| Objective:Tripterygium wilfordii is a commonly used traditional chinese medicine for the treatment of immune abnormalities such as rheumatoid arthritis,but its toxicity severely limits its clinical use.Previous studies have found that Xiaoyaosan has anti-hepatotoxicity effect of Tripterygium wilfordii,but its medicinal taste is numerous,which is not conducive to clinical application.The simplified prescription of Xiaoyaosan is composed of traditional thinese medicine.The experiment verifies whether the simplified prescription of Xiaoyaosan can also relieve the hepatotoxicity of Tripterygium wilfordii without affecting the therapeutic effect of Tripterygium wilfordii.Methods:Study 1: From the four databases of Chinese medicine prescription database,Chinese herbal medicine database,Chinese herbal medicine chemical composition database,disease/symptom target database,the traditional thinese medicine composition of Xiaoyaosan was input into the integrated pharmacological computing platform,and the "hepatotoxicity" was used as the disease keyword to retrieve,through the " traditional thinese medicine-chemical composition-key target-pathway" multi-level association network diagram as well as the " traditional thinese medicine-chemical composition-key target-pathway" database.The key target was to analyze the main antidote of Xiaoyaosan.Study 2 :On the basis of AA model,the attenuation effect of Xiaoyaosan simplified formula on hepatotoxicity of Tripterygium Wilfordii in the treatment of rheumatoid arthritis was verified.Rats were randomly divided into 10 groups: blank group,model group,Tripterygium wilfordii group,Xiaoyuan group,simple low group,simple middle group,simple high group,non-core group,liver protection group and similar Yang group.The blank group and model group were given normal saline in the morning and afternoon;the other groups were given Tripterygium wilfordii solution(6.5 g/kg)in the morning and Xiaoyuan group(6.75 g/kg)in the afternoon;the new low group was given simple low prescription solution(3.375 g/kg);the new middle group was given simple Chinese prescription solution(6.75 g/kg);the new group was given simple high prescription solution(13.5 g/kg),and the non-core group was given simple high prescription solution(13.5 g/kg).In the afternoon,non-core traditional thinese medicine solution(6.75 g/kg)was administered;Huganning liquid was administered in Baogan group;and total paeonyglycosides liquid was administered in Liyang group.The traditional thinese medicine was administered continuously for 28 days.During the experiment period,the degree of foot swelling and body weight of rats were measured weekly.After killing animals,the indexes of ALT,AST,TNF-a,SOD and MDA were measured in serum.The liver weight of rats was weighed to calculate the organ index.Another part of liver tissue was taken to measure Nrf2.Finally,the liver and ankle joints were made into pathological sections and observed and scored.Results:Study 1: The key targets of Xiaoyaosan for detoxification of Tripterygium wilfordii were GCK,COX7 C,ATP1A1 and ATP5C1 through integrated pharmacological platform.Through searching the key targets,we found that the GCK-related traditional thinese medicine were Paeonia lactiflora and Licorice;the COX7C-related traditional thinese medicine were Poria cocos and Licorice;the ATP1A1-related drugs were Angelica,Paeonia lactiflora,Bupleurum,Licorice;the ATP5C1-related drugs were Paeonia lactiflora,Bupleurum.Licorice.The first four key targets synthetically analyzed that the main detoxification traditional thinese medicine in Xiaoyaosan might be Paeonia lactiflora,Poria cocos,Angelica sinensis,Bupleurum chinense and Glycyrrhiza uralensis.Study 2 : Compared with the normal group,the levels of ALT and AST in the Tripterygium wilfordii group are significantly higher than those in the blank group(P <0.01);compared with the Tripterygium wilfordii group,the levels of ALT and AST in the original group,the middle group,the high group and the hepatoprotective group are significantly lower than those in the Tripterygi Compared with the blank group,the serum MDA level in the Tripterygium wilfordii group increased significantly(P < 0.05);compared with the Tripterygium wilfordii group,the serum MDA level in the Xiaoyuan group decreased significantly(P < 0.05),while that in the simple high group decreased significantly(P < 0.05).Compared with the blank group,the SOD level in Leigong group increased significantly(P < 0.01).Compared with Leigong group,the levels of Xiaoyuan group,Jianzhong group,Jiangao group and Baogan group were all higher(P < 0.01).Compared with the blank group,the pathological score of Tripterygium wilfordii group was significantly higher(P < 0.01);compared with Tripterygium wilfordii group,the pathological score of Xiaoyuan group,simple low group,simple middle group,simple high group,liver protection group and non-core group was significantly lower(P < 0.01).Compared with the blank group,the liver index of the Tripterygium wilfordii group increased significantly(P < 0.01);compared with the Tripterygium wilfordii group,the liver index of the Xiaoyuan group,the simple low group,the simple high group,the liver protection group and the non-core group decreased significantly(P < 0.01),and the liver index of the simple middle group decreased significantly(P < 0.05).Compared with the blank group,the level of model group increased significantly(P < 0.05);compared with model group,the level of Xiaoyuan group decreased(P < 0.05),while that of simple high group decreased(P < 0.05).Conclusion:Xiaoyaosan simplified prescription has detoxification effect on the hepatotoxicity of tripterygium wilfordii in the treatment of rheumatoid arthritis,among which xiaoyaosan simplified prescription medium dose effect is lower than the original prescription of xiaoyaosan,xiaoyaosan simplified prescription high dose is better than the original prescription of xiaoyaosan. |
PDF Full Text Request