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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 HO-1 in cerebral homogenates 24 h after thromboembolic stroke in rats. Data are presented as the mean ± S.E.M. ∗∗∗P < 0.001, compared to the sham-operated group, and ###P < 0.001, compared to the MCAO group.
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fig2: Effects of the extracts of A. camphorata combined with aspirin on the expressions of HO-1 in cerebral homogenates 24 h after thromboembolic stroke in rats. Data are presented as the mean ± S.E.M. ∗∗∗P < 0.001, compared to the sham-operated group, and ###P < 0.001, compared to the MCAO group.

Mentions: A study has revealed that HO-1 is a key player for drugs upon neuroprotection in transient MCAO model [17]. In this study, Western blot was done to investigate whether A. camphorata affects the level of HO-1 expression. The results showed that A. camphorata and aspirin alone significantly (P < 0.001) reduced the expression of HO-1 protein in brain tissues of MCAO-induced rats (Figure 2). However, this protein expression was not changed when A. camphorata was treated with aspirin, since HO-1 expression seemed quite similar as appeared in their individual treatment.


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 HO-1 in cerebral homogenates 24 h after thromboembolic stroke in rats. Data are presented as the mean ± S.E.M. ∗∗∗P < 0.001, compared to the sham-operated group, and ###P < 0.001, compared to the MCAO group.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig2: Effects of the extracts of A. camphorata combined with aspirin on the expressions of HO-1 in cerebral homogenates 24 h after thromboembolic stroke in rats. Data are presented as the mean ± S.E.M. ∗∗∗P < 0.001, compared to the sham-operated group, and ###P < 0.001, compared to the MCAO group.
Mentions: A study has revealed that HO-1 is a key player for drugs upon neuroprotection in transient MCAO model [17]. In this study, Western blot was done to investigate whether A. camphorata affects the level of HO-1 expression. The results showed that A. camphorata and aspirin alone significantly (P < 0.001) reduced the expression of HO-1 protein in brain tissues of MCAO-induced rats (Figure 2). However, this protein expression was not changed when A. camphorata was treated with aspirin, since HO-1 expression seemed quite similar as appeared in their individual treatment.

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