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Oral treatment with the herbal formula B401 protects against aging-dependent neurodegeneration by attenuating oxidative stress and apoptosis in the brain of R6/2 mice.

Wang SE, Lin CL, Hsu CH, Sheu SJ, Wu CH - Clin Interv Aging (2015)

Bottom Line: R6/2 HD mice with oral B401 treatment significantly reduced reactive oxygen species levels in the blood, but markedly increased expressions of superoxide dismutase 2 in the brain tissue.Furthermore, R6/2 HD mice with oral B401 treatment significantly increased expressions of B-cell lymphoma 2 (Bcl-2), but significantly reduced expressions of Bcl-2-associated X protein (Bax), calpain, and caspase-3 in the brain tissue.We suggest that the herbal formula B401 can be developed as a potential health supplement for ameliorating aging-dependent neurodegeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan ; Department of Pathological Inspection, Saint Paul's Hospital, Taoyuan, Taiwan.

ABSTRACT

Background: Neurodegeneration is characterized by progressive neurological deficits due to selective neuronal loss in the nervous system. Huntington's disease (HD) is an incurable neurodegenerative disorder. Neurodegeneration in HD patients shows aging-dependent pattern. Our previous study has suggested that a herbal formula B401 may have neuroprotective effects in the brains of R6/2 mice.

Objective: To clarify possible mechanisms for neurodegeneration, which improves the understanding the aging process. This study focuses on clarifying neurodegenerative mechanisms and searching potential therapeutic targets in HD patients.

Methods: The oxidative stress and apoptosis were compared in the brain tissue between R6/2 HD mice with and without oral B401 treatment. Expressions of proteins for oxidative stress and apoptosis in the brain tissue of R6/2 HD mice were examined by using immunostaining and Western blotting techniques.

Results: R6/2 HD mice with oral B401 treatment significantly reduced reactive oxygen species levels in the blood, but markedly increased expressions of superoxide dismutase 2 in the brain tissue. Furthermore, R6/2 HD mice with oral B401 treatment significantly increased expressions of B-cell lymphoma 2 (Bcl-2), but significantly reduced expressions of Bcl-2-associated X protein (Bax), calpain, and caspase-3 in the brain tissue.

Conclusion: Our findings provide evidence that the herbal formula B401 can remedy for aging-dependent neurodegeneration of R6/2 mice via suppressing oxidative stress and apoptosis in the brain. We suggest that the herbal formula B401 can be developed as a potential health supplement for ameliorating aging-dependent neurodegeneration.

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Related in: MedlinePlus

Huntingtin aggregations in the brain tissue of R6/2 (HD) mice were reduced under oral B401 treatment.Notes: (A) IHC staining shows that the expressions of huntingtin in the striatum, hippocampus, and medulla of the 10-week-old R6/2 mice given the oral B401 treatment were obviously weaker than those given the sham treatment but were obviously more intense than their WT. Scale bars: 30 µm. Western blotting analysis shows the following: (Ba) expression levels of huntingtin in whole brain tissue of the 10-week-old R6/2 mice given both the oral B401 and sham treatments, and their WT and (Bb) a significant increase in quantified brain huntingtin levels in the 10-week-old R6/2 mice in comparison with their WT, and a significant reduction under oral B401 treatment. The number of R6/2 mice under oral B401 and sham treatments and their WT was six for each group. Values are mean ± SEM (*P<0.05, **P<0.01, two-way ANOVA followed by a Student–Newman–Keuls multiple comparison posttest).Abbreviations: HD, Huntington’s disease; IHC, immunohistochemistry; WT, wild-type littermate; ANOVA, analysis of variance; SEM, standard error of the mean.
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f4-cia-10-1825: Huntingtin aggregations in the brain tissue of R6/2 (HD) mice were reduced under oral B401 treatment.Notes: (A) IHC staining shows that the expressions of huntingtin in the striatum, hippocampus, and medulla of the 10-week-old R6/2 mice given the oral B401 treatment were obviously weaker than those given the sham treatment but were obviously more intense than their WT. Scale bars: 30 µm. Western blotting analysis shows the following: (Ba) expression levels of huntingtin in whole brain tissue of the 10-week-old R6/2 mice given both the oral B401 and sham treatments, and their WT and (Bb) a significant increase in quantified brain huntingtin levels in the 10-week-old R6/2 mice in comparison with their WT, and a significant reduction under oral B401 treatment. The number of R6/2 mice under oral B401 and sham treatments and their WT was six for each group. Values are mean ± SEM (*P<0.05, **P<0.01, two-way ANOVA followed by a Student–Newman–Keuls multiple comparison posttest).Abbreviations: HD, Huntington’s disease; IHC, immunohistochemistry; WT, wild-type littermate; ANOVA, analysis of variance; SEM, standard error of the mean.

Mentions: We compared aggregated mHTT in the brains of 10-week-old R6/2 mice under the oral B401 treatment, sham treatment, and their WT by IHC stain and Western blotting analysis in Figure 4. The deposition of mHTT is a neuropathological hallmark of HD.14 As observed from IHC staining of the brain, expressions of mHtt aggregation were obvious in the striatum, hippocampus, and medulla of R6/2 mice given the sham treatment, whereas they were not obvious in the striatum and hippocampus of R6/2 mice given the oral B401 treatment, and their WT (Figure 4A). As analyzed from Western blotting analysis of the brain, quantified brain huntingtin levels in 10-week-old R6/2 mice given the sham treatment were significantly higher than those in 10-week-old R6/2 mice given the oral B401 treatment and their WT (Figure 4Bi and Bii, P<0.01). Huntingtin levels of 10-week-old R6/2 mice given the oral B401 treatment were significantly lower than those of their WT (Figure 4Bi and Bii, P<0.05).


Oral treatment with the herbal formula B401 protects against aging-dependent neurodegeneration by attenuating oxidative stress and apoptosis in the brain of R6/2 mice.

Wang SE, Lin CL, Hsu CH, Sheu SJ, Wu CH - Clin Interv Aging (2015)

Huntingtin aggregations in the brain tissue of R6/2 (HD) mice were reduced under oral B401 treatment.Notes: (A) IHC staining shows that the expressions of huntingtin in the striatum, hippocampus, and medulla of the 10-week-old R6/2 mice given the oral B401 treatment were obviously weaker than those given the sham treatment but were obviously more intense than their WT. Scale bars: 30 µm. Western blotting analysis shows the following: (Ba) expression levels of huntingtin in whole brain tissue of the 10-week-old R6/2 mice given both the oral B401 and sham treatments, and their WT and (Bb) a significant increase in quantified brain huntingtin levels in the 10-week-old R6/2 mice in comparison with their WT, and a significant reduction under oral B401 treatment. The number of R6/2 mice under oral B401 and sham treatments and their WT was six for each group. Values are mean ± SEM (*P<0.05, **P<0.01, two-way ANOVA followed by a Student–Newman–Keuls multiple comparison posttest).Abbreviations: HD, Huntington’s disease; IHC, immunohistochemistry; WT, wild-type littermate; ANOVA, analysis of variance; SEM, standard error of the mean.
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Related In: Results  -  Collection

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f4-cia-10-1825: Huntingtin aggregations in the brain tissue of R6/2 (HD) mice were reduced under oral B401 treatment.Notes: (A) IHC staining shows that the expressions of huntingtin in the striatum, hippocampus, and medulla of the 10-week-old R6/2 mice given the oral B401 treatment were obviously weaker than those given the sham treatment but were obviously more intense than their WT. Scale bars: 30 µm. Western blotting analysis shows the following: (Ba) expression levels of huntingtin in whole brain tissue of the 10-week-old R6/2 mice given both the oral B401 and sham treatments, and their WT and (Bb) a significant increase in quantified brain huntingtin levels in the 10-week-old R6/2 mice in comparison with their WT, and a significant reduction under oral B401 treatment. The number of R6/2 mice under oral B401 and sham treatments and their WT was six for each group. Values are mean ± SEM (*P<0.05, **P<0.01, two-way ANOVA followed by a Student–Newman–Keuls multiple comparison posttest).Abbreviations: HD, Huntington’s disease; IHC, immunohistochemistry; WT, wild-type littermate; ANOVA, analysis of variance; SEM, standard error of the mean.
Mentions: We compared aggregated mHTT in the brains of 10-week-old R6/2 mice under the oral B401 treatment, sham treatment, and their WT by IHC stain and Western blotting analysis in Figure 4. The deposition of mHTT is a neuropathological hallmark of HD.14 As observed from IHC staining of the brain, expressions of mHtt aggregation were obvious in the striatum, hippocampus, and medulla of R6/2 mice given the sham treatment, whereas they were not obvious in the striatum and hippocampus of R6/2 mice given the oral B401 treatment, and their WT (Figure 4A). As analyzed from Western blotting analysis of the brain, quantified brain huntingtin levels in 10-week-old R6/2 mice given the sham treatment were significantly higher than those in 10-week-old R6/2 mice given the oral B401 treatment and their WT (Figure 4Bi and Bii, P<0.01). Huntingtin levels of 10-week-old R6/2 mice given the oral B401 treatment were significantly lower than those of their WT (Figure 4Bi and Bii, P<0.05).

Bottom Line: R6/2 HD mice with oral B401 treatment significantly reduced reactive oxygen species levels in the blood, but markedly increased expressions of superoxide dismutase 2 in the brain tissue.Furthermore, R6/2 HD mice with oral B401 treatment significantly increased expressions of B-cell lymphoma 2 (Bcl-2), but significantly reduced expressions of Bcl-2-associated X protein (Bax), calpain, and caspase-3 in the brain tissue.We suggest that the herbal formula B401 can be developed as a potential health supplement for ameliorating aging-dependent neurodegeneration.

View Article: PubMed Central - PubMed

Affiliation: Department of Life Science, National Taiwan Normal University, Taipei, Taiwan ; Department of Pathological Inspection, Saint Paul's Hospital, Taoyuan, Taiwan.

ABSTRACT

Background: Neurodegeneration is characterized by progressive neurological deficits due to selective neuronal loss in the nervous system. Huntington's disease (HD) is an incurable neurodegenerative disorder. Neurodegeneration in HD patients shows aging-dependent pattern. Our previous study has suggested that a herbal formula B401 may have neuroprotective effects in the brains of R6/2 mice.

Objective: To clarify possible mechanisms for neurodegeneration, which improves the understanding the aging process. This study focuses on clarifying neurodegenerative mechanisms and searching potential therapeutic targets in HD patients.

Methods: The oxidative stress and apoptosis were compared in the brain tissue between R6/2 HD mice with and without oral B401 treatment. Expressions of proteins for oxidative stress and apoptosis in the brain tissue of R6/2 HD mice were examined by using immunostaining and Western blotting techniques.

Results: R6/2 HD mice with oral B401 treatment significantly reduced reactive oxygen species levels in the blood, but markedly increased expressions of superoxide dismutase 2 in the brain tissue. Furthermore, R6/2 HD mice with oral B401 treatment significantly increased expressions of B-cell lymphoma 2 (Bcl-2), but significantly reduced expressions of Bcl-2-associated X protein (Bax), calpain, and caspase-3 in the brain tissue.

Conclusion: Our findings provide evidence that the herbal formula B401 can remedy for aging-dependent neurodegeneration of R6/2 mice via suppressing oxidative stress and apoptosis in the brain. We suggest that the herbal formula B401 can be developed as a potential health supplement for ameliorating aging-dependent neurodegeneration.

Show MeSH
Related in: MedlinePlus