Journal of Ethnopharmacology ( IF 4.8 ) Pub Date : 2021-10-15 , DOI: 10.1016/j.jep.2021.114753 Dong Zhen 1 , Tian-Qi Xuan 1 , Boqin Hu 1 , Xue Bai 1 , Dan-Ni Fu 1 , Yu Wang 1 , Yun Wu 2 , Jingfeng Yang 3 , Qianqian Ma 1
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Ethnopharmacological relevance
Pteryxin is a natural coumarin compound that is found in “Qianhu”, a traditional Chinese medicine, which possesses heat-clearing and detoxifying functions according to the theory of Traditional Chinese Medicine. Despite its medicinal effects, its anti-inflammatory and mechanisms of actions have not been established.
Aim of this study
This study aims to evaluate the anti-inflammatory property and reveal the possible anti-inflammatory mechanisms of pteryxin.
Material and methods
LPS-induced RAW 264.7 macrophages and LPS-induced zebrafish model were used for the anti-inflammatory activity determination of pteryxin. The level of NO, PEG2, TNF-α and IL-6 were measured by ELISA. The accumulation of NO and ROS was stained and observed by a fluorescence microscopy. The nuclear translocation of NF-κB p65 and formation of NLRP3 inflammasome complex in LPS-induced RAW 264.7 macrophage cells were analyzed by immunofluorescence assay. The expression level of iNOS, IL-6, COX-2, TNF-α, p-p38, p38, ERK, JNK, p-ERK, p-JNK, IKK, IκB-α, p-IKK, p-IκB-α, p65, NLRP3, p-p65, Caspase 1 (p 20), ASC, and GAPDH were determined by Western blotting.
Results
Lipopolysaccharide (LPS)-induced prostaglandin E2 (PGE2) and nitric oxide (NO) secretions were found to be downregulated by pteryxin. Moreover, pteryxin significantly suppressed inflammatory factor secretion in LPS-treated RAW 264.7 cells. Mechanistically, pteryxin significantly downregulated NF-κB/MAPK activation. Moreover, pteryxin inhibited caspase-1 and NLRP3 activation and formation of ASC specks in RAW 264.7 cells, implying that pteryxin inhibits inflammasome assembly, which is a signal for NLRP3 inflammasome activation. In conclusion, pteryxin blocks NF-κB/MAPK signaling, and suppresses the initiation and activation of NLRP3 thereby preventing inflammation.
Conclusion
Pteryxin is a potential treatment option for inflammatory-related diseases.
中文翻译：
Pteryxin 减弱 LPS 诱导的炎症反应并抑制 RAW264.7 细胞中 NLRP3 炎症小体的活化
民族药理学相关性
蕨菜素是一种天然香豆素类化合物，存在于中药“千胡”中，根据中医理论具有清热解毒功能。尽管具有药用效果，但其抗炎作用和作用机制尚未确定。
本研究的目的
本研究旨在评估翼霉素的抗炎特性并揭示可能的抗炎机制。
材料与方法
LPS 诱导的 RAW 264.7 巨噬细胞和 LPS 诱导的斑马鱼模型用于测定翼状蛋白酶的抗炎活性。ELISA测定NO、PEG 2、TNF-α和IL-6的水平。通过荧光显微镜对 NO 和 ROS 的积累进行染色和观察。通过免疫荧光法分析LPS诱导的RAW 264.7巨噬细胞中NF-κB p65的核转位和NLRP3炎性体复合物的形成。iNOS、IL-6、COX-2、TNF-α、p-p38、p38、ERK、JNK、p-ERK、p-JNK、IKK、IκB-α、p-IKK、p-IκB-的表达水平通过蛋白质印迹测定α、p65、NLRP3、p-p65、Caspase 1 (p 20)、ASC 和 GAPDH。
结果
发现脂多糖 (LPS) 诱导的前列腺素 E2 (PGE2) 和一氧化氮 (NO) 分泌物被 pteryxin 下调。此外，pteryxin 显着抑制 LPS 处理的 RAW 264.7 细胞中的炎症因子分泌。从机制上讲，pteryxin 显着下调 NF-κB/MAPK 活化。此外，pteryxin 抑制 RAW 264.7 细胞中 caspase-1 和 NLRP3 的活化和 ASC 斑点的形成，这意味着 pteryxin 抑制炎性体组装，这是 NLRP3 炎性体活化的信号。总之，pteryxin 阻断 NF-κB/MAPK 信号传导，并抑制 NLRP3 的启动和激活，从而预防炎症。
结论
Pteryxin 是炎症相关疾病的潜在治疗选择。
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