Title:

Signature Genes of Human Macrophage for Herbal Extracts

Inventor(s): Chin-Fu Chen
Abstract:

The present disclosure is directed to methods of determination of cellular targets of herbal extracts. While much of this discussion is directed to feverfew, the methods and process are applicable to other extracts as well, and in one particular embodiment, to other herbal extracts.

The herb feverfew is a folk remedy for various symptoms including inflammation. Inflammation has recently been implicated in the genesis of many diseases including cancers, atherosclerosis, and rheumatoid arthritis. The mechanisms of action of feverfew in the human body are largely unknown. To determine the cellular targets of feverfew extracts, oligo microarrays have been utilized to study the gene expression profiles elicited by feverfew extracts in human monocytic THP-1 cells. 400 genese have been identified that are consistently regulated by feverfew extracts. Most of the genes are involved in cellular metabolism. However, the genes undergoing the highest degree of change by feverfew treatments are involved in other pathways including cheokine function, water homeostasis, and heme-mediated signaling. Our results also suggest that feverfew extracts suppress LPS-mediated TNF-a and CCL@ (MCP-1) releases by THP-1 cells. It is hypothesized that feverfew extracts components inhibit inflammatory cytokine functions in human monocytes/macrophages.

Three feverfew extracts (SFE, SRE, and DeWE) have been prepared using different extraction methods to test the hypothesis that certain extraction methods can produce more active ingredients with anti-migraine activity than others. Utilizing microarray to profile the gene expression in human THP-1 monocytes, our results suggests that SFE and SRE affect many more genes than DeWE does. We have identified 198 genes in human macrophages that are responding to SRE and SFE but not to DeWE (presumptive inactive) and 10 selected genes were confirmed by RT-PCR. We hypothesize that AQP-1, CCL2, and HMOX-1 may represent major targets of feverfew functions. To address the functional roles of feverfew extracts in the inflammatory pathways, we assayed the effects of feverfew extracts on LPS-mediated cytokine releases of human THP-1 monocytes. Our results suggest that feverfew extracts strongly suppressed LPS-mediated productions of both TNF-alpha and CCL2 (MCP-1). We utilized network analysis and identified new candidate pathways as functional targets of feverfew extracts in human monocytes.

Patent Status: Patent application has been filed. Detailed information must be provided under a confidential disclosure agreement. Please download the confidential disclosure form and mail the completed form to:

Vincie Albritton, Associate Director
Clemson Research Park
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