Effects of Psoraleae Crude Plysaccharide on Metabolism and Toxicity/Efficacy Relationship of Coumarin Components from Psoraleae Fructus Based on Zebrafish Integrated Evaluation

OBJECTIVE To evaluate the effects of psoraleae crude polysaccharide(PPS) on metabolism and toxicity/efficacy relationship of coumarin components of Psoraleae Fructus(CCPF) by zebrafish integrated evaluation. METHODS Zebrafish(1-6 days post fertilization, dpf) was used to evaluate the safety of CCPF, PPS and their combination; the morphologies of zebrafish organs was observed and the number of deaths was recorded and the half death concentration of zebrafish(LC₅₀) was calculated. Zebrafish(1-6 dpf) were exposed to CCPF and its combination with PPS; the dynamic changes of psoralenoside and isopsoralenoside and their metabolites psoralen and isopsoralen were analyzed. The zebrafish osteoporosis model was induced with 25 μmol·L^-1 prednisolone; microscopic observation and digital imaging of zebrafish larvae of each treatment group cultured to 8 dpf were performed using alizarin red, and the bone staining area was quantitatively analyzed by image software to evaluate the anti-osteoporosis activity of above samples. RESULTS Evaluation of the safety of CCPF, PPS and their combination by interaction with zebrafish juveniles. The toxicity of the combination of CCPF and PPS to zebrafish was greater than that of CCPF or PPS alone, and the toxicity increased with the increase of the proportion of PPS: PPS reduced the poisoning concentration of zebrafish, causing serious morphological distortion of zebrafish organs, shortening the death time of zebrafish and increasing the death rate of zebrafish. PPS obviously accelerated the deglycosylation of psoralenoside and isopsoralenoside in CCPF into psoralen and isopsoralen, which were potential metabolites of liver injury. CCPF and its combination with PPS increased the mineralized area and cumulative optical density of zebrafish skull and the combination had a certain synergistic effect, which suggested that PPS increased the anti-osteoporosis activity of CCPF to some extent. CONCLUSION Based on the integrated evaluation of zebrafish, the effects of PPS on the metabolism and toxicity/efficacy relationship of CCPF are revealed, which provides an efficient method and idea for revealing the toxicity/efficacy relationship action of PPS on other structural components.