Experimental Study On Reducing Hepatotoxicity In Rats By Alcohol Extract Of Dodder And Tripterygium Wilfordii Polyglycoside

ObjectivesTripterygium wilfordii is a traditional Chinese medicine which was widely used for more than two thousand years in our country. Modern pharmacology study shows that it has anti-inflammatory and immune regulation, antibacterial, antitumor, inhibit reproductive effects of pharmacological activities, And therefore is widely used for a variety of diseases such as rheumatoid immune system disease, kidney disease, neural degeneration disease, tumor regression therapy and can be used in the treatment of transplant rejection after organ transplantation. But the toxicity of Tripterygium wilfordii is very obvious, and liver is the main target of its toxic effects. In this study, we focus on the most commonly used Glycosides Of Triptericium Wilfordii Hook.f (GTW), by using the method of animal experiments over conventional dose and high dose of GTW to evaluate its hepatotoxic effects, and on the basis of that we research on the ethanol extracts of Cuscutae Semen to reduce the hepatotoxicity of tripterygium wilfordii and to explore its pharmacological mechanism.Material and MethodsTime-toxicity relationship and model evaluation on rats liver injury caused by high dose of GTW:Wistar rats were given 150mg/kg/d of GTW orally, and were sacrificed after 1 week, 2 weeks, and 4 weeks. By observing Behavior and liver morphology, comparing the animal body weight, serological indexes and pathology changes, we could confirm the Time-toxicity relationship and model evaluation on rats liver injury caused by high dose of GTW.Study on the intervention effect of Cuscutae Semen ethanol extracts on high dose of GTW:Wistar rats were randomly divided into normal control group model group and treatment group. Model group were given 150mg/kg/d of GTW orally, treatment group were given 150mg/kg/d of GTW and 0.2mg/kg/d Cuscutae Semen ethanol extracts, normal control group were given deionized water. After 4 weeks of modeling all rats were sacrificed, than we can research on the intervention effect of Cuscutae Semen ethanol extracts on high dose of GTW on the aspects of cell apoptosis and proliferation.ResultsThe dynamic observation shows that high dosage of GTW could induce liver injury after 2 weeks of gavage, and shows significant changes in animal behavior, weight, liver morphology, serology, and liver pathology after 4 weeks.Study on the intervention effect of Cuscutae Semen ethanol extracts on high dose of GTW shows that Cuscutae Semen ethanol extracts can significantly reduce the hepatotoxicity on the aspects of animal behavior, weight, liver morphology, serology, and liver pathology, and we can see less apoptosis and proliferation induced by autophagy in liver tissues in the treatment group.ConclusionHigh dosage of GTW could induce explicit liver injury in rat, and it can be characterized by animal behavior, weight, liver tissue morphology and structure and serological indexes. Cuscutae Semen ethanol extracts can significantly reduce liver injury induced by high dose of GTW in rat, and decrease apoptosis and proliferation induced by autophagic cell death in liver, Supporting the validity of the principle of drug matching to reduce toxicity in traditional Chinese medicine, and Providing the basis for further research and development of Cuscutae Semen and make it an effective medicine to prevent and control drug-induced liver injury.