Mechanisms of Action

COLD-FX^® is an innate immune modulator. Working through Toll-like receptors (TLRs), COLD-FX increases the number and enhances the function of immune cells within both the innate and adaptive immune systems. This inhibits viral reproduction and/or leads to destruction of viruses leading to the prevention or faster resolution of cold and flu symptoms.

Mechanism of Action – Glossary of Terms

Adaptive immune system	part of the immune system that recognizes and remembers speciﬁc pathogens and mounts stronger attacks each time the pathogen is encountered. It involves both B cells and T cells and is activated by the innate immune system.
Antibodies	proteins produced by B cells that identify and specifically bind to pathogens such as viruses.
B cells	a type of lymphocyte (white blood cell) that is part of the adaptive immune system. B cells are part of the humoral immune response and produce antibodies.
Cytokines	small proteins that are secreted by cells of the immune system. Cytokines activate cells or moderate their function by binding to receptors on the cell surface.
Dendritic cells	cells of the innate immune system. Their main function is to process antigen material and present it to T cells, thus functioning as antigen-presenting cells.
Helper T cells	lymphocytes (white blood cells) that activate and direct other immune cells, including B cells, killer T cells, and macrophages. Helper T cells are part of the adaptive immune system.
Innate immune system	part of the immune system that defends against infection in a non-speciﬁc manner. Cells of the innate system recognize and respond to pathogens in a generic way, but unlike the adaptive immune system, it does not confer long-lasting immunity. Innate immune systems provide immediate defence against infection.
Killer T cells	lymphocytes (white blood cells) that kill cells that are infected with viruses (or other pathogens), or are otherwise damaged or dysfunctional, like tumour cells. Killer T cells are part of the adaptive immune system.
Macrophages	cells of the innate immune system. They phagocytose (engulf and then digest) cellular debris and pathogens and stimulate lymphocytes and other immune cells to respond to the pathogen.
Natural killer (NK) cells	a type of lymphocyte that is a major component of the innate immune system. NK cells kill tumour cells and cells infected by viruses.
Toll-like receptors	receptors that are present on cells of the innate immune system (macrophages, NK cells, dendritic cells). They recognize molecules associated with pathogens (such as molecules in the cell membrane of bacteria) and act as key components of the immune early detection system.

Deng, Y. 2001. CVT-E002™ stimulates macrophages and activates natural killer cells to secrete interferon-gamma in response to influenza virus. Internal report.
Adamko, D.J., Davoine, F., Ilarraza, R., and Wu, Y. 2007. Human dendritic cells generate an enhanced antiviral immune response when stimulated by CVT-E002. Internal report.
Newton, J., Patrick, A., and Rosenthal, K.L. 2008. CVT-E002, a proprietary extract of North American ginseng, activates the vertebrate innate immune system to produce proinflammatory and anti-viral factors via MyD88 signaling. Presented at the American Association of Immunologists annual meeting in April 2008, San Diego.
Chen, N., Deng, Y., Gravenstein, S., and Jing, Y. 2005. A proprietary extract of Panax quinquefolius (CVT-E002) stimulates inflammatory cytokine secretion from monocytes and augments IFN-g secretion from NK cells in response to influenza virus stimulation. Internal report.
Adamko, D., Wu, Y., Ilarraza, R., and Davoine, F. 2008. CVT-E002, a proprietary North American Ginseng extract, increases anti-viral immune responses in an in vitro model of virus-induced asthma exacerbation. Presented at the annual Natural Health Products Research Conference in March 2008, Toronto.

CVT-E002 the active ingredient of COLD-FX^® has been shown to significantly enhance the innate and acquired immune responses.

CVT-E002 enhances innate immune responses by:

Activation of Macrophages to release TNF-alpha and Nitric Oxide (NO).
Macrophages are able to kill intracellular pathogens or release cytokines which are intracellular mediators, such as TNF-alpha and NO, that stimulate neighboring cells to kill intracellular infections.
Increasing the number of Natural Killer (NK) cells.
NK cells are important in natural resistance. They can directly kill a wide variety of infected or oncologically transformed cells. Macrophages and NK cells cross communicate with each other by amplifying each other’s killing capacity while activating the acquired immune responses.

CVT-E002 enhances acquired immune responses (humoral and cell-mediated) as demonstrated by an:

Increase in interleukin-1 (IL-1) and interleukin-6 (IL-6) by stimulation of Macrophages.
Both IL-1 and IL-6 are involved in maintaining the inflammatory process which is a major defensive reaction initiated by infection. IL-1 stimulates proliferation of B- and T- cells. IL-6 stimulates the growth and differentiation of B-cells and subsequent increase of antibody production.
Increase in B cell proliferation in the spleen.
B cells are transformed into plasma cells which produce large amounts of antibodies against pathogens.
Increase in circulating IgG.
Immunoglobulin G (IgG) is the main antibody response against bacteria and viruses. IgG acts on pathogens through agglutination, opsonization, activation of complement-mediated reactions against cellular pathogens and by the neutralization of toxins.
Increase in interleukin-2 (IL-2).
IL-2 is a regulator of cell-mediated immunity. It is secreted by TH1 CD4 cells to activate the growth of T- and B-Cells. IL-2 also activates NK cells.
Increase in interferon-gamma (IFN-gamma).
IFN-gamma is also a regulator of cell-mediated immunity. It is secreted by T cells. It has protective properties by activating macrophages, stimulating the differentiation of cytotoxic T cells and activating B cells to produce antibodies.

Immune modulating effects of CVT-E002 (COLD-FX) have been published in the following laboratory studies:

Wang M. et al. 2001. Immunomodulating activity of CVT-E002, a proprietary extract from North American ginseng (Panax quinquefolium). Journal of Pharmacy and Pharmacology. 53 (11):1515-23.
Abstract available via PubMed: click here
Wang M. et al. 2001. A proprietary extract from North American ginseng (Panax quinquefolium) enhances IL-2 and IFN-gamma productions in murine spleen cells induced by Con-A. International Immunopharmacology. 4(2):311-5.
Abstract available via PubMed: click here
Predy, G. et al. 2006. Immune Modulating Effects of Daily Supplementation of COLD-FX (a Proprietary Extract of North American Ginseng) in Healthy Adults. Journal of Clinical Biochemistry and Nutrition. 39:162-167.
Further laboratory research on CVT-E002 is ongoing in the Department of Pathology and Molecular Medicine at McMaster University to investigate the precise molecular mechanism of action of CVT-E002. The objective of this research is to further understand how CVT-E002 enhances the immune system. This study is conducted with the support of National Research Council Industrial Research Assistance Program (NRC-IRAP).

For further information about this study click here