NF-B has been identified as a major regulator of inflammation. Constitutive activation of NF-B leads to a morbid production of inflammatory mediators such as COX-2, IL-8, and TNF- and contributes to the development of a variety of chronic diseases (e.g. atherosclerosis, asthma, diabetes, cancer). Therefore, the NF-B pathway has become an attractive target in the search for novel therapeutics in the treatment of inflammatory diseases. Using an in vitro COX-2 gene expression assay in THP-1 macrophages, 22 plants from traditional Chinese medicine were selected for screening based on their traditional use against inflammatory diseases. In case of an active extract, the plant with the least published information was selected for further bioassay-guided fractionation in order to find promising COX-2 gene expression inhibitors. Identified compounds were further tested in HUVECs for possible IL-8 production inhibition and in a NF-B reporter assay to confirm the inhibition via NF-B pathway. Extracts from Momordica charantia, Pinellia ternata, Lobelia chinensis and Epipremnum pinnatum displayed promising COX-2 mRNA inhibition at 20 g/ml. Epipremnum pinnatum was investigated. Citroside A, gusanlungionoside C, and phenylmethyl-2-O-(6-O-rhamnosyl)-ß-D-galactopyranoside could be isolated from Epipremnum pinnatum. One of their aglycons, -damascenone, showed promising COX-2 mRNA inhibition (IC50 = 25.8 M). IL-8 synthesis in HUVECs was inhibited with an IC50 value of 11.2 M. Furthermore, using the luciferase gene reporter assay, we could demonstrate that these effects were due to the inhibition of the NF-B pathway. -Damascenone was not cytotoxic up to 50 M. -Damascenone is a potent Michael acceptor and might interact with cysteine residues of the NF-B subunit p65 and/or inhibit the TLR4 receptor. We could show for the first time that -damascenone is one of the active principles of Epipremnum pinnatum, which expresses its anti-inflammatory effect by targeting NF-B.