title: Paeonol promotes microRNA-126 expression to inhibit monocyte adhesion to ox-LDL-injured vascular endothelial cells and block the activation of the PI3K/Akt/NF-κB pathway.
abstract: Paeonol (2'-hydroxy-4'-methoxyacetophenone) is an active component isolated from the root of Paeonia Suffruticosa Andrews. We previously found that paeonol inhibited vascular cell adhesion molecule-1 (VCAM‑1) expression, and thus may be useful for the prevention and treatment of rabbit atherosclerosis (AS); however, the underlying mechanisms are not yet well known. Recently, microRNAs (miRNAs or miRs) have been reported to play an important role in the pathogenesis of AS. In the present study, we examined the effects of paeonol on miRNA-126 (miR‑126) expression, and its ability to inhibit monocyte adhesion to oxidized low-density lipoprotein (ox-LDL)-injured vascular endothelial cells (VECs). VECs were isolated from the rat thoracic aorta and stimulated with ox-LDL (20 mg/l) in the presence of paeonol. We found that miR‑126 had a lower expression in the ox-LDL-injured VECs, and VCAM‑1 was identified as a target gene of miR‑126. Furthermore, paeonol promoted miR‑126 expression and suppressed VCAM‑1 expression at the mRNA and protein level. It also inhibited monocyte adhesion to ox-LDL-injured VECs through the promotion of miR‑126 expression. Furthermore, it was demonstrated that paeonol blocked the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/nuclear factor-κB (NF-κB) signaling pathway by promoting miR-126 expression. Taken together, and to the best of our knowledge, the findings of this study provide the first evidence that paeonol promotes miR‑126 expression to inhibit monocyte adhesion to ox-LDL-injured VECs and block the activation of the PI3K/Akt/NF-κB signaling pathway. Our data suggest that miR‑126 plays a crucial role in vascular inflammation and may be an important therapeutic target in the treatment of AS with the use of paeonol.
authors.affiliation: Key Laboratory of Chinese Medicine Research and Development, Department of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui 230038, P.R. China.
authors.forename: Xusheng
authors.initials: X
authors.lastname: Yuan
authors.affiliation: Key Laboratory of Xin'an Medicine, Department of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui 230038, P.R. China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Chen
authors.affiliation: Key Laboratory of Chinese Medicine Research and Development, Department of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui 230038, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Dai
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D008077:Lipoproteins, LDL / Q000633:toxicity*; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D009000:Monocytes / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
chemical_list: D000098:Acetophenones; D008077:Lipoproteins, LDL; C527111:MIRN126 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D012333:RNA, Messenger; D019010:Vascular Cell Adhesion Molecule-1; C099252:oxidized low density lipoprotein; C013638:paeonol; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt