Chapter 16
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Nontoxic and Nonorgan Specific Cancer Preventive Effect of Panax ginseng C. A. Meyer
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Taik-Koo Yun , Soo-yong Choi , and Yun-Sil Lee 1
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Laboratory of Experimental Pathology and Laboratory of Clinical Research, Korea Cancer Center Hospital, Seoul 139-240, Korea
Panax ginseng C. A. Meyer has been recognized as non-toxic mysterious tonic in the Orient. The prolonged administration of red ginseng extract inhibited the incidence and also proliferation of pulmonary tumors induced by various chemical carcinogens. Statistically significant anticarcinogenic effects were observed in powders and extract of 6 year-dried fresh ginseng, 5 and 6 year-white ginseng and 4, 5 and 6 year-red ginseng by newly established 9 week medium-term anticarcinogenicity test using benzo[a]pyrene (BP). In case-control studies, odds ratios (OR) of the cancer of lip, oral cavity and pharynx, larynx, lung, esophagus, stomach, liver, pancreas, ovary, and colorectum were significantly reduced. On the type of ginseng, the ORs for cancer were reduced in fresh ginseng extract intakers, white ginseng extract intakers, white ginseng powder intakers, and red ginseng intakers. In cohort study with 5 years follow-up conducted in ginseng cultivation area, ginseng intakers had a decreased relative risk (RR) compared with non-intakers. The RRs of ginseng intakers were decreased in gastric cancer and lung cancer. These findings strongly suggest that Panax ginseng C. A. Meyer in non-toxic and non-organ specific cancer preventive effects against various cancers. Ginseng should be recognized as a functional food for cancer prevention, and that further studies for the identification of its active components, mechanism of action and clinical interventions should undertaken with worldwide collaboration. Rapid advances in scientific and medical knowledge, coupled with the rise in health consciousness of the population and increased emphasis on health promotion, have focused worldwide attention on food as on important component in the prevention 3
Current address: 215-4 Gongneung Dong, Nowon Ku, Seoul 139-240, Korea.
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©1998 American Chemical Society
In Functional Foods for Disease Prevention II; Shibamoto, T., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1998.
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of diseases. On the other hand, fifty years already passed since alkylating agent, nitrogen mustard was developed as first cancer chemotherapeutics (1), but many cancers still remain difficult to cure (2). With the discovery and clinical application of cancer chemotherapeutics, five year survival rate, which was less than one in five in the 1930s increased to one in four in the 1950s and one in three in the 1960s. By the 1970s, the goal of five year cancer survival rate was to achieve one out of two patients, but it was not successful. At present, it is only two out of five patients corresponding to 40% of "observed" survival rate (3). It has been believed that cancer should be conquered by prevention since 1978, and that it is not desirable the use synthetic agents for chemoprevention due to their toxicity problems. Therefore, I have been trying to discover non-toxic cancer preventives in natural products. The necessity of developing new preventives for chemoprevention or immunoprevention from natural products, which we have been taking for a long time, was also understood. We hypothesized that the life-prolongation effect of ginseng described by Shennong (4) in Liang Dynasty China may due to the preventive activity of ginseng against the development of cancers. Our study has focused on whether ginseng has anticarcinogenicity against various chemical carcinogens, such as urethane, 9, 10dimethyl-l,2-benzanthracene (DMBA), N-2-fluorenylacetamide (FAA), N-methylN'-nitroso-N-nitroguanine (MNNG), aflatoxin Bj and tobacco smoke condensates for long-term period maximum 67 weeks (5,6). Thereafter, we established new 9 week medium-term anticarcinogenicity model (termed Yun's anticarcinogenicity test) using one of the environmental carcinogens, BP at our laboratory to conform the anticarcinogenicity of red ginseng (7-10) and compare the anticarcinogenicity of various types and ages of ginseng (11, 12). In 1987 we began to conduct an epidemiological study to confirm whether red ginseng extracts have as much anticarcinogenic effect on human beings as on mice. In relation to this work we made three studies; two case-control studies on cancer patients (13, 14) and a cohort study on a population of a ginseng cultivation area (15). Here, experimental and epidemiological evidence of the preventive effect of ginseng is reviewed. Nomenclature and types of ginseng The species of ginseng are Panax ginseng C. A. Meyer (Korean ginseng), which is cultivated in Korea, Japan, China and Russia; Panax quinquefolius L.(American ginseng), which is raised in the eastern United States and Canada; Panax japonicus C. A. Meyer (Japanese ginseng), which is also called Bamboo ginseng; and Panax notoginseng (Burk) F. H. Chen (Sanchi-ginseng), a native of southwest China (Yunnan and Kwangsi Provinces). In Korea, Panax ginseng C. A. Meyer is collected after 2 to 6 years of cultivation, and it is classified into three types
In Functional Foods for Disease Prevention II; Shibamoto, T., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1998.
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depending on how it is processed: (a)freshginseng (less than 4 years old and can be consumed in the fresh state); (b) white ginseng (4-6 years old and then dried after peeling); and (c) red ginseng, which is harvested when 6 years old and then steamed and dried. Each type of ginseng was categorized further into several forms of ginseng products,freshsliced, juice, extract (tincture or boiled extract), powder, tea, tablet, capsule, and other forms (Fig. 1).
Long-term anticarcinogenicity experiment This investigation was carried out to evaluate the effects of ginseng in inhibition or prevention of carcinogenesis induced by various chemical carcinogens. Red ginseng extract (lmg/ml of drinking water) was administered orally to the weaned mice. Chemical carcinogens, 9,10-demethyl-l, 2-benzanthracene (DMBA, 30^ig), urethane (lmg), N-2 fuorenylacetamide (FAA, 100|ig x 5), aflatoxin Bj (8^ig),and Hansando tobacco smoke condensates (320^g) were injected in the subscapular region of ICR mice within 24 hours after birth. Controls comprised three groups of ICR newborn mice: normal (100), ginseng (200), and vehicle (316). The ten experimental groups of ICR newborn-mice comprised DMBA (101), DMBA combined with ginseng (103), urethane (94), urethane combined with ginseng (92), FAA (90), FAA combined with ginseng (88), aflatoxin B, (50), aflatoxin B combined with ginseng (47). In the MNNG group, MNNG (3mg) was injected subcutaneously into the backs of Wistar rats once a week for 10 weeks (5). The mice and rats autopsied immediately following sacrifice. All major organs were examined grossly and weighed. Histopathological examinations were also made. In the-group sacrificed at 48 weeks after the treatment with DMBA (DMBA combined with ginseng), the incidence of diffuse infiltration of pulmonary adenoma decreased by 61% (pO.Ol), and the average lung weight of male mice decreased by 21% (p
