Antimalarial Activity of Tropical Meliaceae Extracts and Gedunin Derivatives

University of Ottawa, Ottawa, Ontario, Canada
Journal of Natural Products (Impact Factor: 3.8). 05/1997; 60(4):336-41. DOI: 10.1021/np9605394
Source: PubMed

ABSTRACT Extracts of 22 species of Meliaceae were examined for antimalarial activity using in vitro tests with two clones of Plasmodium falciparum, one sensitive to chloroquine (W2) and one chloroquine-resistant (D6). Twelve extracts were found to have activity, including extracts of Cedrela odorata wood and Azadirachta indica leaves, which contained the limonoid gedunin. These extracts were more effective against the W2 clone than the D6 clone, suggesting there is no cross-resistance to chloroquine. Gedunin was extracted in quantity, and nine derivatives prepared for a structure-activity study, which revealed essential functionalities for activity. The study also included four other limonoids derived from related Meliaceae. Only gedunin had better activity than chloroquine against the W2 clone. This active principle could be used to standardize a popular crude drug based on traditional use of A. indica in West Africa.

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    • "In addition, there is a report that the root and trunk bark is used to reduce fever and pain; the trunk is harvested to prepare a decoction for abortive and the seeds are believed to have vermifugal properties (Orwa et al., 2009). The anti-fungal, antibacterial, antimalarial, antileishmanial and antitrypanosomal properties have been documented in some studies (MacKinnon et al., 1997; Omar et al., 2003; González- Coloma et al., 2012; Rosas-Piñón et al., 2012). Essential oils of Cedrela odorata have been subjects of various investigations, including the leaf and bark oil from different countries (Asekun and Ekundayo, 1999; Maia et al., 2000; Villanueva, et al., 2009). "
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    ABSTRACT: Cedrela odorata L. (Meliaceae) is a native plant of the Amazon region and its inner stem bark is used in the treatment of diabetes in the form of maceration in Brazilian popular medicine. Until now, there is no scientific study on this activity. The present study was aimed at evaluating the anti-hyperglycemic activity, anti-diabetic, toxicity, antioxidant and potential mechanism of action of hydroethanolic extract of the inner stem bark of Cedrela odorata. The inner stem bark extract of C. odorata was prepared by maceration in 70% ethanol for 7 days to obtain hydroethanolic extract of Cedrela odorata (HeECo). The preliminary phytochemical analysis was performed according to procedures described in the literature. Selected secondary metabolites detected were quantified by high performance liquid chromatography (HPLC). Acute toxicity of HeECo was investigated in male and female mice with oral administration of graded doses of HeECo from10 to 5000mg/kg. Subchronic oral toxicity study was done by oral administration of HeECo (500mg/kg) and vehicle for 30 days to both sexes of Wistar rats. Clinical observations and toxicological related parameters were determined. Blood was collected for biochemical and hematological analyses, while histological examinations were performed on selected organs. Anti-hiperglycemic and antidiabetic effects were evaluated in streptozotocin-induced diabetic rats. In acute evaluation, the animals received pretreatment with 250 and 500mg/kg of HeECo, before carbohydrate overload. For subchronic effect, the antidiabetic activity of HeECo was evaluated using the same doses for 21 days. At the end of the treatments, the levels of triacylglycerols, malondialdehyde, total antioxidant status, superoxide dismutase and glutathione peroxidase activities were evaluated in the plasma. The extract showed low acute toxicity. HeECo exhibited inhibitory activity against α-glucosidase and caused a lowering in the peak levels of blood glucose in animals that received glucose overload by 36.7% and 24.1% in the area under the glucose curve (AUC). When the overload was sucrose, HeECo reduced the blood glucose level by 44.4% without affecting AUC. Treatment with HeECo of the blood glucose the diabetic animals for 21 days did not lead to improvement in weight gain and regularization of the blood glucose level, but exhibited triacylglycerol and malondialdehyde levels by 36.6% and 48.1%, respectively. The activity of the antioxidant enzymes, superoxide dismutase and glutathione peroxidase were significantly increased when compared to diabetic control rats. HPLC analysis showed the presence of polyphenols, such as gallic acid, (-)- gallocatechin and (+)- catechin, the latter is present in higher quantity. Collectively, these data showed that HeECo could blunt the postprandial glycemic surge in rats; possibly through inhibition of alpha-glucosidase and positive modulation of antioxidant enzymes. Our findings confirmed the anti-hiperglycemic activity of HeECo in STZ- diabetic rats. Cedrela odorata is effective in diminishing glucose levels in vitro and in vivo and in ameliorating oxidative damage that occurs in diabetes and/or due to hyperglycemia in rats. According to our results, the efficacy of Cedrela odorata preparation could be due to the presence of active principles with different mode of actions at the molecular level, including α-glycosidases inhibitors and antioxidant property. Copyright © 2014. Published by Elsevier Ireland Ltd.
    Journal of Ethnopharmacology 01/2015; 162. DOI:10.1016/j.jep.2014.12.059 · 3.00 Impact Factor
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    • "The efficacy of these preparations has been associated with the large number of secondary metabolites present in the plant, including at least 50 bioactive limonoids [18]. Studies aimed at detecting the molecules responsible for the antimalarial activity of neem extracts found that the limonoids nimbolide and gedunin displayed major inhibitory effects on in vitro growth of P. falciparum asexual blood stages [19-22]. Azadirachtin, moderately active on asexual blood stages [23], has been demonstrated to inhibit the exflagellation process of P. falciparum and P. berghei microgametocytes in vitro, the initial phase of sporogonic development in the vector [24,25]. "
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    ABSTRACT: Targeting the stages of the malaria parasites responsible for transmission from the human host to the mosquito vector is a key pharmacological strategy for malaria control. Research efforts to identify compounds that are active against these stages have significantly increased in recent years. However, at present, only two drugs are available, namely primaquine and artesunate, which reportedly act on late stage gametocytes. In this study, we assessed the antiplasmodial effects of 5 extracts obtained from the neem tree Azadirachta indica and Guiera senegalensis against the early vector stages of Plasmodium falciparum, using field isolates. In an ex vivo assay gametocytaemic blood was supplemented with the plant extracts and offered to Anopheles coluzzii females by membrane feeding. Transmission blocking activity was evaluated by assessing oocyst prevalence and density on the mosquito midguts. Initial screening of the 5 plant extracts at 250 ppm revealed transmission blocking activity in two neem preparations. Up to a concentration of 70 ppm the commercial extract NeemAzal(R) completely blocked transmission and at 60 ppm mosquitoes of 4 out of 5 replicate groups remained uninfected. Mosquitoes fed on the ethyl acetate phase of neem leaves at 250 ppm showed a reduction in oocyst prevalence of 59.0% (CI95 12.0 - 79.0; p < 10-4) and in oocyst density of 90.5% (CI95 86.0 - 93.5; p < 10-4 ), while the ethanol extract from the same plant part did not exhibit any activity. No evidence of transmission blocking activity was found using G. senegalensis ethyl acetate extract from stem galls. The results of this study highlight the potential of antimalarial plants for the discovery of novel transmission blocking molecules, and open up the potential of developing standardized transmission blocking herbal formulations as malaria control tools to complement currently used antimalarial drugs and combination treatments.
    Parasites & Vectors 04/2014; 7(1):185. DOI:10.1186/1756-3305-7-185 · 3.43 Impact Factor
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    • "Plants have been recognized as rich sources of bioactive secondary metabolites with potential in the control of disease vectors and/or the diseases they transmit (e.g. de Omena et al., 2007; Githua et al., 2010; Khalid et al., 1989; Kihampa et al., 2009; Mackinnon et al., 1997; Singh et al., 2006; Sukumar et al., 1991). Given the high incidence of malaria in Africa and other tropical countries, the search for alternative tools and tactics for the control of mosquitoes has assumed special importance. "
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    ABSTRACT: Acetone and methanol extracts of different parts of three Vitex species (leaves and stem bark of Vitex trifolia, leaves, stem bark and root bark of Vitex schiliebenii and stem and root bark of Vitex payos) were evaluated for their potential to control Anopheles gambiae Giles s.s. larvae (Diptera: Culicidae). The extracts gave different levels and rate of mortality of the larvae. Some (methanol extract of V. trifolia leaves, acetone extracts of stem bark and leaves of V. schiliebenii, acetone extract of root bark of V. payos) caused 100% mortality at 100ppm in 72hours, with those of V. schiliebenii and V. payos showing faster rate of mortality (LT50=8h) than that of V. trifolia (LT50=14h). At lower doses of these extracts (≤ 50ppm), most of the larvae failed to transform to normal pupae but gave larval-pupal intermediates between 4-14 days of exposure. Some pupated normally but the adults that emerged appeared to be weak and died within 48hours. Extracts of the stem bark of V. payos showed interesting effects on the larvae. Initially, the larvae were relatively hyperactive compared to those in control treatments. Later, the ones that did not transform to larval-pupal intermediates became stretched and inactive and died and floated in clusters on the surface. These observations suggest some interesting growth-disrupting constituents in the plants, with possible application in the practical control of mosquito larvae in aquatic ecosystems.
    Acta tropica 05/2013; 127(3). DOI:10.1016/j.actatropica.2013.05.003 · 2.27 Impact Factor
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