cardiovascular-agents and stachydrine

Traditional Chinese medicine Leonurus japonicus Houtt. has a long history in the treatment of cardiovascular diseases. Stachydrine hydrochloride, the main bioactive ingredient extracted from Leonurus japonicus Houtt., has been shown to have cardioprotective effects. However, the underlying mechanisms of stachydrine hydrochloride haven't been comprehensively studied so far.. The aim of this study was to investigate the protective role of stachydrine hydrochloride in heart failure and elucidate its possible mechanisms of action.. In vivo, transverse aorta constriction was carried out in C57BL/6J mice, and thereafter, 7.2 mg/kg telmisartan (a selective AT1R antagonist as positive control) and 12 mg/kg stachydrine hydrochloride was administered daily intragastrically for 4 weeks. Cardiac function was evaluated by assessing morphological changes as well as echocardiographic and haemodynamic parameters. In vitro, neonatal rat cardiomyocytes or adult mice cardiomyocytes were treated with stachydrine hydrochloride and challenged with phenylephrine (α-AR agonist). Ventricular myocytes were isolated from the hearts of C57BL/6J mice by Langendorff crossflow perfusion system. Intracellular calcium was measured by an ion imaging system. The length and movement of sarcomere were traced to evaluate the systolic and diastolic function of single myocardial cells.. Stachydrine hydrochloride improved the cardiac function and calcium transient amplitudes, and inhibited the SR leakage and the amount of sparks in cardiac myocytes isolated from TAC mice. We also demonstrated that stachydrine hydrochloride could ameliorated phenylephrine-induced enhance in sarcomere contraction, calcium transients and calcium sparks. Moreover, our data shown that stachydrine hydrochloride blocked the hyper-phosphorylation of CaMKII, RyR2, PLN, and prevented the disassociation of FKBP12.6 from RyR2.. Our results suggest that stachydrine hydrochloride exerts beneficial therapeutic effects against heart failure. These cardioprotective effects may be associated with the regulation of calcium handling by stachydrine hydrochloride through inhibiting the hyper-phosphorylation of CaMKII.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Aorta; Arterial Pressure; Calcium Signaling; Calcium-Binding Proteins; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Cardiovascular Agents; Cells, Cultured; Disease Models, Animal; Heart Failure; Male; Mice, Inbred C57BL; Myocytes, Cardiac; Phosphorylation; Proline; Rats; Rats, Sprague-Dawley; Ryanodine Receptor Calcium Release Channel; Sarcomeres; Sarcoplasmic Reticulum; Telmisartan; Ventricular Function, Left

Stachydrine is a major constituent of Chinese herb leonurus heterophyllus sweet, which is used in clinics to promote blood circulation and dispel blood stasis. Our study aimed to investigate the role of stachydrine in human umbilical vein endothelial cells (HUVECs) injury induced by anoxia-reoxygenation. Cultured HUVECs were divided randomly into control group, anoxia-reoxygenation (A/R) group and 4 A/R+stachydrine groups. HUVECs in the control group were exposed to normoxia for 5 hours, while in all A/R groups, HUVECs underwent 3 hours anoxia followed by 2 hours reoxygenation, and HUVECs in the 4 A/R+stachydrine groups were treated with 10(-8) M, 10(-7) M, 10(-6) M and 10(-5) M (final concentration) of stachydrine respectively. After anoxia-reoxygenation, tissue factor (TF) was over-expressed, cell viability and the concentrations of SOD, GSH-PX and NO were declined, while LDH, MDA and ET-1 were over-produced (p < 0.05 to 0.001 vs. the control group). However, in stachydrine treated groups, TF expression was inhibited at both mRNA and protein levels, while the declined cell viability and SOD, GSH-PX, NO as well as the enhanced LDH, MDA and ET-1 levels occurred during anoxia-reoxygenation were ameliorated and reversed effectively (p < 0.05 to 0.01 versus A/R group). Consequently, our findings indicate that TF plays an important role in the development of anoxia-reoxygenation injury of HUVECs, stachydrine ameliorates HUVECs injury induced by anoxia-reoxygenation and its putative mechanisms are related to inhibition of TF expression.

Topics: Cardiovascular Agents; Cell Culture Techniques; Cell Survival; Drugs, Chinese Herbal; Endothelial Cells; Endothelin-1; Glutathione Peroxidase; Humans; L-Lactate Dehydrogenase; Leonurus; Malondialdehyde; Nitric Oxide; Phytotherapy; Proline; Reperfusion Injury; RNA, Messenger; Superoxide Dismutase; Thromboplastin; Umbilical Veins