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

Abstract

Aim of the study Uncaria tomentosa, commonly known as Cat's Claw or Uña 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-α while augmenting the production of IL-1β. Since TNF-α and IL-1β are usually regulated similarly and share a number of common promoter elements, including NF-κB 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-κB 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-κB and AP-1 components. In addition, treatment with Uncaria tomentosa enhanced cell death when NF-κB was inhibited. The ability of Uncaria tomentosa to inhibit TNF-α production was diminished when NF-κB activation was prevented by drugs that mask NF-κB subunit nuclear localization signals, while IL-1β expression was unchanged. Conclusions These results demonstrate that Uncaria tomentosa is able to elicit a response via an NF-κB-dependent mechanism. Further studies to characterize the mechanism by which Uncaria tomentosa can affect this pathway could provide a means to develop anti-TNF-α therapies.