Mechanisms of Chinese Medicine Xinmailong's protection against heart failure in pressure-overloaded mice and cultured cardiomyocytes.
Animal; Animals; Cardiac/cytology/*drug effects/metabolism; Cell Nucleus/metabolism; Cell Survival/drug effects; Cells; Chinese Herbal/*administration & dosage/pharmacology; Constriction; Cultured; Disease Models; Drugs; Echocardiography; GABA Plasma Membrane Transport Proteins/*metabolism; Gene Expression Regulation/drug effects; Glycogen Synthase Kinase 3 beta/metabolism; Heart Failure/etiology/metabolism/physiopathology/*prevention & control; Humans; MAP Kinase Signaling System/drug effects; Mice; Myocytes; Pathologic; Phosphorylation; Proto-Oncogene Proteins c-akt/metabolism; Rats
Patients with heart failure (HF) have high mortality and mobility. Xinmailong (XML) injection, a Chinese Medicine, is clinically effective in treating HF. However, the mechanism of XML's effectiveness on HF was unclear, and thus, was the target of the present study. We created a mouse model of pressure-overload-induced HF with transverse aortic constriction (TAC) surgery and compared among 4 study groups: SHAM (n = 10), TAC (n = 12), MET (metoprolol, positive drug treatment, n = 7) and XML (XML treatment, n = 14). Dynamic changes in cardiac structure and function were evaluated with echocardiography in vivo. In addition, H9C2 rat cardiomyocytes were cultured in vitro and the phosphorylation of ERK1/2, AKT, GSK3beta and protein expression of GATA4 in nucleus were detected with Western blot experiment. The results showed that XML reduced diastolic thickness of left ventricular posterior wall, increased ejection fraction and fraction shortening, so as to inhibit HF at 2 weeks after TAC. Moreover, XML inhibited the phosphorylation of ERK1/2, AKT and GSK3beta, subsequently inhibiting protein expression of GATA4 in nucleus (P \textless 0.001). Together, our data demonstrated that XML inhibited the TAC-induced HF via inactivating the ERK1/2, AKT/GSK3beta, and GATA4 signaling pathway.
Qi Jianyong; Yu Juan; Tan Yafang; Chen Renshan; Xu Wen; Chen Yanfen; Lu Jun; Liu Qin; Wu Jiashin; Gu Weiwang; Zhang Minzhou
Scientific reports
2017
2017-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1038/srep42843" target="_blank" rel="noreferrer noopener">10.1038/srep42843</a>
Songling Xuemaikang Capsule inhibits isoproterenol-induced cardiac hypertrophy via CaMKIIdelta and ERK1/2 pathways.
ERK1/2; Cardiac hypertrophy; Isoproterenol; CaMKIIdelta; Songling xuemaikang capsule; CaMKIIδ
ETHNOPHARMACOLOGICAL RELEVANCE: Cardiac hypertrophy is a key pathologic process in heart failure. Songling Xuemaikang Capsule (SXC), is a formulae of Chinese Medicine commonly used in China to treat hypertension and heart failure. However, its mechanism of effects on cardiac hypertrophy is still unclear. AIM OF THE STUDY: The aims of the present study were to investigate the cardio-protection roles and detailed mechanisms of SXC on cardiac hypertrophy in vivo and in vitro. MATERIALS AND METHODS: A rat model of cardiac hypertrophy was constructed by isoproterenol (ISO) intraperitoneal injection (i.p), 10 mg/kg/day for 3 days, and 4 groups were compared: CON (n = 8), ISO (n = 8), MET (metoprolol, positive drug treatment, n = 7), and SXC (SXC treatment, n = 6). Cardiac structure and function were evaluated with echocardiography in vivo. Dose-dependent curve was obtained with SXC different concentrations. In addition, H9C2 rat cardiomyocytes were cultured in vitro and the phosphorylation of ERK1/2, p38, JNK, AKT, and protein expression of CaN, CaMKIIdelta, GATA4 were detected with Western blot test. RESULTS: The results showed that SXC reduced diastolic thickness of left ventricular posterior wall, while did not change ejection fraction and fraction shortening significantly (P > 0.05). SXC inhibit ISO-induced cardiac hypertrophy dose-dependently with 50% inhibiting concentration (IC50) is 0.504 g/kg/day. Moreover, SXC inhibited the protein expression of CaMKIIdelta, and the phosphorylation of ERK1/2, so inhibiting protein expression of GATA4 in nucleus, and brain natriuretic peptide in serum (P < 0.001). CONCLUSION: The mechanism of SXC in the treatment of heart diseases involves SXC dose-dependently inhibited the ISO-induced cardiac hypertrophy via inhibiting CaMKIIdelta and ERK1/2/GATA4 signaling pathway.
Qi Jianyong; Tan Yafang; Fan Dancai; Pan Wenjun; Yu Juan; Xu Wen; Wu Jiashin; Zhang Minzhou
Journal of ethnopharmacology
2020
2020-02
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1016/j.jep.2020.112660" target="_blank" rel="noreferrer noopener">10.1016/j.jep.2020.112660</a>