Farrerol, a dihydroflavone isolated from Rhododendron dauricum L., can inhibit vascular smooth muscle cell (VSMC) proliferation and exert a protective effect on H₂O₂-induced vascular endothelial cells injury. In this study, we investigated the effects of farrerol on VSMC phenotypic modulation and balloon injury-induced vascular neointimal formation and explored the underlying mechanisms. Serum-starved rat thoracic aorta SMCs (RASMCs) were first pretreated with farrerol (3, 10, and 30 μM, respectively), U0126 (a MEK kinase inhibitor), and SB203580 (a p38 kinase inhibitor), and followed by treatment with serum (10% FBS). The expression of several VSMC-specific markers, including α-SMA, SM22α, and OPN, were analyzed by western blot. Phosphorylation of extracellular signal-regulated protein kinase 1/2 (ERK 1/2) and p38 mitogen-activated protein kinase (MAPK) was also investigated. Farrerol inhibited the serum-induced transition of RASMCs from the contractile to the synthetic phenotype, and this was associated with a decrease in α-SMA and SM22α expression, and an increase in OPN expression. Farrerol also inhibited serum-induced phosphorylation of ERK1/2 and p38MAPK in RASMCs. Moreover, U0126 and SB203580 both inhibited the serum-induced phenotypic transition of RASMCs. These findings indicate that farrerol can maintain the contractile phenotype of VSMCs partly via inactivating the ERK1/2 and p38 MAPK signaling pathways. Using a rat model of carotid artery balloon injury, inhibition of VSMC phenotypic transition and suppression of neointimal formation were confirmed in vivo following the perivascular application of farrerol. Our results suggested that farrerol could be a promising lead compound for the treatment of vascular proliferative diseases.

分离自杜鹃杜鹃的二氢黄酮法雷洛尔可抑制血管平滑肌细胞（VSMC）增殖并对H ₂ O ₂产生保护作用诱导的血管内皮细胞损伤。在这项研究中，我们调查了法瑞罗尔对VSMC表型调节和球囊损伤诱导的血管内膜形成的影响，并探讨了其潜在机制。首先用Farrerol（分别为3、10和30μM），U0126（一种MEK激酶抑制剂）和SB203580（一种p38激酶抑制剂）预处理血清饥饿的大鼠胸主动脉SMC（RASMC），然后进行血清治疗（10％FBS）。通过蛋白质印迹分析了几种VSMC特异性标志物的表达，包括α-SMA，SM22α和OPN。还研究了细胞外信号调节蛋白激酶1/2（ERK 1/2）和p38丝裂原活化蛋白激酶（MAPK）的磷酸化。Farrerol抑制了血清诱导的RASMC从收缩型转变为合成型，这与α-SMA和SM22α表达的减少以及OPN表达的增加有关。Farrerol还抑制RASMC中血清诱导的ERK1 / 2和p38MAPK磷酸化。而且，U0126和SB203580都抑制了血清诱导的RASMC表型转化。这些发现表明，法雷洛尔可以部分地通过使ERK1 / 2和p38 MAPK信号通路失活来维持VSMC的收缩表型。使用大鼠颈动脉球囊损伤模型，证实在血管内施用法雷洛尔后体内抑制了VSMC表型转变并抑制了新内膜形成。我们的研究结果表明，法雷洛尔可能是治疗血管增生性疾病的有前途的先导化合物。Farrerol还抑制RASMC中血清诱导的ERK1 / 2和p38MAPK磷酸化。而且，U0126和SB203580都抑制了血清诱导的RASMC表型转化。这些发现表明，法雷洛尔可以部分地通过使ERK1 / 2和p38 MAPK信号通路失活来维持VSMC的收缩表型。使用大鼠颈动脉球囊损伤模型，证实在血管内施用法雷洛尔后体内抑制了VSMC表型转变并抑制了新内膜形成。我们的研究结果表明，法雷洛尔可能是治疗血管增生性疾病的有前途的先导化合物。Farrerol还抑制RASMC中血清诱导的ERK1 / 2和p38MAPK磷酸化。而且，U0126和SB203580都抑制了血清诱导的RASMC表型转化。这些发现表明，法雷洛尔可以部分地通过使ERK1 / 2和p38 MAPK信号通路失活来维持VSMC的收缩表型。使用大鼠颈动脉球囊损伤模型，证实在血管内施用法雷洛尔后体内抑制了VSMC表型转变并抑制了新内膜形成。我们的结果表明，法雷洛尔可能是治疗血管增生性疾病的有前途的先导化合物。这些发现表明，法雷洛尔可以部分地通过使ERK1 / 2和p38 MAPK信号通路失活来维持VSMC的收缩表型。使用大鼠颈动脉球囊损伤模型，证实在血管内施用法雷洛尔后体内抑制了VSMC表型转变并抑制了新内膜形成。我们的研究结果表明，法雷洛尔可能是治疗血管增生性疾病的有前途的先导化合物。这些发现表明，法雷洛尔可以部分地通过使ERK1 / 2和p38 MAPK信号通路失活来维持VSMC的收缩表型。使用大鼠颈动脉球囊损伤模型，证实在血管内施用法雷洛尔后体内抑制了VSMC表型转变并抑制了新内膜形成。我们的结果表明，法雷洛尔可能是治疗血管增生性疾病的有前途的先导化合物。