Joint International Committee of Basic Pharmacology of the Ministry of Education; Key Laboratory of Basic Pharmacology of the Ministry of Education; Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical University, Zunyi, Guizhou 563099, China; Zunyi Medical University, Zhuhai Campus, Zhuhai, Guangdong 519041, China.
Joint International Committee of Basic Pharmacology of the Ministry of Education; Key Laboratory of Basic Pharmacology of the Ministry of Education; Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical University, Zunyi, Guizhou 563099, China.
Eur J Pharmacol. 2017 Sep 15;811:232-239. doi: 10.1016/j.ejphar.2017.06.025. Epub 2017 Jun 23.
Osthole (7-methoxy-8-isopentenoxy-coumarin), a compound extracted from Cnidiummonnieri (L.) Cusson seeds, has been found to exhibit potent therapeutic effects in cancer due to its ability to inhibit inflammation and cell proliferation. However, its effects on arterial wall hypertrophy-related diseases remain unclear. Therefore, in this study, we aimed to investigate the effects of Osthole on intimal hyperplasia in a rat model of carotid artery balloon injury. We established the balloon-induced carotid artery injury rat model in male Sprague-Dawley rats, after which we administered Osthole (20mg/kg/day or 40mg/kg/day) or volume-matched normal saline orally by gavage for 14 consecutive days. Intimal hyperplasia and the degree of vascular smooth muscle cell proliferation were then evaluated by histopathological examination of the changes in the carotid artery, as well as by examination of proliferating cell nuclear antigen (PCNA) expression. Tumour necrosis factor-ɑ (TNF-α), interleukin-1β (IL-1β), transforming growth factor-beta (TGF-β1) and PCNA mRNA expression levels were examined by real-time RT-PCR, while nuclear factor-κB (NF-κB (p65)), IκB-α, TGF-β1 and phospho-Smad2 (p-Smad2) protein expression levels were analysed by immunohistochemistry or western blot analysis. We found that Osthole significantly attenuated neointimal thickness and decreased the elevations in PCNA protein expression induced by balloon injury. Moreover, Osthole down-regulated the pro-inflammatory factors TNF-α and IL-1β and NF-κB (p65), whose expression had been upregulated after balloon injury. Moreover, IκB-α protein expression levels increased following Osthole treatment. In addition, the elevations in TGF-β1 and p-Smad2 protein expression induced by balloon injury were both significantly attenuated by Osthole administration. We concluded that Osthole significantly inhibited neointimal hyperplasia in balloon-induced rat carotid artery injury and that the mechanism by which this occurs may involve NF-κB, IL-1β and TNF-ɑ down-regulation, which alleviates the inflammatory response, and TGF-β1/Smad2 signalling pathway inhibition.
蛇床子素（7-甲氧基-8-异戊烯氧基香豆素）是从蛇床子（Cnidium monnieri（L.）Cusson）种子中提取的一种化合物，由于其能够抑制炎症和细胞增殖，已被发现对癌症具有强大的治疗效果。然而，其对动脉壁肥厚相关疾病的影响尚不清楚。因此，在本研究中，我们旨在研究蛇床子素对大鼠颈动脉球囊损伤模型内膜增生的影响。我们建立了雄性 Sprague-Dawley 大鼠颈动脉球囊损伤模型，然后通过灌胃给予蛇床子素（20mg/kg/天或 40mg/kg/天）或体积匹配的生理盐水，连续 14 天。通过对颈动脉变化的组织病理学检查以及增殖细胞核抗原（PCNA）表达的检查，评估内膜增生和血管平滑肌细胞增殖的程度。通过实时 RT-PCR 检查肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、转化生长因子-β1（TGF-β1）和 PCNA mRNA 表达水平，通过免疫组织化学或 Western blot 分析检查核因子-κB（NF-κB（p65））、IκB-α、TGF-β1 和磷酸化 Smad2（p-Smad2）蛋白表达水平。我们发现蛇床子素显著减轻了球囊损伤引起的新生内膜厚度增加和 PCNA 蛋白表达升高。此外，蛇床子素下调了炎症因子 TNF-α和 IL-1β以及 NF-κB（p65）的表达，这些因子在球囊损伤后表达上调。此外，蛇床子素治疗后 IκB-α 蛋白表达水平增加。此外，蛇床子素给药显著减轻了球囊损伤引起的 TGF-β1 和 p-Smad2 蛋白表达升高。我们得出结论，蛇床子素显著抑制了球囊诱导的大鼠颈动脉损伤的内膜增生，其作用机制可能涉及 NF-κB、IL-1β 和 TNF-α 的下调，从而减轻炎症反应，以及 TGF-β1/Smad2 信号通路的抑制。
