Anti-inflammation action of xanthones from Swertia chirayita by regulating COX-2/NF-κB/MAPKs/Akt signaling pathways in RAW 264.7 macrophage cells
Anti-inflammation action of xanthones from Swertia chirayita by regulating COX-2/NF-κB/MAPKs/Akt signaling pathways in RAW 264.7 macrophage cells
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獐牙菜中的呫吨酮通过调节 RAW 264.7 巨噬细胞中的 COX-2/NF-kappa B/MAPKs/Akt 信号通路发挥抗炎作用
DOI：
10.1016/j.phymed.2018.08.001
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发表时间：
2019-03-01
期刊：
影响因子：
7.9
通讯作者：
Cheng Bao-Hui
中科院分区：
文献类型：
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作者：
Hu Tian-Yong;Ju Jian-Ming;Cheng Bao-Hui
工作背景：藏医常用的中药名为“藏茵陈”，用于治疗肝脏感染、炎症、腹痛和细菌感染。然而，具有抗炎活性和潜在机制的生物活性成分仍然很差evaluated.Study设计/方法：重复柱层析产生两个主要的吨酮从石油醚（PE）和乙酸乙酯馏分的整个植物的S。根据光谱数据和文献分析，确定其结构为bellidifolin（1）和swerchirin（2）。采用脂多糖（LPS）刺激小鼠RAW 264.7巨噬细胞，采用酶联免疫吸附试验（ELISA）和western blot方法，研究了这两种氧杂蒽酮化合物的抗炎活性及其机制。抗炎实验表明，1和2抑制LPS-1中促炎细胞因子白细胞介素-6（IL-6）和TNF-α的产生。刺激RAW 264.7巨噬细胞。氧杂蒽酮1还通过抑制LPS刺激的RAW 264.7巨噬细胞中环氧合酶-2（考克斯-2）的蛋白表达而有效抑制前列腺素E-2（PGE（2））的产生。Western blot结果显示，1浓度依赖性地抑制c-Jun N-末端激酶（JNK）、细胞外信号调节激酶（ERK）和p38 MAPK的磷酸化。特别地，化合物1抑制抑制剂κ B激酶-β（IKK-β）、Akt和核因子-κ B的p65亚基（NF-κ B）的磷酸化。chirayita通过阻断考克斯-2的表达和Akt、IKK-β、MAPK和NF-κ B的磷酸化，在LPS刺激的巨噬细胞中的活化来抑制炎症介质，表明1可以是用于管理炎症介导的免疫疾病的预防性治疗候选物。
Background: Swertia chirayita, has been commonly used under the name "Zang-yin-chen" for the treatment of liver infections, inflammation, abdominal pain, and bacterial infection in traditional Tibetan medicine. However, the bioactive components with anti-inflammatory activities and underlying mechanisms remain poorly evaluated.Study design/methods: Repeated column chromatography yielded two main xanthones from petroleum ether (PE) and ethyl acetate fractions of whole plants of S. chirayita, and their structures were determined as bellidifolin (1) and swerchirin (2) on the basis of spectroscopic data and literature analysis. The anti-inflammatory activities and mechanisms of anti-inflammation of these two isolated xanthones were determined via enzyme-linked immunosorbent assay (ELISA) and western blot in lipopolysaccharide (LPS)-stimulated RAW 264.7 murine macrophages in vitro.Results: Anti-inflammation assay demonstrated that 1 and 2 inhibit the production of the pro-inflammatory cytokines interleukin-6 (IL-6) and TNF-alpha in LPS-stimulated RAW 264.7 macrophages. Xanthone 1 also potently inhibited the production of prostaglandin E-2 (PGE(2)) by suppressing the protein expression of cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 macrophages. Western blot showed that the phosphorylation of c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinase (ERK), and p38 MAPKs were remarkably attenuated by 1 in a concentration-dependent manner. Particularly, Compound 1 suppressed the phosphorylation of the inhibitor kappa B kinase-beta (IKK-beta), Akt, and p65 subunit of nuclear factor-kappaB (NF-kappa B).Conclusion: The potent suppressive effects of 1 from S. chirayita on inflammatory mediators by blocking the expression of COX-2 and phosphorylation of Akt, IKK-beta, MAPK and NF-kappa B, activation in LPS-stimulated macrophages suggest that 1 can be a preventive therapeutic candidate for the management of inflammatory-mediated immune disorders.