3.13 Paeonol
Paeonol is one of the main active compounds in Tree Peony Bark, which has been found to have anti-inflammatory, anti-thrombotic and antioxidant properties (M. H. Bao, Zhang, & Zhou, 2013; P. K. Fu, Wu, Tsai, & Hsieh, 2012). Paeonol could increase the expression of miR-223 in macrophage-derived exosomes, and after the uptaking of exosomes by endothelial cells, the STAT3 signaling and the related inflammatory response in endothelial cells can be attenuated (Y. Liu et al., 2018). Another study also found similarly protective results of paeonol on endothelial cells in hyperlipidemia-induced atherosclerosis, which is also attributed to cellular uptake of exosomal miR-223 (Shi et al., 2020). Additionally, paeonol also promotes miR-126 expression to inhibit monocyte adhesion to endothelial cells and block the activation of the PI3K/Akt/NF-κB signaling pathway (X. Yuan, Chen, & Dai, 2016). Moreover, miR-21 and its target PTEN also contribute to the protective effects of paeonol on ox-LDL-induced endothelial injury (Y. R. Liu, Chen, & Dai, 2014). MiR-338-3p was proved to be increased in atherosclerotic lesions, and paeonol treatment could downregulates the expression of miR-338-3p and upregulates the expression of Tet methylcytosine dioxygenase 2 (TET2), thereby relieving ox-LDL-induced endothelial cell damage (Yin, Hou, & Yang, 2019; Yu, Yan, Chen, Sun, & Yan, 2020). Paeonol can also weaken ox-LDL-induced endothelial autophagy through regualting miR-30a/beclin-1 signaling (C. Li, Yang, Wu, & Dai, 2018). Overall, these studies indicate that paeonol has strong endothelial protective effects, which is associated with regulation of various miRNAs and their targets.