Novel and known constituents from Buddleja species and their activity against leukocyte eicosanoid generation.

We have undertaken a systematic survey of the genus Buddleja used in traditional Chinese medicine for antiinflammatory and other indications by testing extracts and isolated natural products for their activity against the enzymes of the arachidonate cascade. This was done by using elicited rat peritoneal leukocytes, a physiologically relevant established whole cell system that expresses both cyclo-oxygenase (COX) and 5-lipoxygenase (5-LOX) activity. Lipophilic extracts of B. globosa roots and B. myriantha stem exhibited inhibitory activities in the 5-LOX and COX enzyme assays, whereas those of B. officinalis flowers, B. yunanesis stems, and B. asiatica stems showed inhibitory activities only against COX. The phytochemical investigation of these extracts, and consequent structure elucidation of isolated compounds using spectroscopic data, led to the isolation from B. globosa of three new terpenoid compounds named dihydrobuddledin A, buddledone A, and buddledone B and four known compounds-buddledins A, B, and C and zerumbone; 12 known compounds from B. officinalis-calceolarioside, campneoside, verbascoside, echinacoside, forsythoside B, angoroside A, crocetin monogentibiosyl ester, acacetin, acacetin-7-O-alpha-L-rhamnopyranosyl (1-6)-beta-D-glucopyranoside, acacetin-7-O-alpha-L-rhamnopyranosyl (1-6)[alpha-L-rhamnopyranosyl (1-2)]-beta-D-glucopyranoside, songarosaponin A, delta-amyrone; and eight known compounds fromB. yunanesis-11,14-dihydroxy-8,11, 13-abietatrien-7-one, beta-sitosterol, verbascoside, echinacoside, forsythoside B, angoroside A, methylcatapol, and sucrose. Tests on the isolated compounds for inhibition of eicosanoid synthesis showed that buddledin A, crocetin monogentibiosyl ester, and acacetin exhibited an inhibitory effect on COX with IC(50) values of 13.7 microM, 28.2 microM, and 77.5 microM, respectively, whereas buddledin A exhibited inhibitory effect on 5-LOX with an IC(50) value of 50.4 microM.