4'-Hydroxywogonin suppresses lipopolysaccharide-induced inflammatory responses in RAW 264.7 macrophages and acute lung injury mice.
4'-Hydroxywogonin suppresses lipopolysaccharide-induced inflammatory responses in RAW 264.7 macrophages and acute lung injury mice.
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DOI：
10.1371/journal.pone.0181191
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Ye RD
中科院分区：
文献类型：
--
作者：
Fan C;Wu LH;Zhang GF;Xu F;Zhang S;Zhang X;Sun L;Yu Y;Zhang Y;Ye RD
4'-Hydroxywogonin (4'-HW) 是一种黄酮类化合物，已从多种植物中分离出来，并被证明可以抑制巨噬细胞中 NO 的产生。然而，其分子机制及其体内活性尚未确定。我们的研究旨在探讨 4'-HW 体外和体内抗炎作用的机制。我们发现，在 LPS 刺激的 RAW 264.7 巨噬细胞中，4'-HW 有效降低了 COX-2 和 iNOS 及其产物前列腺素 E2 (PGE2) 和一氧化氮 (NO) 的表达水平。 4'-HW 还在 mRNA 和蛋白质水平上抑制 LPS 诱导的促炎细胞因子。此外，4'-HW 阻断 LPS 刺激的 RAW 264.7 巨噬细胞中 TAK1 和 TAB1 的相互作用，从而抑制 TAK1/IKK/NF-κB 信号通路。此外，4'-HW 还降低了 LPS 刺激的 RAW 264.7 巨噬细胞中 MAPK 和 PI3/Akt 信号通路的磷酸化。 4'-HW 还显着降低细胞内活性氧 (ROS) 水平。 4'-HW的作用在体内得到证实。 4'-HW 对 LPS 诱导的小鼠 ALI 表现出有效的保护作用。这些发现表明 4'-HW 在体外和体内抑制 LPS 诱导的反应。 TAK1/IKK/NF-κB、MAPK 和 PI3/AKT 信号通路的抑制可能有助于 4'-HW 的抗炎作用。我们的研究表明4'-HW可能是植物中的重要功能成分，具有开发为新型抗炎剂的潜在价值。
4'-Hydroxywogonin (4'-HW), a flavonoid, has been isolated from various plants and shown to inhibit NO production in macrophages. However, the molecular mechanisms and its in vivo activity have not been determined. Our study aimed to investigate the mechanisms underlying the anti-inflammatory effects of 4'-HW in vitro and in vivo. We showed that 4'-HW potently reduced the expression levels of COX-2 and iNOS as well as their products, prostaglandin E2 (PGE2) and nitric oxide (NO) respectively, in LPS-stimulated RAW 264.7 macrophages. 4'-HW also suppressed LPS-induced pro-inflammatory cytokines at mRNA and protein levels. Moreover, 4'-HW blocked the interaction of TAK1 and TAB1 in LPS-stimulated RAW 264.7 macrophages, resulting in an inhibition of the TAK1/IKK/NF-κB signaling pathway. Furthermore, 4'-HW also reduced the phosphorylation of MAPKs and PI3/Akt signaling pathways in LPS-stimulated RAW 264.7 macrophages. 4'-HW was also significantly decreased the intracellular reactive oxygen species (ROS) level. The effect of 4'-HW was confirmed in vivo. 4'-HW exhibited potent protective effect against LPS-induced ALI in mice. These findings indicate that 4'-HW suppresses the LPS-induced response in vitro and in vivo. It is likely that the inhibition of the TAK1/IKK/NF-κB, MAPKs and PI3/AKT signaling pathways contribute to the anti-inflammatory effects of 4'-HW. Our study suggests that 4'-HW may be an important functional constituent in the plants and has the potential value to be developed as a novel anti-inflammatory agent.
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