title: Antrodia camphorata Potentiates Neuroprotection against Cerebral Ischemia in Rats via Downregulation of iNOS/HO-1/Bax and Activated Caspase-3 and Inhibition of Hydroxyl Radical Formation.
abstract: Antrodia camphorata (A. camphorata) is a fungus generally used in Chinese folk medicine for treatment of viral hepatitis and cancer. Our previous study found A. camphorata has neuroprotective properties and could reduce stroke injury in cerebral ischemia animal models. In this study, we sought to investigate the molecular mechanisms of neuroprotective effects of A. camphorata in middle cerebral artery occlusion (MCAO) rats. A selective occlusion of the middle cerebral artery (MCA) with whole blood clots was used to induce ischemic stroke in rats and they were orally treated with A. camphorata (0.25 and 0.75 g/kg/day) alone or combined with aspirin (5 mg/kg/day). To provide insight into the functions of A. camphorata mediated neuroprotection, the expression of Bax, inducible nitric oxide synthase (iNOS), haem oxygenase-1 (HO-1), and activated caspase-3 was determined by Western blot assay. Treatment of aspirin alone significantly reduced the expressions of HO-1 (P < 0.001), iNOS (P < 0.001), and Bax (P < 0.01) in ischemic regions. The reduction of these expressions was more potentiated when rats treated by aspirin combined with A. camphorata (0.75 g/kg/day). Combination treatment also reduced apoptosis as measured by a significant reduction in active caspase-3 expression in the ischemic brain compared to MCAO group (P < 0.01). Moreover, treatment of A. camphorata significantly (P < 0.05) reduced fenton reaction-induced hydroxyl radical (OH(•)) formation at a dose of 40 mg/mL. Taken together, A. camphorata has shown neuroprotective effects in embolic rats, and the molecular mechanisms may correlate with the downregulation of Bax, iNOS, HO-1, and activated caspase-3 and the inhibition of OH(•) signals.
authors.affiliation: Department of Surgery, Mackay Memorial Hospital and Mackay Medical College, Taipei, Taiwan ; Department of Pharmacology, School of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Po-Sheng
authors.initials: PS
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, School of Medicine, Taipei Medical University, Taipei, Taiwan ; Cardiovascular Division, Department of Surgery, Yuan's General Hospital, Kaohsiung, Taiwan.
authors.forename: Po-Yen
authors.initials: PY
authors.lastname: Lin
authors.affiliation: Department of Cardiology, Cathay General Hospital, Taipei, Taiwan.
authors.forename: Chao-Chien
authors.initials: CC
authors.lastname: Chang
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Meng-Che
authors.initials: MC
authors.lastname: Yu
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Ting-Lin
authors.initials: TL
authors.lastname: Yen
authors.affiliation: Sheen Chain Biotechnology, Co., Ltd., Taipei, Taiwan.
authors.forename: Chang-Chou
authors.initials: CC
authors.lastname: Lan
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Thanasekaran
authors.initials: T
authors.lastname: Jayakumar
authors.affiliation: Department of Pharmacology, School of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chih-Hao
authors.initials: CH
authors.lastname: Yang