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The use of plant extracts to alleviate in ammatory diseases is centuries old and continues to this day. This review assesses the current understanding of the use of such plants and natural products isolated from them in terms of their action against the ubiquitous transcription factor, nuclear factor kappa B (NF-j B). As an activator of many pro-in ammatory cytokines and in ammatory processes the modulation of the NF-j B transduction pathway is a principal target to alleviate the symptoms of such diseases as arthritis, in ammatory bowel disease and asthma.Two pathways of NF-j B activation will rst be summarised, leading to the IKK (Ij B kinase) complex, that subsequently initiates phosphorylation of the NF-j B inhibitory protein (Ij B).Natural products and some extracts are reviewed and assessed for their activity and potency as NF-j B inhibitors. A large number of compounds are currently known as NF-j B modulators and include the isoprenoids, most notably kaurene diterpenoids and members of the sesquiterpene lactones class, several phenolics including curcumin and avonoids such as silybin. Additional data on cellular toxicity are also highlighted as an exclusion principle for pursuing such compounds in clinical development. In addition, where enough data exists some conclusions on structure-activity relationship are provided.

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Crude extracts of Witheringia solanacea leaves showed inhibition of NF-kappaB activation at 100 microg/mL induced by phorbol 12-myristate-13-acetate (PMA) in HeLa cells stably transfected with a luciferase reporter gene controlled by the IL-6 promoter. Three physalins were isolated from an active fraction, namely, physalins B (1), F (2), and D (3). Of these compounds, 1 and 2 demonstrated inhibitory activities on PMA-induced NF-kappaB activation at 16 and 8 microM and induced apoptosis after 24 h in a cell-cycle analysis using a human T cell leukemia Jurkat cell line. Compound 2 also inhibited TNF-alpha-induced NF-kappaB activation at 5 microM through the canonical pathway, but was inactive in the Tet-On-Luc assay, indicating specificity of action, although it interfered with Tet-On-Luc at higher concentrations. It is suggested that the presence of a double bond and an epoxy ring between carbons 5 and 6 in compounds 1 and 2, respectively (which are not present in compound 3), are related to their anti-inflammatory activity.