| Purpose: Under the guidance of TCM theory, Research the chemical composition, efficacy and toxicity changes about Radix aconitum processing and compatibility. Clarify the chemical fundamental substances and toxicity mechanism of action about Radix aconitum processing and compatibility. By the studies toxicity of different diseases animal models, to reveal the role of traditional Chinese medicine toxicity associated with the body, analysis the impact of Changes in chemical composition of toxic, Deepen the understanding of chemical change in the course of processing and compatibility, Using scientific data evaluation the traditional Chinese medicines Aconitum associated with "Eighteen Incompatible Pairs", To revealed the rules of toxicity about traditional Chinese medicine properties.Method: Study the material basis of chemical composition changes in Aconitum hygiene products, processed products and decoction of compatibility using HPLC and LC-MS techniques. Determination the LD50 values about aconiti hygiene products, processed products and the decoction of compatibility with"Pinellia tuber, Trichosanthes fructus, Fritillaria, Ampelosis Radix, Common Bletilla Tuber"using bliss techniques in order to evaluate and study of their toxicity. Through the study of pharmacological effects about decoction with anti-inflammatory and acute heart failure experiment, review the changes of pharmacological effects and toxicity about processing before and after. Selective less toxic and more clinical compatibilities on long-term toxicity experiments, carried out on normal animals and chronic heart failure animal model and adjuvant arthritis animal symptoms. Evaluate the toxicity of main organs according to pathological, physiological and biochemical. Study the effects of its toxic about animal models with different disease and syndrome, to explore the mechanism of its toxicity.Result: 1 The analysis of contents of diester type alkaloids---the main chemical ingredient, conclusion: the contents of Radix Aconiti more than Radix Aconiti Preparata; Radix Aconiti compatibility with Fritillaria thunbergii Miq higher than Radix Aconiti compatibility with Trichosanthes Fructus Pericarpium higher than Radix Aconiti compatibility with Trichosanthes Fructus higher than Radix Aconiti compatibility with Trichosanthes Fructus Semen higher than Radix Aconiti compatibility with Common Bletilla Tuber higher than Radix Aconiti compatibility with Ampelosis Radix higher than Radix Aconiti compatibility with Pinellia Tuber higher than Radix Aconiti higher than Radix Aconiti compatibility with Fritillaria cirrhosa D. Don higher than Radix Aconiti compatibility with Pinellia Tuber Preparata. Radix Aconiti Preparata compatibility with Fritillaria thunbergii Miq higher than Radix Aconiti Preparata compatibility with higher than Radix Aconiti Preparata higher than Radix Aconiti Preparata compatibility with Common Bletilla Tuber higher than Radix Aconiti Preparata compatibility with Trichosanthes Fructus Semen higher than Radix Aconiti Preparata compatibility with Fritillaria cirrhosa D. Don higher than Radix Aconiti Preparata compatibility with Pinellia Tuber higher than Radix Aconiti Preparata compatibility with Trichosanthes Fructus higher than Radix Aconiti Preparata compatibility with Ampelosis Radix higher than Radix Aconiti Preparata compatibility with Trichosanthes Fructus Pericarpium higher than Radix Aconiti Preparata compatibility with Pinellia Tuber Preparata.2 The results of acute toxicity indicate that the degree of toxicity is in direct proportion to the contents of diester type alkaloids. Show: Processing attenuated the toxin of Radix Aconiti, Radix Aconiti compatibility with Trichosanthes fructus, Fritillaria thunbergii Miq, Ampelosis Radix, Common Bletilla Tuber make accreted their toxicity. Radix Aconiti compatibility with Pinellia tuber, Fritillaria cirrhosa D. Don reduced their toxicity. Radix Aconiti Preparata compatibility with Fritillaria thunbergii Miq enhance its toxicity. Others compatibility lessened their toxicity.3 The results of experiment on the pharmacological effects of Radix Aconiti and Radix Aconiti Preparata. By the anti-inflammatory experiments conclude: In the equivalent dose of conditions, the function of inhibition of foot swelling, Radix Aconiti was stronger than the Radix Aconiti Preparata, but the duration of efficacy, Radix Aconiti was shorter than Radix Aconiti Preparata. By the acute heart failure experiments obtained: both Radix Aconiti and Radix Aconiti Preparata have the functions of enhance contractility. Radix Aconiti was stronger than the Radix Aconiti Preparata, but the duration of efficacy, Radix Aconiti Preparata was longer than Radix Aconiti.4 The results of long-term toxicity on the model of chronic heart failure indicate: (1) Results of administration Radix Aconiti Preparata compatibility with Trichosanthes fructus for 30 days observation. The normal administration group rats appeared mild symptoms of poisoning, such as less active, lethargy, weight loss, etc. the organ index of liver and kidney were significantly increased, no significant changes in hematology testing, blood viscosity increased, hemodynamics detected no significant changes, in blood serum triglyceride levels,glutamic pyruvic transaminase levels and Kalium ion increased, albumin reduced, creatinine, blood urea nitrogen, Natrium ion content decreased, HE staining showed liver, kidney mild pathological damage. Model administration group rats breathing difficulties, edema, cyanosis, loss of appetite, lethargy and other more obvious symptoms of heart failure and poisoning, the organ index of heart, liver, kidney, thymus, adrenal gland, testis have significant change, in the blood red blood cells, hemoglobin, platelet, hematocrit, mean corpuscular hemoglobin volume and mean corpuscular hemoglobin concentration were significantly increased, whole blood viscosity increased, in blood serum glutamic pyruvic transaminase, creatinine, Kalium ion levels increased, albumin,Chlorine ion,Natrium ion contents reduced. The test of hemodynamics display Model administered group left ventricular systolic pressure increased, left ventricular end-diastolic pressure reduction, heart rate reduced. Flow cytometer dectect cardiomyocyte apoptosis- index reduced, immune histochemical staining show the expression of Bcl-2 protein increased, Bax protein expression was decreased, Bcl-2/Bax ratio increased. (2) The results of stop administration Radix Aconiti Preparata compatibility with Trichosanthes fructus withdrawal for 15 days observation, the normal administration group symptoms of poisoning disappeared, body weight, food intake, activity levels rose gradually, blood biochemical parameters of normalcy. Model administration group with heart failure symptoms, rat organ indices, hematology testing, Blood serum tests have no change significantly, compared with the previous administration, hemodynamics testing was no significant difference, the cardiomyocyte apoptosis- index increased, Bcl-2 protein expression decreased, Bax protein expression increased, Bcl-2/Bax ratio decreased.The results of long-term toxicity on the model of adjuvant arthritis indicate that: (1) Results of administration Radix Aconiti Preparata compatibility with Pinellia Tuber Preparata for 30 days observation. The normal administration group rats appeared mild symptoms of poisoning, the organ index of heart, liver and kidney were significantly increased, no significant changes in hematology testing, in blood serum triglyceride levels,glutamic pyruvic transaminase, alkaline phosphatase and Kalium ion levels increased, albumin and blood urea nitrogen reduced, Model administration group rats action difficulties, reduced food intake, body weight significantly reduced, the secondary lesions of joint swelling obviously, foot pad thickness, the organ of heart, liver, kidney, spleen, thymus gland have significant changes, in the blood white blood cells increased, platelet reduced, blood viscosity high shear rat increased, red blood cell aggregation index increased, in blood serum glutamic pyruvic transaminase, creatinine, alkaline phosphatase, creatine phosphokinase, Kalium ion levels increased, albumin, blood urea nitrogen, Chlorine ion, contents reduced. Toe swelling subsided, arthritis index was reduced compared with the model control group. (2) The results of stop administration Radix Aconiti Preparata compatibility with Pinellia Tuber Preparata withdrawal for 15 days observation, the normal administration group symptoms of poisoning disappeared, body weight rose gradually, organ indices normally, blood biochemical indicators showed no significant pathological changes. The rats of model administration group blood biochemistry test treatment group tended to be normal, as compared with the model control group rats food intake increased, joint swelling and lighter, spleen, thymus organ index has fallen markedly.Conclusion: 1 Contents of diester type alkaloids are directly proportional to the degree of Radix Aconiti and Radix Aconiti Preparata's toxicity. Namely the greater content of diester type alkaloids the higher the toxicity, processing attenuated mechanism is due to toxic components witch are diester type alkaloids changes during the processing, produce low toxic pyrolysis, hydrolysis, or esterification reaction products. At the same time the chemical composition changes also caused changes in efficacy, indicating "poison" and "efficiency" of Chinese medicines is a dialectical unity. Processing has played an effective role in keeping attenuated, thereby affecting the changes in potency.2 The Eighteen Incompatible Pairs about"Pinellia tuber, Trichosanthes fructus, Fritillaria, Ampelosis Radix, Common Bletilla Tuber attack Radix Aconiti"is not absolute incompatibility. View from the chemical composition analysis, the contents of diester type alkaloids witch are included in Radix Aconiti compatibility with Pinellia Tuber Preparata and Fritillaria cirrhosa D. Don are lessen. The contents of diester type alkaloids are reduced Except Radix Aconiti Preparata compatibility with Fritillaria thunbergii Miq. View from the acute toxicity study, the toxic of Radix Aconiti compatibility with Pinellia Tuber Preparata are less than Radix Aconiti. The toxic of Radix Aconiti Preparata compatibility with Ampelosis Radix and Trichosanthes Fructus Pericarpium and Pinellia Tuber Preparata are less than Radix Aconiti. View from the long-term toxicity study, The drugs witch are Radix Aconiti Preparata compatibility with Trichosanthes fructus have toxin on liver and kidney, but this toxicity is reversible after discontinuation could be removed. Drugs have function of improve the role of cardiac function, its cardiac effects may be related to improve the Bcl-2 and Bax expression imbalance, inhibit apoptosis of cardiomyocyte. The drugs witch are Radix Aconiti Preparata compatibility with Pinellia Tuber Preparata have toxin on heart, liver, kidney. The toxicity would disappear immediately after withdrawal. Aconiti Preparata compatibility with Pinellia Tuber Preparata would control toe swelling. The mechanism of anti-inflammatory may be relate to Aconiti Preparata compatibility with Pinellia Tuber Preparata suppress PGE2 synthesis or release.3 The processing and compatibility of Chinese medicine can affect its toxicity, change their efficacy. Toxicity of drugs closely related with the symptoms of animal model. Confirmed the primary attribute of potency were taken out by environment interact with the body.
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