| Background:"Eighteen antagonisms"—the controversial prohibited combinations in traditional Chinese medicine, have experienced a history of thousands of years so far. Whether and how they could be used in clinic, has been a problem that people have argued without reaching a decision. Recent studies showed that the Eighteen antagonisms are conditional prohibited combinations. Theses researches were mostly aimed at single medicinal combinations. However, instead of single combination, it is prescription that was more often used in clinic. Therefore, in order to be accord with the clinical application, in this study, we selected a prescription, Gansui Banxia Tang, which contains a prohibited combination, namely Gansui (kansui radix) and Gancao (glycyrrhizae radix et rhizoma). By means of changing the dosage ratio, dosage and prepared varieties, we explored the relation between Gansui and Gancao, and the taboo conditions of this prohibited combination.Object:The aim of this study was to reveal the compatibility of Gancao and Gansui from a clinical point of view, and to explore the taboo conditions of this prohibited combination, which could lead to toxicity or efficacy. It could provide a basis for guiding rational use of this prohibited combination in clinic and enriching content of theory of compatibility of traditional Chinese hebs.Method:First,we performed acute toxicity test to find out the Maximum tolerance dose or median lethal dose of Gancao and Gansui.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 software, we analysed the dose range whether Gancao was used concomitantly with Gansui or not. Third, we chose a ratio of marked effect to conduct the expeiment of different dose and preparata compatibility of Gancao and Gansui. Finally, we made a comprehensive analysis to reveal the compatibility and the taboo conditions of Gancao and Gansui.Result:1. The Gancao group had the largest number of death in acute toxicity test. Followed by compatibilities of Prepared Gancao and vinegar-preparing Gansui> compatibilities of Gancao and vinegar-preparing Gansui> Gansuibanxia decoction (Prepared Gancao)> Gancao> vinegar-preparing Gansui> Gansuibanxia decoction(Gancao).The number of mouse deaths could not reach to half in Gansuibanxia decoction (Gancao) group and vinegar-preparing Gansui group. Thus, we took the largest dose of drug as the maximum tolerance, respectively57.6g/kg,10g/kg.The number of mouse death in Prepared Gancao and compatibilities of Gancao and vinegar-preparing Gansui could reach to half in short time. The number of death would increase with the time of the administration of drug.2. According to the results from the optimized formula soft analysis, when the ratio is15g:1g in compatibility of Prepared Gancao (A) and vinegar-preparing Gansui (B), it could increase urine output, and decrease VEGF content, and the ratio of AST/ALT in malignat ascits rats. It also could rise ALD and BUN concent, and reduce CK activity. The above results showed the ratio might have the profits of water, and relatively less liver toxicity. However, it might have a certain degree of renal damage and cardiotoxicityIn addition, it had no effect on liver function and renal function, when the dose of vinegar-preparing Gansui is1g, and the dose of Prepared Gancao is8g-20g, or the dose of Prepared Gancao is15g, the dose of vinegar-preparing Gansui is0.35g-1.75g. Therefor, we thought the above compatibility dose might not demonstrate the opposite directions. But, it might have an influence on CK activity. These conclusions are only initial analysis, we still need further study.4. The drug combination of A and B in different proportions could up-regulate AQP2mRNA expression in kidney and down-regulate CYP1A2mRNA expression in liver. When the ratio is2.23g:6.94g or0.05g:13.87g, it could down-regulate CYP2E1mRNA expression, the ratio of0.39g:3.47g up-regulating CYP2E1mRNA expression. There was no significant difference among every groups for CYP3A2mRNA expression.5.The combination groups of Gansui and Gancao could increase urine output and ascites output in different dose and different processing varieties conditions. There was no significant difference among every groups for serum Na+and K+content. Urine K+content was reduced in low dose group and SS group, compared with model group, and increased in high dose group.The plasma PRL1, All, ADH level had no significant difference among every groups; SS group could decrease plasma ADH level.6. The combination groups of Gansui and Gancao could increase thymus index, but no significant difference among every groups as well as spleen index in different dose and different processing varieties conditions. The high dose group could elevate IgG content in ascites, reduce the albumin content in ascites.Plasma IL-2, IL-6, TNF-α, VEGF level and blood CD3, CD8relatively cell count had no significant difference among every groups. Model and the herb group could low CD4level.compared with normal group.7.Cardiac index was increased in SZ group, compared with model group.liver index was increased in SS group, compared with the model group; there was no significant difference among every groups for kidney index. AST (glutamic-oxalacetic transaminease) rise in high dose group, compared with the model group; Content of Protein was significantly reduced in high dose and CS groups. Model and the herb group could increase BUN content, with significant difference in model and others groups except SS group. The low dose and the different processing varieties compatibilities of kansui radix and glycyrrhizae radix et rhizoma groups could decrease CK activity, compared with the normal group, the low dose group could decrease LDH (lactic dehydrogenase) activity, compared with the normal group.Conclusion:The results illustrate that compatibilities of Gancao and vinegar-preparing Gansui group might represente the opposite effect with large dose. Compound prescription included incompatible medicaments are basically safe in acute toxicity test. The compatibility of Gancao and Gansui shows opposite action under a certain condition in Gansuibanxia decotion. Liver is the main target organ for toxicity. When Gancao is used with vinegar-preparing Gansui at the ratio of15, it has the diuresis with little liver injury. However, other compatibilities of Gancao and Gansui could lead to more toxicity in this paper. Maybe CYP450plays a role in hepatic impairment. The aquaorins may be associated with diuresis. |
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