Abstract
BackgroundPlasmodium falciparum has become resistant to some of the available drugs. Several plant species are used for the treatment of malaria, such as Himatanthus articulatus in parts of Brazil. The present paper reports the phyto-chemistry, the anti-plasmodial and anti-malarial activity, as well as the toxicity of H. articulatus.MethodsEthanol and dichloromethane extracts were obtained from the powder of stem barks of H. articulatus and later fractionated and analysed. The anti-plasmodial activity was assessed against a chloroquine resistant strain P. falciparum (W2) in vitro, whilst in vivo anti-malarial activity against Plasmodium berghei (ANKA strain) was tested in mice, evaluating the role of oxidative stress (total antioxidant capacity - TEAC; lipid peroxidation – TBARS, and nitrites and nitrates - NN). In addition, cytotoxicity was evaluated using the HepG2 A16 cell-line. The acute oral and sub-chronic toxicity of the ethanol extract were evaluated in both male and female mice.ResultsPlumieride was isolated from the ethyl acetate fraction of ethanol extract, Only the dichloromethane extract was active against clone W2. Nevertheless, both extracts reduced parasitaemia in P. berghei-infected mice. Besides, a significant reduction in pulmonary and cerebral levels of NN (nitrites and nitrates) was found, as well as in pulmonary TBARS, indicating a reduced oxidative damage to these organs. The ethanol extract showed low cytotoxicity to HepG2 A16 cells in the concentrations used. No significant changes were observed in the in vivo toxicity studies.ConclusionsThe ethanol extract of H. articulatus proved to be promising as anti-malarial medicine and showed low toxicity.
Highlights
Plasmodium falciparum has become resistant to some of the available drugs
The present study describes, for the first time, the anti-plasmodial activity of H. articulatus against a chloroquine resistant clone of P. falciparum (W2), as well as the anti-malarial activity in Plasmodium berghei-infected mice
This study reports changes in oxidative stress caused in Plasmodium berghei-infected mice
Summary
Plant material and phytochemical studies Stem barks from H. articulatus were collected in Altamira city, state of Pará, Brazil (S 01°10’86” W 41°53’51.6”), in Figure 1 Chemical structure of compouds occurring in Himatanthus articulatus. (A) plumieride, (B) isoplumieride, (C) plumericin, (D) isoplumericin, (E) lupeol cinnamate, (F) α-amyrin cinnamate, (G) β-amyrin cinnamate, (H) lupeol acetate. Evaluation of acute oral and subchronic toxicity Male (n = 8) and female (n = 8, nulliparous and nonpregnant) albino Swiss mice, weighing 25-27g, obtained from the animal facility of the Instituto Evandro Chagas, (IEC), Ananindeua, Pará, Brazil, were kept in the vivarium of the Faculty of Pharmacy (UFPA) under controlled temperature and humidity, light and dark cycle of 12 h each, with pelleted food and filtered tap water ad libitum. They were daily submitted, weighed, and assessed for food and water intake. 62.6 62.4 d-doublet, dd-double doublet, s-singlet, m-multiplet
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