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.