RESUMEN
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.