Paeonol Inhibits Oxidized Low-Density Lipoprotein-Induced Vascular Endothelial Cells Autophagy by Upregulating the Expression of miRNA-30a

Abstract

Paeonol from Cortex Moutan root is a potential therapeutic agent for atherosclerosis (AS). However, its mechanisms of action are still not fully understood. Vascular endothelial cells (VECs) autophagy plays a vital role in the initiation and progression of AS. In this study, we aim to investigate whether the protective effect of paeonol on ox-LDL-induced VECs injury by regulating autophagy. To address this question, we used ox-LDL-induced rat VECs as a model system to elucidate the protective effect of paeonol on VECs injury. This study displayed that ox-LDL (100 mg/L) treatment inhibited VEC growth in dose- and time-dependent manners, paeonol (60 μM) shown potential in inhibiting ox-LDL-induced death. Furthermore, paeonol significantly reduced ox-LDL-induced the formation of autophagy vacuoles and the expression of LC3II in VECs. Further double-luciferase reporter assay shown that miR-30a specifically binds to the 3′-UTR of Beclin-1 mRNA in VECs. Moreover, we found that ox-LDL decreased miR-30a and increased Beclin-1 expression, pretreatment with paeonol could reverse the process of regulation in dose-dependent manners. In ox-LDL treated VECs, transfection with a miR-30a mimic significantly increased miR-30a expression and inhibited Beclin-1 and LC3II expression, thus enhanced the protective effects of paeonol. Whereas transfection with a miR-30a inhibitor significantly decreased miR-30a expression and increased Beclin-1 and LC3II expression, thus attenuated the protective effects of paeonol. In conclusion, this study has, for the ?rst time, highlighted that miR-30a might be a critical target of paeonol against ox-LDL-induced VECs injury by inhibiting excessive autophagy. Paeonol may be one of promising candidate drug for treatment of AS.

RETRACTED ARTICLE: MicroRNA-9 modified bone marrow-derived mesenchymal stem cells (BMSCs) repair severe acute pancreatitis (SAP) via inducing angiogenesis in rats

“…HEK-293T cells (human embryonic kidney-293 cells expressing the large T-antigen of simian virus 40) were purchased from the cell bank of Chinese Academy of Sciences and cultured in DMEM-HG supplemented with 10% FBS, 100 U/ml penicillin, and 100 μg/ml streptomycin. Vascular endothelial cells (VECs) were isolated from the abdominal aortic of SD rats as previously described [ 22 ] and cultured in DMEM-HG complete medium. Finally, these cells were digested and passaged when reaching 80% of confluence.…”

Paeonol Attenuated Inflammatory Response of Endothelial Cells via Stimulating Monocytes-Derived Exosomal MicroRNA-223

“…Exosomes can be used not only as a marker of disease diagnosis, drug targeting transport carrier, is also expected to become a therapeutic target for diseases ( Milane et al, 2015 ; Zhang et al, 2015 ; Suchorska and Lach, 2016 ). Several studies showed that miR-223 could transfer from monocytes to vascular cells by means of exosomes and play a pivotal role in normal physiological processes and pathological processes of AS ( Cheng et al, 2017 ; Li et al, 2018 ; Liu et al, 2018 ). The miR-223 overexpression significantly attenuated macrophage foam cell formation, lipid accumulation and pro-inflammatory cytokine production ( Bao et al, 2014 ).…”

Therapeutic Effect of Ecdysterone Combine Paeonol Oral Cavity Direct Administered on Radiation-Induced Oral Mucositis in Rats

“…In addition, Paeonol has a good transdermal absorption, which is suitable for oral direct administration. Moreover, Paeonol has been applied for its anti-inflammatory, antioxidant, and antibacterial properties for a long time in traditional Chinese medicine [26,27,28].…”