The objective of our study was to compare death signalling pathways triggered by lupulone, a beta-acid of hops, in TRAIL-sensitive human colon cancer cells (SW480) and in their derived TRAIL-resistant metastatic cells (SW620). We showed that lupulone (74 μM) up-regulated the expression of TRAIL DR4/DR5 death receptors at the cell surface of both cell lines. In SW480 cells, lupulone triggered cell death through a cross-talk between TRAIL-DR4/DR5 and the mitochondrial (intrinsic) pathways involving caspase-8 activation and Bid protein cleavage. As a consequence depolarization of the mitochondrial membrane occured and cytochrome c was released into the cytosol leading to the activation of caspases-9 and -3. In the metastatic SW620 cells, lupulone restored the sensitivity of these cells to TRAIL and activated the extrinsic apoptotic pathway via DR4/DR5 death receptors and the direct involvement of the caspase-8/caspase-3 cascade. The demonstration that lupulone is able to activate TRAIL-death signalling pathways even in TRAIL resistant cancer cells (SW620) highlights the potential of this natural compound for cancer therapy.

Several rich sources of polyphenols have been shown to strongly increase the endothelial formation of nitric oxide (NO), a potent vasoprotecting factor, via the redox-sensitive activation of the PI3-kinase/Akt pathway leading to the phosphorylation of endothelial NO synthase. The purpose of the present study was to investigate the molecular mechanisms underlying the stimulatory effect of catechins on the endothelial formation of NO using different catechins (flavan-3-ols). Vascular reactivity studies were performed using porcine coronary artery rings, which were suspended in organ chambers for the measurement of changes in isometric tension. All experiments were performed in the presence of indomethacin (an inhibitor of cyclooxygenases), and the combination of apamin and charybdotoxin (two inhibitors of endothelium-derived hyperpolarizing factor-mediated effects) to assess only the NO component of the relaxation. Cultures of porcine coronary artery endothelial cells (P1) were used to determine the phosphorylation level of Akt and endothelial NO synthase by Western blot analysis. Both natural and synthetic catechins were evaluated. (-)-Epigallocatechin-3-O-gallate (EGCg) induced potent endothelium-dependent relaxations in porcine coronary artery rings. The EGCg-induced relaxation was inhibited by MnTMPyP (a membrane permeant analogue of superoxide dismutase, SOD) whereas extracellular SOD had no effect, indicating a major role of the intracellular formation of ROS. Relaxations to EGCg were minimally affected by rotenone (an inhibitory of the mitochondrial respiratory chain), sulphenazol (an inhibitor of cytochrome P450), apocynin (an inhibitor of NADPH oxidase) or allopurinol (an inhibitor of xanthine oxidase). The replacement of all hydroxyl groups of EGCg by O-methyl groups resulted in the total loss of the relaxing activity whereas partial replacement decreased the relaxing activity. EGCg caused endothelium-dependent relaxations of coronary arteries via the redox-sensitive formation of NO in endothelial cells. The stimulatory effect does not involve major intracellular sources of ROS including the mitochondrial respiratory chain, xanthine oxidase, NADPH oxidase and cytochrome P450 but is critically dependent on the presence of hydroxyl groups possibly leading to auto-oxidation of the polyphenol.

Previous studies have shown that Red Wine Phenolic extracts induce nitric oxide (NO)-mediated vasoprotective effects, mainly by causing a redox-sensitive activation of endothelial NO synthase (eNOS). However, Red Wine Phenolic extracts are complex mixtures of a several hundreds of phenolic compounds. Therefore, the aim of the present study was to isolate active phenolic compounds using multi-step bioguided fractionation of the red wine extract. Red Wine Phenolic Extract was submitted to a bioguided fractionation using chromatographic methods. The fractions obtained at each step were tested for their potential to induce the activation of eNOS in endothelial cells. Cultures of porcine coronary artery endothelial cells (P1) were used to determine the phosphorylation level of Akt and endothelial NO synthase by Western blot analysis. Identification of phenolic compounds in each active fraction was performed by MALDI-TOF and HPLC-MS techniques. The first step of fractionation on lipophilic Sephadex® yielded 9 fractions of which 4 of them significantly increased the phosphorylation level of Akt and eNOS in endothelial cells. The active fractions contained mainly procyanidins and some anthocyanins compounds. The fractionation of one of the active fractions by preparative reverse-phase HPLC yielded 11 subfractions ; all of these sub-fractions significantly increased the phosphorylation level of Akt and eNOS. The analysis of the phenolic compounds indicated that these sub-fractions contained mixtures of procyanidin dimers or conjugated anthocyanins. The red wine extract contains several types of phenolic compounds, which are able to enhance the activity of NO synthase in endothelial cells including procyanidins dimers and oligomers as well as several conjugated anthocyanins.

The ethanolic extract of a Malagasy species Euphorbia stenoclada (ES) (Euphorbiaceae), traditionally used as a herbal remedy against asthma and acute bronchitis, was tested to evaluate possible anti-proliferative activity on human airway smooth muscle cells (HASMC). The ES ethanolic extract totally abolished the interleukin-1beta (IL-1beta) induced proliferation of HASMC (IC(50)=0.73+/-0.08 microg/mL). No cytotoxic effect was observed up to 20 microg/mL. A bioassay-guided fractionation of the ethanolic extract was performed by reversed-phase (RP) flash chromatography, giving five fractions (FA to FE) where fraction FE was the only active one (IC(50)=0.38+/-0.02 microg/mL). The purification of this bioactive fraction FE was carried out by RP-HPLC affording six sub-fractions 1-6, and only sub-fraction 5 kept the anti-proliferative activity. Its major constituent was identified as quercetin (IC(50)=0.49+/-0.12 microg/mL) by means of HPLC/UV/MS and co-elution with the authentic standard. Quercitrin was also identified in the fraction FE but was inactive. A structure-activity relationship with flavonols determined that methylation reduced the anti-proliferative activity whereas glycosylation abolished it. The present study shows that the anti-proliferative properties of Euphorbia stenoclada are mediated through the presence of quercetin that may explain the traditional use of this plant as a remedy against asthma.

In the framework of our interest in antimalarial natural products from Clusiaceae family [1,2], the apolar extract of the stem bark of Vismia laurentii showed good antimalarial activity (IC50=4.6µg/ml). Thus, the isolation of its constituents led to the identification of a new tetracyclic triterpene, (20-ethylnortirucalla-7,24-dien-3-one) vismiaturucallone (1) (Fig.1) along with eight known compounds namely 3-geranyloxyemodin, vismiaquinone A (3), vismiaquinone B, bivismiaquinone, epifriedelinol, betulinic acid, tirucalla-7,24-dien-3-one, and stigmasta-7,22-dien-3-ol. Compounds (1) and (3) showed antiplasmodial activity against chloroquine-resistant W2 strain of Plasmodium falciparum with IC50 of 1.17µM and 1.42µM, respectively.

Fourteen extracts from seven Cameroon medicinal plants [1, 2], traditionally used to treat malaria and other parasitic diseases were screened for their antiprotozoal activities against Plasmodium falciparum K1 chloroquine resistant strain and Trypanosoma brucei rhodesiense, protozoa responsible for malaria and trypanosomiasis, respectively. The most active extract against P. falciparum was the methanolic extract of Albizia zygia stembark, with an IC50 value of 1.04µg/mL. Three of the tested extract showed IC50 below 7.15µg/mL against T.b. rhodesiense, with Albizia zygia methanolic extract showing again the best activity (IC50 =0.18µg/mL). These results contribute to the validation of the traditional antiprotozoal use of these medicinal species in Cameroon.

Salmonella enterica ssp. enterica is a leading cause of bacterial food-borne outbreaks in developed countries and is also a public-health concern in developing countries. Diarrhoea, a common symptom of human salmonellosis, kills 3-million children each year in developing countries [1]. The emergence of strains of S. enterica with multiple drug resistance is of great concern worldwide. Our preliminary work showed that the aqueous extract of Thonningia sanguinea (Balanophoraceae), an Ivorian plant used traditionally for the treatment of diarrhoea [2] demonstrate growth inhibitory effect in vitro against different strains of Salmonella such as S. Typhi (CMI=4.16mg/mL), S. Typhimurium (CMI=4,16mg/mL), S. Hadar (CMI=3.33mg/mL), S. Essen (CMI=4.16mg/mL).

In the frame work of our research on African species presenting antiparasitic activities, we reported previously the good antiprotozoal activity of Anogeissus leiocarpus (DC.) Guill. & Perr. (Combretaceae) [1]. In continuation of our work, we examined the constituents of the bark of this species.