Eupatorium perfoliatum L.: Antiinflammatory and antiplasmodial activity of the dichloromethane extract and novel sesquiterpene lactones

Eupatorium perfoliatum L., Asteraceae, is a medicinal herb from North America with a well documented use for the treatment of fever, flu, and malaria. At present, it is widely used as homeopathic remedy with immunomodulatory activity (e.g. in Contramutan®). In order to elucidate the active compounds and the mechanisms of action, the aerial parts of the plant were extensively studied. From the methanolic-aqueous (7/3 V/V) extract three uncommon glucaric acid derivatives have been isolated [1]. Soxhlet extraction with dichloromethane followed by column chromatography yielded eight sesquiterpene lactones, two germacranolides (euperfolitin [2] and a new heliangolide) and six new guaianolides. Five guaianolides are members of a homologous group with 8-O-tiglic acid, 11-methyl, and 2-oxo-3,4-en functionality. They mainly differ in the degree of oxidation of C-14, ranging from a methyl group up to a free carboxylic acid function. Furthermore, an unusual dimeric guaianolide with a novel mode of linkage between C-14 and C-4 was identified. In vitro tests with the macrophage cell line RAW 264.7 indicated that potential immunomodulatory effects of the dichloromethane extract are not due to enhanced phagocytosis but are rather mediated by antiinflammatory activity. This was shown by concentration dependent (1µg/mL up to 100µg/mL) inhibition of NO-production from LPS-stimulated macrophages. This effect correlated with a significantly reduced activation of iNOS (Western Blot). Microarray investigation revealed new insights into potential modes of actions. Fractions of the dichloromethane extract also exhibited a moderate inhibitory activity against Plasmodium falciparum, which is in accordance with the reported traditional antimalarial use.

References: 1. Maas, M. et al. (2009) Molecules 14:36–45.

2. Herz, W. et al. (1977)J. Org. Chem. 42:2264–2271.