Study On Toxicity Observation And Rational Processing Use Of Radix Et Rhizoma Rhei On The Basis Of Hepatic Injury Animal Model

In renent years,the Adverse Drug Reaction (ADR) of Chinese Materia Medica occurred frequently.These ADR events not only endanger the people's health but also suffer the sustainable development of Chinese Materia Medica.As one of four common herbs,Radix et Rhizoma Rhei is usually used to treat icteric hepatitis,chronic renal failure,constipation and acute pancreatitis.However,it is reported that it could cause hepatotoxicity, nephrotoxicity and carcinogenicity because of containing anthraquinone,"toxic component",such as archen.Meanwhile,Radix Polygoni Multiflori as another anthraquinone-containing drug is reported could cause hepatotoxicity occasionally.Therefore, Based on one of national NO.15 project of tackle key problems in science and technology,"study on the Adverse Drug Reaction and security of Radix et Rhizoma Rhei and its compound preparation", this paper investigated Radix et Rhizoma Rhei's and its processed and compound products'security using CCL4 acute and chronic hepatic injury animal models,aimed to offer some accordances for Radix et Rhizoma Rhei's clinical rational use.Through observing the toxic reactions of CCL4 acute hepatic injury mice which administered the total extractive of Radix et Rhizoma Rhei,this research investigated the safety coefficient of the total extractive of Radix et Rhizoma Rhei when it was used to treat hepatopathy.The results showed that Radix et Rhizoma Rhei could made the ALT serum content and the acute hepatic histopathology variations of CCL4 acute hepatic injury mouse impoved remarkably(P<0.01).These hinted that Radix et Rhizoma Rhei could protect hepar from CCL4 acute hepatic injury.Through observing the toxic reactions of CCL4 chronic hepatic injury rats which administered the total extractive of Radix et Rhizoma Rhei and its processed and compound products for three months and recovered for one month, this research investigated the security of Radix et Rhizoma Rhei when it was used to treat chronic hepatopathy,aimed to offer an accordance for clinical medication.The reaults showed that the minimum toxic dose of the total extractive of Radix et Rhizoma Rhei is 20g(crude drug)·kg-1·d-1(equal to 40 times of pharmacopeia max dose);the minimum toxic dose of prepared Radix et Rhizoma Rhei is 40g(crude drug)·kg-1·d-1(equal to 80 times of pharmacopeia max dose); the minimum toxic dose of Dahuangzhechongwan is 44g(crude drug)·kg-1·d-1(equal to 220 times of pharmacopeia max dose).Kidney and hepar were the probalbly toxic target organs,meanwhile, kidney impairment was reversible.The results showed that Radix et Rhizoma Rhei was safe if used normally,but it was toxical when it was used with large dose and for a long time.Therefore,the toxicity of Radix et Rhizoma Rhei was objectively existed.Secondly,after processing and compounding Radix et Rhizoma Rhei's toxicity was reduced and its'action was improved.This result validated that the theory of traditional Chinese medicine that processing and componding could reduced the drugs'toxicity was scientific and objective.As well as,compared with normal animal's toxic actions which administered Radix et Rhizoma Rhei investigated by others of this project,the results showed that the toleration of hepatic injury animal was larger than normal animal.It hinted that differentiation of symptoms and signs could reduce the Radix et Rhizoma Rhei's toxicity,and Radix et Rhizoma Rhei's hepatoprotective action and toxicity had"double"effect.It further confirmed that differentiation of symptoms and signs was the important route of attenuation theory of traditional Chinese medicine,and also confirmed the view of Qing dynasty great physician Zhangxichun that although Radix et Rhizoma Rhei was a fierce eliminate,it was safe even with large dose when it was used in correct symptoms and signs.Processing attenuation,componding attenuation and differentiation of symptoms and signs attenuation are the peculiarity and great preponderance of traditional Chinese medicine.The results of this research gave an accordance to stick up for the great preponderance and good prestige of Chinese materia medica security.This mode could used for the demonstration investigation of Chinese materia medica safety evaluation.