Antrodia camphorata attenuates cigarette smoke‐induced ROS production, DNA damage, apoptosis, and inflammation in vascular smooth muscle cells, and atherosclerosis in ApoE‐deficient mice
Antrodia camphorata attenuates cigarette smoke‐induced ROS production, DNA damage, apoptosis, and inflammation in vascular smooth muscle cells, and atherosclerosis in ApoE‐deficient mice
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DOI：
10.1002/tox.22422
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发表时间：
2017-08
影响因子：
4.5
通讯作者：
Hsin-Ling Yang;Mallikarjuna Korivi;Cheng-Hsien Chen;Wei‐Jung Peng;Chee-shan Chen;Mei-Ling Li;L. Hsu;J. Liao;Y. Hseu
中科院分区：
文献类型：
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作者：
Hsin-Ling Yang;Mallikarjuna Korivi;Cheng-Hsien Chen;Wei‐Jung Peng;Chee-shan Chen;Mei-Ling Li;L. Hsu;J. Liao;Y. Hseu
香烟烟雾暴露激活了几种易患动脉粥样硬化的细胞机制，包括氧化应激、血脂异常和血管炎症。在香烟烟雾提取物（CSE）处理的血管平滑肌细胞（SMC）和ApoE缺陷小鼠中，研究了台湾著名的药用蘑菇牛樟芝（Antrodia acidorata）的抗氧化、抗炎和抗动脉粥样硬化特性。牛樟芝发酵培养液（AC，200 - 800 µg/mL）对CSE诱导的ROS产生具有有效的抗氧化活性。用AC（30 - 120 µg/mL）处理SMC（A7 r5）可显著改善CSE诱导的形态畸变和细胞死亡。AC抑制ROS水平证实了AC处理的A7 r5细胞中CSE诱导的DNA损伤的实质性抑制。我们发现CSE通过增加Bax/Bcl-2比率诱导的凋亡在A7 r5细胞中被AC显著抑制。值得注意的是，AC处理的A7 r5细胞中的SOD和过氧化氢酶表达上调可能有助于消除CSE诱导的ROS产生，并防止DNA损伤和凋亡。此外，AC通过抑制c-Fos/c-Jun表达来抑制AP-1活性，并通过抑制I-κBα降解来抑制NF-κB活化以对抗CSE-刺激。AC的这种抗炎特性伴随着A7 r5细胞中CSE诱导的VEGF、PDGF和EGR-1过表达的抑制。此外，AC保护肺成纤维细胞（MRC-5）免于CSE诱导的细胞死亡。体内数据显示，AC经口给药（0.6 mg/d/8周）可预防ApoE缺陷小鼠中CSE加速的动脉粥样硬化。这种抗动脉粥样硬化的特性与血清总抗氧化状态增加，总胆固醇和三酰甘油水平降低有关。因此，牛樟芝可能有助于预防CSE诱导的氧化应激和疾病。© 2016 Wiley Periodicals，Inc.环境毒理学32：2070-2084，2017年。
Cigarette smoke exposure activates several cellular mechanisms predisposing to atherosclerosis, including oxidative stress, dyslipidemia, and vascular inflammation. Antrodia camphorata, a renowned medicinal mushroom in Taiwan, has been investigated for its antioxidant, anti‐inflammatory, and antiatherosclerotic properties in cigarette smoke extracts (CSE)‐treated vascular smooth muscle cells (SMCs), and ApoE‐deficient mice. Fermented culture broth of Antrodia camphorata (AC, 200‐800 µg/mL) possesses effective antioxidant activity against CSE‐induced ROS production. Treatment of SMCs (A7r5) with AC (30‐120 µg/mL) remarkably ameliorated CSE‐induced morphological aberrations and cell death. Suppressed ROS levels by AC corroborate with substantial inhibition of CSE‐induced DNA damage in AC‐treated A7r5 cells. We found CSE‐induced apoptosis through increased Bax/Bcl‐2 ratio, was substantially inhibited by AC in A7r5 cells. Notably, upregulated SOD and catalase expressions in AC‐treated A7r5 cells perhaps contributed to eradicate the CSE‐induced ROS generation, and prevents DNA damage and apoptosis. Besides, AC suppressed AP‐1 activity by inhibiting the c‐Fos/c‐Jun expressions, and NF‐κB activation through inhibition of I‐κBα degradation against CSE‐stimulation. This anti‐inflammatory property of AC was accompanied by suppressed CSE‐induced VEGF, PDGF, and EGR‐1 overexpressions in A7r5 cells. Furthermore, AC protects lung fibroblast (MRC‐5) cells from CSE‐induced cell death. In vivo data showed that AC oral administration (0.6 mg/d/8‐wk) prevents CSE‐accelerated atherosclerosis in ApoE‐deficient mice. This antiatherosclerotic property was associated with increased serum total antioxidant status, and decreased total cholesterol and triacylglycerol levels. Thus, Antrodia camphorata may be useful for prevention of CSE‐induced oxidative stress and diseases. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 2070–2084, 2017.