Flavonoid apigenin inhibits lipopolysaccharide-induced inflammatory response through multiple mechanisms in macrophages.
Flavonoid apigenin inhibits lipopolysaccharide-induced inflammatory response through multiple mechanisms in macrophages.
复制标题
类黄酮芹菜素通过巨噬细胞中的多种机制抑制脂多糖诱导的炎症反应。
DOI：
10.1371/journal.pone.0107072
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Zhou H
中科院分区：
文献类型：
--
作者：
Zhang X;Wang G;Gurley EC;Zhou H
芹菜素是一种无毒的天然类黄酮，大量存在于常见的水果和蔬菜中。据报道，芹菜素具有各种有益的健康作用，如抗炎和化学预防。多项研究表明，炎症是动脉粥样硬化、糖尿病、败血症、各种肝病和其他代谢疾病的重要危险因素。芹菜素具有抗炎活性，但其抗炎机制尚不完全清楚。在本研究中，我们研究了芹菜素对LPS诱导的炎症反应的影响，并进一步阐明了人THP-1诱导的巨噬细胞和小鼠J774A.1巨噬细胞的潜在机制。通过使用PrimePCR阵列，我们能够确定芹菜素在LPS介导的免疫应答中调节的主要靶基因。结果表明，芹菜素通过调节巨噬细胞内多条信号通路，显著抑制LPS诱导的巨噬细胞产生IL-6、IL-1β和TNF-α等促炎细胞因子。芹菜素通过破坏NLRP 3炎性体组装抑制caspase-1活化来抑制LPS诱导的IL-1β产生。芹菜素还通过抑制ERK 1/2激活降低mRNA稳定性来阻止LPS诱导的IL-6和IL-1β的产生。此外，芹菜素还能显著抑制TNF-α和IL-1β诱导的NF-κB活化。芹菜素在巨噬细胞中通过多种机制抑制LPS诱导的炎症反应。这些结果为芹菜素作为炎症性疾病治疗剂的潜在应用提供了重要的科学依据。
Apigenin is a non-toxic natural flavonoid that is abundantly present in common fruits and vegetables. It has been reported that apigenin has various beneficial health effects such as anti-inflammation and chemoprevention. Multiple studies have shown that inflammation is an important risk factor for atherosclerosis, diabetes, sepsis, various liver diseases, and other metabolic diseases. Although it has been long realized that apigenin has anti-inflammatory activities, the underlying functional mechanisms are still not fully understood. In the present study, we examined the effect of apigenin on LPS-induced inflammatory response and further elucidated the potential underlying mechanisms in human THP-1-induced macrophages and mouse J774A.1 macrophages. By using the PrimePCR array, we were able to identify the major target genes regulated by apigenin in LPS-mediated immune response. The results indicated that apigenin significantly inhibited LPS-induced production of pro-inflammatory cytokines, such as IL-6, IL-1β, and TNF-α through modulating multiple intracellular signaling pathways in macrophages. Apigenin inhibited LPS-induced IL-1β production by inhibiting caspase-1 activation through the disruption of the NLRP3 inflammasome assembly. Apigenin also prevented LPS-induced IL-6 and IL-1β production by reducing the mRNA stability via inhibiting ERK1/2 activation. In addition, apigenin significantly inhibited TNF-α and IL-1β-induced activation of NF-κB. Apigenin Inhibits LPS-induced Inflammatory Response through multiple mechanisms in macrophages. These results provided important scientific evidences for the potential application of apigenin as a therapeutic agent for inflammatory diseases.