Suxiao Jiuxin Pills Prevent Ventricular Fibrillation from Inhibiting L-type Calcium Currents CaV1.2 in vivo and in vitro

Objective: To investigate whether Suxiao Jiuxin Pills(SJP), a Chinese herbal remedy, is an anti-ventricular fibrillation(VF) agent. Methods: VF was induced by isoproterenolol(ISO) intraperitoneal injection followed by electrical pacing in mice and rabbits. The effects of SJP on the L-type calcium channel current(CaV1.2), voltage-dependent sodium channel current(INa), rapid and slow delayed rectifier potassium channel current(IKr and IKs, respectively) were studied by whole-cell patch-clamp method. Computer simulation was implemented to incorporate the experimental data of SJP effects on the CaV1.2 current into the action potential(AP) and pseudo-electrocardiography(pseudo-ECG) models. Results: SJP prevented VF induction and reduced VF durations significantly in mice and rabbits. Patch-clamp experiments revealed that SJP decreased the peak amplitude of the CaV1.2 current with a half maximal concentration(IC50) value of 16.9 mg/L(SJP-30 mg/L, –32.8±6.1 pA;Verapamil, –16.2±1.8 pA;vs. control, –234.5±16.7 pA, P<0.01, respectively).The steady-state activation curve, inactivation curve, and the recovery from inactivation of the CaV1.2 current were not shifted significantly. Specifically, SJP did not altered INa, IKr, and IKs currents significantly(SJP vs.control, P>0.05). Computer simulation showed that SJP-reduced CaV1.2 current shortened the AP duration,transiting VF into sinus rhythm in pseudo-ECG. Conclusion: SJP reduced VF via inhibiting the CaV1.2 current with in vivo, in vitro, and in silico studies, which provide experimental basis for SJP anti-VF clinical application.

Protective Mechanisms of Suxiao Jiuxin Pills(速效救心丸) on Myocardial Ischemia-Reperfusion Injury in vivo and in vitro

Objective:To study the protective mechanism of Chinese medicine Suxiao Jiuxin Pills(速效救心丸,SXJ)on myocardial ischemia and reperfusion(I/R)injury.Methods:Mouse myocardial I/R injury model was created by 30-min coronary artery occlusion followed by 24-h reperfusion,the mice were then divided into the sham group(n=7),the I/R group(n=13),the tirofiban group(TIR,positive drug treatment,n=9),and the SXJ group(n=11).Infarct size(IS),risk region(RR),and left ventricle(LV)were analyzed with double staining methods.In addition,H9C2 rat cardiomyocytes were cultured with Na2S2O4 to simulate I/R in vitro.The phosphorylation of extracellular regulated protein kinases1/2(ERK1/2),protein kinase B(AKT),glycogen synthase kinase-3β(GSK3β),and protein expression of GATA4 in nucleus were detected with Western blot assay.Results:The ratio of IS/RR in SXJ and TIR groups were lower than that in I/R group(SXJ,22.4%±6.6%;TIR,20.8%±3.3%;vs.I/R,35.4%±3.7%,P<0.05,respectively).In vitro experiments showed that SXJ increased the Na2S2O4-enhanced phosphorylation of AKT/GSK3βand nuclear expression of GATA4.Conclusion:SXJ prevents myocardial I/R injury in mice by activating AKT/GSK3βand GATA4 signaling pathways.

Effects of Suxiao Jiuxin Pill (速效救心丸) on Oxidative Stress and Inflammatory Response in Rats with Experimental Atherosclerosis

Objective: To observe the preventive role of Suxiao Jiuxin Pill (SX速效救心丸) on atherosclerosis (AS) and to probe into the mechanism in the atherosclerosis rat model. Methods: The AS rat model was established by a high fat diet and a large dose of calcium (vitamin D3, 0.6 million U/kg, i.p, once). Sixty healthy male adult Sprague-Dawlay (SD) rats were randomly divided into 6 groups, a normal control group (N), a model group (M), a SX low dose group (SXL), a SX middle dose group (SXM), a SX high dose group (SXH), and an atorvastatin group (ATO) (n=10 in each group). The rats in the treatment groups were given with the specific drugs from the first day by oral administration, and the normal control group and the model group were given with normal saline for 12 weeks. Afterwards, the content of malondialdehyde (MDA), the activity of superoxide dismutase (SOD) and the content of oxidized low density lipoprotein (ox-LDL) in the serum were detected. In addition, the expression of peroxisome proliferator-activated receptor γ (PPARγ) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) proteins were tested by Western-blot method. Results: The serum ox-LDL and MDA level significantly decreased, SOD activity increased in the SX middle, high dose groups and the atorvastatin group compared to the model group (all P<0.05). While the expression of PPARγ and NF-κb proteins significantly decreased in the SX low, middle, high dose groups and the atorvastatin group compared to the model group (all P<0.01), with the best effect in the SX high dose group .These results indicate that SX could elevate the activity of serum SOD, decrease serum level of MDA and ox-LDL, and reduce the expression of PPARγ and NF-κB proteins. Conclusion: SX plays an important role in anti-inflammation and inhibition of oxidative stress, which possibly are the mechanism of its preventing and treating atherosclerosis.

Effectiveness and safety of Suxiao Jiuxin pill in treating acute coronary syndrome:a systematic review and Meta-analysis

OBJECTIVE:To evaluate the effectiveness and safety of Suxiao Jiuxin pill(SX)in acute coronary syndrome(ACS)treatment.METHODS:An extensive search of four English databases(Medline/PubMed,Cochrane Library,Embase,and World Health Organization International Clinical Trials Registration Platform)and four Chinese databases(Chinese National Knowledge Infrastructure,Wanfang,China Science and Technology Journal,and Chinese Biomedical Literature Service System)was performed.Randomized,controlled trials(RCTs)involving SX combined with conventional therapy versus conventional therapy were included.The extracted data included populations,interventions,outcomes,and risk of bias.The cardiovascular events served as the primary outcome.Review Manager 5.3 software was used for data analysis.Relative risks(RRs)with 95%confidence intervals(CIs)were the effect measure.RESULTS:A total of eight RCTs with 979 patients were included.There were 559 patients with unstable angina(UA)in six RCTs and 420 patients with acute myocardial infarction(AMI)in two RCTs.Our review showed that SX plus conventional therapy might reduce the incidence of the total endpoint(RR:0.34,95%CI:0.17,0.68,P=0.002),with no obvious adverse events(RR:1.29,95%CI:0.60,2.77,P=0.52)compared with conventional therapy for patients with UA.Additionally,SX plus conventional therapy also reduced the incidence of the total endpoint(RR:0.35,95%CI:0.18,0.68,P=0.002)compared with conventional therapy in patients with AMI.SX plus conventional therapy also reduced the incidence of ventricular fibrillation(RR:0.23,95%CI:0.10,0.57,P=0.001)compared with conventional therapy in patients with AMI.CONCLUSION:Our results suggest that SX is beneficial for treating patients with UA or AMI.However,our findings should be treated with caution because of the poor methodological quality of the included trials.Therefore,more multicenter,large-sample,high-quality RCTs are required to provide high-quality evidence.