Procyanidin A1 Alleviates Inflammatory Response induced by LPS through NF-κB, MAPK, and Nrf2/HO-1 Pathways in RAW264.7 cells
Procyanidin A1 Alleviates Inflammatory Response induced by LPS through NF-κB, MAPK, and Nrf2/HO-1 Pathways in RAW264.7 cells
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DOI：
10.1038/s41598-019-51614-x
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发表时间：
2019-10-21
影响因子：
4.6
通讯作者：
Yang, Shilin
中科院分区：
文献类型：
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作者：
Han, Shan;Gao, Hongwei;Yang, Shilin
炎症是一个复杂的生理过程，严重威胁着人们的健康。然而，炎症的潜在分子机制仍不清楚。此外，目前还缺乏符合临床要求的有效抗炎药物。原花青素A1(PCA1)是从原花青素中分离得到的一种单体成分，具有多种药理活性。本研究进一步证实了PCA1对内毒素刺激的RAW264.7细胞炎症反应和氧化应激的调节作用。我们的数据显示，PCA1显著减少了脂多糖诱导的RAW264.7细胞产生的促炎细胞因子，如NO、iNOS、IL-6和TNF-α。PCA1可抑制脂多糖诱导的RAW264.7细胞中I kappa B-α的降解，抑制IKKα/β和I kappa Bα的磷酸化，抑制p65的核转位。PCA1还抑制了脂多糖刺激的RAW264.7细胞中JNK1/2、p38和ERK1/2的磷酸化。此外，PCA1还上调了脂多糖刺激的RAW264.7细胞HO-1的表达，降低了Keap1的表达，促进了Nrf2的核化。细胞热漂移分析表明PCA1与TLR4结合。同时，PCA1抑制细胞内ROS的产生，减轻线粒体膜电位的耗竭。总之，我们的数据表明PCA1显示出显著的抗炎作用，这表明它是一种潜在的炎症性疾病的治疗药物。
Inflammation is a complex physiological process that poses a serious threat to people's health. However, the potential molecular mechanisms of inflammation are still not clear. Moreover, there is lack of effective anti-inflammatory drugs that meet the clinical requirement. Procyanidin A1 (PCA1) is a monomer component isolated from Procyanidin and shows various pharmacological activities. This study further demonstrated the regulatory role of PCA1 on lipopolysaccharide (LPS)-stimulated inflammatory response and oxidative stress in RAW264.7 cells. Our data showed that PCA1 dramatically attenuated the production of pro-inflammatory cytokines such as NO, iNOS, IL-6, and TNF-alpha in RAW264.7 cells administrated with LPS. PCA1 blocked I kappa B-alpha degradation, inhibited IKK alpha/beta and I kappa B alpha phosphorylation, and suppressed nuclear translocation of p65 in RAW264.7 cells induced by LPS. PCA1 also suppressed the phosphorylation of JNK1/2, p38, and ERK1/2 in LPS-stimulated RAW264.7 cells. In addition, PCA1 increased the expression of HO-1, reduced the expression of Keap1, and promoted Nrf2 into the nuclear in LPS-stimulated RAW264.7 cells. Cellular thermal shift assay indicated that PCA1 bond to TLR4. Meanwhile, PCA1 inhibited the production of intracellular ROS and alleviated the depletion of mitochondrial membrane potential in vitro. Collectively, our data indicated that PCA1 exhibited a significant anti-inflammatory effect, suggesting that it is a potential agent for the treatment of inflammatory diseases.