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 tradit ional Chinese medicine for antiinflammatory and other indications by testin g extracts and isolated natural products for their activity against the enz ymes of the arachidonate cascade. This was done by using elicited rat perit oneal leukocytes, a physiologically relevant established whole cell system that expresses both cyclo-oxygenase (COX) and 5-lipoxygenase (5-LOX) activi ty. 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 i nhibitory activities only against COX. The phytochemical investigation of t hese extracts, and consequent structure elucidation of isolated compounds u sing 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 c ompounds from B. officinalis-calceolarioside, campneoside, verbascoside, ec hinacoside, forsythoside B, angoroside A, crocetin monogentibiosyl eater, a cacetin, acacetin-7-O-alpha-L-rhamnopyranosyl (1-6)-beta-D-glucopyranoside, acacetin-7-O-alpha-L-rhamnopyranosyl (1-6)[alpha-L-rhamnopyranosyl(1-2)]-b eta-D-glucopyranoside, songarosaponin A, delta-amyrone; and eight known com pounds from B. yunanesis-11,14-dihydroxy-8,11,13-abietatrien-7-one, beta-si tosterol, verbascoside, echinacoside, forsythoside B, angoroside A, methylc atapol, and sucrose. Tests on the isolated compounds for inhibition of eico sanoid synthesis showed that buddledin A, crocetin monogentibiosyl ester, a nd acacetin exhibited an inhibitory effect on COX with IC50 values of 13.7 mu M, 28.2 mu M, and 77.5 mu M, respectively, whereas buddledin A exhibited inhibitory effect on 5-LOX with an IC50 value of 50.4 mu M.