Thymol, benzofuranoid, and phenylpropanoid derivatives: anti-inflammatory constituents from Eupatorium cannabinum subsp. asiaticum

Abstract

Eupatorium cannabinum L. subsp. asiaticum Kitam. (Compositae) [1] is a perennial herb distributed in Himalaya mountain range, China, and Taiwan. E. cannabinum, locally called 'Taiwan ze-lan' or 'liu-yue-xue', has been used as a folk medicine to treat hepatitis, headache, diarrhea, hypertension, and Diabetes mellitus in Taiwan. Sesquiterpene lactones, diterpenoids, flavonoids, pyrrolizidine alkaloids, thymols, benzofurans, and their derivatives are widely distributed in plants of the genus Eupatorium. Many of these compounds were found to exhibit cytotoxic, antimicrobial, and anti-inflammatory activities. In our studies on the anti-inflammatory constituents of Formosan plants, many species have been screened for in vitro inhibitory activity on neutrophil pro-inflammatory responses, and E. cannabinum has been found to be an active species. Five new compounds, 9-O-angeloyl-8,10-dehydrothymol (1), 9-(3-methylbutanoyl)-8,10-dehydrothymol (2), eupatobenzofuran (3), 2-hydroxy-2,6-dimethylbenzofuran-3(2H)-one (4), and 1-(2-hydroxy-4-methylphenyl)propan-1,2-dione (5) and 16 known compounds have been isolated and identified from the aerial part of E. cannabinum subsp. asiaticum. Compounds 6–8, 11, 13, and 15 exhibited inhibition (IC50 values <18.4µM) of superoxide anion generation by human neutrophils in response to formyl-L-methionyl-L-leucyl-L-phenylalanine/cytochalasin B (fMLP/CB). Compounds 2, 3, 10, 13, and 15 inhibited fMLP/CB-induced elastase release with IC50 values <18.3µM.