Cafestol-Type Diterpenoids from the Twigs of Tricalysia fruticosa with Potential Anti-inflammatory Activity

Eight new cafestol-type diterpenoids, tricalysins A-H (1-8), along with five known analogues (9-13), were isolated from the twigs of Tricalysia fruticosa. The structures of 1-8 were elucidated by the application of spectroscopic methods. Inhibitory effects of the isolates on nitric oxide (NO) production in lipopolysaccaride-activated RAW 264.7 macrophages were evaluated, and compound 8 exhibited the most potent bioactivity, with an IC50 value of 6.6 +/- 0.4 mu M. It was shown further that compound 8 inhibits inflammatory responses via suppression of the expression of iNOS and reduction of the production of the pro-inflammatory cytokines IL-6 and TNF-alpha, resulting from activation of nuclear factor-kappaB (NF-kappa B) and phosphorylation of MAPKs (ERK, JNK, and p38).