Abstract
Accumulating evidence suggests that Astragaloside IV (AS-IV) improves cardiac function and protects the cardiovascular system. However, the molecular targets involved remain ambiguous. In this work, we report research suggesting that AS-IV can antagonize arrhythmias and reduce the cardiac damage induced by aconitine in zebrafish. Zebrafish have certain benefits with respect to studying the effect of drugs on cardiovascular disease. The possible mechanisms involved are analyzed, and hub gene targets are predicted. First, a model of cardiac damage induced by aconitine was created, and then a safe drug concentration of AS-IV was screened, and the appropriate drug dose gradient was selected within a safe drug concentration range. Second, we confirmed the protective effect of AS-IV in the cardiovascular system by observing changes in zebrafish heart rates and the cardiac and vascular structure. Third, we aimed to demonstrate the antagonistic mechanism of AS-IV on heart rate and cardiac damage induced by aconitine in zebrafish, with differentially expressed genes (DEGs) detected by RNA sequencing. The DEGs were then further analyzed by bioinformatic techniques, such as function enrichment analysis, protein-protein interaction network, and DNA-microRNA networks, for example. Next, we predicted the hub genes of the cardiac protective effects of AS-IV. Finally, we validated these genes in different transcriptome sequence datasets of cardiac damage. Thus, we conclude that miR-26b-5p/ATF3/JUN are key targets of AS-IV and play an important role in maintaining cardiac homeostasis and regulating cardiac remodeling.
Highlights
Cardiovascular disease (CVD) may be considered a series of pathological conditions involving the heart and circulatory system at all levels
Our results show that the heart rates of the aconitine 15 mg/L group increased significantly compared with the control group (Table 1, Figure 2A) (P* < 0.01)
Our study demonstrated that Astragaloside IV (AS-IV) can improve the manifestations of aconitine-induced cardiac damage, such as increased heart rate, pericardial edema, and increased sinus venous and bulbus arteriosus (SV-BA) interval induced by aconitine in zebrafish
Summary
Cardiovascular disease (CVD) may be considered a series of pathological conditions involving the heart and circulatory system at all levels. A better understanding of the factors that result in the occurrence and development of CVD could reveal potential therapeutic targets for the disease. Radix Astragali (Astragalus mongholicus Bunge) is an important herb that has been used in the clinic in China for more than 2,000 years. Astragaloside IV (ASIV), a key bioactive component of Radix Astragali, has attracted increasing attention over recent years due to its potential therapeutic benefits in terms of improving cardiac function and protecting the myocardium (Zhao et al, 2012). The study of its pharmacological effects and mechanism of cardiovascular protection will contribute to the further development and utilization of AS-IV
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