Uncaria tomentosa acts as a potent TNF-alpha inhibitor through NF-kappaB.
OBJECTIVE
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-alpha while augmenting the production of IL-1beta. Since TNF-alpha and IL-1beta are usually regulated similarly and share a number of common promoter elements, including NF-kappaB and AP-1, the ability of Uncaria tomentosa to differentially regulate these inflammatory cytokines is of particular interest.


METHODS
To determine the mechanism of action of Uncaria tomentosa, we investigated the effects of specific inhibitors of NF-kappaB 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-kappaB and AP-1 components. In addition, treatment with Uncaria tomentosa enhanced cell death when NF-kappaB was inhibited. The ability of Uncaria tomentosa to inhibit TNF-alpha production was diminished when NF-kappaB activation was prevented by drugs that mask NF-kappaB subunit nuclear localization signals, while IL-1beta expression was unchanged.


CONCLUSIONS
These results demonstrate that Uncaria tomentosa is able to elicit a response via an NF-kappaB-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.
Allen-Hall
Lisa
L
Laurentian University, Biomolecular Science, Sudbury Regional Hospital, Sudbury, Ontario, Canada.
Arnason
John T
JT
Cano
Pablo
P
Lafrenie
Robert M
RM
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D020948:Cat's Claw; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D008070:Lipopolysaccharides; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics; D052002:NF-kappa B p50 Subunit; D008517:Phytotherapy; D024301:Plant Bark; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D010936:Plant Extracts; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha