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基于实验支持和网络药理学策略的综合方法探索桂枝甘草汤对心力衰竭的作用及机制

Exploring the effects and mechanisms of Guizhigancao Decoction on heart failure using an integrated approach based on experimental support and network pharmacology strategy.

作者信息

Qu Jianhua, Wang Jiao, Zheng Biao, Jiang Xiaoxiao, Liu Jikui, Chen Jing

机构信息

Department of Hepatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong Province, China.

Flow Cytometry Center, The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning Province, China.

出版信息

J Tradit Complement Med. 2023 Apr 1;13(5):454-464. doi: 10.1016/j.jtcme.2023.03.010. eCollection 2023 Sep.

Abstract

BACKGROUND AND AIM

HF (Heart Failure) is the leading cause of mortality and is a significant clinical problem affecting millions of patients worldwide. To date, the mechanisms of HF remain largely elusive. The effective treatments contributing to HF remain incompletely understood. Therefore, the development of an effective strategy for HF is urgently needed.

EXPERIMENTAL PROCEDURE

In the present study, we devoted to investigating the effective treatments and sought to systematically decipher the related molecular mechanisms of Guizhigancao Decoction (GZGCD, Cinnamomum cassia Presl and Glycyrrhizae Radix Et Rhizoma Praeparata Cum Melle) for treating HF. We examined the therapeutic effect of GZGCD on HF . An integrative approach combining biomarker examination, echocardiography, myocardial fibrosis and cardiac apoptosis condition using Masson and TUNEL staining was performed to assess the efficacy of GZGCD against HF. Subsequently, comprehensive network pharmacology analyses were performed to explore the mechanisms involved in GZGCD therapeutic effects on HF.

RESULTS AND CONCLUSIONS

The results showed that GZGCD could reverse cardiac function in rats with HF by reducing NT-proBNP, increasing EF, decreasing LVESV, LVEDV, LVIDs, LVIDd, increasing running time, and ameliorate myocardial collagen fiber hyperplasia and cardiomyocyte apoptosis. We showed that GZGCD might contribute to HF treatment via oxidative related pathways through bioinformatics. Eventually, promising compound quercetin in GZGCD for HF therapeutics was proposed in database-based analysis. Collectively, our findings indicate that GZGCD has a treatment effect on HF. We proposed that GZGCD might contribute HF treatment via oxidative response-related pathways.

摘要

背景与目的

心力衰竭(HF)是导致死亡的主要原因,是影响全球数百万患者的重大临床问题。迄今为止,HF的发病机制仍 largely难以捉摸。对导致HF的有效治疗方法仍未完全了解。因此,迫切需要制定一种有效的HF治疗策略。

实验步骤

在本研究中,我们致力于研究有效治疗方法,并试图系统地解读桂枝甘草汤(GZGCD,肉桂和蜜炙甘草)治疗HF的相关分子机制。我们检测了GZGCD对HF的治疗效果。采用结合生物标志物检测、超声心动图、心肌纤维化和心肌细胞凋亡情况(使用Masson染色和TUNEL染色)的综合方法来评估GZGCD抗HF的疗效。随后,进行了全面的网络药理学分析,以探索GZGCD对HF治疗作用的相关机制。

结果与结论

结果表明,GZGCD可通过降低NT-proBNP、增加EF、降低LVESV、LVEDV、LVIDs、LVIDd、增加跑步时间来逆转HF大鼠的心脏功能,并改善心肌胶原纤维增生和心肌细胞凋亡。我们通过生物信息学表明,GZGCD可能通过氧化相关途径有助于HF的治疗。最终,在基于数据库的分析中提出了GZGCD中对HF治疗有前景的化合物槲皮素。总体而言,我们的研究结果表明GZGCD对HF有治疗作用。我们提出GZGCD可能通过氧化反应相关途径有助于HF的治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9900/10491989/a30efc3ff923/ga1.jpg

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