, 8-(2-methylbutanoyl)-3,10-epoxy- , 8-dihydroxyl-4, 11(13)-germacradien-12, 6-olide (Elufioye et al., 2004) and the efficacy of an ethanolic extract showed in vivo anti- malarial effects in mice (Elufioye and Agbedahunsi, 2004). With the good parasitemia suppression that was found in our previous study with the plant extract (Elufioye and Agbedahunsi, ∗ Corresponding author. E-mail address: peter.houghton@kcl.ac.uk (P.J. Houghton). 2004), we expected the mean survival of the animals to be better than that of control, just as found in other plant extracts (Makinde et al., 1988). However, the mean survival of the mice who had repeated doses of the extract was lower than the control. This motivated us to evaluate the extract for acute toxicity before it is recommended for public use. This report focuses on the toxicity study of the plant, with particular emphasis on the effect of the extract on the mor- phology of some vital organs in the body. 2. Materials and methods 2.1. Plant materials Aerial parts of Tithonia diversifolia, were collected along the Ede road in Ile-Ife, Osun State, Nigeria in August 2002 and were identified by Mr. Daramola of the Botany Department, Obafemi Awolowo University, Ile-Ife, Nigeria. A voucher specimen IFE 14963 is deposited at the herbarium of Obafemi Awolowo University, Ile-Ife. 2.2. Extraction 1.5kg of the plant was macerated with 70% ethanol and was soaked for 72 h with constant shaking, using the Griffin mechani- cal shaker. After filtration, the extract was concentrated in vacuo at 40 ◦ C to dryness using a rotary evaporator to give a yield of 12.52% (w/w). 0378-8741/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.jep.2008.12.007