Impact of Yiqi Huoxue Decoction on the Relationship between Remodeling of Cardiac Nerves and Macrophages after Myocardial Infarction in Rats.

Sympathetic nerve remodeling after myocardial infarction (MI) has an indispensable role in cardiac remodeling. Numerous works have shown that sympathetic nerve remodeling can be delayed by inhibition of inflammatory response. Earlier studies have shown improvement in ventricular remodeling and inhibited chronic stage neural remodeling by Yiqi Huoxue decoction (YQHX). Therefore, the current study looked at the inhibitory effect of YQHX prescription on proinflammatory mediators and macrophages and the effect on neural remodeling at 3 and 7 days after MI. YQHX inhibited the expression of Toll-like receptor 4 (TLR4) and nuclear factor kappa B (NF-κB) proteins and macrophage infiltration within 7 days after myocardial infarction. YQHX could decrease Th-positive nerve fiber density in the area around infarction and reduce the expression of growth-associated protein 43 (GAP43), nerve growth factor (NGF), and tyrosine hydroxylase (TH) proteins, which was associated with the remodeling of sympathetic nerves. Thus, the nerve remodeling inhibition after MI due to YQHX may be through its anti-inflammatory action. These data provide direct evidence for the potential application of traditional Chinese medicine (TCM) in the remodeling of sympathetic nerves after MI.

Effects of Yiqi Huoxue Decoction on Post-Myocardial Infarction Cardiac Nerve Remodeling and Cardiomyocyte Hypertrophy in Rats.

Myocardial infarction can lead to ventricular remodeling and arrhythmia, which is closely related to nerve remodeling. Our previous study found that Yiqi Huoxue decoction (YQHX) can improve ventricular remodeling and reduce myocardial damage. Therefore, in this study, we observed the effect of YQHX on cardiac neural remodeling and cardiomyocyte hypertrophy and its possible mechanism. This research is composed of two parts: animal and H9c2 cells experiments. The animal model of acute myocardial infarction was established by ligating the left anterior descending coronary artery in Sprague Dawley (SD) rats. H9c2 cells were placed in 94% N2, 5% CO2, and 1% O2 hypoxic environment for 12 hours to replicate the hypoglycemic hypoxia model. The experimental results showed that, compared with the MI group, YQHX can significantly improve heart function after myocardial infarction and reduce nerve remodeling and myocardial hypertrophy. Pathological structure observation demonstrated reducing myocardial tissue damage and decreasing of cell cross-sectional area, diameter, and circumference. The positive rate of TH declined apparently, and the sympathetic nerve density was lower than that of the MI group. After YQHX was given for 28 days, the proneural remodeling factors TH, NGF, and GAP43 in the marginal zone of infarction and stellate ganglion decreased obviously while the inhibitory nerve remodeling factor Sema-3A increased. The myocardial hypertrophic protein ANP and ß-MHC were also significantly inhibited with p-ERK1/2 protein expression level prominently reduced. There was no difference between the YQHX group and the Meto group. After myocardial infarction, nerve remodeling was seen in the marginal area of infarction and stellate ganglion, and the neuropeptides released by which promoted myocardial hypertrophy. The mechanism may be related to the ERK1/2 signaling pathway. YQHX could regulate the ERK1/2 signaling pathway, inhibit the release of nerve remodeling factors and myocardial hypertrophy protein to reduce nerve remodeling, and relieve myocardial hypertrophy.

The clinical efficacy and safety of the Chinese herbal medicine Astragalus (Huangqi) preparation for the treatment of acute myocardial infarction: A systematic review of randomized controlled trials.

BACKGROUND: In recent years, with the enormous advances in the field of cardiac intervention technology, the survival rate of patients with acute myocardial infarction (AMI) has been improved significantly. However, the risk of arrhythmias and heart failure remains very high in AMI patients for long-term prognosis. Chinese herbal medicine (CHM) is more and more used in the treatment of AMI because of its good curative effect and less side effects. The target of this research is to analyze the efficacy and safety of Astragalus (Huangqi) preparation in the treatment of AMI by meta-analysis and also to provide a better evidence for clinical practice. METHODS: Seven databases will be searched in this study: The Cochrane Library, PubMed, Web of Science, the Chinese National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal Database (CSJD), the Chinese Biomedical Literature Database (CBM), and Wanfang DATA. The following search terms will be used: (Huangqi OR Huang Qi OR Astragalus OR radix astragali) AND (acute myocardial infaction OR myocardial infaction OR AMI) AND (randomized controlled trial OR RCT OR randomized). No language limitations and the searches will be conducted up to March, 2019. INCLUSION CRITERIA: randomized controlled trial (RCT) of Astragalus (Huangqi) preparation in patients with AMI. Main outcome measures will be left ventricular end systolic volume (LVESV), left ventricular end diastolic volume (LVEDV), left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), recanalization rate, mortality rate, incidence of reperfusion arrhythmias, postinfarction angina pectoris, and re-infarction rate. Secondary outcome indicators were the incidence of adverse reactions and the effective rate of traditional Chinese medicine (TCM) treatment. Two independent reviewers will filter the literature and extract data which based to the Cochrane manual. The relevant data, including bias risk assessment, data synthesis, subgroup analysis, meta-analysis, and final meta-analysis, will be analyzed with RevMan 5.3 software. The funnel diagram will be used to evaluate the reported deviation, and the Egger test will be used to evaluate the symmetry of the funnel graph. RESULTS: This systematic review study will provide a clear basis for evaluating the efficacy and safety of Astragalus (Huangqi) preparation with the treatment of AMI. CONCLUSION: This study will provide an up-to-date evidence for evaluating the efficacy and safety of Astragalus (Huangqi) preparation. PROSPERO REGISTRATION NUMBER: CRD42019124843.

Yiqihuoxue decoction protects against post-myocardial infarction injury via activation of cardiomyocytes PGC-1α expression.

BACKGROUND: Mitochondrial dysfunction has been implicated in the pathogenesis of ischemic heart disease, exacerbating cardiomyocytes injury in myocardial infarction (MI). Peroxisome proliferator-activated receptor gamma co-activator (PGC-1α) has been recognized as the key regulator of mitochondrial biogenesis and energy metabolism. Yiqihuoxue decoction (YQHX), a Traditional Chinese Medicine (TCM) prescription, can prevent and treat ischemic heart disease. However, the mechanisms of YQHX on PGC-1α expression in the ischemic heart have remained unclear. METHODS: Myocardial ischemia rat model and ischemia/hypoxia injury model in the cardiomyocytes were used to minic human cardiovascular disease. Rats were randomly assigned into 4 groups: Sham, Model, YQHX (8.2 g/kg) and Trimetazidine (10 mg/kg) group. 28 days after MI, cardiac functions and morphology were detected by echocardiography and HE staining, respectively. In vitro, the effects of YQHX on H9c2 cell viability, LDH and ROS were detected, respectively. PGC-1α relevant proteins were evaluated by Western blotting. RESULTS: In vivo, echocardiography and HE staining results showed that YQHX improved cardiac functions and modified pathological changes. YQHX enhanced PGC-1α expression and improved the mitochondrial ultrastructure and functions in rats MI model for 4 weeks. Further, we explored its potential mechanisms in cardiomyocytes. In vitro, YQHX significantly enhanced cell viability and reduced LDH release and ROS production induced by hypoxia in cardiomyocytes. Interestingly, exposure of cardiomyocytes to hypoxic conditions for 12 h induced the downregulation of PGC-1α expression, but the expression levels nearly returned to the normal state after hypoxia for 24 h. YQHX significantly enhanced PGC-1α expression between 12 h and 24 h induced by hypoxia through a mechanism associated with the activation of AMPK phosphorylation in H9c2 cells. In addition, YQHX upregulated the expression of Tfam and NRF-1, while NRF-1 expression was completely blocked by an AMPK inhibitor. YQHX largely restored the mitochondrial morphology and increased mitochondrial membrane potential in hypoxia-induced injury. Furthermore, the UHPLC-LTQ-Orbitrap-MSn analysis found that there were 87 chemical constituents in YQHX. CONCLUSIONS: These results suggest that the protective effect of YQHX on cardiomyocytes against hypoxia-induced injury may be attributed to activation of PGC-1α and maintenance of mitochondrial functions through a mechanism involving the activation of AMPK phosphorylation.