| Background:"Eighteen antagonisms" is an important part of the controversial prohibited combinations in traditional Chinese medicine.Seaweed and Liquorice are one of a compatibility of the eighteen antagonisms,should they be used in clinic or not that different people have different ideas.Part of doctors think that the controversial prohibited combinations were summarized the clinical experience of the ancients,Both used of the body might be produce toxic side effects;while others believe physicians with the use of anti-drug can treat chronic ills.Therefore,in order to solve this problem,many scientific researches have been done different studies.They were mainly focus on single medicinal combinations,however,to explore the essence of the controversial prohibited combinations needs to combine pathological models.Our completed experimental study selected Haizao Yuhu decoction and thyroid enlargement pathological model,change the compatibility proportion,dosage and prepared varieties to reveal the relation between Haizao and Gancao,and its suitable/contraindicated conditions of this prohibited combination,this experiment will continue to explore the basis of previous studies.Purpose:We chose a dose close to clinical application,valid and not showed significant toxicity with seaweed and liquorice specific ratio,specific doses and different varieties in Haizao Yuhu decoction to do experimental study.This study include the whole full formula group of Haizao Yuhu decoction,full formula group removed seaweed,full formula group removed liquorice,full formula group removed seaweed and liquorice.The study will investigate that the "effect" of Haizao Yuhu decoction is associated with the anti-drug combination.Method:?Early researches had studied acute toxicity of seaweed,liquorice,seaweed with liquorice and Haizao Yuhu decoction.The results showed that seaweed and seaweed with prepared Licorice belong to a small toxicity of LD50.Liquorice,prepared licorice,Haizao Yuhu decoction(liquorice),Haizao Yuhu decoction(prepared licorice)showed no toxicity.So in order to explain the "effect" or "toxicity" of anti-drug combinations,we choose the whole full formula group of Haizao Yuhu decoction,full formula group removed seaweed,full formula group removed liquorice,full formula group removed seaweed and liquorice to do the study of LD50(n).?The effect and toxicity of Haizao Yuhu decoction with different proportions of seaweed and liquorice in goiter rats,the proportion of group four(liquorice:seaweed is 4.84:2.08)can inhibit thyroid enlargement induce by PTU in some degree,and do not show significant toxicity of heart,liver and kidney.In addition,the proportion of group four transformed adult dosage that were close to the doses of "People's Republic of China Pharmacopoeia·I ",so we will choose this proportion to do the next sthdy.The Chinese medicine prescription optimization software of analysis and calculation,the Haizao Yuhu decoction with liquorice:seaweed compatibility proportion in 9:5.5 application,the effect is best.Therefore,according to the proportion of different doses of set dose group(liquorice:seaweed =27g:16.5g),dose group two(liquorice:seaweed =9g:5.5g),dose group three(liquorice:seaweed =3g:1.83g),dose group four(liquorice:seaweed=1g:0.61g).The results show that the dose group four can inhibit thyroid enlargement induce by PTU in some degree,and do not show significant toxicity of heart,liver and kidney.In addition,the dose group four transformed adult dosage that were conform with the doses of "People's Republic of China Pharmacopoeia·I",so we will choose this proportion to do the next sthdy,Haizao Yuhu decoction with a ratio of Radix Glycyrrhizae:Sargassum is 9:5.5 application compatibility,different processing varieties at different levels can improve the related thyroid content caused by propylthiouracil abnormal hormone levels in hypothyroid rats.According to the above results we will choose the whole full formula group of Haizao Yuhu decoction,full formula group removed seaweed,full formula group removed liquorice,full formula group removed seaweed and liquorice to do the study,we can investigate that the"effect" of Haizao Yuhu decoction is associated with the anti-drug combination,and at the same time we can verification the earlier experimental results.Result:1.Experiment of Acute toxicity or the LD50(n)There is no LD50 of every group which was treated by different drug.The mice were fed with Haizao Yuhu decoction(liquorice),Haizao Yuhu decoction(prepared licorice),Haizao Yuhu decoction removed liquorice,Haizao Yuhu decoction removed seaweed(liquorice),removed seaweed and liquorice,which groups reached lethal dose after 16,3,12,22,21 days,and which LD50(n)were 71.08?68.28?55.78?72.27?79.62g/kg.The mice were fed Haizao Yuhu decoction removed(prepared licorice)for 28 days,however,it could not to be up to the LD50,so the maximum dose was definited the maximum tolerated dose which is 80g/kg respectively.After the end of the experiment,we detect relevant indicators of liver and kidney function on mice,and do not show significant toxicity2.The biological effect and mechanism of Haizao Yuhu decoction plus or minus seaweed and liquorice anti-drug combination on rats in preferred compatibility proportion conditions(1)Efficacy evaluationThe thyroid coefficient of Haizao Yuhu decoction full formula group,full formula group removed seaweed,full formula group removed liquorice,full formula group removed liquorice and seaweed obviously reduces,and had the significant difference(p<0.05);the full formula group,full fonnula group removed seaweed and liquorice had a trend of increase of T3 compared with the model group in rat but had no significant difference.Compared with full formula group,T3 of full formula group removed liquorice decrease obviously and had the significant difference(p<0.05);the full formula group had a trend of increase of T4 compared with the model group in rat but had no significant difference.Compared with model group,T4 of full formula group removed seaweed and liquorice decrease obviously and had the significant difference(p<0.05);Compared with model group,urinary iodine of each groups had a trend of increase but had no significant difference.(2)Toxicity CharacterizationLiver function:The liver coefficient of Haizao Yuhu decoction full formula group,full formula group removed seaweed,full formula group removed liquorice,full formula group removed liquorice and seaweed were higher than the model group,but had no significant difference.Compared with model group,ALT of full formula group decrease obviously and had the significant difference(p<0.05),AST of full formula group had a trend of decrease.Compared with full formula group,ALT and AST of full formula group removed seaweed,full formula group removed liquorice,full formula group removed liquorice and seaweed had a trend of increase but had no significant difference.Compared with model group,ALB of full formula group decrease obviously,ALB of full formula group removed liquorice and seaweed increase obviously and had the significant difference(p<0.05).Compared with model group,ALB of full formula group removed seaweed,full formula group removed liquorice,had a trend of decrease but had no significant difference.Compared with model group,TP of full formula group,full formula group removed liquorice increase obviously and had the significant difference(p<0.05)Kidney function:The kidney coefficient of Haizao Yuhu decoction full formula group was higher than the model group,full formula group removed seaweed,full formula group removed liquorice,full formula group removed liquorice and seaweed were lower than the model group but had no significant difference.Compared with model group and full formula group,BUN of full formula group removed seaweed,full formula group removed liquorice and seaweed increase obviously and had the significant difference(p<0.05);Compared with model group,UA of full formula group removed liquorice decrease obviously and had the significant difference(p<0.05);Compared with model group,full formula group removed seaweed,full formula group removed liquorice,blood sodium of full formula group removed liquorice and seaweed increase obviously and had the significant difference(p<0.05),blood sodium of full formula group removed had a trend of increase but had no significant difference.Compared with model group,urinary sodium of full formula group removed liquorice and seaweed decrease obviously,urinary potassium of full formula group removed seaweed decrease obviously and had the significant difference(p<0.05).Cardiac function:The cardiac coefficient of full formula group removed liquorice,full formula group removed liquorice and seaweed were higher than the model group,full formula group,full formula group removed seaweed had a trend of decrease but had no significant difference,Compared with full formula group,the cardiac coefficient of full formula group removed seaweed increase obviously and had the significant difference(p<0.05).Compared with model group and full formula group,CK of full formula group removed liquorice and seaweed increase obviously and had the significant difference(p<0.05).Oxidative Stress:Compared with model group,SOD of full formula group removed seaweed increase obviously,full formula group removed seaweed and liquorice decrease obviously and had the significant difference(p<0.05).Compared with model group,MDA and GSH-PX of each groups had a trend of decrease but had no significant difference.(3)MechanismThyroid:Compared with model group,TPO mRNA of Haizao Yuhu decoction full formula group,full formula group removed seaweed,full formula group removed liquorice,full formula group removed seaweed and liquorice decrease obviously and had the significant difference(p<0.05);Compared with model group,Tg mRNA of each groups increase obviously and had the significant difference(p<0.05),Compared with model group.Tg in serum of full formula group decrease obviously and had the significant difference(p<0.05),other groups had a trend of decrease but had no significant difference.Liver:Compared with model group,CYP2E1 mRNA of Haizao Yuhu decoction full formula group,full formula group removed seaweed,full formula group removed liquorice,full formula group removed seaweed and liquorice decrease obviously and had the significant difference(p<0.05);CYP3A1 mRNA of full formula group,full formula group removed seaweed,full formula group removed liquorice increase obviously and had the significant difference(p<0.05).Compared with model group,CYP3A2 mRNA of each groups had a trend of increase but had no significant difference.Compared with model group,CYP2E1 protein expression of full formula group removed seaweed,full formula group removed liquorice decrease obviously and had the significant difference(p<0.05),full formula group,full formula group removed seaweed and liquorice had a trend of decrease but had no significant difference.3.The biological effect and mechanism of Haizao Yuhu decoction plus or minus seaweed and liquorice anti-drug combination on rats in preferred dosage conditions(1)Efficacy evaluationThe thyroid coefficient of each groups were lower than the model group and had the significant difference(p<0.05).Compared with model group,T3 and T4 of each groups had a trend of increase but had no significant difference.TSH of each groups decrease obviously and had the significant difference(p<0.05).Compared with model group,TBG of full formula group removed liquorice,full formula group removed seaweed and liquorice increase obviously,TRH of full formula group decrease obviously and had the significant difference(p<0.05),full formula group removed seaweed,full formula group removed liquorice,full formula group removed seaweed and liquorice had a trend of decrease but had no significant difference.Compared with model group,urinary iodine of full formula group,full formula group removed seaweed,full formula group removed liquorice increase obviously and had the significant difference(p<0.05)(2)Toxicity CharacterizationLiver function:Compared with model group,ALT and AST of full formula group removed seaweed,full formula group removed liquorice,full formula group removed seaweed and liquorice decrease obviously and had the significant difference(p<0.05),full formula group had a trend of decrease but had no significant difference.Compared with model group,ALP of full formula group removed liquorice increase obviously,ALB of full formula group removed seaweed increase obviously,GLB of full formula group removed liquorice,full formula group removed seaweed and liquorice decrease obviously and had the significant difference(p<0.05).Kidney function:The kidney coefficient of each groups were lower than the model group but had no significant difference.Compared with model group,BUN of full formula group increase obviously,UA of full formula group removed liquorice,full formula group removed seaweed and liquorice decrease obviously and had the significant difference(p<0.05),full formula group,full formula group removed seaweed had a trend of decrease but had no significant difference.Compared with model group,blood sodium of each groups increase obviously and had the significant difference(p<0.05),urinary sodium of full formula group removed seaweed,full formula group removed liquorice,full formula group removed seaweed and liquorice had a trend of increase but had no significant difference.Compared with model group,urinary potassium of full formula group,full formula group removed liquorice decrease obviously and had the significant difference(p<0.05),full formula group removed seaweed,full formula group removed seaweed and liquorice had a trend of decrease but had no significant difference.Cardiac function:The cardiac coefficient of full formula group,full formula group removed liquorice were lower than the model group and had the significant difference(p<0.05),full formula group removed seaweed,full formula group removed seaweed and liquorice had a trend of decrease but had no significant difference.Compared with model group,CK of full formula group,full formula group removed seaweed and liquorice had a trend of decrease,LDH of each group had a trend of increase but had no significant difference.Oxidative Stress:SOD of full formula group,full formula group removed seaweed,full formula group removed seaweed and liquorice decrease obviously and had the significant difference(p<0.05),MDA of full formula group,full formula group removed seaweed,full formula group removed liquorice had a trend of increase but had no significant difference.(3)MechanismThyroid:Compared with model group,TPO mRNA of each groups decrease obviously,Tg mRNA of each groups increase obviously and had the significant difference(p<0.05).Compared with model group,Tg in serum of full formula group,full formula group removed seaweed had a trend of decrease,TPOAb of each groups had a trend of decrease but had no significant difference.Liver:Compared with model group,CYP2E1 mRNA of full formula group decrease obviously,Compared with full formula group,CYP2E1 mRNA of full formula group removed seaweed,full formula group removed liquorice,full formula group removed seaweed and liquorice decrease obviously and had the significant difference(p<0.05).CYP3A1 and CYP3A2 of each groups had a trend of decrease but had no significant difference.Compared with model group,CYP2E1 protein expression of full formula group,full formula group removed seaweed,full formula group removed liquorice decrease obviously and had the significant difference(p<0.05),full formula group removed seaweed and liquorice had a trend of increase but had no significant difference.4.The biological effect and mechanism of Haizao Yuhu decoction plus or minus seaweed and liquorice anti-drug combination on rats with different varieties of liquorice(1)Efficacy evaluationThe thyroid coefficient of each groups were higher than the model group but had no significant difference.T3 of each group had a trend of increase but had no significant difference.T4 of full formula group removed seaweed(liquorice),full formula group(prepared licorice),full formula group removed seaweed(prepared licorice)had a trend of increase but had no significant difference.FT3 of full formula group removed seaweed(liquorice),full formula group(prepared licorice),full formula group removed seaweed(prepared licorice),full formula group removed liquorice increase obviously and had the significant difference(p<0.05),full formula group(liquorice)had a trend of increase but had no significant difference.Compared with model group,TSH of full formula group(liquorice),full formula group removed seaweed(liquorice),full formula group(prepared licorice),full formula group removed liquorice decrease obviously and had the significant difference(p<0.05),full formula group removed seaweed(prepared licorice)had a trend of decrease but had no significant difference.TBG of full formula group removed seaweed(liquorice),full formula group(prepared licorice),full formula group removed seaweed(prepared licorice),full formula group removed liquorice increase obviously and had the significant difference(p<0.05),TRH of full formula group(liquorice),full formula group removed liquorice decrease obviously and had the significant difference(p<0.05),other groups had a trend of decrease but had no significant difference.(2)Toxicity CharacterizationLiver function:the liver coefficient of each groups were higher than the model group,but had no significant difference.Compared with model group,ALT of full formula group removed seaweed(liquorice),full formula group removed seaweed(prepared licorice)decrease obviously and had the significant difference(p<0.05),full formula group(liquorice),full formula group(prepared licorice)had a trend of decrease,full formula group removed liquorice had a trend of increase but had no significant difference.Compared with model group,AST of full formula group(liquorice),full formula group removed seaweed(liquorice),full formula group(prepared licorice),and full formula group removed seaweed(prepared licorice)decrease obviously and had the significant difference(p<0.05),ALP of each groups had a trend of decrease but had no significant difference.ALB of full formula group(liquorice),full formula group removed seaweed(liquorice),full formula group(prepared licorice)decrease obviously and had the significant difference(p<0.05),full formula group(prepared licorice)and full formula group removed liquorice had a trend of decrease but had no significant difference.GLB of full formula group removed seaweed(liquorice)decrease obviously and had the significant difference(p<0.05)Kidney function:Compared with model group,the kidney coefficients of full formula group removed seaweed(liquorice)were lower than the model group,other groups were higher than the model group,but had no significant difference.UA of each groups decrease obviously,blood sodium of each groups increase obviously and had the significant difference(p<0.05),Cre of each groups had a trend of decrease but had no significant difference.Urinary sodium of full formula group(liquorice),full formula group removed seaweed(liquorice),full formula group(prepared licorice),full formula group removed seaweed(prepared licorice)had a trend of decrease but had no significant difference.Urinary potassium of full formula group removed liquorice decrease obviously and had the significant difference(p<0.05).Cardiac function:The cardiac coefficient of full formula group(liquorice),full formula group removed seaweed(liquorice),full formula group removed seaweed(prepared licorice),and full formula group removed liquorice were lower than the model group but had no significant difference.Compared with model group,CK of full formula group removed seaweed(liquorice)decrease obviously and had the significant difference(p<0.05),other groups had a trend of increase but had no significant difference.LDH of full formula group removed seaweed(prepared licorice)decrease obviously and had the significant difference(p<0.05),other groups had a trend of decrease but had no significant difference.Oxidative Stress:Compared with model group,SOD of full formula group removed seaweed(prepared licorice)and full formula group removed liquorice decrease obviously and had the significant difference(p<0.05).MDA of each group had a trend of decrease;GSH-PX of each group had a trend of increase but had no significant difference.(3)MechanismThyroid:TPO mRNA of each groups decrease obviously,and Tg mRNA of each groups increase obviously and had the significant difference(p<0.05).TPOAb of full formula group removed seaweed(liquorice),full formula group removed seaweed(prepared licorice)decrease obviously and had the significant difference(p<0.05),other groups had a trend of decrease but had no significant difference.Tg in serum of full formula group(liquorice),full formula group removed liquorice decrease obviously and had the significant difference(p<0.05).TSHR of each group had a trend of increase but had no significant difference.Liver:Compared with model group,CYP2E1 mRNA of full formula group(liquorice),full formula group removed seaweed(prepared licorice),full formula group removed liquorice decrease obviously and had the significant difference(p<0.05),other groups had a trend of decrease but had no significant difference.CYP3A1 mRNA of full formula group(liquorice),full formula group removed seaweed(liquorice),full formula group(prepared licorice)increase obviously and had the significant difference(p<0.05),full formula group removed liquorice had a trend of increase but had no significant difference.CYP2E1 protein expression of full formula group(liquorice),full formula group removed seaweed(liquorice),full formula group removed liquorice decrease obviously and had the significant difference(p<0.05),other groups had a trend of decrease but had no significant difference.Conclusion:? In preferred compatibility proportion conditions,Haizao Yuhu decoction full formula group can recovery goiter and callback indicators,which was better than full formula group removed seaweed,full formula group removed liquorice or full formula group removed seaweed and liquorice.Each group do not show significant toxicity.The result of full formula group is identical with early experiments in general.? In preferred dosage conditions,Haizao Yuhu decoction full formula group can recovery goiter and callback indicators,which was better than full formula group removed seaweed,full formula group removed liquorice or full formula group removed seaweed and liquorice.Each group does not show significant toxicity.The result of full formula group is identical with early experiments in general.? With different varieties of liquorice,full formula group removed seaweed(liquorice)can recovery goiter and callback indicators,which was better than full formula group(liquorice),full formula group(prepared licorice)better than full formula group removed seaweed(prepared licorice),Each group does not show significant toxicity.The result of full formula group(liquorice)and full formula group(prepared licorice)is identical with early experiments in general. |
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