Uncaria tomentosa acts as a potent TNF-α inhibitor through NF-κB

Aim of the study: Uncaria tomentosa, commonly known as Cat's Claw or Una de gato, is a medicinal plant that has been shown to have effective anti-inflammatory activities. We have previously shown that treatment of monocyte-like THP-1 cells with Uncaria tomentosa inhibits the production of the pro-inflammatory cytokine TNF-alpha while augmenting the production of IL-1 beta. Since TNF-alpha and IL-1 beta are usually regulated similarly and share a number of common promoter elements, including NF-kappa B and AP-1, the ability of Uncaria tomentosa to differentially regulate these inflammatory cytokines is of particular interest. Materials and methods: To determine the mechanism of action of Uncaria tomentosa, we investigated the effects of specific inhibitors of NF-kappa B on cellular responses including transcription factor activation using TransAM assays, the expression of cytokines as measured by ELISA, and cell survival as measured by changes in cell number following treatment. Results: Treatment with Uncaria tomentosa inhibited the LPS-dependent activation of specific NF-kappa B and AP-1 components. in addition, treatment with Uncaria tomentosa enhanced cell death when NF-kappa B was inhibited. The ability of Uncaria tomentosa to inhibit TNF-alpha production was diminished when NF-kappa B activation was prevented by drugs that mask NF-kappa B subunit nuclear localization signals, while IL-1 beta expression was unchanged. Conclusions: These results demonstrate that Uncaria tomentosa is able to elicit a response via an NF-kappa B-dependent mechanism. Further studies to characterize the mechanism by which Uncaria tomentosa can affect this pathway could provide a means to develop anti-TNF-alpha therapies. (C) 2009 Elsevier Ireland Ltd. All rights reserved.