소시호탕의 유전독성시험 및 약물대사효소 기반 안전성 평가 = Safety Assessment Based on Sosiho-tang Genotoxicity Test and Drug-Metabolizing Enzymes

다국어 초록 (Multilingual Abstract)

Objectives: This study aimed to evaluate the safety of Sosiho-tang (SST) and to provide clinical guidance for patient medication by conducting genotoxicity assays and assessing drug-metabolizing enzyme activity.
Methods: A bacterial reverse mutation assay was performed using Salmonella typhimurium (TA100, TA1535, TA98, and TA1537) and Escherichia coli (WP2uvrA), both with and without metabolic activation with rat liver S9 mix. Also, we used an in vitro chromosomal aberration assay using Chinese hamster lung (CHL) cells and an in vivo micronucleus test using mouse bone marrow were conducted. Additionally, to predict potential herb-drug interactions, the inhibitory effects of SST on cytochrome P450 (CYP450) and uridine diphosphate (UDP)-glucuronosyltransferase (UGT) enzymes were evaluated.
Results: The Ames and chromosomal aberration tests revealed weak genotoxic potential of SST. SST induced a moderate, dose-dependent increase in the number of revertant colonies in TA1537. In the WP2uvrA strain, revertant colonies increased 2.3-fold at 5,000 μg/plate with S9 mix. SST also induced chromosomal abnormalities at concentrations above 800 μg/mL, suggesting that it may be a potential mutagenic agent. However, the in vivo micronucleus test showed no evidence of genotoxic activity. SST inhibited the activities of CYP1A2, 2B6, 2C9, and UGT1A1, 1A4, and 2B7 in a concentration-dependent manner, though all IC50 values remained above 200 μg/mL.
Conclusions: Under these experimental conditions, SST is considered to have a low likelihood of manifesting genotoxicity in vivo. SST exhibited a relatively low risk for herb-drug interactions involving medications metabolized by the assessed CYP450 and UGT enzymes.