4 Conclusions and prospects
Atherosclerosis is a major cause of coronary heart disease, cerebral infarction, and some peripheral vascular diseases (Figure 1). With the improvement of living standards, the incidence and mortality of atherosclerosis-induced cardiovascular diseases have increased rapidly in recent years. During the development of atherosclerosis, abnormal expressions of ncRNAs affect the physiological functions of endothelial cells, macrophages, and VSMCs by regulating related signaling pathways or specific proteins. China has a long history of using herbal medicine to treat cardiovascular diseases and the anti-atheroscleroic effects of several herbal medicine are also demonstrated in animal experiments and human studies. The traditional Chinese medicine monomers have recently attracted more attention in the treatment of diseases because they have certain molecular structures, predicted pharmacological effects, less drug-drug interactions, and clear mechanisms of action. Many active monomers derived from traditional Chinese medicines have been evaluated in vivo and in vitro to ameliorate the development of atherosclerosis by targeting ncRNAs. This article reviews 16 kinds of active monomers in traditional Chinese medicine that can improve the development of atherosclerosis by targeting ncRNAs in endothelial cells, macrophages, and VSMCs (Table 1, Figure 2-4). Their structures are shown in Figure 5. Besides monomeric Chinese herbal extracts, Chinese herbal formulas and decoctions have also been proved to treat atherosclerosis by targeting ncRNAs. For example, Tongxinluo Capsule inhibits vascular inflammation and neointimal hyperplasia by inhibiting the expression of miR-155, thereby blocking the feedback loop between miR-155 and TNF-α (R. N. Zhang et al., 2014). Alismatis rhizoma decoction, a classic traditional Chinese Medicinal formula used for the treatment of cardiovascular and cerebrovascular diseases, can inhibit the expression of ERK1/2 and miR-17-92a to inhibit ox-LDL-stimulated VSMCs proliferation (J. Shen et al., 2020). Among the ncRNAs regulated by active monomers of traditional Chinese medicine, miRNAs are the most studied. However, whether traditional Chinese medicine can exert functions via regulating lncRNAs, circRNAs or other ncRNAs are not well studied. Since ncRNAs are the most abundant transcripts in cells, it can be expected that future studies will find more and more ncRNAs that related to atherosclerosis and these ncRNAs can be used as drug targets for discover and development of anti-atherosclerotic drugs.
NcRNAs are involved in most atherosclerosis-related processes, such as endothelial cell apoptosis and macrophage inflammatory response. Over the past decades, substantial effort has been made towards the clinical application of RNA-based therapeutics, such as small interfering RNAs and antisense oligonucleotides. However, since the hurdle of immunogenicity, specificity, and delivery, some studies demonstrated limited efficacy or toxicity of ncRNAs-based therapies. Therefore, traditional Chinese medicine may become alternative drugs by targeting ncRNAs to treat atherosclerosis.
At present, studies showed that the active monomers of traditional Chinese medicine generally target one ncRNA to improve atherosclerosis. However, the mechanism of ceRNA suggests that ncRNAs may have complex interactions in cells. What’s more, one ncRNA may also have multiple targets. Therefore, we should further explore the anti-atherosclerotic mechanisms and clinical safety of these traditional Chinese medicine in more detail. It is hoped that by studying the regulation of ncRNAs by traditional Chinese medicine, it will provide theoretical support for the future research and clinical application of traditional Chinese medicine for treatment of atherosclerosis.