With Algae And Licorice Against Drug Combination Of Seaweed Yuhu Soup Is Applied To Strumous Avoid Compatibility Of Appropriate Conditions In The Rat Model

Background:"Eighteen antagonisms" has been through a history of thousand years until now which is the controversial prohibited combinations in traditional Chinese medicine.should they be used in clinic or not has been a historical matters that people have been argued about it. Recently, the researches indicate that the Eighteen antagonisms are conditional prohibited combinations. These scientific research were mainly focus on single medicinal combinations. However, instead of single combination, the compound which have the drug combination was often used in clinic. Therefore, in order to close to clinical application, we selected Haizao Yuhu decoction which contains a prohibited combination, namely Haizao(Sargassum)and Gancao (glycyrrhizae radix et rhizoma) in this study. Change the compatibility proportion,, dosage and prepared varieties, we attempts to reveal the the relation between Haizao and Gancao, and its suitable/contraindicant conditions of this prohibited combination.Object:From a clinical perspective, through animal experiments, reveals the application compatibility Haizao and Gancao the anti drug combinations under different conditions and conditions, to explore the more close to clinical use increase toxicity (reduction) of the taboo conditions and toxic characteristics, or synergistic (attenuated) of the appropriate conditions and work characteristics, in order to provide scientific support for the safe use of reasonable guide clinicians in algae and licorice anti drug combination, provide a reliable basis for enriching and perfecting the incompatibility of Chinese medicine theory.Method:First of all, we performed acute toxicity test to find out the lethal median dose of Gancao and Haizao.Secondly,based on the results of acute toxicity,we set up seven matched groups according to the principle uniform design(two factors seven level) compared with normal, model, positive group.Using ANOVA (analysis of variance) in combination with optimized formula soft, we analysed the dose range whether Gancao was used concomitantly with Haizao or not.Third, we chose a ratio of marked effect to conduct the expeiment of different dose and preparata compatibility of Gancao and Haizao. Finally, we made a comprehensive analysis to reveal the compatibility and the taboo conditions of Gancao and Gansui.Result:1. Acute Toxicity①The acute toxicity of different groups on mice is:Sargassum>Sargassum with prepared Radix Glycyrrhizae>Sargassum with Radix Glycyrrhizae>prepared Radix Glycyrrhizae>Haizao Yuhu decoction Radix Glycyrrhizae)>Haizao Yuhu decoction(Radix Glycyrrhizae)>Radix Glycyrrhizae.②Application of Sargassum alone has toxicity strongest, the reason of poison maybe related that the seaweed contains large amounts of iodine and sodium. Iodine overdose, abdominal pain, nausea and vomiting, can behave convulsions and coma, shock and other symptoms of poisoning, in addition, seaweed is rich in sodium, one-time large doses can cause hypernatremia. The hypertonic condition can cause brain cell loss, cause irritability, muscle tension, convulsions, seizures and other symptoms of nervous system. The causes of death of Zhigancao (prepared Radix Glycyrrhizae) mice may be liquid sticky, affect the absorption, causing the cause flatulence, may not belong to the toxicity, need further verification.③A large number of long-term use has certain toxicity of Sargassum and Radix Glycyrrhizae/Radix Glycyrrhizae, but the compound containing anti drug combinations showed no obvious toxicity.2The effect and toxicity of Haizao Yuhu decoction with different proportions of Sargassum and Radix Glycyrrhizae in goiter rats①Effect:Haizao Yuhu decoction with different proportions of Sargassum and Radix Glycyrrhizae can inhibit thyroid enlargement induce by PTU in some degree. the proportion of group one, group three,group six was the most obvious, group one and the five also can callback the thyroid stimulating hormone increased, five, group five, six, seven can make the content of iodine in urine increased obviously.Toxicity:The cardiac coefficient of group twoobviously reduces, pathological changes showed that the myocardial cells arranged in disorder, cardiac muscle fiber atrophy, change a small amount of inflammatory cell infiltration in pathology; AST/ALT of group one and group two increased significantly, and the liver cell and tissue of group one,six and seven damage than other group slightly heavier; kidney coefficient ratio in group one, group three, group six, group seven increased obviously, ratio of the group three, group four, group five, group six, groups seven of blood K+concentration significantly reduced, pathology results showed group one, three of lesions were heavier; these seven groups of female rats ovary weight was significantly lower than the model group, the pathological results were reduced, cortical atrophy. Seven different groups had no significant effect for blood system. The Haizao Yuhu decoction overall toxicity algae licorice in different compatibility proportion is not serious, no obvious linear relationship between Sargassum and Radix Glycyrrhizae.②The effect mechanism:The one to seven groups of Sargassum and Radix Glycyrrhizae can enhanced the expression of TPO mRNA in the thyroid, ratio of group one and the five had the strongest effect. The transcript level of Tg was not inhibited by PTU, group one, five and six groups can promote Tg transcription, with recovery of thyroid hormone to reach the normal level to some extent.Possible causes of liver toxicity:increased CYP3A1mRNA content in group one, group two, group three, group seven of rat liver, with ratio of the seven group expression is highest, with licorice dose increasing trend. Ratio of the three group, five group, seven group have the extremely individual rat liver CYP3A2mRNA expression, no differences between groups.③According to the compatibility of Sargassum and Radix Glycyrrhizae seven different set of experimental results, combined with Chinese medicine prescription optimization software analysis. The results, suitable condition of Sargassum and Radix Glycyrrhizae: Sargassum:Radix Glycyrrhizae between9:10-24:11, which can reduce the weight of thyroid of rats, abnormal callback rats thyroid hormone levels, changes in hypothyroid rats cognitive ability is low, and the liver, kidney toxicity is low etc. According to the proportions of use may not show the opposite effect, but the result is only the result of software analysis, to be verified by experiment.When the dosage of Sargassum is5.5g>15g or Radix Glycyrrhizae dose; dose was9g, seaweed dose>24g, may cause some toxic effects on the liver, kidney system. The results are consistent with the pathological changes in renal tissue of liver, and the proportion of different proportions of experimental liver injury heavier.3. Experimental study on the proportion of different dosage of Radix Glycyrrhizae: Sargassum (9:5.5)①The Chinese medicine prescription optimization software of analysis and calculation, the Haizao Yuhu decoction with Radix Glycyrrhizae:Sargassum compatibility proportion in9:5.5application,the effect is best. Therefore, according to the proportion of different doses of set dose group (Radix Glycyrrhizae:Sargassum=27g:16.5g), dose group two (Radix Glycyrrhizae:Sargassum=9g:5.5g), dose group three (Radix Glycyrrhizae: Sargassum=3g:1.83g), dose group four (Radix Glycyrrhizae:Sargassum=1g:0.61g). The results show that the four dose groups were improved in varying degrees by propylthiouracil caused by hypothyroidism rats body weight, food consumption, body temperature and abnormal expression of thyroid hormone. The dose of4groups (Radix Glycyrrhizae: Sargassum as1g:0.61g) for the most obvious role, the serum hypothyroid rats weight, the amount of water, the hypothalamus pituitary thyroid axis, rats in T3, T4, FT3, FT4, TBG content and behavioral abnormalities showed good effect. The mechanism may be related with the expression of TPO and Tg mRNA of thyroid. The equivalent of the11g:7g, is the2010version of<Chinese Pharmacopoeia> Regulations of measurement range②the mechanism may be related with the dose of group1increased CYP3A1mRNA in rat liver expression of rat liver cells; renal dose group1rats appeared slight pathological changes; the Haizao Yuhu decoction four dose groups of female rats are in a certain extent, reduce ovarian coefficient of rats, pathological display the follicle number reduce, atrophy of cortex, showed some reproductive toxicity; in addition to dose group3, testis coefficient of all rats were decreased. Show the opposite effect. Based on the above indexes, using large dose dose group1(27g:16.5g) in liver and kidney damage is more obvious, the equivalent dose and the dose equivalent of302g:185g, dosage is too large, so it should not be compatible for use.4. Experimental study on the proportion of different processing varieties of Radix Glycyrrhizae:SargassumHaizao Yuhu decoction with a ratio of Radix Glycyrrhizae:Sargassum is9:5.5application compatibility, different processing varieties at different levels can improve the body weight, caused by propylthiouracil abnormal hormone levels in hypothyroid rats feed temperature and related thyroid content, expression, and no significant difference between groups. But the licorice and seaweed compatibility on rat liver, kidney and blood system showed certain toxicity, raw licorice compatibility is serious, has the opposite effect, so not compatible for use.Conclusion:From the above result, Radix Glycyrrhizae:Sargassum in the compound containing the drug combination is not in all circumstances "reverse", select the compatibility conditions suitable, also showed better efficacy. When the raw licorice and seaweed (9g:5.5g) and has better efficacy, and liver, kidney toxicity is small; when the compatibility proportion of the same, with small dose of1g:0.61g (Pharmacopoeia range dose) effective application compatibility, liver, kidney injury is light; the same proportion, the same dose of different processed varieties, application compatibility, the compatibility of Radix Glycyrrhizae and seaweed on liver kidney function was not affected. The two combined opposite the main toxicity target organ is the liver and kidney, the specific mechanism needs further experimental research.