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Abstract：
BACKGROUND: Corilagin possesses a diverse range of pharmacologic bioactivities. However, the specific protective effects and mechanisms of action of corilagin in the context of atherosclerosis remain unclear. In this study, we investigated the impact of corilagin on the toll-like receptor (TLR)4 signaling pathway in a mouse vascular smooth muscle cell line (MOVAS) stimulated by oxidized low-density lipoprotein (ox-LDL). Additionally, we examined the effects of corilagin in Sprague-Dawley rats experiencing atherosclerosis.
METHODS: The cytotoxicity of corilagin was assessed using the CCK8 assay. MOVAS cells, pre-incubated with ox-LDL, underwent treatment with varying concentrations of corilagin. TLR4 expression was modulated by either downregulation through small interfering (si)RNA or upregulation via lentivirus transfection. Molecular expression within the TLR4 signaling pathway was analyzed using real-time polymerase chain reaction (PCR) and Western blotting. The proliferation capacity of MOVAS cells was determined through cell counting. In a rat model, atherosclerosis was induced in femoral arteries using an improved guidewire injury method, and TLR4 expression in plaque areas was assessed using immunofluorescence. Pathological changes were examined through hematoxylin and eosin staining, as well as Oil-Red-O staining.
RESULTS: Corilagin demonstrated inhibitory effects on the TLR4 signaling pathway in MOVAS cells pre-stimulated with ox-LDL, consequently impeding the proliferative impact of ox-LDL. The modulation of TLR4 expression, either through downregulation or upregulation, similarly influenced the expression of downstream molecules. In an in vivo context, corilagin exhibited the ability to suppress TLR4 and MyD88 expression in the plaque lesion areas of rat femoral arteries, thereby alleviating the formation of atherosclerotic plaques.
CONCLUSIONS: Corilagin can inhibit the TLR4 signaling pathway in VSMCs, possibly by downregulating TLR4 expression and, consequently, relieving atherosclerosis.
METHODS: The cytotoxicity of corilagin was assessed using the CCK8 assay. MOVAS cells, pre-incubated with ox-LDL, underwent treatment with varying concentrations of corilagin. TLR4 expression was modulated by either downregulation through small interfering (si)RNA or upregulation via lentivirus transfection. Molecular expression within the TLR4 signaling pathway was analyzed using real-time polymerase chain reaction (PCR) and Western blotting. The proliferation capacity of MOVAS cells was determined through cell counting. In a rat model, atherosclerosis was induced in femoral arteries using an improved guidewire injury method, and TLR4 expression in plaque areas was assessed using immunofluorescence. Pathological changes were examined through hematoxylin and eosin staining, as well as Oil-Red-O staining.
RESULTS: Corilagin demonstrated inhibitory effects on the TLR4 signaling pathway in MOVAS cells pre-stimulated with ox-LDL, consequently impeding the proliferative impact of ox-LDL. The modulation of TLR4 expression, either through downregulation or upregulation, similarly influenced the expression of downstream molecules. In an in vivo context, corilagin exhibited the ability to suppress TLR4 and MyD88 expression in the plaque lesion areas of rat femoral arteries, thereby alleviating the formation of atherosclerotic plaques.
CONCLUSIONS: Corilagin can inhibit the TLR4 signaling pathway in VSMCs, possibly by downregulating TLR4 expression and, consequently, relieving atherosclerosis.
摘要：
背景：Corilagin具有多种药理生物活性。然而,Corilagin在动脉粥样硬化中的具体保护作用和作用机制尚不清楚.在这项研究中,我们研究了corilagin对氧化低密度脂蛋白(ox-LDL)刺激的小鼠血管平滑肌细胞系(MOVAS)中Toll样受体(TLR)4信号通路的影响.此外,我们研究了corilagin在经历动脉粥样硬化的Sprague-Dawley大鼠中的作用。
方法:使用CCK8测定法评估corilagin的细胞毒性。MOVAS细胞,用ox-LDL预孵育，接受不同浓度的corilagin治疗。通过小干扰(si)RNA下调或通过慢病毒转染上调来调节TLR4表达。使用实时聚合酶链反应(PCR)和蛋白质印迹分析TLR4信号通路内的分子表达。通过细胞计数测定MOVAS细胞的增殖能力。在大鼠模型中,使用改进的导丝损伤方法在股动脉中诱发动脉粥样硬化，使用免疫荧光评估斑块区域的TLR4表达。通过苏木精和伊红染色检查病理变化，以及油红O染色。
结果：Corilagin对ox-LDL预刺激的MOVAS细胞的TLR4信号通路有抑制作用，因此阻碍了ox-LDL的增殖影响。TLR4表达的调控，通过下调或上调，同样影响下游分子的表达。在体内环境中，corilagin表现出抑制TLR4和MyD88在大鼠股动脉斑块病变区域表达的能力，从而减轻动脉粥样硬化斑块的形成。
结论：Corilagin可抑制VSMC中TLR4信号通路，可能通过下调TLR4表达和，因此,缓解动脉粥样硬化.
方法:使用CCK8测定法评估corilagin的细胞毒性。MOVAS细胞,用ox-LDL预孵育，接受不同浓度的corilagin治疗。通过小干扰(si)RNA下调或通过慢病毒转染上调来调节TLR4表达。使用实时聚合酶链反应(PCR)和蛋白质印迹分析TLR4信号通路内的分子表达。通过细胞计数测定MOVAS细胞的增殖能力。在大鼠模型中,使用改进的导丝损伤方法在股动脉中诱发动脉粥样硬化，使用免疫荧光评估斑块区域的TLR4表达。通过苏木精和伊红染色检查病理变化，以及油红O染色。
结果：Corilagin对ox-LDL预刺激的MOVAS细胞的TLR4信号通路有抑制作用，因此阻碍了ox-LDL的增殖影响。TLR4表达的调控，通过下调或上调，同样影响下游分子的表达。在体内环境中，corilagin表现出抑制TLR4和MyD88在大鼠股动脉斑块病变区域表达的能力，从而减轻动脉粥样硬化斑块的形成。
结论：Corilagin可抑制VSMC中TLR4信号通路，可能通过下调TLR4表达和，因此,缓解动脉粥样硬化.
