Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center of South China, College of Life Science, Fujian Normal University, Fuzhou 350117, China.
Department of Neurosurgery & Neurocritical Care, Huashan Hospital, Fudan University, Shanghai 200040, China.
J Agric Food Chem. 2023 Aug 23;71(33):12497-12510. doi: 10.1021/acs.jafc.3c03247. Epub 2023 Aug 10.
Suppression of excessive inflammatory responses improves the survival of patients with sepsis. We previously illustrated the anti-inflammatory effects of fucoxanthin (FX), a natural carotenoid isolated from brown algae; nevertheless, the underlying mechanism remains unknown. In this study, we examine the mechanism of the action of FX by targeting interferon regulatory factor 3 (IRF3) to inhibit inflammatory response. We observed that FX regulated innate immunity by inhibiting IRF3 phosphorylation . The approach demonstrated a good binding mode between FX and IRF3. To examine the effects of FX, a mouse model of sepsis induced by cecal ligation and puncture (CLP) was created using both wild-type (WT) and 3 mice. FX significantly reduced pro-inflammatory cytokine levels and reactive oxygen species production, changed the circulating immune cell composition, and increased the survival rate of the CLP-induced sepsis model. Overall, FX ameliorated sepsis by targeting IRF3 activation, providing novel insights into the therapeutic potential and molecular mechanism of action of FX in the treatment of sepsis and suggesting that it may be used clinically to improve the survival rate in mice undergoing sepsis.
抑制过度的炎症反应可提高脓毒症患者的生存率。我们之前已经证明了从褐藻中分离出的天然类胡萝卜素岩藻黄质 (FX) 具有抗炎作用,但其潜在机制尚不清楚。在这项研究中,我们通过靶向干扰素调节因子 3 (IRF3) 来抑制炎症反应,研究了 FX 的作用机制。我们观察到 FX 通过抑制 IRF3 磷酸化来调节先天免疫。该方法显示了 FX 与 IRF3 之间良好的结合模式。为了研究 FX 的作用,我们使用野生型 (WT) 和 3 种小鼠建立了盲肠结扎和穿刺 (CLP) 诱导的脓毒症小鼠模型。FX 显著降低了促炎细胞因子水平和活性氧的产生,改变了循环免疫细胞组成,并提高了 CLP 诱导的脓毒症模型的存活率。总的来说,FX 通过靶向 IRF3 激活改善了脓毒症,为 FX 在治疗脓毒症中的治疗潜力和作用机制提供了新的见解,并表明它可能在临床上用于提高脓毒症小鼠的生存率。