Update 12 december 2009: onderstaande informatie is nog steeds waardevol en is o.i. een interessant artikel om te lezen.

Bron: van Canmedbotanics. kregen we deze informatie over ginseng toegestuurd. We hebben een arts en voedingsdeskundige gevraagd wat hij vond van deze informatie en was hierover lovend. "Dit kan je gerust op de website zetten Kees, goeie informatie." Wat we dus hierbij doen.
Met dank dus aan directeur E. Steketee van Canmedbotanics voor deze informatie. Voor alle duidelijkheid we hebben geen enkele commerciële binding met dit bedrijf en ook hier is onze disclaimer van toepassing uiteraard. Alleen het originele Engelstalige artikel, waardoor het o.i. alleen interessant lijkt voor artsen en voedingsdeskundigen, maar met de vertaalknop van google, zie bovenaan pagina is dit artikel in goed leesbaar  Nederlands te vertalen. Conclusie uit dit artikel is dat Ginseng een belangrijke rol kan vervullen in een behandeling bij kanker.

. Cancer Prevention and Therapeutics: Panax Ginseng
Alternative Medicine Review, Sept, 2004 by Steve Helmes

Introduction
The root and rhizome of Panax ginseng C.A. Meyer (Araliaceae) has been used as a medicine by the people of Eastern Asia for at least 2,000 years. Native to Korea and northeastern China, this red-berried plant, commonly called Korean ginseng, is now cultivated throughout the world. It appears in the pharmacopoeias of several countries including China, Japan, Germany, Austria, the United Kingdom, and France, and is often employed for cancer, diabetes mellitus, and cardiovascular concerns. As in the past, P. ginseng is still thought of as a panacea, perpetuated by its name panax, meaning "cure all" in Greek. For these reasons P. ginseng is one of the most sought-after medicines throughout the world. It was the second-highest selling herbal supplement in the United States in 2000, with gross retail sales of $US62 million. (1) Many herbal products are often mistakenly called ginseng. These include P. quinquefolium (American ginseng), from the northeastern parts of the United States and Canada; P. notoginseng, from Yun-nan Province in China and northern Vietnam; P. vietnamensis, from central Vietnam: P. japonicus, from Japan; and P. pseudoginseng, from the Himalayan region. Adding to the confusion, other botanical medicines are commonly called ginseng that do not belong to the same family as P. ginseng--Eleutherococcus senticosus (Siberian ginseng) and Pfaffia paniculata (Brazilian ginseng). Each so-called "ginseng," however, ranges widely in both similarity and disparity to the constituents of P. ginseng, and despite any overlap observed in their actions, the traditional uses and more current studies illuminate many distinctive therapeutic applications.

Biochemistry
The active principals of P. ginseng include saponins, polysaccharides, flavonoids, and volatile oils. In cancer therapeutics the saponins and polysaccharides have engendered the greatest investigation. Acidic polysaccharides (10,000-150,000 MW) have been observed to have immunomodulating and antiproliferative effects in tumor cell lines. Readily soluble in water, these polysaccharides contain various sugar moieties, uronic acid, and less than five-percent protein by weight. Ginseng's saponins, generally called ginsenosides (Rx), are emphasized in cancer chemoprevention and therapeutics. The primary ginsenosides and their metabolic cousins have a steroid-like structure (2-3) and are generated by acid hydrolysis of saponins (4) and human intestinal bacteria. (5-7) With the exception of ginsenoside Ro, which is an oleanane-type triterpenoid, all ginsenosides are the dammarane-type separated into panaxadiol and panaxatriol classes (Table 1).

In Asia, the traditional preparations of fresh white and red ginseng have various concentrations of ginsenosides that develop in complexity with age (Table 2) and preparation. Classically, fresh ginseng is anything picked before four years of growth. White ginseng (picked at 4-6 years) is peeled and then dried, and contains high concentrations of Rb1, Rb2, Rc, and Rd of the -diol group. Red ginseng (harvested at 6 years) traverses both ginsenoside classes speaking to liberation of new constituents--Rh1, Rh2, and Rg3--from steaming the dry whole root. (4,8) These traditional preparations generate a therapeutic dose by stockpiling specific metabolites for direct absorption and creating a similar composite of primed metabolites for digestive processes to complex for absorption (Figure 1). A 1994 comparison study found that wild, harvested plants contain more of the Rg, Rd, and Re fractions, while cultivated plants possess a greater total ginsenoside content and Rb fraction. (9) In a related study, cultured tissue cells of P ginseng rarely contained half the fractional constituents of the cultivated plant. (10) In 2003 the World Health Organization's new guidelines list P. ginseng as endangered due to overharvesting. (11) The given scarcity of natural ginsenosides has prompted the search for routes of synthesis from more accessible products. The common birch, Betula alba L. (Betulaceae), contains betulafolienetriol that has been used as a starting compound in at least one study to prepare semi-synthetic ginsenosides. (12)
The standardization of ginseng formulations varies in concentration from 4-7 percent ginsenosides (calculated as ginsenoside Rg1), (13) although polysaccharides may need to be added as an additional reference point in specific cancer preparations. (14) In both cases the bioavailable dose is a function of horticultural variables, preparation methods, and the interaction of individual variation of digestive processes that, in the case of ginsenosides, diversify and concentrate constituents.

Panax Ginseng and the Phases of Cancer: Mechanisms of Action
A search of PubMed for "cancer," "tumor," and "Panax ginseng" yields over 200 articles, signaling the progressive search for help in a society that has just been informed the current five-year survival rate with cancer is 64 percent, up from 50 percent in 1975. (15)
From the initiation of cancer, pathogenesis proceeds to promotion until progression. Initiation phase is rapid (within hours to days) where irreversible DNA changes occur that are successfully perpetuated via mitosis. Promotion stage may take years or decades to establish an actively proliferating premalignant lesion. While in the progression phase, new clones with increased proliferative capacity, invasiveness, and metastatic potential are produced within a narrow window, perhaps within a year (Figure 2). (16) The result of successive mutations, cancer establishes a state of disharmonious intercellular communication. As the discord widens, the cell becomes less capable of inducing apoptosis (programmed cell death) to quell the escalating cellular chaos. Immune cells are therein deflected from surveillance and/or overrun by the cascade of dividing cells, unable to restore order by inducing apoptosis or even necrosis (cell death with inflammation) in these errant cells. This cumulative loss in intracellular and intercellular communication is incremental in malignant cells and is referred to as chemotolerance. Chemotolerance first stops the cellular defenses and thereafter impedes the success of immune cells, chemotherapy, and radiation.

Fortunately, surgery has become a successful treatment for cancer, to the degree that 90 percent of cancer-related deaths are due to non-primary metastatic growths. (17) It is now understood that many of these unreachable growths develop from more than one aberrant cell line. Tumors consisting of more than one genetic cell line are explained by field carcinogenesis, which specifies that different cells within a tissue may mutate distinctively from each other due to disparities in input interpretation. (18) Subsequent post-surgical treatment may be complicated by dissimilar chemotolerance between cell lines, thwarting chemotherapy and radiation. Therefore, success in cancer care is continually dependent on development of specific and even multifaceted therapies.

Mitigating DNA Damage
Inducing Differentiation
Ginseng's induction of repair or reverse transformation of cells into more differentiated (genetically stable) cells has been noted in hepatoma, (19,20) melanoma, (21,22) and teratocarcinoma cells. (23) However, these recognized changes in gene expression have not, in and of themselves, shown promising avenues in chemoprevention or therapeutics.

Reduced Effects from Chemical Carcinogens
Reduction in induced carcinogenesis by various chemical carcinogens has been well documented. Yun et al found red ginseng reduced 9, 10-dimethyl-1,2-benzanthracene (DMBA) cancer cell infiltration by 63 percent. With urethane exposure, red. ginseng availed a 22-percent decrease in lung adenoma, while aflatoxin [B.sub.1]-induced lung adenoma and hepatoma were reduced 29 and 75 percent, respectively. (24) Different ages and types of ginseng were studied with benzo(a)pyrene, noting more significant lung anticarcinogenic effects with red ginseng than fresh ginseng. (25) It was further noted that Rg3 and Rg5 demonstrated significant reductions in benzo(a)pyrene-induced adenocarcinoma, while Rh2 did not reach significance (26) Inhibition was also found in lung tumors induced by dimethylbenz(a)anthracene in mice. (27) Bespalov has shown strong inhibitory effects on the development of rat mammary adenocarcinoma induced by methyl-N-nitrosourea and N-ethyl-N-nitrosourea administration, as well as in DMBA-induced uterine and vaginal tumors. (28) Other investigations that use inducers of cytotoxicity suggest the efficacy of P. ginseng extracts in cancer treatment. (29,30) Despite dose-dependent antigenotoxic properties in extracts (31) and metabolites, (32) the reasons for reduced carcinogenesis with concomitant use of P. ginseng are unknown, although genetic ties may have connection with ginseng's reduction in inflammation and oxidizing radicals.

Mitigating Anti-inflammatory Carcinogenesis
Repeated insult by inflammatory processes has long been implicated in all phases of cancer. (18) Cyclooxygenase-2 (COX-2), omnipresent in inflammatory processes, releases inflammatory metabolites and reactive elements, and is induced by growth factors, carcinogens, and oncogenes. (33) Recent studies have shown that the 20(S)-protopanaxatriols as well as Rg3 inhibit induced COX-2 expression. This process has been attributed to inactivation of nuclear factor-kappaB (NF-B), a transcription factor whose activation inhibits the cell death signaling of oncogenic ras. (34-36) Inducible nitrous oxide synthetase (iNOS) is another inflammatory enzyme curtailed by this down-regulation of NF-B. (37-38) Finally, a derivative of Rb1 and Rb2, often called Compound K, reduces inflammation (39) and has been found to have a stronger inhibitory effect on histamine release than disodium cromoglycate--an anti-allergy preparation. (40)

Antioxidant Chemoprevention
The antioxidant activities of P. ginseng also help explain its DNA-preserving qualities with respect to chemical carcinogens and inflammation. Ginseng extracts have been shown to scavenge reactive oxidative species (ROS) (41-43) as well as attenuate lipid peroxidation. (34,41,44) Panaxadiol ginsenosides (particularly Rb2), but not total saponins, have also been found to up-regulate the transcription of other known antioxidant enzymes (superoxide dismutase and catalase) by two- to three-fold in human hepatoma cells. (45) Rb3, Rb1, and Rc are antioxidants that, alone or in combination, show significant synergistic interaction with alpha-tocopherol (aTOC). With the exception of Rg1, the 20(S)-protopanaxatriols show synergistic antioxidant interaction with aTOC. All ginsenoside antioxidants have a sugar at position 6, and a pro-oxidant molecule results when glucose is not bound to position 20. Rg3, Rd, and Rh2 have pro-oxidative effects when used alone or in combination with aTOC. (42,43)

Induction of Apoptosis
Apoptosis can be induced by immune cells and cytotoxins, and by changes in homeostatic signals (Figure 3). (46) The mechanisms associated with changes in gene expression require caspase activation through two main pathways. (47) The first involves the interaction of a death receptor with its ligand, and the second depends on the participation of mitochondria involving pro- and anti-apoptotic members of the Bcl2 family (Figures 4 and 5). (16)
Rb1 metabolites (Rh2, Compound K, and panaxydiol) have been shown to encourage apoptosis by inducing caspase-3 without any known activation of caspase-8. (48-50) Recently, however, Compound K was noted to initiate the caspase-8 model of apoptosis and has produced a link between caspase-3 and caspase-8 by an amplification loop perhaps initiated by cytochrome-c. (51) Interestingly, the loss of cytochrome-c from the mitochondrial membrane has been shown to be a function of pro-apoptotic Bcl-2 proteins, (52) although no affect on Bcl-2 expression has been found with Rh2 and Compound K. (50,53) A further conundrum is the ability of Rh2 to activate the caspase pathway in a Bcl-[X.sub.L]-independent manner, suggesting additional apoptotic induction pathways available to ginsenosides. (53) Other studies support the use of Rb1 metabolites for inducing programmed cell death. First, Compound K produces apoptosis in cells otherwise safeguarded from apoptosis by fibroblast growth factor over-expression. (54) Second, caspase-induced apoptosis is promoted by the additional ginsenoside actions of inducing cyclindependent kinases to depolarize the mitochondrial membrane (panaxydiol) (53-55) and by the concomitant production of ROS (Rh2). (53) Finally, these Rb1 metabolites have induced known promoters of apoptosis, including the cleavage of poly-ADP ribose polymerase (PARP); the up-regulation of Bax, Bid, p53, p21, and p27 proteins; and the decreased expression of c-myc and cyclin D, E andA kinases. (48-51,55-59) (The inducing effects of P. ginseng in all these studies were abrogated by inhibitors verifying ginsenoside action.)

Inhibition of Proliferation
The proliferation phase, including tumor-cell migration, invasion, and metastasis, is modulated by neurotransmitters and chemokines (Figure 6). (17) The protopanaxadiol metabolites of P. ginseng have been shown to reduce catecholamine secretion through binding to nicotinic receptors and blocking sodium influx through the receptors. (2) Catecholamines have been noted as a chemo-attractant of breast carcinoma cells (59) and as an activator for the migration of colon carcinoma cells. (60) The therapeutic benefit of P. ginseng in neurotransmission warrants further investigation.
P. ginseng has also been noted to reduce lung metastasis in two highly metastatic tumor cell lines-colon 26-M3.1 and B16-BL6 melanoma; Rb2 inhibits their angiogenesis. (61) Rg3 inhibits the adhesion of tumor cells to extracellular matrix and basement membrane components (62,63) and, despite inhibiting metastasis, does not change the growth or vascularity of induced intestinal cancers. (64) Rb1 and its metabolite (Compound K) have shown reduction in lung metastasis in mice injected with Lewis lung carcinoma. Compound K was found to be twice as effective as Rb1 and to have almost the same antimetastatic potential as 5-fluorouracil (5-FU)--a chemotherapeutic agent. Because of the potential toxicity of 5-FU, Compound K may provide promising long-term therapy, given its low toxicity--L[D.sub.50] > 5g/kg. (65) One study does note all increased metastatic potential of P. ginseng. In an experimental cell line, Rh2 was found to increase metastatic potential, perhaps through the inhibition of Cdk2 (a cyclin-dependent kinase) producing all apoptoticresistant state. The same study of BALB/c3T3 cells showed Rh2 suppression of tumor growth in the initiation stage. (66)

Immunomodulation
No direct evidence confirms the cancer therapeutics of P. ginseng through immunomodulation. However, recognition of the concert of immune functions that incite apoptosis in cancerous cells is well known. It is understood that natural killer (NK) cells are pivotal in inhibiting tumor cell proliferation, and that the dynamic interplay of both cellular and humoral immunity is paramount to the containment of aberrant cell lines. In all these domains, P. ginseng has been studied and has demonstrated these actions with ginsenosides (67-71) and the polysaccharide fractions. (14.72-75) The immunomodulating quailities of P. ginseng may also be associated with a dampening of glucocorticoid levels and its activity. Mixed outcomes have been reported involving ginsenosides' action as a functional ligand to glucocorticoid receptors. (76-79) Nonetheless, a recent rat study displays significant reduction in serum corticosterone levels after oral administration of whole ginseng root at a daily dose of 100 mg/kg body weight. (80) In addition, red ginseng has reduced immune suppression through lowering elevated corticosterone. although the mechanism is unknown.

Applications of Ginseng or its Constituents in Specific Cancer Types

Colon Cancer
In a dose-dependent manner (2.5 and 5.0 mg/kg), a rat study using Rg3 found reduction in metastasis and tumor number as well as increased body weight. (64) Red ginseng, also in a dose-dependent manner 10.5 and 2.0 mg/kg), significantly reduced dysplastic crypts, although initiation phase inhibition was weak, limiting a prophylactic effect. (81,82)

Gastric Cancer
Red ginseng was found effective in patients with stage III gastric cancer for improving both post-operative immunity and survival. Increased CD3 and CD4 activity was reported with a five-year survival for P. ginseng patients markedly higher than control (68.2% versus 33.3&). Reported dose was 4.5 g/day for the first six months after surgery. (83) Inhibitory effects have also been found in cell-line cultures. (84-86)

Hepatic Cancer
Red ginseng (3.78 g/kg/wk) was shown to act as a highly significant preventative to induced liver cancer. In a rat study, when taken for 15 weeks prior to diethylnitrosamine exposure, only 14.3 percent of the rats had liver morphological changes indicative of cancer, while the control group tallied 100-percent induction. P. ginseng g acts to decrease the speed of tumor development and protect the ultrastructure of hepatocytes. (87) P. ginseng metabolites (Rg3, Rg5, Rkl, Rs5, and Rs4) have a 50-percent growth inhibition concentration in hepatoma cells--significantly lower than cisplatin (CDDP). (88) Other positive studies from 1978-2004 are noted with hepatoma cell lines. (19,20,45,48,49,51,55,57)

Kidney Cancer
The proliferation of renal cell carcinoma is reduced with red ginseng via a decrease in c-fos and c-jun gene expression. Only partial inhibition was produced with use of -diol or -triol fractions independently. (89)

Leukemia
In the human promyelocytic leukemia cells (HL-60) P. ginseng (fresh steamed) has been shown to scavenge ROS (44) and Compound K to induce apoptosis and inhibit proliferation. (50)

Melanoma
In mice, ginseng extracts and ginsenosides both significantly inhibited lung metastasis from melanoma. (90) Cell-line studies have shown control of differentiation (by Rh1 and Rh2), (21,22) inhibition of proliferation (by red ginseng). (8) inhibition of tumor angiogenesis and metastasis (by Rb2). (61) and most recently proliferation inhibition via up-regulation of p27 and down-regulation of c-Muc and cyclin D1 (by Compound K). (56)

Ovarian Cancer
Rh2 was found to inhibit ovarian tumor growth in mice by induction of apoptosis and increased NK-cell activity. Oral, but not intraperitoneal, treatment was found effective. The dose of 0.4-1.6 mg/kg was significant when given daily, but not weekly. The antitumor activity was similar to 4 mg/kg of CDDP, while also expressing a significant increase in survival. (91)

Prostate Cancer
Rg3 has displayed growth inhibitory activity as well as reduced biomarkers for prostate cancer (notably prostate specific antigen, androgen receptors, and 5 alpha-reductase). This study suggests induction of apoptosis through caspase-3 with the activated expression of cyclin-kinase inhibitors, p21 and p27. (92)

Pulmonary Cancer
Compound K has been shown to treat CDDP-resistant pulmonary cancer, with only a 20.3 microM concentration needed to inhibit cell proliferation by 50 percent (CDDP 60.8 microM). (86) Ginsenosides have shown significant effect ill induced lung cancers. (24-26,65,93,94) A polysaccharide fraction has also shown dose-dependent inhibition in mouse lung tumor incidence. (72)

Other Cancer-related Uses Ultraviolet Radiation Protection
Prepared under high heat. red ginseng extract has protected DNA from UV-induced fragmentation--the heralding of apoptosis. (44) P. ginseng has also been shown to protect different cell lines from ultraviolet radiation by increasing the rate of DNA repair (31) and by impeding apoptosis by maintaining constant levels of anti-apoptotic Bcl-2. (95)

Radiation Therapy Adjunct
In one study, water-extracted polysaccharides were injected into mice before treatment with ionizing radiation. Mice pretreated with 100 mg/kg survived a radiation dose (L[D.sub.50/30]) 45-percent more intense than control (10.93 Gy vs. 7.54 Gy). Cytokines, including interleukins (IL-1, IL-6, IL-l2) and interferon-gamma, required for hematopoietic recovery were induced with enhanced T-helper 1 function. The pretreated cells had a significantly increased number of bone marrow, spleen cells, granulocyte-macrophage colony-forming cells, and circulating neutrophils. (96)

Chemotherapy Adjunct
P. ginseng has been shown to improve the delivery and action of chemotherapeutic agents in addition to curtailing negative effects. Rc and Rd are capable of significantly reversing multidrug-resistant lymphoma cells by decreasing the expression of the mdrl glycoprotein gene--effectively inhibiting the efflux pump function on tumor cells. (69)
Rg1 and Re have been shown to reverse P-glycoprotein (Pgp) mediated multidrug resistance, thereby increasing the intracellular accumulation of drugs. Furthermore, ginsenosides decrease the levels of Pgp affording possible long-term treatment where verapamil and cyclosporin A increase Pgp levels at maximum non-cytotoxic concentrations. (97)
Panaxytriol was found to promote cellular accumulation of mitomycin C into gastric carcinoma and enhance its cytotoxicity. (85) In NIH3T3 mouse fibroblast cells, a mixture of -diol and -triol ginsenosides potentiated the apoptotic cell death of the alkylating agent methyl methanesulfonate. (58) In addition, Rg1 was found to restore cyclophosphamide-impaired cellular and humoral responses through activation of macrophage IL-1 production. (98)
Ginsenosides at 2-20 mcg/mL have increased tumor antigen expression, (69) and associated antigen-guided cancer therapies may gain insight from studies concerning the concurrent use of P. ginseng with immunization outcomes. Rg1 given before general immunizations resulted in increased titers of circulating antibodies, increased activity of NK cells, and increased number of T-helper cells. (98) Furthermore, daily administration of 100 mg of four-percent standardized ginsenosides to patients for 12 weeks enhanced the efficacy of polyvalent influenza vaccine. (67)

End of Life
Morphine is often used as a palliative in metastatic cancer. P. ginseng exerts protective effects against morphine-induced depression of B-cell and T-cell functions. (78) Rf potentiates a kappa opioid-induced analgesia and demonstrates the ability to inhibit the tolerance to this analgesia in a dose-dependent manner. (99) This may lead to reduced morphine dosing and a subsequent increase in social functioning.

Toxicity and Adverse Effects
P. ginseng is unlikely to cause pharmacokinetic interactions. Ginseng does not significantly induce cytochrome P450 (CYP) activity, (100) has no effect on warfarin pharmacokinetics, (101) and the attainment of serum concentrations capable of modulating CYP activity in vivo seems unlikely after oral administration. (102) A 30-percent greater ethanol clearance, however, may imply CYP induction after alcohol dehydrogenase pathway exhaustion. (103)
Data from clinical trials suggest the incidence of adverse events with ginseng is similar to placebo. Case reports reveal the following correlated side effects with P. ginseng intake: cerebral arteritis (1), mastalgia (6), postmenopausal vaginal bleeding (2), metrorrhagia (1), gynaecomastia (1), increased mania in depressive illness (1), hypertension (2), and eye symptoms associated with mydriasis and disturbed accommodation (2). (104)
Intake over 15 g/day resulted in depersonalization and confusion in four patients, while inducing depression in higher doses. A "ginseng abuse syndrome" has also been reported with doses up to 15 g/day, averaging 3 g/day, with concomitant use of caffeinated beverages. Symptoms were characterized by hypertension coupled with nervousness, sleeplessness, skin eruptions, and morning diarrhea in 14 patients. The syndrome was reported to reappear throughout the first year of the trial, but was found to be rare at 18 and 24 months. (105)
Ginseng standardized to four-percent ginsenosides has been found to increase the lumenal clearance of albendazole sulfoxide, an antihelminthic drug, speaking to both the need for concern with lowering serum levels of the benzimidazole-containing drugs and the possible adjunctive delivery of therapeutic agents to disturbances of the bowel. (106) Studies with P. ginseng are often of short duration and the majority of trials include a relatively small number of patients, thus reducing potential reports of rare and delayed adverse events. Conversely, three case control studies in Korea with more than 10,000 patients provided no information regarding adverse effects. (107-109) Reports of toxicity are rare in Germany and other European countries in which ginseng is medically prescribed. Indeed, both the World Health Organization and the Commission E conclude that, in recommended doses (1-2 g of the crude drug or 200-600 mg of standardized extracts--calculated to 4-7 percent ginsenosides), there are no known side effects of P. ginseng. (13)

Conclusion
Cancer is both a systemic concern and a specific disease. The goal of cancer chemoprevention is to inhibit the induction and suppress the progression of preneoplastic lesions to invasive cancer. P. ginseng's protective effects from toxic insult are well documented and speak well to prophylactic use, especially in patients at high risk for liver cancer. The ability to decrease inflammation and increase antioxidant activity sustains ginseng's role as an antitumor agent. Induction of apoptosis is an area where the genetic mechanisms of ginseng are becoming best understood. Unfortunately, the inhibition of proliferation has had limited success, with future therapeutics on the horizon via neurotransmitter modulation. Therefore, given the short interval of initiation and progression (which are generally considered irreversible), the promotion phase may provide the best target for cancer prevention.
Much anecdotal evidence is claimed, but there is no conclusive proof P. ginseng cures any type of cancer. Nonetheless, evidence points to ginseng's ability to limit and slow growth as well as to enhance the ability of the immune system and tumor cells to overcome chemotolerance and incite apoptosis. The ability of P. ginseng to increase the effectiveness of other chemotherapeutic agents, to act synergistically, and to help lower doses and therefore adverse side effects, is increasingly documented. Ginseng and its constituents exhibit key properties that allow precancerous cells to be limited to the promotion phase or to be destroyed altogether.

Despite the lack of Western-style scientific experimentation, the use of P. ginseng for cancer is well accepted in China. This herbal therapeutic agent has only gained scientific attention in the West since 1972 when U.S. President Nixon visited China and successfully opened relations. Nonetheless as P. ginseng experimentation continues, its recognized potential in cancer therapeutics continues to grow. Table 1. Noteworthy Ginsenosides (28 are known)
,br> Panaxadiols Panaxatriols Key Ginsenosides Rb1,Rb2, Rc, Rd, Rg3, Rh2 Re, Rf, Rg1, Rg2, Rhi Metabolites 20(S)- protopanaxadiols 20(S)- protopanaxatriols (i.e., 20(S)-Rg3) (i.e., 20(S)-Rg2 and 20(S)-Rh1) Further Metabolites Compound K, M1, IH901 Panaxytriol (20-O--D-glucopyranosyl-20(S)- (heptadeca-1-ene-4,6-diyne- protopanaxadiol); Panaxydiol 3,9,10-triol) Table 2. Concentrations of Ginsenosides with Age Years Total Saponins Rb Rg Ro (%) (%) (%) (%) 2 1.97 0.88 0.54 0.13 3 2.20 1.03 0.62 0.17 4 4.75 2.27 1.10 0.40 5 4.60 2.08 1.19 0.21 6 3.84 1.94 0.81 0.29 9 3.81 2.32 0.46 0.40 From: Liu CX, Xiao PG. Recent advances on ginseng
research in China. J Ethnopharmacol 1992;36(1):27-38.

References
(1.) Blumenthal M. Herb sales down 15 percent in mainstream market. Herbalgram 2001 ;51:69.
(2.) Tachikawa E, Kudo K, Hasegawa H. et al. In vitro inhibition of adrenal catecholamine secretion by steroidal metabolites of ginseng saponins. Biochem Pharmacol 2003,66:2213-2221.
(3.) Lee Y, Jin Y, Lim W. et al. A ginsenoside-Rh1, a component of ginseng saponin, activates estrogen receptor in human breast carcinoma MCF-7 cells. J Steroid Biochem Mol Biol 2003:84:463-468.
(4.) Shibata S. Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds. J Korean Med Sci 2001:16:S28-S37.
(5.) Akao T, Kanaoka M, Kobashi K. Appearance of compound K, a major metabolite of ginsenoside Rbl by intestinal bacteria, in rat plasma after oral administration--measurement of compound K by enzyme immunoassay. Biol Pharm Bull 1998:21:245-249.
(6.) Bae EA. Park SY, Kim DH. Constitutive betaglucosidases hydrolyzing ginsenoside Rb1 and Rb2 from human intestinal bacteria. Biol Pharm Bull 2000:23:1481-1485.
(7.) Bae EA, Han MJ, Choo MK. et al. Metabolism of 20(S)- and 20(R)-ginsenoside Rg3 by human intestinal bacteria and its relation to in vitro biological activities. Biol Pharm Bull 2002:25:58-63.
(8.) Xiaoguang C. Hongyan L, Xiaohong L, et al. Cancer chemopreventive and therapeutic activities of red ginseng. J Ethnolpharmacol 1998:60:71-78.
(9.) Mizuno M, Yamada J, Terai H, et al. Differences in immunomodulating effects between wild and cultured Panax ginseng. Biochem Biophys Res Commun 1994:200:1672-1678.
(10.) Liu CX, Xiao PG. Recent advances on ginseng research in China. J Ethnopharmacol 1992:36:27-38.
(11.) WHO guidelines on good agricultural and collection practice (GACP) for medicinal plants. Geneva: World Health Organization 2003.
(12.) Atopkina LN, Malinovskaya GV, Elyakov GB. et al. Cytotoxicity of natural ginseng glycosides and scmisynthetic analogues. Planta Med 1999:65:30-34. (13.) Blumenthal M. German Federal Institute for Drugs and Medical Devices. Commission E. The Complete German Commission E monographs: Therapeutic Guide to Herbal Medicines. Austin, TX: American Botanical Council; 1998:239.
(14.) Lim TS, Na K, Choi EM, et al. Immunomodulating activities of polysaccharides isolated from Panax ginseng. J Med Food 2004;7: 1-6.
(15.) No authors listed. Cancer survivorship--United Slates, 1971-2001. Morb Mortal Wkly Rep 2004:53:526-529.
(16.) Sun SY, Hail N Jr. Lotan R. Apoptosis as a novel target for cancer chemoprevention. J Natl Cancer Inst 2004:96:662-672.
(17.) Entschladen F, Drell TL 4th, Lang K, et al. Tumour-cell migration, invasion, and metastasis: navigation by neurotransmitters. Lancet Oncol 2004;5:254-258.
(18.) Tsao AS. Kim ES, Hong WK. Chemoprevention of cancer. CA Cancer J Clin 2004:54:150-180.
(19.) Odashima S, Nakayabu Y, Honjo N. et al. Induction of phenotypic reverse transformation by ginsenosides in cultured Morris hepatoma cells. Eur J Cancer 1979;15:885-892.
(20.) Abe H, Arichi S, Hayashi T, Odashima S. Ultrastructural studies of Morris hepatoma cells reversely transformed by ginsenosides. Experientia 1979:35:1647-1649.
(21.) Odashima S, Ohta T, Kohno H, et al. Control of phenotypic expression of cultured B16 melanoma cells by plant glycosides. Cancer . Res 1985:45:2781-2784.
(22.) Ota T, Fujikawa-Yamamoto K, Zong ZP, et al. Plant-glycoside modulation of cell surface related to control of differentiation in cultured B16 melanoma cells. Cancer Res 1987:47:3863-3867.
(23.) Lee YN. Lee HY, Chung HY, et al. In vitro induction of differentiation by ginsenosides in F9 teratocarcinoma cells. Eur J Cancer 1996:32A: 1420-1428.
(24.) Yun TK, Yun YS. Han IW. Anticarcinogenic effect of long-term oral administration of red ginseng on newborn mice exposed to various chemical carcinogens Cancer Detect Prey 1983:6:515-525.
(25.) Yun TK, Experimental and epidemiological evidence of the cancer-preventive effects of Panax ginseng C.A. Meyer. Nutr Rev 1996:54:S71-S81.
(26.) Yun TK, Lee YS, Lee YH, et al. Anticarcinogenic effect of Panax ginseng C.A. Meyer and identification of active compounds. d Korean Med Sci 2001:16:S6-S18.
(27.) Shin HR, Kim JY, Yun TK, et al. The cancer-preventive potential of Panax ginseng: a review of human and experimental evidence. Cancer Causes Control 2000:11:565-576.
(28.) Bespalov VG, Alexandrov VA, Limarenko AY, et al. Chemoprevention of mammary, cervix and nervous system carcinogenesis in animals using cultured Panax ginseng drugs and preliminary clinical trials in patients with precancerous lesions of the esophagus and endometrium. J Korean Med Sci 2001:16:S42-S53. (29.) Radad K, Gille G, Moldzio R, et al. Ginsenosides Rb1 and Rg1 effects on survival and neurite growth of MPP+-affected mesen-cephalic dopaminergic cells. J Neural Transm 2004;111:37-45.
(30.) Kim EH, Jang MH, Shin MC, et al. Protective effect of aqueous extract of ginseng radix against I-methyl-4-phenylpyridinium-induced apoptosis in PC12 cells. Biol Pharm Bull 2003;26:1668-1673.
(31.) Rhee YH, Ahn JH, Choe J, et al. Inhibition of mutagenesis and transformation by root extracts of Panax ginseng in vitro. Planta Med 1991;57:125-128.
(32.) Lee BH, Lee S.J. Hur JH, et al. In vitro antigenotoxic activity of novel ginseng saponin metabolites formed by intestinal bacteria. Planta Med 1998;64:500-503.
(33.) Kelloff GJ. Perspectives on cancer chemoprevention research and drug development. Adv Cancer Res 2000;78:199-334.
(34.) Surh YJ, Na HK. Lee JY, Keum YS. Molecular mechanisms underlying anti-tumor promoting activities of heat-processed Panax ginseng C.A. Meyer. J Korean Med Sci 2001;16:S38-S41.
(35.) Keum YS, Han SS, Chun KS. et al. Inhibitory effects of the ginsenoside Rg3 on phorbol ester-induced cyclooxygenase-2 expression. NF-kappaB activation and tumor promotion. Mutat Res 2003;523-524:75-85.
36.) Oh GS, Pae HO, Choi BM, et al. 20(S)-Protopanaxatriol, one of ginsenoside metabolites, inhibits inducible nitric oxide synthase and cyclooxygenase-2 expressions through inactivation of nuclear factor-kappaB in RAW 264.7 macrophages stimulated with lipopolysaccharide. Cancer Lett 2004;205:23-29.
(37.) Lala RK, Chakrabotty C. Role of nitric oxide in carcinogenesis and tumor progression. Lancet Oncol 2001;2:149-156.
(38.) Kisley LR, Barrett BS, Bauer AK, et al. Genetic ablation of inducible nitric oxide synthase decreases mouse lung tumorigenesis. Cancer Res 2002;62:6850-6856.
(39.) Park EK, Choo MK, Han MJ, Kim DH. Ginsenoside Rh1 possesses antiallergic and anti-inflammatory activities. Int Arch Allergy Immunol 2004;133:113-120.
(40.) Choo MK, Park EK. Han MJ. Kim DH. Antiallergic activity of ginseng and its ginsenosides. Planta Med 2003;69:518-522.
(41.) Zhang D, Yasuda T. Yu Y, et al. Ginseng extract scavenges hydroxyl radical and protects unsaturated fatty acids from decomposition caused by iron-mediated lipid peroxidation. Free Radio Biol Med 1996;20:145-150.
(42.) Liu ZQ, Luo XY, Sun YX, et al. Can ginsenosides protect human erythlocytes against free-radical-induced hemolysis? Biochim Biophys Acta 2002;1572:58-66.
(43.) Liu ZQ. Luo XY, Liu GZ, et al. In vitro study of the relationship between the structure of ginsenoside and its antioxidative or prooxidative activity in free radical induced hemolysis of human erythrocytes. J Agric Food Chem 2003;51:2555-2558.
(44.) Keum YS, Park KK, Lee JM, et al. Antioxidant and anti-tumor promoting activities of the methanol extract of heat-processed ginseng. Cancer Lett 2000;150:41-48.
(45.) Chang MS, Lee SG, Rho HM. Transcriptional activation of Cu/Zn superoxide dismutase and catalase genes by panaxadiol ginsenosides extracted from Panax ginseng. Phytoter Res 1999;13:641-644.
(46.) Eastman A. Apoptosis: a product of programmed and unprogrammed cell death. Toxicol Appl Pharmacol 1993;121:160-164.
(47.) Faleiro L, Kobayashi R, Fearnhead H, Lazebnik Y. Multiple species of CPP32 and Mch2 are the major active caspases present in apoptotic cells. EMBO J 1997;16:2271-2281.
(48.) Park JA. Lee KY, Oh YJ. et al. Activation of caspase-3 protease via a Bcl-2-insensitive pathway during the process of ginsenoside Rh2-induced apoptosis. Cancer Lett 1997;121:73-81.
(49.) Park JA, Kim KW, Kim SI, Lee SK. Caspase 3 specifically cleaves p21WAF1/CIP1 in the earlier stage of apoptosis in SK-HEP-1 human hepatoma cells. Eur J Biochem 1998;257:242-248.
(50.) Lee SJ, Ko WG, Kim JH, et al. Induction of apoptosis by a novel intestinal metabolite of ginseng saponin via cytochrome c-mediated activation of caspase-3 protease. Biochem Pharmacol 2000;60:677-685.
(51.) Oh SH, Lee BH. A ginseng saponin metabolite-induced apoptosis in HepG2 cells involves a mitochondria-mediated pathway and its downstream caspase-8 activation and Bid cleavage. Toxicol Appl Pharmacol 2004;194:221-229.
(52.) Sun SY. Apoptosis induction by chemopreventive agents. Drug News Perspect 2001;14:75-80.
(53.) Kim HE, Oh JH, Lee SK, Oh YJ. Ginsenoside RH-2 induces apoptotic cell death in rat C6 glioma via a reactive oxygen- and caspase-dependent but Bcl-X(L)-independent pathway. Life Sci 1999;65:PL33-PL40.
(54.) Choi HH, Jong HS, Park JH, et al. A novel ginseng saponin metabolite induces apoptosis and down-regulates fibroblast growth factor receptor 3 in myeloma cells. Int J Oncol 2003;23:1087-1093.
(55.) Jin YH, Yim H, Park JH, Lee SK. Cdk2 activity is associated with depolarization of mitochondrial membrane potential during apoptosis. Biochem Biophys Res Commun 2003;305:974-980.
(56.) Wakabayashi C, Murakami K, Hasegawa H, et al. An intestinal bacterial metabolite of ginseng protopanaxadiol saponins has the ability to induce apoptosis in tumor cells. Biochem Biophys Res Commun 1998;246:725-730.
(57.) Kim SE, Lee YH, Park JH, Lee SK. Ginsenoside-Rs4. a new type of ginseng saponin concurrently induces apoptosis and selectively elevates protein levels of p53 and p21WAF1 in human hepatoma SK-HEP-1 cells. Eur J Cancer 1999;35:507-511.
(58.) Hwang SJ, Cha JY, Park SG, et al. Diol- and triol-type ginseng saponins potentiate the apoptosis of NIH3T3 cells exposed to methyl methanesulfonate. Toxicol Appl Pharmacol 2002;181:192-202.
(59.) Drell TL 4th, Joseph J, Lang K, et al. Effects of neurotransmitters on the chemokinesis and chemotaxis of MDA-MB-486 human breast carcinoma cells. Breast Cancer Res Treat 2003;80:63-70.
(60.) Masur K, Niggemann B, Zanker KS, Entschladen F. Norepinephrine-induced migration of SW 480 colon carcinoma cells is inhibited by beta-blockers. Cancer Res 2001;61: 2866-2869.
(61.) Sato K, Mochizuki M, Saiki I, et al. Inhibition of tumor angiogenesis and metastasis by a saponin of Panax ginseng, ginsenoside-Rb2. Biol Pharm Bull 1994;17:635-639.
(62.) Mochizuki M, Yoo YC, Matsuzawa K, et al. Inhibitory effect of tumor metastasis in mice by saponins, ginsenoside-Rb2, 20(R)- and 20(S)-ginsenoside-Rg3, of red ginseng. Biol Pharm Bull 1995;18:1197-1202.
(63.) Shinkai K, Akedo H, Mukai M, et al. Inhibition of in vitro tumor cell invasion by ginsenoside Rg3. Jpn J Cancer Res 1996;87:357-362.
(64.) Iishi H, Tatsuta M, Baba M, et al. Inhibition by ginsenoside Rg3 of bombesin-enhanced peritoneal metastasis of intestinal adenocarcinomas induced by azoxymethane in Wistar rats. Clin Exp Metastasis 1997;15:603-611.
(65.) Hasegawa H, Uchiyama M. Antimetastatic efficacy of orally administered ginsenoside Rb1 in dependence on intestinal bacterial hydrolyzing potential and significance of treatment with an active bacterial metabolite. Planta Med 1998;64:696-700.
(66.) Tatsuka M, Maeda M, Ota T. Anticarcinogenic effect and enhancement of metastatic potential of BALB/c 3T3 cells by ginsenoside Rh(2). Jpn J Cancer Res 2001;92:1184-1189.
(67.) Scaglione F, Catttaneo G, Alessandria M, Cogo R. Efficacy and safety of the standardized ginseng extract G115 for potentiating vaccination against the influenza syndrome and protection against the common cold. Drugs Exp Clin Res 1996;22:65-72.
(68.) Liu J, Wang S, Liu H, et al. Stimulatory effect of saponin from Panax ginseng on immune function of lymphocytes in the elderly. Mech Ageing Dev 1995;83:43-53.
(69.) Molnar J, Szabo D, Pusztai R, et al. Membrane associated antitumor effects of crocine-, ginsenoside- and cannabinoid derivates. Anticancer Res 2000;20:861-867.
(70.) Cho JY, Kim AR, Yoo ES, et al. Ginsenosides from Panax ginseng differentially regulate lymphocyte proliferation. Planta Med 2002;68:497-500.
(71.) Lee EJ, Ko E, Lee J, et al. Ginsenoside Rg1 enhances CD4(+) T-cell activities and modulates Th1/Th2 differentiation. Int Immunopharmacol 2004;4:235-244.
(72.) Yun YS, Lee YS, Jo SK, Jung IS. Inhibition of autochthonous tumor by ethanol insoluble fraction from Panax ginseng as an immunomodulator. Planta Med 1993;59:521-524.
(73.) Kim KH, Lee YS, Jung IS, et al. Acidic polysaccharide from Panax ginseng, ginsan, induces Th1 cell and macrophage cytokines and generates LAK cells in synergy with rIL-2. Planta Med 1998;64:110-115.
(74.) Lee YS, Chung IS, Lee IR, et al. Activation of multiple effector pathways of immune system by the antineoplastic immunostimulator acidic polysaccharide ginsan isolated from Panax ginseng. Anticancer Res 1997;17:323-331.
(75.) Shin JY, Song JY, Yun YS, et al. Immunostimulating effects of acidic polysaccharides extract of Panax ginseng on macrophage function. Immunopharmacol Immunotoxicol 2002;24:469-482.
(76.) de Kloet ER, Reul JM, van den Bosch FR, et al. Ginsenoside Rg1 and corticosteroid receptors in rat brain. Endocrinol Jpn 1987;34:213-220.
(77.) Lee YJ, Chung E, Lee KY, et al. Ginsenoside-Rg1, one of the major active molecules from Panax ginseng, is a functional ligand of glucocorticoid receptor. Mol Cell Endocrinol 1997;133:135-140.
(78.) Kim YR, Lee SY, Shin BA, Kim KM. Panax ginseng blocks morphine-induced thymic apoptosis by lowering plasma corticosterone level. Gen Pharmacol 1999;32:647-652.
(79.) Chung E, Lee KY, Lee Y J, et al. Ginsenoside Rg1 down-regulates glucocorticoid receptor and displays synergistic effects with cAMP. Steroids 1998;63:421-424.
(80.) Rai D, Bhatia G, Sen T, Palit G. Anti-stress effects of Ginkgo biloba and Panax ginseng: a comparative study. J Pharmacol Sci 2003;93:458-464.
(81.) Wargovich MJ. Colon cancer chemoprevention with ginseng and other botanicals. J Korean Med Sci 2001;16:S81-S86.
(82.) Fukushima S, Wanibuchi H, Li W. Inhibition by ginseng of colon carcinogenesis in rats. J Korean Med Sci 2001;16:S75-S80.
(83.) Suh SO, Kroh M, Kim NR, et al. Effects of red ginseng upon postoperative immunity and survival in patients with stage III gastric cancer. Am J Chin Med 2002;30:483-494.
(84.) Matsunaga H, Katano M, Yamamoto H, et al. Cytotoxic activity of polyacetylene compounds in Panax ginseng C.A. Meyer. Chem Pharm Bull (Tokyo) 1990;38:3480-3482.
(85.) Matsunaga H, Katano M, Saita T, et al. Potentiation of cytotoxicity of mitomycin C by a polyacetylenic alcohol, panaxytriol. Cancer Chemother Pharmacol 1994;33:291-297.
(86.) Lee SJ, Sung JH, Lee SJ, et al. Antitumor activity of a novel ginseng saponin metabolite in human pulmonary adenocarcinoma cells resistant to cisplatin. Cancer Lett 1999;144:39-43.
(87.) Wu XG, Zhu DH, Li X. Anticarcinogenic effect of red ginseng on the development of liver cancer induced by diethylnitrosamine in rats. J Korean Med Sci 2001;16:S61-S65.
(88.) Park IH, Piao LZ, Kwon SW, et al. Cytotoxic dammarane glycosides from processed ginseng. Chem Pharm Bull (Tokyo) 2002;50:538-540.
(89.) Han HJ, Yoon BC, Lee SH, et al. Ginsenosides inhibit EGF-induced proliferation of renal proximal tubule cells via decrease of c-fos and c-jun gene expression in vitro. Planta Med 2002;68:971-974.
(90.) Wakabayashi C, Hasegawa H, Murata J, Saiki I. In viva antimetastatic action of ginseng protopanaxadiol saponins is based on their intestinal bacterial metabolites alter oral administration. Oncol Res 1997;9:411-417.
(91.) Nakata H, Kikuchi Y, Tode T, et al. Inhibitory effects of ginsenoside Rh2 on tumor growth in nude mice bearing human ovarian cancer cells. Jpn J Cancer Res 1998;89:733-740.
(92.) Liu WK, Xu SX, Che CT. Anti-proliferative effect of ginseng saponins on human prostate cancer cell line. Life Sci 2000;67:1297-1306.
(93.) Yun TK, Kim SH, Lee YS. Trial of a new medium-term model using benzo(a)pyrene induced lung tumor in newborn mice. Anticancer Res 1995;15:839-845.
(94.) Yun TK. Experimental and epidemiological evidence on non-organ specific cancer preventive effect of Korean ginseng and identification of active compounds. Mutat Res 2003;63-74.
(95.) Lee EH, Cho SY, Kim S J, et al. Ginsenoside F1 protects human HaCaT keratinocytes from ultraviolet-B-induced apoptosis by maintaining constant levels of Bcl-2. J Invest Dennatol 2003;121:607-613.
(96.) Song JY, Hart SK, Bae KG, et al. Radioprotective effects of ginsan, an immunomodulator. Radiat Res 2003;159:768-774.
(97.) Choi CH, Kang G, Min YD. Reversal of P-glycoprotein-mediated multidrug resistance by protopanaxatriol ginsenosides from Korean red ginseng. Planta Med 2003;69:235-240.
(98.) Kenarova B. Neychev H. Hadjiivanova C. Petkov VD. Immunomodulating activity of ginsenoside Rg1 from Panax ginseng. Jpn J Pharmacol 1990;54:447-454.
(99.) Nemmani KV, Ramarao P. Ginsenoside Rf potentiates U-50.488H-induced analgesia and inhibits tolerance to its analgesia in mice. Life Sci 2003;72:759-768.
(100.) Gurley BJ, Gardner SF, Hubbard MA, et al. Cytochrome P450 phenotypic ratios fin. predicting herb-drug interactions in humans. Clin Pharmacol Ther 2002;72:276-287.
(101.) Zhu M, Chan KW, Ng LS, et al. Possible influences of ginseng on the pharmacokinetics and pharmacodynamics of warfarin in rats. Y Pharm Pharmacol 1999;51:175-180.
(102.) De Smet PA, Brouwers JR. Pharmacokinetic evaluation of herbal remedies. Basic introduction, applicability, current status and regulatory needs. Clin Pharmacokinet 1997;32:427-436.
(103.) Lee FC, Ko JH, Park JK, Lee JS. Effects of Panax ginseng on blood alcohol clearance in man. Clin Exp Pharmacol Physiol 1987;14:543-546.
(104.) Coon JT. Ernst E. Panax ginseng: a systematic review of adverse effects and drug interactions. Drug Saf 2002;25:323-344.
(105.) Siegel RK. Ginseng abuse syndrome. Problems with the panacea. JAMA 1979;241:1614-1615.
(106.) Merino G, Molina AJ, Garcia JL, et al. Ginseng increases intestinal elimination of albendazole sulfoxide in the rat. Comp Biochem Physiol C Toxicol Pharmacol 2003;136:9-15.
(107.) Yun TK, Choi SY. Non-organ specific cancer prevention of ginseng: a prospective study in Korea. Int J Epidemiol 1998;27:359-364.
(108.) Yun TK, Choi SY. A case-control study of ginseng intake and cancer. Int J Epidemiol 1990;19:871-876.
(109.) Yun TK. Choi SY. Preventive effect of ginseng intake against various human cancers: a case-control study on 1987 pairs. Cancer Epidemiol Biomarkers Prey 1995;4:401-408.


Plaats een reactie ...

Reageer op "Ginseng: De waarde van Ginseng in een behandeling van kanker en tegengaan van bijwerkingen. Een overzichtsartikel voor artsen en voedingsdeskundigen. Artikel geplaatst 12 december 2009"


Gerelateerde artikelen