A simplified herbal formula for the treatment of heart failure: Efficacy, bioactive ingredients, and mechanisms

A simplified herbal formula for the treatment of heart failure: Efficacy, bioactive ingredients, and mechanisms
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治疗心力衰竭的简化草药配方:功效、生物活性成分和机制

DOI:
10.1016/j.phrs.2019.104251
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发表时间:
2019-09-01
影响因子:
9.3
通讯作者:
Xiang, Shaoxiang
Xiang, Shaoxiang
中科院分区:
医学1区
文献类型:
--
作者:
Chen, Zixin;Luo, Tong;Xiang, Shaoxiang

文献摘要

被引文献

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心力衰竭(HF)是一种复杂的病理,单药治疗无法提供全面的疗效。因此,HF的有效联合治疗越来越受到重视。当给予HF患者时,源自中草药配方的多组分药物提供有效性和安全性。暖心康是一种简化的中药配方,已被广泛应用于HF几十年。作为辅助治疗,它在HF患者中表现出全面的心脏保护作用,包括改善心脏功能和生活质量,减少炎症和调节神经激素。然而,NXK的生物活性成分和作用机制尚不清楚,这阻碍了其进一步应用。在这里,我们研究了NXK在HF小鼠模型中的治疗效果。使用转录组分析和药物相似性分析,我们发现NXK抑制细胞凋亡和炎症,同时改善心脏收缩和逆转心肌纤维化。此外,我们使用UHPLC-MS分析检测到21种生物活性物质。基于这些数据,我们进行了网络药理学分析,以研究成分-靶点-途径的相互作用。我们进一步确认了13个基因作为潜在的靶点,并评估了NICK对AKT的影响,以验证NXK在体内和体外的抗凋亡作用。因此,我们的工作已经确定了一个简化的草药配方,通过探索其成分和作用机制,对HF的有效性,为HF的创新治疗策略和新的治疗靶点提供了证据。
Heart failure (HF) is a complex pathology for which single-agent therapy cannot provide comprehensive efficacy. Therefore, effective combination therapies for HF are increasingly emphasized. Multiple-component drugs derived from Chinese herbal formulae provide efficacy and safety when administered to patients with HF. Nuanxinkang (NXK) is a simplified Chinese herbal formula which has been widely applied in HF for decades. It exhibits comprehensive cardiac protective effects in HF patients as an adjuvant therapy, including improving heart function and quality-of-life, reducing inflammation, and regulating neurohormones. Nevertheless, the bioactive ingredients and mechanisms of action of NXK are unknown, which hinders its further application. Here, we examined the therapeutic efficacy of NXK in a mouse model of HF. Using transcriptome analysis and drug similarity analysis we found that NXK inhibits apoptosis and inflammation, while improving cardiac contraction and reversing myocardial fibrosis. In addition, we detected 21 bioactive species in NICK using UHPLC-MS analysis. Based on these data, we performed network pharmacology analysis to investigate ingredient-target-pathway interactions. We further confirmed 13 genes as potential targets, and assessed the effects of NICK on the AKT to validate the anti-apoptotic role of NXK both in vivo and in vitro. Thus, our work has identified a simplified herbal formula with efficacy against HF by exploring its constituents and mechanism of action, providing evidence for an innovative treatment strategy and novel therapeutic targets for HF.