Neoplasm prevention and immuno-enhancement mediated by daily consumption of a proprietary extract from North American ginseng by elderly mice of a cancer-prone strain.

Cells belonging to the innate immune system, known as natural killer (NK) cells, act as the first line of defense against developing neoplasms. We have previously shown in a leukemia-induced tumor model (mouse) that a proprietary extract (CVT-E002), of North American ginseng, administered in the diet, significantly increased the absolute numbers of NK cells, significantly decreased leukemia cells and significantly increased the life span of CVT-E002-fed leukemic mice. In the present study, we assessed the efficacy of this extract to inhibit the spontaneous development of tumors in elderly mice of the cancer-prone C3H strain. Dietary CVT-E002 was fed for approximately a year beginning when mice were almost 2 years of age. Control mice, consuming the same chow without CVT-E002, all developed assorted, palpable tumors between 22 and 33 months, while all mice consuming CVT-E002 remained alive and tumor-free until they were purposely euthanized as healthy animals. The absolute numbers of NK cells at euthanasia, in CVT-E002-consuming mice, were significantly elevated in both the spleen and bone marrow. Given these profoundly positive results and the fact that CVT-E002 already exists in the marketplace under the label Cold-fX®, the potential for cancer prevention in humans becomes apparent.

Dietary supplementation with an extract of North American ginseng in adult and juvenile mice increases natural killer cells.

Cells belonging to the innate immune system are referred to as natural killer (NK) cells. We recently demonstrated that normal, pre-weaned infant mice, injected with a proprietary extract of ginseng (CVT-E002) had augmented NK cell numbers vs. sham-injected mice. In the present study, we extended these observations into juvenile and adult mice. Thus, young adult (age: 8-9 wk) C3H mice were given daily dietary CVT-E002 for 4 wk followed by untreated chow for the following 2 months, then euthanized (age: 20-21 wk). Other C3H mice (juvenile: 4-wk-old) were given CVT-E002 under the same protocol and sampled at 18 wk of age. In spite of withdrawing the extract 2 months earlier, the absolute numbers of NK cells in the young adults, remained significantly (p < 0.01), and slightly, elevated in the spleen and bone marrow (BM), respectively. The relative numbers (%) of NK cells in the blood also remained elevated (p < 0.05). In juvenile mice fed CVT-E002, the absolute numbers (spleen, BM) and % (blood) of NK cells were all elevated (p<0.01 - p<0.05). The mechanisms responsible for these super-normal numbers of NK cells long after withdrawal of CVT-E002, is as yet unknown.

The sustained influence of short term exposure to a proprietary extract of North American ginseng on the hemopoietic cells of the bone marrow, spleen and blood of adult and juvenile mice.

This study assessed the influences of CVT-E002, a proprietary extract of North American ginseng, Panax quinquefolius (Afexa Life Sciences, Inc., Edmonton, AB, Canada), in vivo, on murine hemopoietic and immune cells when administered as a dietary additive. The extract was given daily to young, adult mice for a period of 4 weeks, immediately following which one group was euthanized and the hemopoietic and immune cells of their bone marrow, spleen and blood were assayed for CVT-E002-mediated alterations in any of five cell lineages (lymphocytes, nucleated erythroid cells, granulocytes, immature granuloid precursors and monocytes). Another group of these mice was left for a subsequent 8 weeks on control diet, following which the same organs and cell lineages were analysed. In another study, juvenile mice immediately upon weaning (age: 4 weeks), were subjected to the above protocol, and their organs/cell lineages assayed. The results revealed that CVT-E002 had a long-lasting, positive quantitative effect on the lymphocytes and monocytes, regardless of age at commencement of daily, dietary CVT-E002. CVT-E002 may therefore have a prophylactic disease defense, immunostimulatory role, or potentially, even a therapeutic role.

Extract of North American ginseng (Panax quinquefolius), administered to leukemic, juvenile mice extends their life span.

In a recent study involving normal, juvenile mice, we showed that CVT-E002, a proprietary extract (Afexa Life Sciences, Inc.) of North American ginseng, Panax quinquefolius, significantly enhanced the absolute levels of cells acting at the first line of defense in tumor combat, i.e., natural killer (NK) cells. The present study evaluated the effect of CVT-E002, on life span when administered intraperitoneally to leukemic, infant/juvenile mice. The extract was administered to groups of mice daily for 14 days in several dosing groups up to 50mg/day from age 7 to 21 days. The tumor was administered intraperitoneally under sterile conditions, in a laminar flow hood at 7 days of age (0.5 x 10(6) leukemic cells), immediately preceding the first CVT-E002 injection for each dose group. The data revealed that CVT-E002 significantly extends the life of leukemic, young mice in a dose-specific manner, i.e., 20 mg/day was effective in extending life, while lower doses of 5, 10 mg as well as higher doses of 30, 40, 50 mg per day were completely ineffective. We have already shown that CVT-E002 significantly elevates NK cells in normal and leukemic, adult mice, as well as in normal, infant/juvenile mice, and we have also shown that CVT-E002 significantly extends the life span of leukemic, adult mice. The results of the present study did indeed show that (i) CVT-E002 extends the life span of leukemic, infant/juvenile mice, and (ii) that the dose of CVT-E002 is critical in achieving life span augmentation in these leukemic infant/juvenile mice.

CVT-E002 stimulates the immune system and extends the life span of mice bearing a tumor of viral origin.

The present study evaluated the dose-related effects of CVT-E002, a proprietary extract of Panax quinquefolius (CV Technologies Inc., Edmonton, AB), in the treatment of a tumor of viral origin, that is, erythroleukemia, in mice. Three treatments including ingestion of 2, 40, and 120 mg/d were compared. The study revealed that the dose of 40 mg/d was particularly effective in stimulating cells mediating nonspecific immunity and extending the life span of tumor-bearing mice. This study represents the first in vivo demonstration of the anticancer efficacy of CVT-E002 in an animal model. CVT-E002 treatment significantly elevated the absolute numbers of natural killer cells and monocytes and reduced the number of tumor cells in the bone marrow and spleen. This study has shown that (1) approximately 30 to 50% of tumor-bearing mice administered CVT-E002 at a dose of 40 mg/d achieved a significantly extended life span, and (2) dosage is critical in producing these ameliorative effects.

The role of melatonin in immuno-enhancement: potential application in cancer.

Melatonin, a neurohormone produced mainly by the pineal gland, is a modulator of haemopoiesis and of immune cell production and function, both in vivo and in vitro. Physiologically, melatonin is associated with T-helper 1 (Th1) cytokines, and its administration favours Th1 priming. In both normal and leukaemic mice, melatonin administration results in quantitative and functional enhancement of natural killer (NK) cells, whose role is to mediate defenses against virus-infected and cancer cells. Melatonin appears to regulate cell dynamics, including the proliferative and maturational stages of virtually all haemopoietic and immune cells lineages involved in host defense - not only NK cells but also T and B lymphocytes, granulocytes and monocytes - in both bone marrow and tissues. In particular, melatonin is a powerful antiapoptotic signal promoting the survival of normal granulocytes and B lymphocytes. In mice bearing mid-stage leukaemia, daily administration of melatonin results in a survival index of 30-40% vs. 0% in untreated mice. Thus, melatonin seems to have a fundamental role as a system regulator in haemopoiesis and immuno-enhancement, appears to be closely involved in several fundamental aspects of host defense and has the potential to be useful as an adjuvant tumour immunotherapeutic agent.

Echinacea: a miracle herb against aging and cancer? Evidence in vivo in mice.

Echinacea has been viewed as an immunoenhancing herb since it became commercially available several years ago. Indeed, its medicinal significance is responsible for billions of dollars in worldwide sales annually. Unfortunately, most of the 'evidence' for the purported medicinal efficacy of Echinacea has been anecdotal and, moreover, to this day, there is no formal proof on how to achieve the best results-whether it should be consumed daily throughout life as a prophylactic; consumed by either young or old; or consumed after diseases, such as cancer, have taken hold. Our work over the past 5 years has led to conclusive answers to some of these questions, at least in mice. Our results have shown that daily consumption of Echinacea is indeed prophylactic, extends the life span of aging mice, significantly abates leukemia and extends the life span of leukemic mice. Given that humans are 97% genetically common with mice and that virtually all our basic physiology is identical, it is neither unjustified to extrapolate these observations to humans nor would it be an arduous task to perform many of these studies in humans, thus establishing viable scientific evidence replacing the anecdotal.

Enhancement of natural killer cells and increased survival of aging mice fed daily Echinacea root extract from youth.

In spite of Echinacea-based products being among the best-selling herbs in the world to date, to allay assorted ailments, the debate is still on-going with respect to the efficacy of ingesting the herb intermittently, continuously, or only at the beginning of an affliction. We sought, therefore, to find out if mice, receiving dietary Echinacea daily, throughout life, from youth until late middle-age, demonstrated any longevity/survival differences, and/or any differences in their various populations of immune/ hemopoietic cells. Sustained and/or high levels of these cells are crucial for longevity. Some mice were maintained on a regular chow diet to which was added Echinacea purpurea daily (2 mg/mouse), from puberty (7 week) until just beyond 13 months of age (late middle-age in mice). Control mice, identically housed and maintained, received identical chow without the herb. Mice consuming untreated diet had a 79% survival by 10 months of age, while those consuming Echinacea daily in the diet were still 100% alive by 10 months. At approximately 13 months of age, mice consuming untreated diet had a 46% survival rate while those consuming Echinacea, were 74% alive at this time. Moreover, the key immune cells, acting as the first line of defense against developing neoplasms in mice and humans, i.e., natural killer (NK) cells, were significantly elevated in absolute number both in their bone marrow production site, as well as in the major organ to which they traffic and function, i.e., the spleen. The cells of the myeloid/granulocyte lineages remained steadfastly at control levels in both the bone marrow and spleen in Echinacea-consuming mice. Thus, it appears that regular intake of Echinacea may indeed be beneficial/prophylactic, if only for the reason that it maintains in an elevated state, NK cells, prime elements in immunosurveillance against spontaneous-developing tumors, a phenomenon which increases in frequency with progressive aging.

The effect of immunization with killed tumor cells, with/without feeding of Echinacea purpurea in an erythroleukemic mouse model.

OBJECTIVE: Tumor amelioration via vaccination/immunization is a practice for which considerable experimental and clinical support is growing. Combination therapies have proven to be more beneficial than treatment with single agents. We hypothesized that immunization of mice with killed erythroleukemia cells prior to the induction of erythroleukemia via injection of viable tumor cells, plus dietary administration of a known immuno-enhancing phytocompound, Echinacea purpurea, would be more effective than immunization alone. DESIGN: A commercially available extract of E. purpurea root, already proven as a natural killer (NK) cell stimulant, was administered via the chow, for periods of 9 days or 3 months after the onset of leukemia to mice which had been injected (immunized) 5 weeks earlier with killed leukemia cells. RESULTS: Immunized mice (+/- E. purpurea) had significantly prolonged life spans versus non-immunized mice, with an even greater proportion of hosts surviving long-term in the E. purpurea-fed group. NK cells, the mediators of nonspecific immunity and well-demonstrated mediators of tumor cytolysis, were very significantly elevated in immunized, leukemic mice receiving E. purpurea in their diet versus those receiving untreated chow. Early in tumor development (9 days), cells mediating specific immunity (T, B lymphocytes) were 10-12 times higher in absolute numbers in the spleens in all immunized, leukemic mice vs unimmunized, leukemic mice at the same stage of tumor progression. CONCLUSIONS: The results demonstrate that combination therapy, involving specific tumor cell immunization, followed by daily phytotherapy (dietary E. purpurea), sensitized the immune cells and led to life span prolongation greater than that provided by immunization alone.