Research On The Correlation Between Material Basis And Toxicity Of Radix Et Rhizoma Sophorae Tonkinensis

OBJECTIVE: To lock the toxical material basis of Radix et Rhizoma Sophorae Tonkinensis(RRST) according to the content detection and the comparison of the acute toxicity and hepatotoxicity of different components of RRST in mice. To settle questions such as the dosage range, the occurrence time, sensitive index, reversibility and the after effect of toxicity through the chronical toxicity study of the clinical common formulation which is rich in toxical material basis. And the experimental basis to be offered by these studies to the safe and rational use of RRST.METHODS: HPLC was used to determine the content of matrine and oxymatrine in all-components, water extract, alcohol extract and percolate extract of RRST. The classical acute toxicity methods were used in the acute toxicity of these different components.The hepatotoxicity of water extract and alcohol extract of RRST was researched through the multiple intragastic administration to mice and the chronical toxicity of water extract was researched.RESULTS: In the determination of matrine and oxymatrine in different components of RRST, it was found that the order of the content of matrine was: water extract> percolate extract> alcohol extract> all-component, and the content of oxymatrine is: all-components> percolate extract> alcohol extract> water extract. The MTD of all-components of RRST was 10.68 g·kg^-1. The LD₅₀ of water extract, alcohol extract and total alkaloid extract of RRST were 17.469 g·kg^-1, 27.135 g·kg^-1, 13.399 g·kg^-1 in mice. The order of mortality of different components in RRST in the same dosage was percolate extract> water extract> all-components> alcohol extract. Restlessness, breathlessness and convulsion were the main acute toxical symptoms. After the intragastic administration of RRST over certain dosage and time, the activities of ALT, AST, AKP and contents of TBI increased, while the contents of ALB decreased. The ratio of liver to body increased and histopathological changes such as acidophilic change, edema, focal necrosisi and patchy necrosis occurred. The changes caused by the water extract is more obvious than that of alcohol extract. After the intragastic administration of water extract with different dosages, the rats were in a poor general condition. The body weight, appetite and water decreased. The activities of ALT, AST and AKP increased. The ratio of liver to body increased and pathological examination showed hepatic injury with different degree. There was little effect on blood routine. There was a certain correlation between hepatic injury degree and dosage. Parts of pathological changes were irreversible.CONCLUSION: The matrine was locked to be the main toxical material basis through the content detection of relevent material basis matrine and the acute toxicity test of different components of RRST. Oxymatrine has little influence on the toxicity of RRST. The liver and nervous were considered to be the toxicity targets. The experimental basis was offered to the determination of toxical components of RRST and the elucidation of toxicity targets. The foundation was layed for reducing clinical adverse reactions, and guiding safe and rational use of RRST in clinical simultaneously.