Table1_Bidirectional regulatory effects of Cordyceps on arrhythmia: Clinical evaluations and network pharmacology.DOCX

Background: Cordyceps is a precious Chinese herbal medicine with rich bio-active ingredients and is used for regulating arrhythmia alongside routine treatments. However, the efficacy and potential mechanisms of Cordyceps on patients with arrhythmia remain unclear.
Methods: Randomized controlled trials of bradycardia treatment with Cordyceps were retrieved from diverse databases and available data. Dichotomous variables were expressed as a risk ratio (RR) with a 95% confidence interval (CI). Continuous variables were expressed as a standardized mean difference (SMD) with a 95% CI. Network pharmacology was used to identify potential targets of Cordyceps for arrhythmia. Metascape was used for gene ontology (GO) and genome (KEGG) pathway enrichment analysis.
Results: Nineteen trials included 1,805 patients with arrhythmia, of whom 918 were treated with Ningxinbao capsule plus routine drugs, and, as a control, 887 were treated with only routine drugs. Six trials reported on bradycardia and the other 13 on tachycardia. Treatment with Cordyceps significantly improved the total efficacy rate in both bradycardia (RR = 1.24; 95% CI, 1.15 to 1.35; Pz <0.00001) and tachycardia (RR = 1.27; 95% CI, 1.17 to 1.39; Pz <0.00001). Cordyceps also had beneficial secondary outcomes. No serious adverse events occurred in patients treated with Cordyceps. The results of KEGG pathway enrichment analysis were mainly connected to adrenergic signaling in cardiomyocytes and the PI3K-Akt signaling pathway. IL6, TNF, TP53, CASP3, CTNNB1, EGF, and NOS3 might be key targets for Cordyceps in the treatment of arrhythmia.
Conclusion: This study confirmed that Cordyceps has a certain positive effect on the treatment of arrhythmia and that its main mechanism may be through the regulation of adrenergic signaling in cardiomyocytes and the PI3K-Akt signaling pathway.

背景：冬虫夏草（Cordyceps）是一味珍贵的中药材，富含多种生物活性成分，常与常规治疗方案联用辅助调节心律失常。然而，冬虫夏草用于心律失常患者治疗的临床疗效及其潜在作用机制仍尚未明确。
方法：本研究从多类数据库中检索了冬虫夏草治疗缓慢性心律失常的随机对照试验，并收集相关可用数据。二分类变量采用风险比（risk ratio, RR）联合95%置信区间（confidence interval, CI）进行统计表述；连续性变量则采用标准化均数差（standardized mean difference, SMD）联合95%置信区间进行分析。本研究通过网络药理学方法鉴定冬虫夏草治疗心律失常的潜在靶点，并使用Metascape工具开展基因本体（Gene Ontology, GO）及京都基因与基因组百科全书（Kyoto Encyclopedia of Genes and Genomes, KEGG）通路富集分析。
结果：本研究共纳入19项随机对照试验，涉及1805名心律失常患者，其中918例接受宁心宝胶囊（Ningxinbao capsule）联合常规药物治疗，887例仅接受常规药物治疗作为对照组。其中6项试验针对缓慢性心律失常展开，剩余13项针对快速性心律失常。与对照组相比，冬虫夏草治疗可显著提升缓慢性心律失常（RR=1.24；95%CI：1.15~1.35；Pz<0.00001）与快速性心律失常患者的总有效率（RR=1.27；95%CI：1.17~1.39；Pz<0.00001）。此外，冬虫夏草对次要结局指标亦具有改善作用，且治疗组未出现严重不良事件。KEGG通路富集分析结果显示，其主要富集通路集中于心肌细胞肾上腺素能信号通路及PI3K-Akt信号通路。IL6、TNF、TP53、CASP3、CTNNB1、EGF及NOS3可能是冬虫夏草治疗心律失常的关键靶点。
结论：本研究证实，冬虫夏草对心律失常的治疗具有一定积极疗效，其核心作用机制可能通过调控心肌细胞肾上腺素能信号通路及PI3K-Akt信号通路实现。