Pharmacological screening of some traditionally-used antimalarial plants from the Democratic Republic of Congo compared to their ecological taxonomic equivalence in Madagascar

Hydro-alcoholic extracts of some plant species growing in two different geographical regions (Democratic Republic of Congo and Madagascar) were evaluated for their inhibitory effects on two malaria parasites strains (P. falciparum FcM29 & P. yoelii subsp nigeriensis) and cytotoxicity towards leukaemia P- 388 cell lines. Results indicate that, the antiplasmodial activity of tested plants varied geographically. Plants growing in continent ecosystem are more active in vitro while their ecological equivalence inhabiting island ecosystems are more active in vivo. It would be conclude that, the development of phytomedicines from plants of different geographical regions selected by bioguided fractionation would allow the populations to reduce the health care cost. The chemotaxonomic approach has also permitted us to detect moderate antiplasmodial activities in Neobegua mahafaliensis, a plant species not previously reported as antimalarial in the traditional medicine knowlegde of Madagascar. The use of a pharmacological property such as the antimalarial activity, in this study, in order to establish genetic filiations between the plants species is an original approach. Keywords: Malaria, medicinal plants, cytotoxicity, Dem. Rep. of Congo, Madagascar, phenotypic marker, genetic filiatio

SIRT1 Signaling Is Involved in the Vascular Improvement Induced by Moringa Oleifera Seeds during Aging

Vascular aging is linked to reduce NO bioavailability, endothelial dysfunction, oxidative stress, and inflammation. We previously showed that a 4-week treatment of middle-aged Wistar rats (MAWRs, 46 weeks old) with Moringa oleifera seed powder (MOI, 750 mg/kg/day) improved vascular function. Here, we investigated the involvement of SIRT1 in MOI-induced vascular improvement. MAWRs were treated with a standard or MOI-containing diet. Young rats (YWR, 16 weeks old) were the controls and received a standard diet. The hearts and aortas were harvested to evaluate SIRT1 and FOXO1 expression via Western blot and/or immunostaining, SIRT1 activity via a fluorometric assay, and oxidative stress using the DHE fluorescent probe. In the hearts and aortas, SIRT1 expression, reduced in MAWRs compared to YWRs, was enhanced in MOI MAWRs. In the hearts, SIRT1 activity did not differ between YWRs and MAWRs, whereas it was increased in MOI MAWRs compared with them. In the aortas, SIRT1 activity decreased in MAWRs, and it was similar in the MOI MAWRs and YWRs. FOXO1 expression increased in the nuclei of MAWR aortas compared to YWR and was reversed in MOI MAWRs. Interestingly, MOI treatment normalized oxidative stress enhanced in MAWRs, in both the heart and aorta. These results demonstrate the protective role of MOI against cardiovascular dysfunction due to aging via enhanced SIRT1 function and subsequently reduced oxidative stress

High-performance liquid chromatographic assay of malagashanine in rat plasma and urine and its pharmacokinetic application

A reversed-phase HPLC method was developed for quantitative analysis of malagashanine in rat plasma and urine. Malagashanine and internal standard were extracted from alkalinized rat plasma. Urine analysis was performed by direct injection onto the HPLC system. Acetonitrile-aqueous 25 mM sodium acetate solution at pH 6.25 (45:55, v/v) was used as the mobile phase. The eluate was monitored by using UV detection at 250 nm. The assay was linear within the concentration range of 10-1000 ng/ml. Both intra- and inter-day accuracy and precision were within acceptable limits. The method was applied to study the pharmacokinetics of malagashanine in rats. (C) 2000 Elsevier Science BN. All rights reserved

Potential antimalarial activity of indole alkaloids

New antimalarial treatments are now urgently required, following the emergence of resistance to the most used drugs. Natural products contribute greatly to the therapeutic arsenal in this area, including artemisinin and quinine (and atovaquone, semi-synthetic). Among the natural products, indole alkaloids represent an interesting class of compounds. Screening carried out to date has revealed several substances active in vitro under the micromolar range and with a good selectivity index. This review covers the indole alkaloids with high antiplasmodial activity (in vitro and in vivo) isolated from natural sources, and is organized according to the different chemical structures of the alkaloids

Alkaloids of Hernandia voyronii: Chloroquine-potentiating activity and structure elucidation of herveline D

Further investigation of Hernandia voyronii led to the isolation of a new pavine-benzyltetrahydroisoquinoline (pavine-BTIQ) dimer, herveline D, together with herveline A, five aporphine alkaloids, two morphinane alkaloids, and their biosynthetic precursor, i.e., the BTIQ (S)-reticuline. Hervelines A-D have a moderate intrinsic in vitro antimalarial activity (IC50 in the range of 1.68-3.28 mu M), but displayed different effects ranging from synergism for herveline B and herveline C to simple additive effect for herveline A, and antagonism for herveline D in a chloroquine (CQ) combination evaluation and this was confirmed in vivo for hervelines A and B. Furthermore, the antiplasmoidal activity of CQ was potentiated in vitro by reticuline and its dimethyl derivative laudanosine (for the latter also in vivo), whereas herveline C moderately potentiated in vitro the antiplasmodial activity of herveline D

Comparative antimalarial and cytotoxic activities of two Vernonia species: V. amygdalina from the Democratic Republic of Congo and V. cinerea subsp vialis endemic to Madagascar

Vernonia amygdalina Del. is a conventional herbal drug in Congolese traditional medicine and is widely used for the treatment of malaria.The aim of this work is to evaluate its efficacy and safety and the potential antimalarial activity of another species originating from Madagascar. Standard bioassay models based on in vitro and in vivo systems that enable bioactivity screening of traditionally used medicinal plants wereused. In particular, hydro-alcoholic extracts of two Vernonia species growing in two different geographical regions(Congo DR and Madagascar) were evaluated for the inhibitory effects on two malaria parasites strainsand cytotoxicity towards leukaemia P-388 cell lines. Results indicate that, V. amygdalina possess a very good in vitro and in vivo activities and a good therapeutic index than V. cinerea subsp vialis endemic to Madagascar, thus validate scientifically the efficacy and safety of Vernonia amygdalina in the traditional treatment of malaria in Congo DR. Using chemotaxonomic approach, we also detected moderate antiplasmodial activities in V. cinerea subsp vialis a plant species not previously reported as antimalarial in the traditional medicine knowlegde of Madagascar. It would be concluded that despite the long spatial isolation of Madagascar and allopatric speciation, Vernonia ecotype as V. cinerea subsp vialis has preserved the antiplasmodial properties. This approach gives the possibility to select plant species of the same genus from different geographical regions in order to increase the chance of discovering new biologically active plants

Isolation from rat urine and human liver microsomes and identification by electrospray and nanospray tandem mass spectrometry of new malagashanine metabolites

Malagashanine has been isolated from indigenous madagasean Strychnos myrtoides alkaloids used traditionally to treat malaria, This alkaloid was found to enhance the action of chloroquine against chloroquine-resistant strains of Plasmodium falciparum when combined with classical antimalarial drugs (chloroquine, quinine), The present study was carried out in order to investigate by electrospray mass and tandem mass spectrometry and NMR spectroscopy the structure of two new metabolites isolated from rat urine and human liver microsomes, We were able to demonstrate the presence of two new metabolites of malagashanine corresponding to a malagashanine N-demethylated metabolite and to the oxidation of malagashanine in the alpha-position of the N-methyl group to produce a carbinolamine function. The latter metabolite may be subject to ring and open-chain tautomerism effects and dimeric species were detected in the electrospray mass spectrum. Copyright (C) 2000 John Wiley & Sons, Ltd

IN-VITRO AND IN-VIVO CHLOROQUINE-POTENTIATING ACTION OF STRYCHNOS-MYRTOIDES ALKALOIDS AGAINST CHLOROQUINE-RESISTANT STRAINS OF PLASMODIUM MALARIA

Crude alkaloids of Strychnos myrtoides Gilg & Busse, empirically used as an adjuvant to chloroquine (CQ) in Malagasy herbal remedies, were practically devoid of intrinsic in vitro and in vivo antimalarial activity. However, when combined with CQ at a dose level much lower than their IC50 value, they markedly enhanced in vitro the effectiveness of the synthetic drug against a CQ-resistant strain of Plasmodium falciparum. They also enhanced in vivo CQ activity against a resistant strain of Plasmodium yoelii. By counter-current distribution (CCD) separation of the crude alkaloid extract, the two major alkaloids strychnobrasiline (1) and malagashanine (2), together with four minor alkaloids, were isolated. Strychnobrasiline and malagashanine were devoid of both intrinsic antimalarial activity and cytotoxicity effect, but exhibited significant CQ-potentiating actions. These findings could account for the above-mentioned empirical use of S. myrtoides. The present state of research on antimalarial drug from Strychnos genus is also discussed

SIRT1 Signaling Is Involved in the Vascular Improvement Induced by Moringa Oleifera Seeds during Aging

Vascular aging is linked to reduce NO bioavailability, endothelial dysfunction, oxidative stress, and inflammation. We previously showed that a 4-week treatment of middle-aged Wistar rats (MAWRs, 46 weeks old) with Moringa oleifera seed powder (MOI, 750 mg/kg/day) improved vascular function. Here, we investigated the involvement of SIRT1 in MOI-induced vascular improvement. MAWRs were treated with a standard or MOI-containing diet. Young rats (YWR, 16 weeks old) were the controls and received a standard diet. The hearts and aortas were harvested to evaluate SIRT1 and FOXO1 expression via Western blot and/or immunostaining, SIRT1 activity via a fluorometric assay, and oxidative stress using the DHE fluorescent probe. In the hearts and aortas, SIRT1 expression, reduced in MAWRs compared to YWRs, was enhanced in MOI MAWRs. In the hearts, SIRT1 activity did not differ between YWRs and MAWRs, whereas it was increased in MOI MAWRs compared with them. In the aortas, SIRT1 activity decreased in MAWRs, and it was similar in the MOI MAWRs and YWRs. FOXO1 expression increased in the nuclei of MAWR aortas compared to YWR and was reversed in MOI MAWRs. Interestingly, MOI treatment normalized oxidative stress enhanced in MAWRs, in both the heart and aorta. These results demonstrate the protective role of MOI against cardiovascular dysfunction due to aging via enhanced SIRT1 function and subsequently reduced oxidative stress

In-vitro and in-vivo antimalarial activity of caffeic acid and some of its derivatives.

OBJECTIVES: To explore the in-vitro and in-vivo antimalarial potential of caffeic acid and derivatives. METHODS: Two common phenolic acids (caffeic acid and chlorogenic acid) were evaluated for in-vitro and in-vivo antiplasmodial activity in comparison with some semi-synthetic derivatives that were synthesized. An in-vitro assay based on plasmodial lactate dehydrogenase activity, and the classical in-vivo 5-day suppressive test from Peters on an artemisinin-resistant Plasmodium berghei strain was used. Parasitic stage sensitivity to ethyl caffeate was determined in this work. KEY FINDINGS: Phenolic acid esters derivatives showed better antiplasmodial activity than corresponding phenolic acids. The derivative with the highest in-vitro activity being caffeic acid ethyl ester, exhibiting an IC50 = 21.9 +/- 9.4 mum. Ethyl caffeate and methyl caffeate were then evaluated for antimalarial activity in vivo and ethyl caffeate showed a growth inhibition of 55% at 100 mg/kg. Finally, it seems that ethyl caffeate blocks the growth of young parasitic forms. CONCLUSIONS: Our study provides evidence for an antimalarial potential of caffeic acid derivatives which are common in several medicinal plants traditionally used against malaria. It also demonstrates the possibility to use such derivatives in the treatment of malaria