|1: J Clin Immunol. 2004 Nov;24(6):623-36.
Hyperforin, the active component of St. John's wort, induces
IL-8 expression in human intestinal epithelial cells via a
MAPK-dependent, NF-kappaB-independent pathway. Results
suggest a previously unsuspected effect of St. John's wort
in modulating the immune and inflammatory responses.
Zhou C, Tabb MM, Sadatrafiei A, Grun F, Sun A, Blumberg
Department of Developmental and Cell Biology, University of California, Irvine,
California 92697-2300, USA.
St. John's wort is widely used as an herbal antidepressant and is among the
top-selling botanical products in the United States. Although St. John's
wort has been reported to have minimal side effects compared with other antidepressants,
here we show that hyperforin, the active component of St. John's wort, can
stimulate interleukin-8 (IL-8) expression in human intestinal epithelia cells
(IEC) and primary hepatocytes. Hyperforin is also able to induce expression
of mRNA, encoding another major inflammatory mediator--intercellular adhesion
molecule-1 (ICAM-1). IEC participate in the intestinal inflammatory process
and serve as a first line of defense through bidirectional communication
between host and infectious pathogens. Although hyperforin is a potent ligand
for the steroid and xenobiotic receptor (SXR), we found that hyperforin induced
IL-8 mRNA through an SXR-independent transcriptional activation pathway.
IL-8 induction by hyperforin required the activation of AP-1 but not the
NF-kappaB transcription factor, thereby distinguishing it from the NF-kappaB-dependent
IL-8 induction mediated by tumor necrosis factor alpha (TNFalpha). Further
study revealed that extracellular signal-regulated kinase 1 and 2 (ERK1/2)
were required for the hyperforin-induced expression of IL-8. Our
results suggest a previously unsuspected effect of St. John's wort in modulating
the immune and inflammatory responses.
PMID: 15622447 [PubMed - in process]