Abstract：
Cynaroside is the primary flavonoid component of honeysuckle which has been widely used as Chinese traditional medicine given its anti-inflammation properties. Overactive systemic inflammatory response and multi-organ injury are the leading causes of life-threatening sepsis. Regulation of macrophage polarization balance may act as a promising strategy for its treatment. In the present study, we aimed to investigate whether cynaroside exerted protective effects against sepsis and its potential mechanism. Building upon a sepsis mouse model, we observed cynaroside alleviated serum levels of inflammatory factors including IL-1β and TNF-α at 5 and 10 mg/kg. The pathological injury of heart, kidney and lung was remarkedly attenuated as the levels of blood urea nitrogen, creatinine, creatine kinase-MB and lactate dehydrogenase were reduced nearly 2.8-, 2.7-, 2.4-, and 2.5-fold as compared with the sepsis mice, respectively. We further demonstrated cynaroside suppressed the biomarker of pro-inflammatory macrophage M1 phenotype (iNOS+) and promotes the anti-inflammatory M2 polarization (CD206+) in the injury organs of septic mice. Mechanistic research verified cynaroside inhibited LPS-induced polarization of macrophage into M1 phenotype, which can be highly blocked by Nrf2 inhibitor. Expectedly, Nrf2 and its downstream (Heme oxygenase-1 (HO-1)) was upregulated in injury organs after treating with cynaroside, indicating the involvement of Nrf2 signaling. Taken together, the data claims cynaroside ameliorated systematic inflammation and multi-organ injury dependent on Nrf2/HO-1 pathway in septic mice.
摘要：
金银花苷是金银花的主要黄酮类成分,因其抗炎特性而被广泛用作中药。过度活跃的全身炎症反应和多器官损伤是危及生命的脓毒症的主要原因。调节巨噬细胞极化平衡可能是其治疗的有希望的策略。在本研究中,我们的目的是研究西纳苷是否对脓毒症具有保护作用及其潜在机制。建立在脓毒症小鼠模型上，我们观察到西纳苷在5和10mg/kg时减轻了血清炎症因子包括IL-1β和TNF-α的水平。心脏的病理损伤，肾和肺随着血尿素氮的水平显著减弱，肌酐,肌酸激酶-MB和乳酸脱氢酶降低近2.8-，2.7-,2.4-,与脓毒症小鼠相比是2.5倍，分别。我们进一步证明了西纳苷抑制了促炎巨噬细胞M1表型（iNOS）的生物标志物，并促进了脓毒症小鼠损伤器官的抗炎M2极化（CD206）。机制研究验证了西纳苷抑制LPS诱导的巨噬细胞极化为M1表型,可以被Nrf2抑制剂高度阻断。期望,Nrf2及其下游（血红素加氧酶-1（HO-1））在用西纳苷治疗后的损伤器官中上调，表明Nrf2信号的参与。一起来看,数据表明，西纳苷改善了脓毒症小鼠的系统性炎症和多器官损伤，依赖于Nrf2/HO-1途径。
