Study On The Efficacy And Safety Of Low Toxic And High Efficient Parts Of Tripterygium Wilfordii

Tripterygium wilfordii is a traditional Chinese medicine with pharmacological effects on intractable diseases,such as rheumatoid arthritis and nephrotic syndrome.It is shown that Tripterygium wilfordii and its main components—diterpenoids compounds and triterpenes compounds have a wide range of pharmacological effects,especially anti-inflammatory effect and immuno-suppressive effect.Nowdays,it is commonly used in the treatment of rheumatoid arthritis,nephrotic syndrome and systemic lupus erythematosus.But at the same time,many patients can not long-term use of it and have poor compliance because of the toxicity of Tripterygium wilfordii.Today,the extraction and purification of Tripterygium wilfordii are simple.The composition of Tripterygium wilfordii is complex and its mechanisms of effect and toxicity are not clear.At the same time,there is difference between the indicator selection and the method evaluation of Tripterygium wilfordii.Those make Tripterygium wilfordii produced by different manufacturers have great differences in efficacy and side effects.In addition,the problem of tolerability has not been effectively solved,which restricts its usage in clinical.Therefore,it is a feasible thought to prepare Tripterygium wilfordii preparations with low toxicity and high effect,and establish a scientific and effective method to evaluate and control the quality of Tripterygium wilfordii preparations by improving the methods of extraction and purification on the basis of clarifying the efficient and main toxic components of Tripterygium wilfordii.On the basis of establishing fingerprints of Tripterygium wilfordii,the previous research group clarified the main efficient and toxic components guiding by the spectrum effect analysis,and prepared different proportion of purified parts.This present study is to evaluate the differences in low toxic and high efficient of different purified parts of Tripterygium wilfordii in vitro and in vivo,and selects some purified parts according to the low toxic and high efficient requirements.And then evaluate the effect of treatment of rheumatoid arthritis and safety,which lay the foundation for preparing low toxic and high efficient preparations of Tripterygium wilfordii and developing quality standards of Tripterygium wilfordii.The research object of this study in vitro is 18 purified parts:Petroleum ether-Ethyl acetate elution(Plan A)to get A1-A8,Dichloromethane-Methanol(Plan B)to get B1-B10.The reference is tripterygium glycoside tablet made by Jiangsu Meitong.The mouse spleen lymphocyte stimulated by LPS are used to evaluate the anti-inflammmatory effect of purified parts of Tripterygium wilfordii.The content of TNF-? and IL-6 are determined as the index.The mouse spleen lymphocyte stimulated by Con A are used to evaluate the immunesuppression effect of purified parts of Tripterygium wilfordii.The content of IFN-? and IL-2 are determined as the index.Choose myocardial cell(H9c2),liver cell(L-02),mesangial cell(GNM-SV40)to evaluate the carditoxicity,renaltoxity and hepatotoxicity.The results show that B3,B7,and B10 have high efficiency and low toxicity,which are corresponding with requirements.Therefore,they are selected for subsequent studies in efficacy and toxicity in vivo.The research object is B3?B7 and B10 in vivo.The reference is tripterygium glycoside tablet made by Jiangsu Meitong.The paw swelling in rats induced by carrageenan and ear swelling in mice induced by xylene are used to evaluate the anti-inflammmatory effect of B3?B7 and B10.The delayed hypersensitivity to DNFB in mice is used to evaluate the immunesuppression effect of B3?B7 and B10.The Adjuvant Arthritis is used to evaluate the effect of B3?B7 and B10 about treating rheumatoid arthritis disease.Acute toxicity in mice and long-term toxicity in rats are used to evaluate the range of safe dose and toxicity in vivo.The results of efficacy in vivo show that B3,B7 and B10 all have strong activity,especially the B10.The results of toxicity in vivo show that the toxicity of B10 is the least,and B10 has the most obvious advantage.Therefore,B10 is the most ideal low toxic and high efficient part of Tripterygium wilfordii.Finally,this study determines that B10 is low toxic and high efficient part of Tripterygium wilfordii,and identifies the extraction and purification,which lay the foundation for preparing low toxic and high efficient preparations of Tripterygium wilfordii and developing quality standards of Tripterygium wilfordii.At the same,it is also significant to use Tripterygium wilfordii in clinical.