Preparation Of Berberine Hydrochloric Dripping Pills And Their Preventive Effect On The Hypertrophy Of Cardiomyocytes From Neonatal Rat

Cardiac hypertrophy is an adaptive response to cardiac overload. It is characterized as cell volume enlarged and cardiomyocyte protein synthesis increased. It has become one of the independent risk factors for increasing the incidence and mortality of cardiovascular diseases. It is a pathologic process of initiating heart failure. Therefore, to research the mechanism and seek medicine for prevention and therapy in cardiac hypertrophy are important subject in the field of cardiovascular system.Berberine is the main active ingredients of Chinese traditional medicinal herbs such as Hydrastis. In recent years,the study found that it is not only cure dysentery, but also treat some cardiovascular diseases, such as congestive heart failure, hypertension, hyperlipidemia and so on. Berberine, however, has many problems in using. For example, it is so hard to dissolve in water that it is poorly absorbed. Its bioavailability is low so that it has low efficacy and high side effects. All of these limit its explitation and clinical application.In the present study, berberine hydrochloride refining were made into dripping pills and get the best preparation process. To observe the effects of berberine dropping pills on angiotensinⅡ(AngⅡ)-induced cardiac hypertrophy. Which would provide theoretical support and experiment proof for increasing water solubility, bioavailability and efficacy of berberine and reducing its side effects.Firstly, the preparation of berberine hydrochloride dripping pills and comprehensive evaluation of their quality. Rrefined berberine hydrochloride were made into dripping pills. To take weight variation of pills, comprehensive quality and disintegration time limited as index. The above factors were observed by orthogonal test in order to select the best prescriptions and dripping conditions.Secondly, the neonatal SD rats cardiomyocytes were cultured in vitro and the myocardial hypertrophy models were induced by AngⅡ. According to different treatments, there are six groups were divided: control group, model group, cap group, low dosage dripping group, middle dosage dripping group, high dosage dripping group. Finally, their protective effects on hypertrophy of cardiomyocytes were observed.The optimized preparation conditions were: extracted and refined income of berberine hydrochloride were regard as apis, PEG-6000 as matrix, and liquid paraffin wax as coolant. Berberine hydrochloride dripping pills and PEG-6000 was 1∶ 5, dropper caliber was 2mm, solution temperature was 80℃, dripping speed was 40d·min-1, dripping distance was 5cm and cooling fluid for the temperature was 2℃.After normal myocardial cells were cultured with different dosage dripping pills, there was no statistical significance among these groups(P>0.05). The protein contents and diameters of cardiomyocytes were significantly increased by AngⅡ in 10-7mol/L(P<0.01). The concentration of nitrid oxide and the activity of endothelial nitric oxide synthase were decreased significantly(P<0.01). When dripping pills were used, the increasing in the cell diameter and the protein content were inhibited significantly. While the concentration of nitrid oxide and the activity of endothelial nitric oxide synthase were increased significantly. Which illustrated that they could protect myocardial hypertrophy cells in a dose dependent manner. Especially there were better effects for high and middle dosage dripping pills(P<0.01). This maybe the result of the increase of the concentration of nitrid oxide by improving the activity of endothelial nitric oxide synthase.Berberine hydrochloride dripping pills were characterized by small disintegration time limited, good comprehensive quality and short pill weight variation. They could be produced in these conditions. The myocardial hypertrophy models of neonatal SD rats were induced by AngⅡ sucessfully. Berberine hydrochloride dripping pills could inhibit the increase in the protein content and the diameters induced by AngⅡ significantly in a dose dependent manner. This effect was resulted from the increase in the concentration of nitrid oxide and the activity of endothelial nitric oxide synthase.