Pierre Cabalion

Traditional Aqueous Kava Extracts Inhibit Cytochrome P450 1A2 in Humans: Protective Effect Against Environmental Carcinogens?

o the Editor: A recent review in the Journal has drawn attention to the otential risk of herb-drug interactions. Because studies have hown that psychoactive kavalactones have an inhibitory efect on cytochrome P450 (CYP) enzymes in vitro, we were nterested in determining whether clinically relevant interacions were to be expected from the consumption of the aqueus extract of kava root (Piper methysticum Forst f), which is ommon in the South Pacific. We studied 6 healthy subjects from New Caledonia (age, 9-55 years; 1 woman; 3 cigarette smokers). All had been egular consumers of the traditional aqueous kava extract for ore than 6 years and drank an estimated 7 to 27 g of avalactones per week up to the beginning of the study, which ad been approved by the institutional ethics committee. The articipants gave informed consent to stop kava consumption or 30 days without any other change in their lifestyle includng diet, smoking, and medication and to undergo 2 sessions f CYP phenotyping by use of model compounds. Metabolic atios for 5 different probe drugs (Table I) reflecting the ctivities of different CYP isozymes were determined before nd after a 30-day complete abstinence from kava. The caffeine metabolic ratio increased 2-fold, from 0.3 ith the consumption of kava to 0.6 at 30 days after cessation f kava (Fig 1); the latter value corresponds to published etabolic ratios in healthy control subjects. No significant hanges were observed for the other probe drugs (Table I).

Antiplasmodial activity of New Caledonia and Vanuatu traditional medicines

Context: With the emergence of strains multiresistant to antimalarial drugs, the search for new active molecules remains a priority. Ethnopharmacology appears to be a good method of selection in such investigations. Objective: The aim of this research work is to select plants used in Melanesian traditional medicine, in New Caledonia and Vanuatu, which should be a promising source for the isolation of new antimalarial drugs. Materials and methods: Forty-seven plant extracts belonging to 12 families, traditionally used by the Melanesian people or belonging to an antimalarial known genus, were screened in vitro for antimalarial activity on Plasmodium falciparum chloroquine (CQ)-resistant (FcB1) and CQ-sensitive (HB3) strains. They were also tested for their inhibitory effects on a protein kinase (Pfnek) and their cytotoxicity on human breast adenocarcinoma (MCF7) cells. Results: Among all extracts, four displayed strong in vitro activities against P. falciparum: Gardenia urvillei Montrouzier, Scleria polycarpa Boeckeler, Terminalia catappa L. and Acronychia laevis J.R. & J.G. Forster, the latter being also toxic on MCF7 cells. Except for the extracts of S. polycarpa, all others that were active on P. falciparum, also possess an inhibitory effect on Pfnek. Discussion and conclusion: These results confirm that ethnopharmacology is an excellent approach for such investigations. The two countries considered clearly present advantages in the field. Indeed, local populations keep their traditional knowledge alive, and their flora is exceptionally rich. In New Caledonia, the high endemicity rate (74%) ranks the island as one of the world’s biodiversity hotspots. As a consequence, chances to discover new active natural compounds are also high.

Screening of Fifty Cunoniaceae Species from New Caledonia for Inhibitors of Xanthine Oxidase and Scavengers of Superoxide Anions

Two-hundred-and-four extracts (101 ethyl acetate extracts and 103 methanol extracts) from 50 species of Cunoniaceae from New Caledonia were screened for antioxidant properties due to free radical scavenging and/or xanthine oxidase (XOD) inhibitory activity. Of the crude extracts, 95.1% were active at a concentration of 50µg/ml. Fifteen (27.8%) extracts showed more than 50% activity at 10µg/ml and were studied for XOD inhibition. All were active against XOD at 50µg/ml but only 6 (40%) showed up to 60% inhibition. Ethyl acetate extracts from the bark of Weinmannia dichotoma Brongniart & Gris, Weinmannia monticola Däniker and Cunonia linearisepala (Guillaumin) Bernardi and from the roots of Codia incrassata Pampanini, as well as methanol extract from the bark of Pancheria brunhesii Pampanini, exhibited the highest activities (between 70% and 86% XOD inhibition at 50µg/ml). In view of these preliminary results, New Caledonian Cunoniaceae species appears to be promising material for the isolation of bioactive compounds.