Abstract
Wenxin Keli (WXKL) is a traditional Chinese medicine drug approved for the treatment of cardiovascular diseases. This study aimed to identify WXKL-targeting genes involved in antiarrhythmic efficacy of WXKL. The Traditional Chinese Medicine Systems Pharmacology (TCMSP) technology platform was used to screen active compounds of WXKL and WXKL-targeting arrhythmia-related genes. A pig model of myocardial ischemia (MI) was established by balloon-expanding the endothelium of the left coronary artery. Pigs were divided into the model group and WXKL group (n = 6). MI, QT interval, heart rate, and arrhythmia were recorded, and the mRNA expression of target genes in myocardial tissues was detected by PCR. Eleven active ingredients of WXKL and eight WXKL-targeting arrhythmia-related genes were screened. Five pathways were enriched, and an “ingredient-gene-path” network was constructed. WXKL markedly decreased the incidence of arrhythmia in the MI pig model (P < 0.05). The QT interval was significantly shortened, and the heart rate was slowed down in the WXKL group compared with the model group (P < 0.05). In addition, the expression of sodium channel protein type 5 subunit alpha (SCN5A) and beta-2 adrenergic receptor (ADRB2) was downregulated, while muscarinic acetylcholine receptor M2 (CHRM2) was upregulated in the WXKL group (P < 0.05). In conclusion, WXKL may shorten the QT interval and slow down the heart rate by downregulating SCN5A and ADRB2 and upregulating CHRM2 during MI. These findings provide novel insight into molecular mechanisms of WXKL in reducing the incidence of ventricular arrhythmia.
Highlights
Acute occlusion of the epicardial coronary artery leads to myocardial ischemia (MI) with a rapid onset of unstable electrocardiograph (ECG) activity, which usually induces fatal ventricular arrhythmias [1]
A meta-analysis showed that Wenxin Keli (WXKL) was effective in the treatment of cardiovascular diseases, more high-quality evidence was needed to support its use in clinical settings [2]
A total of eight WXKL-target genes related to arrhythmia were retrieved from Traditional Chinese Medicine Systems Pharmacology (TCMSP), including sodium channel protein type 5 subunit alpha (SCN5A), potassium voltage-gated channel subfamily H member 2 (KCNH2), beta-1 adrenergic receptor (ADRB1), beta-2 adrenergic receptor (ADRB2), alpha-1D adrenergic receptor (ADRA1D), muscarinic acetylcholine receptor M2 (CHRM2), alpha-2A adrenergic receptor (ADRA2A), and gap junction alpha-1 protein (GJA1) (Table 1)
Summary
Acute occlusion of the epicardial coronary artery leads to myocardial ischemia (MI) with a rapid onset of unstable electrocardiograph (ECG) activity, which usually induces fatal ventricular arrhythmias [1]. A meta-analysis showed that WXKL was effective in the treatment of cardiovascular diseases (angina, heart failure, and arrhythmia), more high-quality evidence was needed to support its use in clinical settings [2]. Compared with Western medicine treatment alone, combined use with WXKL could lower the heart rate, reduce the occurrence of arrhythmia (ventricular premature beats, ventricular tachycardia, and ventricular fibrillation), and improve heart function [3, 4]. WXKL significantly reduced ventricular arrhythmia after MI [5]. A recent study reported that WXKL could relieve recent-onset atrial fibrillation, without significant difference in the efficacy on male or female patients [6]
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