Objective:Heart failure(HF),a worldwide health condition,is the result of many cardiovascular diseases.The traditional Chinese medicine(TCM)Xiaoyu Jiangzhi capsule(XYC)has long been in use in China to treat hyperlipidemia and inhibit platelet aggregation.This study explores the effects of XYC on heart failure(HF)and its detailed mechanisms.Methods:Isoproterenol(ISO,30 mg/kg)was injected intraperitoneally for 7 days to copy a HF model of 10-12 weeks old,20-30 g male mice.We then compared the CON(control)group,ISO(HF model)group,MET(metoprolol)group,and XYC group.Cardiac systolic function and left wall thickness were evaluated by echocardiograph.Using western blot analysis,we detected the proteins of calmodulin dependent protein kinase Ⅱ(CaMKII)and sarco/endoplasmic reticulum Ca2+-ATPase(Serca).Further-more,tsA201 cells were cultured and the human CaV1.2 calcium channel current(hCaV1.2)were detected by patch clamp experiments.Results:XYC reduced HF,inhibiting the protein expression of CaMKII,but Serca did not change signifi-cantly.Moreover,XYC inhibited the peak amplitude of the hCaV1.2 current,depolarizing shifted the activation curve 27.6 mV,and shifted the inactivation curve toward a positive potential 17.6 mV.The fraction recovered from inaction was reduced in XYC group compared with that in CON group.Conclusion:XYC could inhibit ISO-induced HF by reducing the Ca2+/CaMKII signaling pathway in mice.

OBJECTIVETo analyze the effects of salvianolate on myocardial infarction in a murine in vivo model of ischemia and reperfusion (I/R) injury.

METHODSMyocardial I/R injury model was constructed in mice by 30 min of coronary occlusion followed by 24 h of reperfusion and pretreated with salvianolate 30 min before I/R (SAL group). The SAL group was compared with SHAM (no I/R and no salvianolate), I/R (no salvianolate), and ischemia preconditioning (IPC) groups. Furthermore, an ERK1/2 inhibitor PD98059 (1 mg/kg), and a phosphatidylinositol-3-kinase (PI3-K) inhibitor, LY294002 (7.5 mg/kg), were administered intraperitoneal injection (i.p) for 30 min prior to salvianolate, followed by I/R surgery in LY and PD groups. By using a double staining method, the ratio of the infarct size (IS) to left ventricle (LV) and of risk region (RR) to LV were compared among the groups. Correlations between IS and RR were analyzed. Western-blot was used to detect the extracellular signal-regulated kinase 1/2 (ERK1/2) and protein kinase B (AKT) phosphorylation changes.

RESULTSThere were no significant differences between RR to LV ratio among the SHAM, I/R, IPC and SAL groups (P>0.05). The SAL and IPC groups had IS of 26.1%±1.4% and 22.3%±2.9% of RR, respectively, both of which were significantly smaller than the I/R group (38.5%±2.9% of RR, P<0.05, P<0.01, respectively). Moreover, the phosphorylation of ERK1/2 was increased in SAL group (P<0.05), while AKT had no significant change. LY294002 further reduced IS, whereas the protective role of salvianolate could be attenuated by PD98059, which increased the IS. Additionally, the IS was not linearly related to the RR (r=0.23, 0.45, 0.62, 0.17, and 0.52 in the SHAM, I/R, SAL, LY and PD groups, respectively).

CONCLUSIONSalvianolate could reduce myocardial I/R injury in mice in vivo, which involves an ERK1/2 pathway, but not a PI3-K signaling pathway.

Animals ; Blotting, Western ; Cardiotonic Agents ; pharmacology ; therapeutic use ; Flavonoids ; pharmacology ; Heart Ventricles ; drug effects ; pathology ; MAP Kinase Signaling System ; drug effects ; Male ; Mice, Inbred C57BL ; Mitogen-Activated Protein Kinase 1 ; metabolism ; Mitogen-Activated Protein Kinase 3 ; metabolism ; Myocardial Reperfusion Injury ; drug therapy ; enzymology ; pathology ; Organ Size ; drug effects ; Phosphorylation ; drug effects ; Plant Extracts ; chemistry ; pharmacology ; therapeutic use ; Protein Kinase Inhibitors ; pharmacology ; Staining and Labeling