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The inducible transcription factor nuclear factor κB (NF-κB) plays a central role in the regulation of immune, inflammatory and carcinogenic responses. While normal activation of NF-κB is required for cell survival and immunity, its deregulated expression is a characteristic of inflammatory and infectious diseases. In this study, we investigated the molecular mechanisms induced by lactones and chalcones isolated from Fijian kava (Piper methysticum) used in traditional medicine against urinary tract infections and asthma. In order to understand underlying regulatory mechanisms, inhibition of both NF-κB-driven reporter gene expression and TNFα-induced binding of NF-κB to a consensus response element was achieved at concentrations of 320μM (flavokavain A), 175μM (flavokavain B) and 870μM (kavain and dihydrokavain). Moreover, kavain and flavokavains A and B treatment led to inhibition of both inhibitor of κB …