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BackgroundWenxin Keli (WXKL) has good clinical value in the treatment of premature ventricular contractions, but there is insufficient evidence to support it. This study evaluates the efficacy and safety of WXKL combined with metoprolol tartrate in the treatment of ventricular premature beats (VPCs).MethodsWe searched seven databases to identify randomized controlled trials (RCTs) for this study. Two reviewers independently screened and extracted the data. The Cochrane Manual criteria were used for methodological quality assessment. Meta-analyses were performed using Review Manager 5.4.1 software. Risk ratios (RR) were used for effect sizes for dichotomous data, demonstrated in effect sizes and 95% confidence intervals (CIs).ResultsA total of 11 RCTs of WXKL combined with metoprolol tartrate in the treatment of premature ventricular contractions were included in this study. Meta-analysis showed that WXKL combined with metoprolol tartrate (treatment group) was more effective than metoprolol tartrate (control group) in improving premature ventricular contractions (RR = 1.32, 95% CI: [1.24, 1.40], P < 0.00001); significantly improved the rate of premature ventricular contractions (RR = 1.32, 95% CI: [1.23, 1.41], P < 0.00001); there was no difference in adverse drug reactions compared with the control group (RR = 0.61, 95% CI: [0.35, 0.1.05], P = 0.08), but the number of adverse reactions (n = 18) was less than that of the control group (n = 32), and the severity was lower than that of the control group. The included studies only mentioned randomization and did not describe the generation of random sequences in detail.ConclusionThis study found that Wenxin Keli combined with metoprolol tartrate in the treatment of premature ventricular contractions increased the efficacy of the drug, reduced the occurrence of adverse reactions, and reduced the severity of adverse reactions. Due to the quality limitations of the included studies, more high-quality RCTs are needed in the future to provide more evidence for longer-term analyses.

This study employed a systems pharmacology approach to identify the active compounds and action mechanisms of Wenxin Keli for arrhythmia treatment. Sixty-eight components identified in vivo and in vitro by UPLC/Q-TOF-MS were considered the potential active components of Wenxin Keli. Network pharmacology further revealed 33 key targets and 75 KEGG pathways as possible pathways and targets involved in WK-mediated treatment, with the CaMKII/CNCA1C/Ca2+ pathway being the most significantly affected. This finding was validated using an AC-induced rat arrhythmias model. Pretreatment with Wenxin Keli reduced the malignant arrhythmias and shortened RR, PR, and the QT interval. Wenxin Keli exerted some antiarrhythmic effects by inhibiting p-CaMKII and intracellular Ca2+ transients and overexpressing CNCA1C. Thus, suppressing SR Ca2+ release and maintaining intracellular Ca2+ balance may be the primary mechanism of Wenxin Keli against arrhythmia. In view of the significance of CaMKII and NCX identified in this experiment, we suggest that CaMKII and NCX are essential targets for treating arrhythmias. [ABSTRACT FROM AUTHOR]

This study employed a systems pharmacology approach to identify the active compounds and action mechanisms of Wenxin Keli for arrhythmia treatment. Sixty-eight components identified in vivo and in vitro by UPLC/Q-TOF-MS were considered the potential active components of Wenxin Keli. Network pharmacology further revealed 33 key targets and 75 KEGG pathways as possible pathways and targets involved in WK-mediated treatment, with the CaMKII/CNCA1C/Ca2+ pathway being the most significantly affected. This finding was validated using an AC-induced rat arrhythmias model. Pretreatment with Wenxin Keli reduced the malignant arrhythmias and shortened RR, PR, and the QT interval. Wenxin Keli exerted some antiarrhythmic effects by inhibiting p-CaMKII and intracellular Ca2+ transients and overexpressing CNCA1C. Thus, suppressing SR Ca2+ release and maintaining intracellular Ca2+ balance may be the primary mechanism of Wenxin Keli against arrhythmia. In view of the significance of CaMKII and NCX identified in this experiment, we suggest that CaMKII and NCX are essential targets for treating arrhythmias.

Wenxin Keli (WXKL) is a widely used Chinese botanical drug for the treatment of arrhythmia, which is consisted of four herbs and amber. In the present study, we analyzed the chemical composition of WXKL using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) to tentatively identify 71 compounds. Through typical separate procession, the total extract of WXKL was divided into fractions for further bioassays. Cardiomyocytes and zebrafish larvae were applied for assessment. In vivo arrhythmia model in Cmlc2-GFP transgenic zebrafish was induced by terfenadine, which exhibited obvious reduction of heart rate and occurrence of atrioventricular block. Dynamic beating of heart was recorded by fluorescent microscope and sensitive camera to automatically recognize the rhythm of heartbeat in zebrafish larvae. By integrating the chemical information of WXKL and corresponding bioactivities of these fractions, activity index (AI) of each identified compound was calculated to screen potential active compounds. The results showed that dozens of compounds including ginsenoside Rg1, ginsenoside Re, notoginsenoside R1, lobetyolin, and lobetyolinin were contributed to cardioprotective effects of WXKL. The anti-arrhythmic activities of five compounds were further validated in larvae model and mature zebrafish by measuring electrocardiogram (ECG). Our findings provide a successful example for rapid discovery of bioactive compounds from traditional Chinese medicine (TCM) by activity index based approach coupled with in vivo zebrafish model.

Wenxin Keli (WXKL) is a widely used Chinese botanical drug for the treatment of arrhythmia, which is consisted of four herbs and amber. In the present study, we analyzed the chemical composition of WXKL using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) to tentatively identify 71 compounds. Through typical separate procession, the total extract of WXKL was divided into fractions for further bioassays. Cardiomyocytes and zebrafish larvae were applied for assessment. In vivo arrhythmia model in Cmlc2-GFP transgenic zebrafish was induced by terfenadine, which exhibited obvious reduction of heart rate and occurrence of atrioventricular block. Dynamic beating of heart was recorded by fluorescent microscope and sensitive camera to automatically recognize the rhythm of heartbeat in zebrafish larvae. By integrating the chemical information of WXKL and corresponding bioactivities of these fractions, activity index (AI) of each identified compound was calculated to screen potential active compounds. The results showed that dozens of compounds including ginsenoside Rg1, ginsenoside Re, notoginsenoside R1, lobetyolin, and lobetyolinin were contributed to cardioprotective effects of WXKL. The anti-arrhythmic activities of five compounds were further validated in larvae model and mature zebrafish by measuring electrocardiogram (ECG). Our findings provide a successful example for rapid discovery of bioactive compounds from traditional Chinese medicine (TCM) by activity index based approach coupled with in vivo zebrafish model. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are the major public health problem and a leading cause of morbidity and mortality on a global basis. Wenxin Keli (WXKL), a formally classical Chinese patent medicine with obvious efficacy and favorable safety, plays a great role in the management of patients with CVDs. Accumulating evidence from various animal and cell studies has showed that WXKL could protect myocardium and anti-arrhythmia against CVDs. WXKL exhibited its cardioprotective roles by inhibiting inflammatory reaction, decreasing oxidative stress, regulating vasomotor disorders, lowering cell apoptosis, and protection against endothelial injure, myocardial ischemia, cardiac fibrosis, and cardiac hypertrophy. Besides, WXKL could effectively shorten the QRS and Q-T intervals, decrease the incidence of atrial/ventricular fibrillation and the number of ventricular tachycardia episodes, improve the severity of arrhythmias by regulating various ion channels with different potencies, mainly comprising peak sodium current (INa), late sodium current (INaL), transient outward potassium current (Ito), L-type calcium current (ICaL), and pacemaker current (If).

Objectives: To evaluate possible adverse effects and efficacy of Wenxin keli (WXKL)-amiodarone combination on heart failure complicated by ventricular arrhythmia.Methods: Nine electronic literature databases (the Cochrane Library, PubMed, EMBASE, IPA, AMED, CBM, CNKI, VIP, and WanFang) were searched up to February 2018. Two authors extracted data and assessed risk of bias of the included studies independently. Randomized controlled trials (RCTs) and quasi-RCTs about WXKL-amiodarone combination and amiodarone alone were eligible for comparison.Results: Thirteen trials involving 1,126 patients were included. Risk of bias was assessed as high in three studies and unclear in the remaining 10 studies. Six trials reported adverse events (AE). There was no obvious difference between WXKL-amiodarone combination group and amiodarone group in reported AEs (OR 0.64; 95%CI 0.39–1.07). The total effective rate of WXKL-amiodarone combination group was greater than that of amiodarone group (RR 1.22; 95%CI 1.16–1.29). The pooled results showed that the combination group was more effective in reducing heart rate (MD −2.25; 95%CI −2.61 to −1.88, P = 0.46, I2 = 0%), the frequency of ventricular premature complexes (MD −2.03; 95%CI −2.41 to −1.65) and QT dispersion (MD 5.59; 95%CI 3.60–7.58).Conclusion: The WXKL-amiodarone combination is safe and shows more protective effects on heart failure combined with ventricular arrhythmia compared with amiodarone alone. Further research is warranted, ideally involving large, prospective, rigorous trials, in order to confirm these findings.