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Pharmacological Actions/Mechanism of Action

Pharmacological Actions/Mechanism of Action

In vitro

In 2001, Wang and colleagues at the University of Alberta reported immunological effects following exposure of cultured mouse spleen cells to CVT-E002 extract.22 Lymphocytes and macrophages were extracted from mouse spleen by standard techniques, then grown in cell culture. CVT-E002 powder was dissolved in Hanks buffered salt solution. Hanks solution without CVT-E002 was used as control. Compared to control, enhanced proliferation of splenocytes, predominantly B lymphocytes, was accompanied by activation of exudate peritoneal macrophages, with enhanced expression of cytokines interleukin 1 (IL-1), IL-6, TNF-α, and nitrous oxide. While not all active-control comparisons reached statistical significance, the pattern of immunostimulation was fairly clear, especially with higher concentration (500 mcg/mL) CVT-E002 exposure.

The same team led by Meiqi Wang continued their investigations, and in 2004 they reported results from exposure of Concanavalin A (Con-A) activated cultured mouse spleen cells to CVT-E002. Compared to control, exposure of immune cells to CVT-E002 at 500 mcg/mL led to increased expression of IL-2 and interferon gamma (IFN-γ), inflammatory cytokines implicated in protection against influenza and other respiratory pathogens.23 Consistency among three different lots was also investigated, with the authors concluding that biological response is consistent between CVT-E002 preparations, both qualitatively and quantitatively.

A yet-to-be-published study provides further support for CVT-E002’s immunomodulatory activities.24 These investigators incubated human peripheral blood mononuclear cells (PBMC) and natural killer (NK) cells with and without various concentrations of CVT-E002, as well as with and without stimulation of influenza virus. Dose-dependent activation of PBMC was evidenced by increased levels of various cytokines, including IL-1α, IL-1β, IL-6, and IL-8. Other cytokines, including IL-2, IL-7, IL-10, IL-12, IL-13, IL-15, TNF-α, and IL-18 were not significantly increased. In the presence of CVT-E002-activated PBMC and influenza, NK cells were activated, suggesting that CVT-E002 may exert its effects upon NK cells through monocyte activation, with enhanced activity when influenza virus was present.

Together, these in vitro immune cell experiments suggest pharmacological immunomodulating activity of the CVT-E002 extract. In this regard, it is perhaps worth noting that a study by Assinewe et al with an aqueous extract of P. quinquefolius provides corroborating information.8 Those investigators exposed rat alveolar macrophages to a polysaccharide-rich aqueous extract (free of ginsenosides) of American ginseng root, and they reported significantly increased production of the inflammatory cytokine TNF-α. The same researchers reported that a methanol extract of the root containing ginsenosides and free of polysaccharides had no cytokine-stimulating activity.

In vivo—Animals

A 2001 study reported immunological effects of feeding mice different doses of CVT-E002.22 Groups of 5 BALB/c mice (a transgenic mouse model bred to exhibit immuno-susceptibility) were randomized to 0 mg, 2 mg, 6 mg, or 18 mg daily dose of CVT-E002, with dose regimens continuing for 7 days. Using blood collected from tail veins, standard ELISA techniques were used to quantify total immunoglobulin G (IgG) antibody. Total (nonspecific) IgG can be considered a marker of potential adaptive immunity. Compared to control, the higher doses (8 mg and 16 mg) led to statistically significant increases in IgG production (p < 0.05). There were no significant differences between the 0 g (control) and 2 mg groups, or between the 6 mg and 18 mg groups.

In May 2006, a conference lecture titled “The role of phytocompounds in immunoenhancement and cancer abatement” was presented by S.C. Miller in Edmonton, Alberta, Canada, at the North American Research Conference on Complementary and Integrative Medicine.25 This investigator reported that young male BDA/2 mice injected with erythroleukemia cells were fed 2 mg per day of CVT-E002 extract incorporated into their food. Compared to controls, mice fed CVT-E002 apparently displayed higher levels of mononuclear and NK cells, and fewer erythroleukemia blast cells. However, until the methodology, details, and specific findings are presented in a peer-reviewed article format and repeated in other laboratory settings, these findings should be considered preliminary.

Potential effects on pain receptor/transmission pathways were investigated in a mouse model. Yang and colleagues treated 23 young male ICR mice with 0.3 mL of a standardized CVT-E002 solution by gastrogavage for 4 consecutive days.26 Twenty control mice received the same volume of water by standard blunt needle gavage technique. A diluted formalin solution was injected into the paws of all mice in both groups in order to elicit pain response. The authors reported that the time spent licking or biting the injured paw at 25 to 30 minutes after injection was significantly less in the CVT-E002-treated group compared to the control group (p < 0.05).

Human

Predy et al27 describe analysis of blood samples from 42 of 323 participants in a randomized, controlled trial testing COLD-fX for the prevention of acute respiratory infection.16 Blood samples were taken before randomization and again at the end of the study for 21 people from the COLD-fX group and 21 people from the placebo group. Basic white blood cell neutrophil and lymphocyte differentials did not vary between treatment and control groups. However, average concentrations of CD4 helper cells and NK cells increased significantly more in the CVT-E002 group compared to the placebo group (p < 0.04 and p < 0.001, respectively). Plasma immunoglobulin A (IgA) levels decreased in both groups but were greater in the COLD-fX group compared to placebo (p < 0.03).