The correlation between chemical ingredients and acute toxicity of Psoraleae Fructus and two classic prescriptions

Objective: To compare the acute toxicity and chemical ingredients of Psoraleae Fructus (PF) with those of two classic prescriptions, Ershen Wan (ESW) and Sishen Wan (SSW). Methods: Based on classical toxicological methods, body weight, food and water consumption, lethal conditions, and toxic reactions were recorded after administering single oral doses of PF, ESW, and SSW. The 50% lethal dose (LD 50 ) values of PF and ESW and the maximum tolerance dose (MTD) of SSW were determined. In addition, PF, ESW, and SSW constituents were detected using ultra-high-performance liquid chromatography/mass spectrometry (UPLC-MS), and the spectrum-toxicity correlation was analyzed. Results: The LD 50 of PF and ESW were 53.9 g/kg/d (46.2–63.0 g/kg/d, 95% CL) and 68.3 g/kg/d (59.0–78.9 g/kg/d, 95% CL), which were respectively about 40 times and 50 times of the human daily dosage. The MTD of SSW was 41.0 g/kg/d, indicating the highest safety. The chemical ingredients and toxicity correlation analyses inferred that compatibility reduced the contents of 13 potential hepatotoxin compounds in PF. Conclusions: The classic compatibility of ESW and SSW effectively attenuated the hepatotoxicity of PF, which was related to the reduced content of potentially toxic substances, particularly coumarins. This study explored the principles of attenuating the toxicity of classic prescriptions to provide a reference for the rational clinical use of PF.