Uncovering the Protective Mechanism of the Volatile Oil of Acorus tatarinowii against Acute Myocardial Ischemia Injury Using Network Pharmacology and Experimental Validation.

Zhen-Zhong Zang,Yong-Mei Guan,Qing Du,Yuan Liu,Pan Xu,Ming Yang,Li-Mei Chen,Qian Shen,Zheng-Gen Liao,Hong-Ning Liu,Abraham Wall Medrano

doi:10.1155/2021/6630795

Abstract

Acorus tatarinowii is a traditional aromatic resuscitation drug that can be clinically used to prevent cardiovascular diseases. The volatile oil of Acorus tatarinowii (VOA) possesses important medicinal properties, including protection against acute myocardial ischemia (MI) injury. However, the pharmacodynamic material basis and molecular mechanisms underlying this protective effect remain unclear. Using network pharmacology and animal experiments, we studied the mechanisms and pathways implicated in the activity of VOA against acute MI injury. First, VOA was extracted from three batches of Acorus tatarinowii using steam distillation, and then, its chemical composition was determined by GC-MS. Next, the components-targets and protein-protein interaction networks were constructed using systematic network pharmacology. Gene Ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were also conducted in order to predict the possible pharmacodynamic mechanisms. Furthermore, animal experiments including ELISAs, histological examinations, and Western blots were performed in order to validate the pharmacological effects of VOA. In total, 33 chemical components were identified in VOA, and ß-asarone was found to be the most abundant component. Based on network pharmacology analysis, the therapeutic effects of VOA against myocardial ischemia might be mediated by signaling pathways involving COX-2, PPAR-α, VEGF, and cAMP. Overall, the obtained results indicate that VOA alleviates the pathological manifestations of isoproterenol-hydrochloride-induced myocardial ischemia in rats, including the decreased SOD (superoxide dismutase) content and increased LDH (lactic dehydrogenase) content. Moreover, the anti-MI effect of VOA might be attributed to the downregulation of the COX-2 protein that inhibits apoptosis, the upregulation of the PPAR-α protein that regulates energy metabolism, and the activation of VEGF and cAMP signaling pathways.

Highlights

Cardiovascular diseases are the leading cause of morbidity and mortality in the world
Fingerprint Analysis of volatile oil of Acorus tatarinowii (VOA). e GC-MS data of three VOA batches were imported into the Chinese medicine chromatographic fingerprint similarity evaluation system version A (2004) for similarity evaluation, and the S1 chromatogram was used as a reference spectrum
By resisting the influence of reactive oxygen species [41,42,43], neroli protects the cells from the oxidative damage induced by lipids, proteins, and DNA. e “components-targets” network constructed in this study reveals that the degrees of ESR1, PPAR-α, P2RX7, and PTGS2 are greater than those of other targets. erefore, these targets may play a critical role in the anti-Myocardial ischemia (MI) effect of VOA

Summary

Introduction

Cardiovascular diseases are the leading cause of morbidity and mortality in the world. Myocardial ischemia (MI), one of the main pathogenic mechanisms of cardiovascular diseases [1, 2], is a pathological state characterized by reduced blood perfusion and oxygen supply to the heart. This state leads to abnormal myocardial energy metabolism and disrupts normal heart function. Patients suffering from mild MI have angina pectoris and arrhythmia; whereas, those suffering from the severe disease exhibit myocardial infarction, which eventually leads to death [3]. Hypoxia, and Evidence-Based Complementary and Alternative Medicine metabolic disorders in the myocardial tissues are caused by severe spasms, sudden coronary artery obstruction, low blood pressure, reduced aortic blood supply, change in blood viscosity, valvular disease, and myocardial disease [4, 5]

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