3.2 Astragaloside IV
Astragaloside IV is a saponin isolated from Astragalus
membranaceus (Fisch.) Bunge, which has excellent cardioprotective
effects (Y. Q. Tan, Chen, & Li, 2020). Astragaloside IV has been
reported to protect endothelial cells from oxidative damage caused by
ox‑LDL through regulating the LOX-1/NLRP3 signaling pathway (Qian et
al., 2019). Recently, a study found that circ_0000231 is the key
downstream target of astragaloside IV, which regulates miR-135a-5p to
target chloride intracellular
channel 4 (CLIC4) and contributes to the protective role of
astragaloside IV in ox-LDL-induced endothelial cell injury (Shao, Liu,
Liu, Lin, & Deng, 2021). CLIC4 is also a protein associated with
endothelial cell apoptosis (X. Zhang et al., 2020), indicating
astragaloside IV may also inhibit endothelial cell apoptosis by
regulating CLIC4 through circ_0000231. Several miRNAs have been shown
to be the targets of astragaloside IV. For example, astragaloside IV can
protect cardiomyocytes from hypoxia-induced injury by downregulating
miR-23a and miR-92a (Gong et al., 2018). ABCA1, a membrane transporter
that mediates cholesterol efflux (L. Chen, Zhao, Zeng, Zhou, & Yin,
2022), has been proved to be a target of miR-33a (J. H. Gao et al.,
2018). A study has found that astragaloside IV can promote cholesterol
efflux in macrophages and inhibit atherosclerosis through regulating
miR-33a/ABCA1 pathway (H. W. Qin et al., 2018). The serum miR-17-5p is
elevated in patients with atherosclerosis and miR-17-5p knockdown can
alleviate atherosclerotic lesions and inhibit the proliferation and
migration of VSMCs by directly up-regulating
very low density lipoprotein
receptor (VLDLR), or indirectly regulate VLDLR by affecting
proprotein convertase subtilisin
kexin 9 (PCSK9) (L. Tan, Meng, Shi, & Yu, 2017). Astragaloside IV has
been shown to down-regulate miR-17-5p and further affect VLDLR
expression, thus inhibiting vascular inflammation (H. W. Qin, Zhang, Li,
Li, & Wang, 2022). In addition, lncRNA H19 has also been reported to
mediate astragaloside IV’s anti-atherosclerotic effect. H19 negatively
regulates dual-specificity
phosphatase 5 (DUSP5) expression and represses DUSP5/ERK1/2 axis (Tao et
al., 2016). Astragaloside IV could attenuate autophagy and
mineralization of VSMCs in atherosclerosis by up-regulating H19 and
inhibiting DUSP5 (Z. Song et al., 2019). In summary, astragaloside IV
can regulate the function of endothelial cells, VSMCs, and macrophages
in atherosclerosis by targeting multiple miRNAs, lncRNAs and circRNAs.
Therefore, it can be expected that astragaloside IV can exert an
excellent anti-atherosclerotic effect through ncRNAs in the clinic.