Ethnopharmacological and Phytochemical Investigation of Melicope Species from Réunion

Henrik Toft Simonsen

Three endemic Melicope species from Réunion Island, M. borbonica used in traditional medicine and the related species M. coodeana and M. obscura have been investigated for antimicrobial and anti-inflammatorial active constituents as well as for constituents of chemotaxonomical importance.

Through the pharmacological approach nine chemically different constituents have been isolated, four acetophenones (e.g. xanthoxylin), three coumarins (e.g. scoparone), an epidioxy-sesquiterpene, and a flavonoid (isorhamnetin). The flavonol isorhamnetin has shown antiinflammatory properties in a NF-kB inhibition assay. The remaining eight constituents showed antifungal and antibacterial properties.

The main interest of the chemotaxonomical approach has been flavonoids and particularly methylendioxyflavonols, but also acetophenones have been of interest. From a taxonomic perspective the isolation of methylendioxyflavonols and methoxyflavonols support the recent reassignment of the investigated species from the genus Euodia to the genus Melicope. Flavonols along with acetophenones are also important on the generic level in the separation between the genera Tetradium and Melicope.

Five new natural products, 3,8-dimethoxy-5,7-dihydroxy-3',4'-methylenedioxyflavone, 3,6,8-trimethoxy-5,7-dihydroxy-3',4'-methylenedioxy-flavone, 3,6,8,3',4'-pentamethoxy-5,7-dihydroxyflavone, 2-(2-hydroxy-1-oxoethyl)-3-hydroxy-5-prenoyl-6-prenyl-6-(8-oxogeranyl)-2,4-cyclohexadienone, and 2-(2-hydroxy-1-oxoethyl)-3-hydroxy-5-prenoyl-6,6-diprenyl-2,4-cyclohexadienone were isolated from the leaves of M. coodeana along with the known flavonols 3,6,3'-trimethoxy-5,7,4'-trihydroxyflavone and 3,3'-dimethoxy-5,7,4'-trihydroxyflavone, which were isolated from this species for the first time. The structural assignment was based on NMR data.

From the leaves of M. borbonica 17 compounds were isolated. Xanthoxylin, scoparone, and limittin are the major constituents in the leaves and they are all active against the fungi Candida albicans with MIA values of 25 µg, 40 µg, and 30 µg, respectively. a-Curcumene, 2,4,6-trimethoxyacetophenone, 1,4-epidioxy-bisabola-2,12-diene, cedrelopsin, (+)-sesamin, 6-methoxy-7-prenoylcoumarin, eugenol, methyleugenol, isorhamnetin, dillenetin, 5,7,4'-trihydroxy-3,3'-dimethoxyflavone and 5,7-dihydroxy-3,3',4'-trimethoxyflavone were isolated from this species for the first time.

Five compounds, (+)-eudesmin, (+)-kobusin, 2,6-dihydroxy-4-O-geranyl-acetophenone, 4-O-geranyl-3-prenyl-2,6,b-trihydroxyacetophenone, 5-hydroxy-3,6,7,8,3',4'-hexamethoxyflavone were isolated from the leaves of Melicope obscura for the first time. Antimicrobial activity was seen for 4-O-geranyl-2,6,b-trihydroxy-3-prenylacetophenone against Candida albicans (MIA = 40 µg), and Penicillium expansum (MIA = 30 µg) and for 2,6-dihydroxy-4-O-geranyl-acetophenone against Staphylococcus aureus (MIA = 5.0 µg).