title: Antrodia camphorata attenuates cigarette smoke-induced ROS production, DNA damage, apoptosis, and inflammation in vascular smooth muscle cells, and atherosclerosis in ApoE-deficient mice.
abstract: 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.
authors.affiliation: Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan.
authors.forename: Hsin-Ling
authors.initials: HL
authors.lastname: Yang
authors.affiliation: Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan.
authors.forename: Mallikarjuna
authors.initials: M
authors.lastname: Korivi
authors.affiliation: Department of Applied Chemistry, Chao Yang University of Technology, Taichung, Taiwan.
authors.forename: Cheng-Hsien
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Applied Chemistry, Chao Yang University of Technology, Taichung, Taiwan.
authors.forename: Wei-Jung
authors.initials: WJ
authors.lastname: Peng
authors.affiliation: Department of Applied Chemistry, Chao Yang University of Technology, Taichung, Taiwan.
authors.forename: Chee-Shan
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Institute of Nutrition, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan.
authors.forename: Mei-Ling
authors.initials: ML
authors.lastname: Li
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Li-Sung
authors.initials: LS
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Veterinary Pathology, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Jiunn-Wang
authors.initials: JW
authors.lastname: Liao
authors.affiliation: Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan.|Department of Cosmeceutics, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan.
authors.forename: You-Cheng
authors.initials: YC
authors.lastname: Hseu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D055491:Antrodia / Q000737:chemistry*; D001057:Apolipoproteins E / Q000235:genetics; D017209:Apoptosis / Q000187:drug effects*; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D002460:Cell Line; D003470:Culture Media / Q000494:pharmacology; D004249:DNA Damage / Q000187:drug effects*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008168:Lung / Q000166:cytology; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012906:Smoke / Q000009:adverse effects*; D062789:Tobacco Products; D018808:Transcription Factor AP-1 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001057:Apolipoproteins E; D003470:Culture Media; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D012906:Smoke; D018808:Transcription Factor AP-1
keywords: Antrodia camphorata; ROS; atherosclerosis; cigarette smoke; inflammation; smooth muscle cells