Abstract 659 Gastroenterology and Nutrition Platform, Monday, 5/3

INTRODUCTION: Cat's claw is a traditional medicine of indigenous cultures of the Amazon River basin. Cat's claw is commonly used in South America and more recently in Western nations, as an anti-inflammatory agent in treating arthritis and gastrointestinal inflammation. Cat's claw is the bark of a vine, Uncaria tomentosa, that is prepared as a tea or taken in capsule form. Despite its widespread use there is little evidence supporting efficacy or detailing mechanisms of action for Cat's claw. The present study was designed to address the potential of Cat's claw as an antioxidant and an anti-inflammatory agents. METHODS: Antioxidant properties of Cat's claw were assessed by its ability to prevent apoptotic cell death in macrophages and colonic epithelial cells in response to peroxynitrite, a mediator of inflammation. Direct interactions between Cat's claw and nitric oxide were assessed electrochemically. Cultured macrophages and epithelial cells treated with bacterial endotoxin, LPS, were assessed for nitrite release, iNOS gene expression and cell death in the presence and absence of Cat's claw. Nuclear translocation of the transcription factor, NF-κB was determined by EMSA. In vivo inflammation was induced by indomethacin, in two protocols (a) acute gastropathy with Cat's claw administered simultaneously with indomethacin or prophylactically (b) repeated indomethacin administration-induced enteropathy, with rats sacrificed at day 7. In these in vivo models damage was assessed by morphological criteria, myeloperoxidase activity and hepatic metallothionein expression. RESULTS: Cat's claw prevented peroxynitrite-induced apoptosis but did not affect NO levels. LPS-induced mediator release, iNOS expression and cell death were all markedly attenuated by Cat's claw. Inhibition of gene expression was accompanied by a suppression of NF-κB activation. Cat's claw resulted in a full restoration of intestinal morphology in indomethacin enteropathy, suppression of inflammatory indices and hepatic metallothionen expression. In the acute gastropathy model, Cat's claw was only effective when administered prophylactically, consistent with its effects on gene expression. CONCLUSION: Cat's claw is an effective anti-inflammatory agent in vivo and in vitro. While it is an antioxidant it does not modify NO levels. Its primary mechanism of action involves suppression of the transcription factor NF-κB, and subsequent inhibition of inflammatory gene expression. In this regard it is unique. The marked effects on NSAID-induced gastropathy and enteropathy suggests that Cat's claw should be considered as an adjunct therapy in the treatment of arthritis and gut inflammation.