Safety evaluation of <i>Gamisoyo-san</i>: genotoxicity, acute toxicity, and influence on drug-metabolizing enzymes

Gamisoyo-san is an herbal formula widely used to treat psychological issues, menopausal symptoms, and dysmenorrhea. However, there is insufficient information on its safety profile. This study aimed to confirm the genotoxic and acute toxic potential of Gamisoyo-san. We performed a battery of tests, which included a bacterial reverse mutation test (Ames test) using five bacterial strains, an in vitro chromosomal aberration test using Chinese hamster lung (CHL) cells, an in vivo micronucleus test in mice, and human Cytochrome P450 (CYP450) and UDP-glucuronosyltransferase (UGT) assays. In the acute toxicity study, male and female rats were orally administered Gamisoyo-san 1000, 2000, or 5000 mg/kg and observed for 14 days. The activities of human CYP450s and UGTs were evaluated using recombinant baculosomes. Gamisoyo-san showed no signs of genotoxicity in the five bacterial strains, CHL cells, or mouse bone marrow cells. The acute toxicity test showed that the median lethal dose (LD50) of Gamisoyo-san was greater than 5000 mg/kg in rats. Gamisoyo-san inhibited the activities of CYP1A2, CYP2C19, and UGT1A1. In conclusion, Gamisoyo-san may not exert severe toxicological events or genotoxic effects at doses up to 5000 mg/kg in rats.