Uncovering Synergistic Mechanism of Chinese Herbal Medicine in the Treatment of Atrial Fibrillation with Obstructive Sleep Apnea Hypopnea Syndrome by Network Pharmacology.

Ting Mao,Shan Zhang,Jingchun Zhang,Yu Qiao,Bei Liu

doi:10.1155/2019/8691608

Abstract

Paroxysmal atrial fibrillation (AF) combined with obstructive sleep apnea hypopnea syndrome (OSAHS) is very common in clinical practice. Traditional Chinese medicine (TCM) rule of regulating the liver based on psycho-cardiology shows satisfactory effectiveness in the treatment of paroxysmal AF combined with OSAHS. However, its underlying pharmacological mechanism has not yet been elucidated. This study applied network pharmacology to identify 94 active components in the six TCM liver-regulating herbs and 182 corresponding targets from several databases and comprehensive literature studies, as well as retrieved AF combined with OSAHS-related targets. Cytoscape software was adopted to construct the component-component target network and component-putative target-AF combined with OSAHS target network. Then, we obtained 38 putative therapeutic targets against AF combined with OSAHS. After the production of a putative therapeutic target interaction network, topological analysis was adopted to determine the core targets of TCM liver-regulating herbs in the treatment of paroxysmal AF combined with OSAHS. For all putative therapeutic targets, biological process analysis and pathway enrichment analysis were utilized to investigate the possible mechanism of TCM liver-regulating herbs in the treatment of paroxysmal AF combined with OSAHS. Mechanistically, it included positive regulation of nitric oxide biosynthetic process, aging, response to hypoxia, TNF signaling pathway, HIF-1 signaling pathway, PI3K-Akt signaling pathway, neuroactive ligand-receptor interaction, and calcium signaling pathway. Especially, six core targets of TCM liver-regulating herbs, namely, TNF, STAT3, AKT1, IL-6, TP53, and INS, were significant in the regulation of the above biological processes and pathways. This study demonstrates the multicomponent, multitarget, and multipathway feature of TCM liver-regulating herbs, provides an extensional foundation for further research, and facilitates the reasonable application of TCM liver-regulating herbs in treating paroxysmal AF combined with OSAHS.

Highlights

Atrial fibrillation (AF) is one of the most common types of arrhythmia during clinical practice and is associated with elevated cardiovascular morbidity and mortality rate [1]
It is widely considered as a supplementary approach to identify components and pharmacological mechanisms of Chinese herbal medicine from a comprehensive perspective [29]. erefore, we apply network pharmacology to construct a component-component target network, component-putative therapeutic targetAF combined with Obstructive sleep apnea hypopnea syndrome (OSAHS) target network, and componentputative therapeutic target-pathway network to systematically explore the pharmacological and molecular mechanisms of Traditional Chinese medicine (TCM) liver-regulating herbs in the treatment of paroxysmal AF combined with OSAHS
We identified 94 active components of six TCM liver-regulating herbs and 182 component targets, showing the characteristic of multicomponent and multitarget of herbs. e herbs exerted therapeutic effects on AF combined with OSAHS by acting on 38 targets, which were primarily hit by quercetin, luteolin, kaempferol, apigenin, stigmasterol, isocorypalmine, and hyndarin

Summary

Introduction

Atrial fibrillation (AF) is one of the most common types of arrhythmia during clinical practice and is associated with elevated cardiovascular morbidity and mortality rate [1]. E latest research shows that Chinese herbal medicine can improve physical fitness, increase the ability to resist hypoxia, and inhibit inflammatory response, implying the possibility of integrating Traditional Chinese medicine (TCM) to improve paroxysmal AF combined with OSAHS and its prognosis [7]. TCM rule of regulating the liver based on psychocardiology combined with tonifying qi to treat paroxysmal AF has comprehensive effectiveness in clinical practice for many years. Our previous analysis showed Chinese herbal medicine including Ziziphi Spinosae Semen (Suan Zao Ren (SZR)), Nardostachys Chinensis Batal (Gan Song (GS)), Corydalis Rhizoma (Yan Hu Suo (YHS)), Agrimony (Xian He Cao (XHC)), Tribulus terrestris (Ji Li (JL)), and Concha Ostreae (Mu Li (ML)) were more frequently used in related diseases [9]. Erefore, these TCM liver-regulating herbs have the potential to treat AF combined with OSAHS. The feature of these above conventional experimental studies is one-drug-one-target-one-pathway, which ignores the multicomponent, multitarget, and multipathway characteristic of herbal formulae. erefore, its active components and underlying pharmacological mechanism remain to be elucidated completely

Methods

Results

Discussion

Conclusion