Study On Druggability Of Sini Decoction Based On Effective Components Compatibility

Sini decoction(SND), composed of Aconitum carmichaelii, Zingiber officinale and Glycyrrhiza uralensis, was first recorded in Shanghan Lun. It is a traditional Chinese Medicine(TCM) which has great effects on warming middle energier, eliminating cold and recuperating the depleted Yang. But Aconitum carmichaelii has highly toxicity without process, while only processed Aconite could be allowed to be used on clinic. The main toxic ingredients in Aconite is the diester diterpene alkaloids(DDAs), which could be hydrolysis into monoester diterpene alkaloids and thus reduce the toxicity of Aconite. Because of the complexity of the decoction of SND, it is important to make the content of DDAs under control in the study of druggability of Sini decoction effective components compatibility.Multi-component Chinese Medicine, a kind of new TCM in light of the TCM theory for its safety, efficacy, stability and controllable, which has the characteristics of qulified composition, clear mechanism and less side effects is one of the important modelsfor study on the modernization of TCM. The aim of this study is to develop a new formula of SND based on effective components compatibility, including qualification of the content of multi-components in SND, optimization the extract of Aconite, Ginger and Licorice and evaluation of cardiotonic action and the protective effect on the acute myocardial infarction, and thus evaluate the druggability of effective component compatibility of SND.1. HPLC-MS methods were established to determine the content of aconitine(AC), mesaconitine(MC), hypaconitine(HC), benzoylaconine(BAC), benzoylmesaconine(BMC), benzoylhypaconine(BHC), 6-gingerol(6-GR), liquiritin(LQ) and glycyrrhizic acid(GA) in SND. The results of method validation showed the nine ingredients were linear dependent in the linear ranges, and the results of method validation could meet the desire of qulification, showing that this method could be applied to the determation of 9 ingredients in SND. Six batches of SND was determined, and the content of AC, MC, HC, BAC, BMC, BHC, 6-GR, LQ and GA was stable.2. The L9(34) orthogonal design experiments were used to optimize the extraction of Aconite, Ginger, Licorice. Orthogonal designs of four factors three levels were taken to study the effect of solvent concentration and volume, times and duration of extraction. The optimal extraction process is as follows: adding 10 times amount of 75% ethanol into crude powders, extracting 2 hours for Aconite; adding 8 times amount of 95% ethanol into crude powders, extracting 2 times, 2 hours each time for Ginger; adding 15 times amount of 75% ethanol into crude powders, extracting 3 times, 2.5 hours each time for Licorice flavonoids; adding 15 times amount of 95% ethanol into crude powders, extracting 2 times, 3 hours each time for Licorice saponins. Based on the result of optimizing, the extraction of Aconite, Ginger, Licorice flavonoids and Licorice saponins were gained through pilot production.3. The cardiotonic action of AC and BAC was evaluated by the change of hemodynamics after intravenous administration. The results showed AC had the effect of cardiotonic action at the dosage of 0.01mg/kg/BW after intravenous administration, while BAC had no effect on it, showing the DDAs were the effective substence in Aconite. The component compatibility of SND(SNDcc), composed of Aconite, Ginger, Licorice flavonoids and Licorice saponins extract in the ratio of 1:1:33:100, was taken to evaluate the cardiotonic action on SD rats by gavage. After oral administration of 7mg/kg/BW, the parameters of hemodynamics had been changed with increasing SBP, DBP and MBP, fasting HR and icreasing LVSP and +dp/dt max, showing the component compatibility of SND had cardiotonic action on SD rats.4.We established the model of acute myocardial infarction(MI) rats by left anterior descending artery to evaluate the pharmacodynamic effect of component compatibility of SND(SNDcc). SD rats were randomly assigned to sham operation, model, SND and SNDcc groups. After oral administration for 21 days, the cardiac function of rats in different groups was investigated. The results of ultrasound cardiogram showed SNDcc and SND could improve the ejection fraction(EF) of MI rats. Heart weight index and MI rate also showed that SNDcc and SND could reduce the area of MI, and recover part of the cardiac function. The primary pharmacological evaluation of SNDcc proved component compatibility of SND had the protective effect on acute MI rats,...