Effects of compounds isolated from a Litsea japonica fruit extract on the TNF-α signaling pathway and cell viability

Tumor necrosis factor-alpha (TNF-alpha) plays an important role in inflammatory responses. Deregulated activation of TNF-alpha signaling is associated with various inflammatory diseases. In view of the finding that the seventy percent ethanol extract of Litsea japonica (LJE) interferes with TNF-alpha-induced NF-kappa B activation, activity -guided fractionation was performed to identify the active components of the extract. The EtOAc, CH2Cl2 and n-Hexane fractions of LJE induced suppression of inhibitor of kappa B (I kappa B) kinase (IKK), p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK), and significant reduction of TNF-alpha-induced NF-kappa B activation. From the CH2Cl2 fraction, hamabiwalactone A, hamabiwalactone B, litsenolide B2 and litsenolide C2 were identified to inhibit TNF-alpha-induced NF-kappa B activation. The cytotoxic activities of these lactone compounds were additionally evaluated.