General and Genetic Toxicology of Enzyme-Treated Ginseng Extract: Toxicology of Ginseng Rh2.
OBJECTIVE
Ginseng Rh2+ is enzyme-treated ginseng extract containing high amounts of converted ginsenosides, such as compound k, Rh2, Rg3, which have potent anticancer activity. We conducted general and genetic toxicity tests to evaluate the safety of ginseng Rh2+.


METHODS
An acute oral toxicity test was performed at a high-level dose of 4,000 mg/kg/day in Sprague-Dawley (SD) rats. A 14-day range-finding study was also conducted to set dose levels for the 90-day study. A subchronic 90-day toxicity study was performed at dose levels of 1,000 and 2,000 mg/kg/day to investigate the no-observed-adverse-effect level (NOAEL) of ginseng Rh2+ and target organs. To identify the mutagenic potential of ginseng Rh2+, we conducted a bacterial reverse mutation test (Ames test) using amino-acid-requiring strains ofSalmonella typhimuriumandEscherichia coli(E. coli), a chromosome aberration test with Chinese hamster lung (CHL) cells, and anin vivomicronucleus test using ICR mice bone marrow as recommended by the Korean Ministry of Food and Drug Safety.


RESULTS
According to the results of the acute oral toxicity study, the approximate lethal dose (ALD) of ginseng Rh2+ was estimated to be higher than 4,000 mg/kg. For the 90-day study, no toxicological effect of ginseng Rh2+ was observed in body-weight changes, food consumption, clinical signs, organ weights, histopathology, ophthalmology, and clinical pathology. The NOAEL of ginseng Rh2+ was established to be 2,000 mg/kg/day, and no target organ was found in this test. In addition, no evidence of mutagenicity was found either on thein vitrogenotoxicity tests, including the Ames test and the chromosome aberration test, or on thein vivoin mice bone marrow micronucleus test.


CONCLUSIONS
On the basis of our findings, ginseng Rh2+ is a non-toxic material with no genotoxicity. We expect that ginseng Rh2+ may be used as a novel adjuvant anticancer agent that is safe for long-term administration.
East West Cancer Center, Dunsan Korean Medicine Hospital of Daejeon University, Daejeon, Korea.
Mi-Kyung
MK
Jeong
East West Cancer Center, Dunsan Korean Medicine Hospital of Daejeon University, Daejeon, Korea.
Chong-Kwan
CK
Cho
East West Cancer Center, Dunsan Korean Medicine Hospital of Daejeon University, Daejeon, Korea.
Hwa-Seung
HS
Yoo
 compound K;  genotoxic;  ginseng;  ginsenoside;  toxicity; cancer
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