Subacute toxicity and stability of Soshiho-tang, a traditional herbal formula, in Sprague–Dawley rats

BACKGROUND Soshiho-tang (SST, Xiao-chai-hu-tang in Chinese and Sho-saiko-to in Japanese), an oriental herbal formula, is used for treatment of chronic liver diseases. Although many researchers have studied the pharmacological properties of SST, information about its safety and toxicity is limited. Therefore, we evaluated the potential safety of SST in Sprague-Dawley rats over a period of 4-weeks. METHODS The SST was administered once daily by gavage to male and female rats at doses of 0, 500, 1000 and 2000 mg/kg/day for 4 weeks. We measured the body weight, mortality, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross pathological findings, absolute/relative organ weights and histopathology. In addition, we analyzed the component of SST and measured the stability of its component in SST according to study periods using high performance liquid chromatography. RESULTS The SST treatment did not result in any toxicologically significant changes in mortality, food consumption, ophthalmoscopy, urinalysis, hematology, serum biochemistry, gross pathological findings, absolute/relative organ weights and histopathology, except for salivation and reduction in body weight in the 2000 mg/kg/day male group. These findings in the 2000 mg/kg/day male group are considered toxicologically insignificant because they are not accompanied by other pathological findings, including in hematology, serum biochemistry and histopatholgy, and they do not exhibit a dose-response relationship. SST is detected three components including liquiritin, baicalin, and glycyrrhizin. In addition, there were not observed the significant differences among the contents of three components in SST according to storage periods. CONCLUSION These results indicate that SST may be a safe material. Based on these results, the no-observed-adverse-effect level was more than 2000 mg/kg for both genders.