Yang Hsin-Ling, Korivi Mallikarjuna, Chen Cheng-Hsien, Peng Wei-Jung, Chen Chee-Shan, Li Mei-Ling, Hsu Li-Sung, Liao Jiunn-Wang, Hseu You-Cheng
Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan.
Department of Applied Chemistry, Chao Yang University of Technology, Taichung, Taiwan.
Environ Toxicol. 2017 Aug;32(8):2070-2084. doi: 10.1002/tox.22422. Epub 2017 Apr 3.
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.
接触香烟烟雾会激活多种易导致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。牛樟芝是台湾一种著名的药用蘑菇，已针对其在香烟烟雾提取物（CSE）处理的血管平滑肌细胞（SMC）和载脂蛋白E缺陷小鼠中的抗氧化、抗炎和抗动脉粥样硬化特性进行了研究。牛樟芝发酵培养液（AC，200 - 800μg/mL）对CSE诱导的活性氧生成具有有效的抗氧化活性。用AC（30 - 120μg/mL）处理SMC（A7r5）可显著改善CSE诱导的形态异常和细胞死亡。AC抑制活性氧水平与AC处理的A7r5细胞中CSE诱导的DNA损伤的显著抑制相一致。我们发现，通过增加Bax/Bcl - 2比值诱导的CSE诱导的细胞凋亡在A7r5细胞中被AC显著抑制。值得注意的是，AC处理的A7r5细胞中超氧化物歧化酶和过氧化氢酶表达上调可能有助于消除CSE诱导的活性氧生成，并防止DNA损伤和细胞凋亡。此外，AC通过抑制c - Fos/c - Jun表达抑制AP - 1活性，并通过抑制I - κBα降解抑制针对CSE刺激的NF - κB激活。AC的这种抗炎特性伴随着A7r5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）免受CSE诱导的细胞死亡。体内数据表明，口服AC（0.6mg/d/8周）可预防载脂蛋白E缺陷小鼠中CSE加速的动脉粥样硬化。这种抗动脉粥样硬化特性与血清总抗氧化状态增加以及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威利期刊公司。环境毒理学32: 2070 - 2084，2017。
