Yuan Xusheng, Chen Junjun, Dai Min
Key Laboratory of Chinese Medicine Research and Development, Department of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui 230038, P.R. China.
Key Laboratory of Xin'an Medicine, Department of Pharmacy, Anhui University of Chinese Medicine, Hefei, Anhui 230038, P.R. China.
Int J Mol Med. 2016 Dec;38(6):1871-1878. doi: 10.3892/ijmm.2016.2778. Epub 2016 Oct 17.
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.
丹皮酚（2'-羟基-4'-甲氧基苯乙酮）是从牡丹皮根部分离出的一种活性成分。我们之前发现丹皮酚可抑制血管细胞黏附分子-1（VCAM-1）的表达，因此可能对预防和治疗兔动脉粥样硬化（AS）有用；然而，其潜在机制尚不清楚。最近，据报道微小RNA（miRNA或miR）在AS的发病机制中起重要作用。在本研究中，我们研究了丹皮酚对miRNA-126（miR-126）表达的影响，以及其抑制单核细胞黏附于氧化型低密度脂蛋白（ox-LDL）损伤的血管内皮细胞（VEC）的能力。从大鼠胸主动脉分离出VEC，并在存在丹皮酚的情况下用ox-LDL（20mg/l）进行刺激。我们发现，在ox-LDL损伤的VEC中miR-126表达较低，且VCAM-1被确定为miR-126的靶基因。此外，丹皮酚在mRNA和蛋白质水平上促进miR-126表达并抑制VCAM-1表达。它还通过促进miR-126表达来抑制单核细胞黏附于ox-LDL损伤的VEC。此外，已证明丹皮酚通过促进miR-126表达来阻断磷脂酰肌醇3激酶（PI3K）/蛋白激酶B（Akt）/核因子-κB（NF-κB）信号通路的激活。综上所述，据我们所知，本研究结果首次证明丹皮酚通过促进miR-126表达来抑制单核细胞黏附于ox-LDL损伤的VEC并阻断PI3K/Akt/NF-κB信号通路的激活。我们的数据表明，miR-126在血管炎症中起关键作用，可能是丹皮酚治疗AS的重要治疗靶点。
