Inhibition of interleukin-8 release in human neutrophils by Melodorum fruticosum

The treatment of inflammatory disorders in Western medicine relies heavily on the use of non-steroidal anti-inflammatory drugs (NSAIDs) and corticosteroids [1]. However, currently available treatment options are often unsatisfactory. In the course of this project we investigated plants used in Vietnamese traditional medicine for the treatment of inflammatory disorders. Dried plant material from Aleurites moluccana (folium and caulis), Alstonia scholaris (folium and caulis), Clinacanthus nutans (folium), Ficus benghalensis (folium), and Melodorum fruticosum (folium) was successively extracted with dichloromethane (DCM) followed by methanol. Extracts were tested for their inhibitory activity on lipopolysaccharide (LPS)-triggered interleukin-8 (IL-8) expression in human neutrophils. At a concentration of 10 µg/mL, the Melodorum fruticosum DCM extract showed highly potent activity with 88% inhibition of IL-8 release. Standard flow cytometric probe using propidium iodide staining [2] revealed that the active Melodorum fruticosum DCM extract also induced apoptosis. Bioactivity guided fractionation of the DCM extract monitored by the IL-8 assay led to the isolation of melodamide A [3], which significantly inhibited the expression/production of IL-8 by stimulated neutrophils at a concentration range of 2.5 – 25µM without showing cytotoxic effects on the tested cells. Further phytochemical analysis resulted in the isolation and identification of several additional compounds including N-trans-cinnamoyltyramine, alpinetin, tsugafolin, 5,7-dimethoxy-4'-hydroxyflavanone, 2',4'-dihydroxy-4,6'-dimethoxydihydrochalcone, 2′,4′-dihydroxy-4,6′-dimethoxychalcone, and 2′,6′-dihydroxy-4′-methoxychalcone from the DCM extract, and 5-methoxy-naringenin, catechin, kaempferol-3-O-α-L-rhamnoside, and quercetin-3-O-α-L-rhamnoside from the ethanol extract. The pharmacological activity of melodamide A may justify the traditional use of Melodorum fruticosum to treat inflammatory disorders.

Keywords: Vietnamese traditional medicine, inflammation, neutrophils, Melodorum fruticosum, melodamide A.

References:

[1] Wang Q, Kuang H, Su Y, Sun Y, Feng J, Guo R, Chan K. Naturally derived anti-inflammatory compounds from Chinese medicinal plants. J Ethnopharmacol 2013; 146: 9 – 39

[2] Schinella G, Aquila S, Dade M, Giner R, Recio MdC, Spegazzini E, de Buschiazzo P, Tournier H, Rios JL. Anti-inflammatory and apoptotic activities of pomolic acid isolated from Cecropia pachystachya. Planta Med 2008; 74: 215 – 220

[3] Chan H-H, Hwang T-L, Thang TD, Leu Y-L, Kuo P-C, Nguyet BTM, Dai DN, Wu T-S. Isolation and synthesis of melodamide A, a new anti-inflammatory phenolic amide from the leaves of Melodorum fruticosum. Planta Med 2013; 79: 288 – 294