School of Pharmaceutical Sciences, Shenzhen University Health Science Center, Shenzhen, Guangdong, 518060, People's Republic of China.
Inflammation. 2017 Dec;40(6):2042-2051. doi: 10.1007/s10753-017-0644-z.
Paeoniflorin, a type of bioactive monoterpene glucoside in Paeoniae Radix, possesses anti-oxidative, anti-inflammatory and anti-hyperglycaemic properties. However, the underlying mechanism of paeoniflorin in treating atherosclerosis is unclear. A rat model of high-fat diet-induced atherosclerosis and palmitic acid (PA)-treated vascular smooth muscle cells (VSMCs) were used in this study. The serum concentrations of total cholesterol (TC), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) were determined, and the results indicated that paeoniflorin remarkably lowered the levels of TC, TG and LDL-C induced by a high-fat diet. Histopathological results showed that paeoniflorin significantly improved the pathological changes in the aorta. In addition, paeoniflorin also maintained a normal weight gain speed. Subsequently, the effects of paeoniflorin on the production of inflammatory cytokines (IL-1β, IL-6 and TNF-α) were detected by qPCR and ELISA. The qPCR and ELISA results showed that paeoniflorin decreased the levels of these inflammatory cytokines. Moreover, the expression of TLR4 and its downstream pathway molecules was measured by Western blot. The results indicated that paeoniflorin significantly reduced the expression of TLR4 and MyD88 as well as the phosphorylation of IκBα and NF-κB p65. Taken together, these results suggested that paeoniflorin could alleviate atherosclerotic inflammation by inhibiting the TLR4/MyD88/NF-κB pathway. Therefore, paeoniflorin may be a potential therapy for atherosclerosis.
芍药苷是白芍中的一种生物活性单萜糖苷,具有抗氧化、抗炎和降血糖作用。然而,芍药苷治疗动脉粥样硬化的机制尚不清楚。本研究采用高脂饮食诱导的动脉粥样硬化大鼠模型和棕榈酸(PA)处理的血管平滑肌细胞(VSMCs)。测定血清总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C)浓度,结果表明芍药苷可显著降低高脂饮食诱导的 TC、TG 和 LDL-C 水平。组织病理学结果表明芍药苷可显著改善主动脉的病理变化。此外,芍药苷还维持了正常的体重增长速度。随后,通过 qPCR 和 ELISA 检测芍药苷对炎症细胞因子(IL-1β、IL-6 和 TNF-α)产生的影响。qPCR 和 ELISA 结果表明,芍药苷降低了这些炎症细胞因子的水平。此外,通过 Western blot 测定 TLR4 及其下游途径分子的表达。结果表明,芍药苷可显著降低 TLR4 和 MyD88 的表达以及 IκBα 和 NF-κB p65 的磷酸化。综上所述,这些结果表明,芍药苷通过抑制 TLR4/MyD88/NF-κB 通路减轻动脉粥样硬化炎症。因此,芍药苷可能是动脉粥样硬化的一种潜在治疗方法。