Astragalin inhibits airway eotaxin-1 induction and epithelial apoptosis through modulating oxidative stress-responsive MAPK signaling.
Astragalin inhibits airway eotaxin-1 induction and epithelial apoptosis through modulating oxidative stress-responsive MAPK signaling.
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DOI：
10.1186/1471-2466-14-122
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发表时间：
2014-07-29
影响因子：
3.1
通讯作者：
Kang YH
中科院分区：
文献类型：
--
作者：
Cho IH;Gong JH;Kang MK;Lee EJ;Park JH;Park SJ;Kang YH
嗜酸性粒细胞趋化因子蛋白是治疗与过敏性气道疾病相关的支气管周围嗜酸性粒细胞增多的潜在治疗靶点。由于炎症通常与活性氧 (ROS) 产生的增加有关，因此氧化应激是哮喘的一个重要机制因素。黄芪素（山奈酚-3-O-葡萄糖苷）是一种具有抗炎活性的黄酮类化合物，新发现于柿叶和绿茶籽中。这项研究阐明黄芪甲苷可抑制内毒素诱导的氧化应激，从而导致气道中嗜酸性粒细胞增多和上皮细胞凋亡。在存在或不存在 1–20 μM 黄芪甲素的情况下，将气道上皮 BEAS-2B 细胞暴露于脂多糖 (LPS)。进行蛋白质印迹和免疫细胞化学分析以确定靶蛋白的诱导。还对细胞和核染色进行 ROS 产生和上皮细胞凋亡。当气道上皮细胞暴露于 2 μg/ml LPS 时，≤20 μM 的无毒黄芪甲素可抑制 Toll 样受体 4 (TLR4) 的细胞诱导，并通过 LPS 增强 ROS 的产生。 LPS 和 H2O2 均诱导上皮嗜酸细胞活化趋化因子 1 的表达，但黄芪甲苷可阻断这种表达。 LPS 激活并诱导上皮细胞中 p22phox 和 p47phox 的 PLCγ1、PKCβ2 和 NADPH 氧化酶亚基，并且这种激活和诱导可通过黄芪或 TLR4 抑制拮抗 eotaxin-1 诱导而减弱。通过向上皮细胞中添加黄芪甲苷，H2O2 上调的 JNK 和 p38 MAPK 磷酸化受到抑制，而该化合物则增强了 Akt 和 ERK 的上皮活化。 H2O2 和 LPS 促进上皮细胞凋亡，并伴有核浓缩或 caspase-3 激活，而黄芪甲苷则可减弱这种作用。黄芪甲苷通过干扰 TLR4-PKCβ2-NADPH 氧化酶响应信号传导来改善氧化应激相关的上皮嗜酸性粒细胞增多和细胞凋亡。因此，黄芪甲苷可能是对抗内毒素诱导的氧化应激（导致气道功能障碍和炎症）的有效药物。
Eotaxin proteins are a potential therapeutic target in treating the peribronchial eosinophilia associated with allergic airway diseases. Since inflammation is often associated with an increased generation of reactive oxygen species (ROS), oxidative stress is a mechanistically imperative factor in asthma. Astragalin (kaempferol-3-O-glucoside) is a flavonoid with anti-inflammatory activity and newly found in persimmon leaves and green tea seeds. This study elucidated that astragalin inhibited endotoxin-induced oxidative stress leading to eosinophilia and epithelial apoptosis in airways. Airway epithelial BEAS-2B cells were exposed to lipopolysaccharide (LPS) in the absence and presence of 1–20 μM astragalin. Western blot and immunocytochemical analyses were conducted to determine induction of target proteins. Cell and nuclear staining was also performed for ROS production and epithelial apoptosis. When airway epithelial cells were exposed to 2 μg/ml LPS, astragalin nontoxic at ≤20 μM suppressed cellular induction of Toll-like receptor 4 (TLR4) and ROS production enhanced by LPS. Both LPS and H2O2 induced epithelial eotaxin-1 expression, which was blocked by astragalin. LPS activated and induced PLCγ1, PKCβ2, and NADPH oxidase subunits of p22phox and p47phox in epithelial cells and such activation and induction were demoted by astragalin or TLR4 inhibition antagonizing eotaxin-1 induction. H2O2-upregulated phosphorylation of JNK and p38 MAPK was dampened by adding astragalin to epithelial cells, while this compound enhanced epithelial activation of Akt and ERK. H2O2 and LPS promoted epithelial apoptosis concomitant with nuclear condensation or caspase-3 activation, which was blunted by astragalin. Astragalin ameliorated oxidative stress-associated epithelial eosinophilia and apoptosis through disturbing TLR4-PKCβ2-NADPH oxidase-responsive signaling. Therefore, astragalin may be a potent agent antagonizing endotoxin-induced oxidative stress leading to airway dysfunction and inflammation.
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影响因子：
7.2
作者：
Saitoh, Tatsuya;Kusunoki, Takeshi;Ikeda, Katsuhisa
通讯作者：
Ikeda, Katsuhisa
影响因子：
5.6
作者：
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作者：
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DOI：
10.1016/j.bbrc.2012.02.005
发表时间：
2012-03-09
影响因子：
3.1
作者：
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通讯作者：
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影响因子：
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作者：
Wu, Mei-Yao;Hung, Shih-Kai;Fu, Shu-Ling
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