A 13-week Repeated Oral Dose Toxicity Evaluation and a 4-week Recovery Evaluation of the Sam So Eum (SSE) in Male and Female Rats

Ethnophamacological relevance: Sam So Eum (SSE), used in traditional Korean medicine, has been prescribed for the treatment of various ailments including emesis, and fever for centuries. SSE is known by several different names (Shen Su Yin in traditional Chinese medicine; Jin So In traditional Japanese Kampo medicine). It is a mixture of medicinal plants including Panax ginseng C. A. Mey., Perilla frutescens (L.) Britton, and Peucedanum praeruptorum Dunn. Studies have revealed that SSE has many pharmacological effects including anti-inflammatory, anti-cancer, and anti-allergic properties, but its toxic effects have not been evaluated in vivo. Recently, the use of traditional medicinal herbs to treat various diseases has increased, owing to increased number of studies supporting their efficacy. However, safety evaluations for toxicity and other adverse effects have not been extensive. It is commonly considered that natural products extracted from traditional medicinal herbs are safer than synthetic drugs, but this lacks a scientific basis. Thus, in this study, we evaluated the toxicity of SSE in male and female rats.

Aim of the study: To evaluated the safety of SSE in male and female rats.

Materials and methods: SSE was administered orally for 13 weeks at 1000, 2000, and 4000 mg kg^-1·day^-1, and then the rats were maintained for 4 weeks without SSE administration (recovery evaluation).

Results: We observed the animals for changes in clinical signs, including hematological parameters, and food consumption; serum chemistry profiling and urinalysis were also carried out. Creatinine levels in the serum were significantly increased following oral administration of SSE at 2000 and 4000 mg kg^-1·day^-1 in male and female rats, but returned to the normal levels during the recovery period. In addition, SSE administration does not cause kidney and liver toxicity. Thus, we determined that the no-observed-adverse-effect level of SSE is 4000 mg kg^-1·day^-1. The no-observed-effect level of SSE was determined to be 1000 mg kg^-1·day^-1, because serum creatinine was increased by oral administration of SSE at 2000 and 4000 mg kg^-1·day^-1 in male and female rats.

Conclusions: SSE administration does not cause toxicity at 4000 mg kg^-1·day^-1 in male and female rats.

Keywords: Oral dose toxicity evaluation; Sam so eum; Traditional medicine.