Maria Fâni Dolabela

Oxidative Stress in Malaria

Malaria is a significant public health problem in more than 100 countries and causes an estimated 200 million new infections every year. Despite the significant effort to eradicate this dangerous disease, lack of complete knowledge of its physiopathology compromises the success in this enterprise. In this paper we review oxidative stress mechanisms involved in the disease and discuss the potential benefits of antioxidant supplementation as an adjuvant antimalarial strategy.

Antiplasmodial activity of the andiroba (Carapa guianensis Aubl., Meliaceae) oil and its limonoid-rich fraction.

ETHNOPHARMACOLOGICAL RELEVANCE From seeds of Carapa guianensis the Amazon native people extracts the andiroba oil, which is traditionally used as febrifuge, anti-malarial, insecticidal and repellant. The non-saponifiable fraction separated from the oil is rich in limonoids, which assigns its pharmacological effects. MATERIALS AND METHODS The andiroba oil and its limonoid-rich fraction were submitted to in vitro antiplasmodial bioassay using W(2) and Dd(2) strains of Plasmodium falciparum. The acute toxicity of andiroba oil was evaluated. The limonoid-rich fraction was subjected to fractionation and identified its major constituents. RESULTS Andiroba oil and its limonoid-rich fraction inhibited the growth of W(2) clone in 100%, between 24 and 72 h, at concentrations of 8.2 μg/mL and 3.1 μg/mL, respectively. Under the same conditions, the parasitaemia of Dd(2) clone provoked by the andiroba oil showed inhibition of 31% (IC(50) >82 μg/mL) with a time-dependent relationship of 24h and inhibition of 88% (IC(50) 8.4 μg/mL) after 72 h, while for the limonoid-rich fraction the inhibition of Dd(2) clone was 56% (IC(50) 2.8μg/mL) at 24h and 82% (IC(50) 0.4 μg/mL) after 72 h. Andiroba oil in acute toxicity test with a fixed dose (LD(50) >2000 mg/kg) was not toxic The limonoids identified in the oil were gedunin, 6α-acetoxygedunin, 7-deacetoxy-7-oxogedunin, 7-deacetylgedunin, 1,2-dihydro-3β-hydroxy-7-deacetoxy-7-oxogedunin and andirobin. Gedunin and derivatives has been reputed as anti-malarials. CONCLUSION The results support the traditional use of andiroba oil as antiplasmodial, which additionally proved not to be toxic in bioassays conducted with mice.

Estudo fitoquímico biomonitorado pelos ensaios de toxicidade frente à Artemia salina e de atividade antiplasmódica do caule de aninga (Montrichardia linifera)

Montrichardia linifera is an aquatic plant widely use in Amazon folkmedicine. However, very little is known about the chemical composition and biological activity. In search of biologically active (s) substance (s) phytochemical bioassay-guided study was conducted evaluating hexane extract and ethanol extract obtained from stems of this species. Since only the ethanol extract presented toxicity against Artemia salina and activity against Plasmodium falciparum, this extract was selected for chromatographic fractionation. The biological activities were concentred in dichloromethane fraction which showed high toxicity against A. saline (LD50< μg mL-1) and high antiplasmodial activity (IC50 <10 μg mL-1), showing promising antimalarial activity. Of this fraction, the aromatic compound p-hydroxybenzaldehyde was isolated for the first time in this plant.

Aspidosperma species as sources of antimalarials. Part III. A review of traditional use and antimalarial activity.

Several plant species belonging to the genus Aspidosperma are traditionally used in Brazil and other Meso- and South American countries for the treatment of malaria and fevers. These traditional uses were motivation for this review. A literature survey completed for this review has identified scientific bibliographical references to the use of 24 Aspidosperma species to treat malaria/fevers and to 19 species that have had their extracts and/or alkaloids evaluated, with good results, for in vitro and/or in vivo antimalarial activity. Indole alkaloids are typical constituents of Aspidosperma species. However, only 20 out of more than 200 known indole alkaloids isolated from this genus have been assayed for antimalarial activity. These data support the potential of Aspidosperma species as sources of antimalarials and the importance of research aimed at validating their use in the treatment of human malaria.

Brazilian Amazon Traditional Medicine and the Treatment of Difficult to Heal Leishmaniasis Wounds with Copaifera

The present study describes the use of the traditional species Copaifera for treating wounds, such as ulcers scarring and antileishmanial wounds. It also relates phytochemical studies, evaluation of the leishmanicidal activity, and toxicity. The species of Copaifera with a higher incidence in the Amazon region are Copaifera officinalis, Copaifera reticulata, Copaifera multijuga Hayne. The copaiba oil is used in the Amazons traditional medicine, especially as anti-inflammatory ingredient, in ulcers healing, and in scarring and for leishmaniasis. Chemical studies have shown that these oils contain diterpenes and sesquiterpenes. The copaiba oil and terpenes isolated have antiparasitic activity, more promising in the amastigote form of L. amazonensis. This activity is probably related to changes in the cell membrane and mitochondria. The oil showed low cytotoxicity and genotoxicity. Furthermore, it may interfere with immune response to infection and also has a healing effect. In summary, the copaiba oil is promising as leishmanicidal agent.

nutritional supplementation with the mushroom Agaricus sylvaticus reduces oxidative stress in children with Hiv

Oxidative stress has been implicated in the progression of HIV and other diseases. The authors of this article aimed to evaluate the effects of supplementation with a mushroom known to exhibit antioxidant properties on the oxidative status of children with HIV. Extensive measurements of oxidative stress markers and antioxidant capacity were obtained before and after 90 days of supplementation with the mushroom extract.

Anti-malarial activity and toxicity assessment of Himatanthus articulatus, a plant used to treat malaria in the Brazilian Amazon

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.

Biological activities of Croton palanostigma Klotzsch

Background: Different species of Croton are used in traditional Amazonian medicine. Among the popular uses are treatment of bacterial diseases, poorly healing wounds and fevers. Objective: This study evaluated the antileishmanial, antiplasmodial and antimicrobial activities of the extracts and diterpenes of Croton palanostigma Klotzsch (Euphorbiaceae). Materials and Methods: Leaves and bark were extracted with dichloromethane and methanol. The bark dichloromethane extract (BDE) was chromatographed on a column, obtaining cordatin and aparisthman. The extracts and diterpenes were assayed thought agar disk diffusion method and their bactericidal or fungicidal effects were evaluated by minimum bactericidal or fungicidal concentration. The antiplasmodial activity was evaluated after 24 and 72 h of exposition. The antileishmanial activity was performed on promastigotes forms of Leishmania amazonensis. Results: The bark methanol extract (BME) and cordatin were not active against any microbial strains tested; BDE and leaves methanol extract (LME) were positive for Pseudomonas aeruginosa and aparisthman was positive for Candida albicans. In the determination of the minimum bactericidal concentration, neither of them were active in the highest concentration tested. The extracts and diterpenes were inactive in Plasmodium falciparum, except the LME in 72 h. Any extract was shown to be active in promastigote forms of L. amazonensis. Conclusion: These results indicate that the BDE and LME did not inhibit the bacterial growth, then they probably had bacteriostatic effect. LME presented activity in P. falciparum.

Uma revisão bibliográfica sobre Araceae com foco nos gêneros Pistia, Philodendron e Montrichardia: aspectos botânicos, fitoquímicos e atividades biológicas

The present paper reports a broad literature review on the Araceae family, focusing the genera with popular allegation of medicinal use. The review was carried through different databases, specialized periodicals and books. The Araceae family comprises ornamental, toxic and medicinal plants. Species with allegations of popular use against serpent bites and scurvy, as well as vermifuge, laxative, and hemostatic, among other uses, are described. The Pistia genus includes P. stratiotes, popularly known as santa-luzia with, repolho-d’agua, alface-d’agua and golfo, with popular allegations of activity as diuretic, antipyretics, stranguria, hematuria, diabetes, hemoptysis, hydropsy, arthritis, liver affections, and treatment of scurvy. However, these popular allegations lack of validation studies. Phytochemically, steroids have been isolated from this species. Certainty the mostly studied genus of this family in terms of biological activities is Montrichardia that has been evaluated for antiplasmodial, antibacterial, antifungal, and antinociceptive activities. Another genus of this family with allegation of popular use is Philodendron, with the following allegations: treatment of serpent bites and pain killer, laxative, hemostatic and vermifuges. Phytochemical studies led to the isolation of sitosteol and other substances. Biological studies confirmed activities against Trypanosoma cruzi and Trichomonas vaginalis, but the mechanisms involved in toxicity are still not completely elucidated. In summary, this family includes different species with therapeutical potential that deserve validation studies.

Antileishmanial Activity of Handroanthus serratifolius (Vahl) S. Grose (Bignoniaceae)

This study aimed to evaluate the leishmanicidal activity of ethanol extract, fractions, and isolated substance from Handroanthus serratifolius against Leishmania amazonensis. Furthermore, this activity was related to cytotoxicity, and the selectivity index was determined. The ethanol extract was obtained by maceration of the stem powder, and the extract was subjected to fractionation on chromatographic column. The lapachol was obtained by acid base extraction followed by purification in chromatographic column. The antipromastigote activity and cytotoxicity tests were carried out by the cell viability method (MTT). Modified THP-1 cells were infected with L. amazonensis promastigotes and treated for 24 h with different concentrations of the extract, fractions, and lapachol. The ethanol extract, dichloromethane, and ethyl acetate fractions were not active against promastigotes (IC50 > 200 μg/mL) or cytotoxic (CC50 > 500 μg/mL), and the selectivity index (SI) was greater than 2.5. The ethyl acetate fraction was active only in promastigotes; it is not cytotoxic (CC50 > 500 μg/mL, SI > 5). The lapachol was selectively active only against amastigote (IS > 2.5, CC50 > 500 μg/mL). In summary, lapachol and ethyl acetate fraction are promising against amastigote and promastigote forms, respectively.