title: Antimalarial activity of the terpene nerolidol.
abstract: Malaria, an infectious disease that kills more than 438,000 people per year worldwide, is a major public health problem. The emergence of strains resistant to conventional therapeutic agents necessitates the discovery of new drugs. We previously demonstrated that various substances, including terpenes, have antimalarial activity in vitro and in vivo. Nerolidol is a sesquiterpene present as an essential oil in several plants that is used in scented products and has been approved by the US Food and Drug Administration as a food-flavouring agent. In this study, the antimalarial activity of nerolidol was investigated in a mouse model of malaria. Mice were infected with Plasmodium berghei ANKA and were treated with 1000 mg/kg/dose nerolidol in two doses delivered by the oral or inhalation route. In mice treated with nerolidol, parasitaemia was inhibited by >99% (oral) and >80% (inhalation) until 14 days after infection (P <0.0001). On Day 30 post-infection, the survival rate of orally treated mice was 90% compared with 16% in controls (P <0.0001). In contrast, inhalation-treated mice showed a survival rate of 50% vs. 42% in controls (P > 0.05). The toxicity of nerolidol administered by either route was not significant, whilst genotoxicity was observed only at the highest dose tested. These results indicate that combined use of nerolidol and other drugs targeting different points of the same isoprenoid pathway may be an effective treatment for malaria.
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Av. Lineu Prestes 1374, CEP 05508-000 São Paulo, SP, Brazil.
authors.forename: Alexandre Y
authors.initials: AY
authors.lastname: Saito
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Av. Lineu Prestes 1374, CEP 05508-000 São Paulo, SP, Brazil.
authors.forename: Adriana A
authors.initials: AA
authors.lastname: Marin Rodriguez
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Av. Lineu Prestes 1374, CEP 05508-000 São Paulo, SP, Brazil.
authors.forename: Danielle S
authors.initials: DS
authors.lastname: Menchaca Vega
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Av. Lineu Prestes 1374, CEP 05508-000 São Paulo, SP, Brazil.
authors.forename: Rodrigo A C
authors.initials: RAC
authors.lastname: Sussmann
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Av. Lineu Prestes 1374, CEP 05508-000 São Paulo, SP, Brazil.
authors.forename: Emília A
authors.initials: EA
authors.lastname: Kimura
authors.affiliation: Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, Av. Lineu Prestes 1374, CEP 05508-000 São Paulo, SP, Brazil. Electronic address: amkatzin@icb.usp.br.
authors.forename: Alejandro M
authors.initials: AM
authors.lastname: Katzin
mesh_terms: D000280:Administration, Inhalation; D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D004195:Disease Models, Animal; D064420:Drug-Related Side Effects and Adverse Reactions; D008288:Malaria / Q000188:drug therapy*; D008297:Male; D008807:Mice, Inbred BALB C; D018512:Parasitemia / Q000188:drug therapy; D010962:Plasmodium berghei / Q000187:drug effects*; D012717:Sesquiterpenes / Q000008:administration & dosage* / Q000009:adverse effects / Q000494:pharmacology; D016019:Survival Analysis; D013729:Terpenes / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D000962:Antimalarials; D012717:Sesquiterpenes; D013729:Terpenes; C037055:nerolidol
keywords: BALB/c mice; Isoprenoids; Malaria; Nerolidol; Plasmodium berghei ANKA; Terpenes