Genotoxicity and acute toxicity of Hyunburikyung-tang: assessing the safety of prescribing traditional Korean medicine for dysmenorrhea

Hyunburikyung-tang exerts an anti-inflammatory effect by suppressing pro-inflammatory cytokines and prostaglandin E2 and is clinically used to improve dysmenorrhea in Korea. It contains various medicinal plants including peach seeds (Prunus persica Batsch) and safflower (Carthamus tinctorius Linn). Peach seeds contain amygdalin, which demonstrates teratogenic effects, and safflower is reported to cause reproductive toxicity and teratogenic effects in mice. These findings raise concerns regarding the teratogenic potential of these substances. A potential correlation exists between genotoxicity and teratogenicity. Genotoxic substances can damage DNA and cause mutations or chromosomal abnormalities, which may result in developmental malformations. Therefore, we aimed to assess whether Hyunburikyung-tang causes acute toxicity or genotoxicity. Seven-week-old male and female Sprague-Dawley rats were orally administered a single dose of Hyunburikyung-tang to assess acute toxicity (625, 1,250, or 2,500 mg/kg). Body weight measurements, general symptom observations, and autopsy examinations were used to confirm toxic responses according to Toxicity Test Guidelines for Drugs, etc. [No. 2022-18, the Ministry of Food and Drug Safety (MFDS) of the Republic of Korea]. Genotoxicity assessment was conducted with bacteria, cells, and mice, according to the organization for economic cooperation and development test guidelines (TG 471, TG473, and TG474). Regarding the acute toxicity assessment, oral administration of Hyunburikyung-tang at doses up to 2,500 mg/kg in male and female rats did not result in body weight loss (p > 0.05), and general symptoms including death, weakening, irregular respiration etc. was did not observed. Upon necropsy, no visible damage was observed in major organs such as the liver and heart. Hyunburikyung-tang not only showed no mutagenic activity in the Bacterial reverse mutation test, but also did not significantly increase the incidence of chromosomal aberrations or the frequency of micronuclei in bone marrow (p > 0.05). Moreover, in the in vitro test, no genotoxicity was induced when metabolic activation by rat liver fractions was applied to mimic hepatic metabolism. Our findings suggested that Hyunburikyung-tang does not induce acute toxicity or genotoxicity. Nevertheless, follow-up research should be conducted to confirm toxicity caused by repeated administration and adverse effects on embryonic cells.