Deciphering mechanism of the herbal formula WuShen in the treatment of postinfarction heart failure.

BACKGROUND: Numerous clinical studies reported the effectiveness of herbal formula WuShen (WS) in treating cardiovascular diseases, yet relevant basic research was rarely conducted. METHODS AND RESULTS: Twelve main bioactive compounds of WS decoction were identified using the ultra-performance liquid chromatography-LTQ-Orbitrap mass spectrometer. A total of 137 active compounds with 613 targets were predicted by network pharmacology; their bioinformatic annotation and human microarray data suggested that wounding healing, inflammatory response, and gap junction were potentially the major therapeutic modules. A rat model of post-myocardial infarction (MI) heart failure (HF) was used to study the effects of WS on cardiac function, adverse cardiac remodeling, and experimental arrhythmias. Rats treated with WS led to a significantly improved pump function and reduced susceptibility to both ventricular tachycardia and atrial fibrillation, and restricted adverse cardiac remodeling partly via inhibiting TGFß1/SMADs mediated extracellular matrix deposition and Rac1/NOX2/CTGF/Connexin43 -involved gap junction remodeling. CONCLUSIONS: The present study highlights that WS can be applied to the treatment of heart failure and the upstream therapy for atrial fibrillation and ventricular tachycardia through its preventive effect on adverse cardiac remodeling.

Salvianolate reduces atrial fibrillation through suppressing atrial interstitial fibrosis by inhibiting TGF-ß1/Smad2/3 and TXNIP/NLRP3 inflammasome signaling pathways in post-MI rats.

BACKGROUND: Salvianolate is the main water-soluble bioactive compound of Salvia Miltiorrhiza Bunge and is now clinically used in the treatment of cardiovascular diseases in China. However, its applications in the prevention of atrial interstitial fibrosis (AIF) and atrial fibrillation (AF) are not fully revealed. PURPOSES: To investigate the preventive effect of salvianolate on the pathogenesis of AF in post-myocardial infarction (MI) rats and to elucidate the potential mechanisms. MATERIALS AND METHODS: Rats underwent left anterior descending coronary artery ligation were randomized into four groups and administered intraperitoneally with vehicle (MI group, n = 13), or 10, 20 and 40 mg/kg salvianolate (Sal-L, Sal-M and Sal-H group, n = 13, 14 and 13 respectively) for totally five weeks. Rats underwent sham operation was used as control group (Sham, n = 10). Then, echocardiography and AF inducibility test were detected. Tissues and serum were collected for Sirius red and fast green counter stain or hematoxylin-eosin to assess atrial interstitial fibrosis and hypertrophy, or for western blot and ELISA analysis. RESULTS: Salvianolate injection significantly improved cardiac function, reduced left atrial enlargement and P-wave duration, and decreased not only the vulnerability to AF but also AF duration. Histologic analysis showed that salvianolate mitigated AIF and atrial hypertrophy. Western blot analysis found that salvianolate inhibited the TGFß1/Smad2/3 mediated-collagen deposition and inhibited the TXNIP/NLRP3 inflammasome /IL-1ß and IL-18 signal pathway. ELISA analysis showed that salvianolate significantly reduced the serum concentrations of BNP, IL-6, CRP and TGFß1. CONCLUSIONS: Salvianolate may constitute a novel upstream therapy for AF by suppressing AIF. The underlying mechanism may be attributable to its inhibitory effects on TGF-ß1/Smad2/3 and TXNIP/NLRP3 inflammasome signaling pathway.

Shensong Yangxin capsule reduces atrial fibrillation susceptibility by inhibiting atrial fibrosis in rats with post-myocardial infarction heart failure.

PURPOSE: Shensong Yangxin (SSYX) capsule is a traditional Chinese medicine that has been used widely to treat cardiac arrhythmia. This study aimed to assess whether SSYX prevents atrial fibrillation (AF) after chronic myocardial infarction (MI)-induced heart failure and to determine the underlying mechanisms. MATERIALS AND METHODS: The study included 45 male Sprague Dawley rats. The rats underwent MI induction or sham surgery. One week after MI induction surgery, we performed serial echocardiography and administered SSYX capsule to some rats that experienced MI. After 4 weeks of treatment, AF inducibility was assessed with transesophageal programmed electrical stimulation technology. Additionally, multielectrode array assessment, histological analysis, and Western blot analysis were performed. RESULTS: AF inducibility was significantly lower in SSYX rats than in MI rats (33.3% vs 73.3%, P<0.05). Additionally, conduction velocities in the left atrium were greater in SSYX rats than in MI rats. Moreover, SSYX decreased left atrial fibrosis, downregulated TGF-ß1, MMP-9, TIMP-I, and type I and III collagen expressions, and inhibited the differentiation of cardiac fibroblasts to myofibroblasts. CONCLUSION: SSYX reduces AF inducibility after MI by improving left atrial conduction function via the inhibition of left atrial fibrosis. It prevents the development of an MI-induced vulnerable substrate for AF.

Traditional Chinese Medicine ShenZhuGuanXin Granules Mitigate Cardiac Dysfunction and Promote Myocardium Angiogenesis in Myocardial Infarction Rats by Upregulating PECAM-1/CD31 and VEGF Expression.

BACKGROUND: Myocardial infarction (MI) is the main cause of global mortality and morbidity despite the development of therapeutic approaches. ShenZhuGuanXin granules (SG) have been shown to possess cardioprotective effects against coronary heart disease (CHD). However, little is known about its specific mechanism. The present study aimed to investigate the therapeutic effect of SG in cardiac dysfunction and to demonstrate whether SG can promote myocardium angiogenesis by establishing a rat model of myocardial infarction with left anterior descending ligating. METHODS AND RESULTS: Three days after MI, rats were randomly divided into six groups: sham group (sham), MI group (MI), MI + low dose SG (SG-L) group, MI + middle dose SG (SG-M) group, MI + high dose SG (SG-H) group, and MI + compound Danshen dropping pills (CDDP) group as a positive control. Four weeks after administration, rats underwent hemodynamics and echocardiography study. Ventricle tissues were processed for histology and immunohistochemistry studies. Compared with MI group, SG treatment dose-dependently improved cardiac hemodynamic function, attenuated infarct size, increased microvessel density, and increased the expression of PECAM-1/CD31 and VEGF. CONCLUSIONS: SG dose-dependently improved cardiac hemodynamic function and attenuated infarct size by promoting angiogenesis through upregulating PECAM-1/CD31 and VEGF expression.