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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.

Yang PS, Lin PY, Chang CC, Yu MC, Yen TL, Lan CC, Jayakumar T, Yang CH - Evid Based Complement Alternat Med (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Mackay Memorial Hospital and Mackay Medical College, Taipei, Taiwan ; Department of Pharmacology, School of Medicine, Taipei Medical University, Taipei, Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus

Effects of the extracts of A. camphorata combined with aspirin on the expressions of (a) Bax and (b) caspase-3 in cerebral homogenates 24 h after thromboembolic stroke in rats. Data are presented as the mean ± S.E.M. ∗∗P < 0.01, compared to the sham-operated group, and ##P < 0.01, compared to the MCAO group.
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Related In: Results  -  Collection


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fig3: Effects of the extracts of A. camphorata combined with aspirin on the expressions of (a) Bax and (b) caspase-3 in cerebral homogenates 24 h after thromboembolic stroke in rats. Data are presented as the mean ± S.E.M. ∗∗P < 0.01, compared to the sham-operated group, and ##P < 0.01, compared to the MCAO group.

Mentions: Bax is the proapoptotic member and caspase-3 is the most abundant cysteine protease in the brain and is acutely cleaved and activated in neurons in the early stages of reperfusion, leading to cell apoptosis. In this study, the expression levels of these apoptotic proteins, which are considered as the most important determining factors for the fate of cell and tissues in response to apoptotic stimulations were determined. We found a significant increase in the expressions of Bax (P < 0.01) and active caspase-3 (P < 0.01) in the injured hemisphere of the MCAO rats as compared to the level obtained in the corresponding area of the sham-operated group (Figures 3(a) and 3(b)). Despite the fact that the individual treatment of aspirin suppresses both the expressions of Bax and activated caspase-3 proteins, the rate of inhibition was potentiated when the treatment was combined with A. camphorata.


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.

Yang PS, Lin PY, Chang CC, Yu MC, Yen TL, Lan CC, Jayakumar T, Yang CH - Evid Based Complement Alternat Med (2015)

Effects of the extracts of A. camphorata combined with aspirin on the expressions of (a) Bax and (b) caspase-3 in cerebral homogenates 24 h after thromboembolic stroke in rats. Data are presented as the mean ± S.E.M. ∗∗P < 0.01, compared to the sham-operated group, and ##P < 0.01, compared to the MCAO group.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4561866&req=5

fig3: Effects of the extracts of A. camphorata combined with aspirin on the expressions of (a) Bax and (b) caspase-3 in cerebral homogenates 24 h after thromboembolic stroke in rats. Data are presented as the mean ± S.E.M. ∗∗P < 0.01, compared to the sham-operated group, and ##P < 0.01, compared to the MCAO group.
Mentions: Bax is the proapoptotic member and caspase-3 is the most abundant cysteine protease in the brain and is acutely cleaved and activated in neurons in the early stages of reperfusion, leading to cell apoptosis. In this study, the expression levels of these apoptotic proteins, which are considered as the most important determining factors for the fate of cell and tissues in response to apoptotic stimulations were determined. We found a significant increase in the expressions of Bax (P < 0.01) and active caspase-3 (P < 0.01) in the injured hemisphere of the MCAO rats as compared to the level obtained in the corresponding area of the sham-operated group (Figures 3(a) and 3(b)). Despite the fact that the individual treatment of aspirin suppresses both the expressions of Bax and activated caspase-3 proteins, the rate of inhibition was potentiated when the treatment was combined with A. camphorata.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Mackay Memorial Hospital and Mackay Medical College, Taipei, Taiwan ; Department of Pharmacology, School of Medicine, Taipei Medical University, Taipei, Taiwan.

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.

No MeSH data available.


Related in: MedlinePlus