Acute and 28-Day Repeated-Dose Oral Toxicity of the Herbal Formula Guixiong Yimu San in Mice and Sprague–Dawley Rats

SIMPLE SUMMARY: Postpartum uterine diseases of dairy cows include retained placenta (RP) and puerperal metritis (PM). Cows suffering from a retained placenta are at an increased danger of developing puerperal metritis or endometritis, and subsequent decreased fertility. The dominant approach to a retained placenta in cows is the local or systemic administration of antibiotics; however, current reports point to the low efficacy of intrauterine and systemic antibiotics in accelerating the separation and removal of the retained placenta. Therefore, substitute approaches to cope with these two disorders in postpartum cows should be developed. Herbal medicines are considered good alternatives to allopathic medicine, and some ethno-veterinary medicines are often used to treat the RP in cows. GYS is primarily used to treat postpartum blood stasis syndrome caused by retained placenta. It was designed based on the therapeutic role of enhancing the blood flow and removing blood stasis, maintaining the qi movement, and releasingthe pain.It can create a very promising state for prior placental detachment and the spontaneous discharge of the RP, but its toxicity has not been completely assessed. In the present study, we demonstrated that GYS did not have any therapeutic side effects in rats, thus providing a practical approach for the clinical control of a retained placenta. ABSTRACT: To evaluate the acute and chronic 28-day repeated-dose oral toxicity of Guixiong Yimu San (GYS) in mice and rats, high-performance liquid chromatography (HPLC) was used to determine the stachydrine hydrochloride in GYS as the quality control. In the acute toxicity trial, the mice were administered orally at a dose rate of 30.0 g GYS/kg body weight (BW) three times a day. The general behavior, side effects, and death rate were noticed for 14 days following treatment. In the subacute toxicity trial, the rats were administered orally at a dose rates of30.0, 15.0, and 7.5 g GYS/kg BW once a day for 28 days. The rats were monitored every day for clinical signs and deaths; changes in body weight and relative organ weights (ROW) were recorded every week, hematological, biochemical, and pathological parameters were also examined at the end of treatment. The results showed that the level of stachydrine hydrochloride in GYS was 2.272 mg/g. In the acute toxicity trial, the maximum-tolerated dose of GYS was more than 90.0 g/kg BW, and no adverse effects or mortalities were noticed during the 14 days in the mice. At the given dose, there were no death or toxicity signs all through the 28-day subacute toxicity trial.The oral administration of GYS at a dose rate of 30.0 g/kg/day BW had no substantial effects on BW, ROW, blood hematology, gross pathology, histopathology, and biochemistry (except glucose), so 30.0 g/kg BW/day was determined as the no-observed-adverse-effect dosage.