Effect Of Vitamin E On The Antihypertension And Toxicity Of Total Veratrine

Objective: Hypertension is the highest incidence of disease in China,which is estimated that 240 million patients with high blood pressure.Cardiovascular and cerebrovascular complications caused by hypertension pose a serious threat to the national health.Different types of antihypertensive drugs on the market have their own contraindications and side effects that cannot be ignored.Now people pay more attention to find more effective and safe antihypertensive drugs from traditional Chinese medicine.Veratrum nigrum L also commonly called Black Veratrum,Sancong,Qilidan,Rentoufa,etc,belonging to a lily plant the roots and rhizomes of which belongs to the Lily family and are poisonous.Its toxicity is mainly genetic toxicity and neurotoxicity.Nevertheless,its medicinal value still cannot be ignored.Many animal experiments have proved that the antihypertension of veratrum alkaloids is lasting and significant.In the 1950 s,many total veratrine drugs were used in clinical practice.Due to side effects,they were gradually reduced in clinical use.How to reduce toxicity has become an urgent problem to be solved.In the early stage,our research group deeply explored the structure-toxicity relationship of each monomer alkaloid and its mechanism of neurotoxic action.It was found that VE had an interventic effect on DNA damage of brain nerve in mice induced by Veratrum alkaloid.It provides an important clue for our further study on drug attenuation.In this study,SHR rat a spontaneously hypertensive model,was used to study the antihypertensive activity of Veratrum alkaloids alone or used with VE and the effect of brain nerve injury.From the perspective of drug interaction,to determine the optimal proportion of Veratrum alkaloids and VE.The effects that the two together reduces toxicity and protect effect were elucidated from oxidative stress.Methods: 5 WKY rats were taken as the normal control group,and 80 SHR rats were taken as the administration group.The rat tail sleeve method was used to measure the systolic blood pressure of the rat,which was not anesthetized and is quiet.The aim is to investigate the antihypertensive activity.The repair of DNA damage were detected by comet assay in cerebellum and cerebral cortex of rats.HE staining method was used to detect the morphological changes of heart and brain tissue.Electrocardiogram monitoring had proved its the role of attenuating toxicity and maintaining efficacy.In order to determine the optimal proportion of veratrum alkaloids used with vitamin E,Elisa and colorimetric assays were used to detect antioxidant indicators,such as NO(Nitric oxide),MDA(Malondialdehyde),8-OHDG(8-hydroxydeoxyguanosine),T-SOD(Totalsuper-oxidedismutase),GSH-PX(glutathioneperoxidase.Results: the antihypertensive study found that veratrum alkaloids used with vitamin E could significantly reduce the blood pressure of spontaneous hypertension rats(SHR)in both high and low dose groups(P<0.05).The results of comet experiment showed that,compared with the blank group,veratrum alkaloids used with VE could antagonize DNA damage induced by veratrum alkaloids in cerebellum and cerebral cortex of SHR rats(P<0.05 ~ 0.001).By principal component factor analysis,the optimum compatibility ratio of veratrum and vitamin E was determined to be 1:4.Electrocardiogram(ecg)changes and pathological section found that: Compared with the normal group,the heart of group Veratrum: VE= 1:4 rats was less affectd in low dose.The phenomenon of myocytes hypertrophy decreased.About 85 min after administration,Q waves got wider and deeper,and occasionally a very transitory arrhythmia occurred.Disordered and hypertrophic myocardial cell of group Veratrum: VE= 1:4 appeared in the high-dose group.Abnormal cardiac wave appeared,and ST segment and T wave changed.QRS electrical axis occurred abnormal,and then RR interval extended,while arrhythmia appeared at about 80 min.It last longer and had a bigger impact.From the pathological sections of brain tissue and the analysis of antioxidant indexes,it was found that veratrum alkaloids used with vitamin E significantly reduced the contents of NO,MDA,8-OHd G(P<0.01),and effectively increased the activity of GSH-PX,T-SOD(P<0.01 ~ 0.001)in the cerebellum and cerebral cortex of SHR rats,suggesting that it improves brain tissue damage.Conclusion: veratrum alkaloids used with vitamin E have no influence on the antihypertensive activity of Veratrum alkaloids.It is the role of attenuating toxicity and maintaining efficiency.The mechanism may be related to antagonistic oxidative stress.Because the cardiac toxicity of Veratrum alkaloids was higher in the high dose group,so the optimal compatibility ratio is Veratrum alkaloids: VE=1:4,and the dosage is 5mg/kg(low dose).