Hyperforin, the Active Component of St. John?s Wort, Induces IL-8 Expression in Human Intestinal Epithelial Cells Via a MAPK-Dependent, NF-?B-Independent Pathway

Abstract

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.

Hyperforin prevents β-amyloid neurotoxicity and spatial memory impairments by disaggregation of Alzheimer's amyloid-β-deposits

“…We first analyzed its effect over the inflammatory process, since one of the faculty described for St John's wort is its antiinflammatory properties. 33 The reactive microglia is associated with the brains of AD patients and is particularly concentrated in the areas of senile plaque formation. 34 We performed immunohistochemical procedures using the antibody OX-42 as a microglial reaction marker in the injection site.…”

Hyperforin, a new lead compound against the progression of cancer and leukemia?

“…38 On the other hand, HF induces interleukin-8 (IL-8) expression in human intestinal epithelial cells and hepatocytes. 39 This induction is time-and dose-dependent and requires the stimulation of extracellular signal-regulated kinase 1 and 2, leading to the activation of the transcription factor AP-1. HF also induces intercellular adhesion molecule-1 (ICAM-1) mRNA.…”

“…HF also induces intercellular adhesion molecule-1 (ICAM-1) mRNA. 39 Both IL-8 and ICAM-1 are proinflammatory mediators, notably IL-8 that stimulates acute-phase protein production in the liver and contributes to intestinal inflammation. HF and HF-containing SJW extracts therefore display both anti-and proinflammatory activities, depending on their concentration and cell type.…”

The influence of extraction methods on composition and antioxidant properties of rice bran oil

“…The outer layer of BlR is enriched with phytochemicals and these bioactive were broadly divided into polar (phenolic acids, flavonoids, anthocyanins) and non-polar components (tocopherols, tocotrienols, γ-oryzanol, and sterols) (Patel & Naik. 2004;Zhou et al, 2004;Holtekjølen, et al, 2006). Studies have proven that the active components of RB improve the human health because of the high content of antioxidants (Laokuldilok et al, 2011).…”