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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

Expressions of ER-stress-related calpain in the brain tissue of the R6/2 (HD) mice were reduced under oral B401 treatment.Notes: (A) IHC staining shows that the expressions of calpain 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 had shown no difference in their WT. Scale bars: 30 µm. Western blotting analysis shows the following: (Ba) expression levels of calpain in whole brain tissue of the 10-week-old R6/2 mice given both oral B401 and sham treatments, and their WT and (Bb) quantified brain calpain levels of the 10-week-old R6/2 mice were significantly higher than their WT and significantly lower 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<0.01, two-way ANOVA followed by a Student–Newman–Keuls multiple comparison posttest).Abbreviations: ER, endoplasmic reticulum; HD, Huntington’s disease; IHC, immunohistochemistry; WT, wild-type littermate; ANOVA, analysis of variance; SEM, standard error of the mean.
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f7-cia-10-1825: Expressions of ER-stress-related calpain in the brain tissue of the R6/2 (HD) mice were reduced under oral B401 treatment.Notes: (A) IHC staining shows that the expressions of calpain 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 had shown no difference in their WT. Scale bars: 30 µm. Western blotting analysis shows the following: (Ba) expression levels of calpain in whole brain tissue of the 10-week-old R6/2 mice given both oral B401 and sham treatments, and their WT and (Bb) quantified brain calpain levels of the 10-week-old R6/2 mice were significantly higher than their WT and significantly lower 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<0.01, two-way ANOVA followed by a Student–Newman–Keuls multiple comparison posttest).Abbreviations: ER, endoplasmic reticulum; HD, Huntington’s disease; IHC, immunohistochemistry; WT, wild-type littermate; ANOVA, analysis of variance; SEM, standard error of the mean.

Mentions: Apoptosis is believed to be involved in the pathogenesis and progression of HD.16 We examined whether the Chinese herbal formula B401 alleviates apoptosis in the brain of R6/2 mice. As observed from IHC staining of the brain, expressions of endoplasmic reticulum (ER) stress-related calpain were obvious in the stratum, hippocampus, and medulla of R6/2 mice given the sham treatment, but were not obvious in those of R6/2 mice given the oral B401 treatment, and their WT (Figure 7A). Furthermore, expressions of anti-apoptosis-related Bcl-2 were not obvious in the stratum, hippocampus, and medulla of R6/2 mice given the sham treatment, but were obvious in those of R6/2 mice given the oral B401 treatment, and their WT (Figure 8Ai and Aii). On the contrary, expressions of mitochondrial dysfunction-related Bax and caspases-3 were obvious in the stratum, hippocampus, and medulla of R6/2 mice given the sham treatment, but were not obvious in those of R6/2 mice given the oral B401 treatment, and their WT (Figures 8Ai, Aii, and 9A). As analyzed from Western blotting analysis of the brain, the quantified ratio of Bcl-2/Bax of the 10-week-old R6/2 mice given the sham treatment was significantly reduced when compared with those of the 10-week-old R6/2 mice given the oral B401 treatment, and their WT (Figure 8Bi and Bii, P<0.01). Quantified brain calpain and caspases-3 levels in the 10-week-old R6/2 mice given the sham treatment significantly increased beyond those of the 10-week-old R6/2 mice given the oral B401 treatment, and their WT (Figures 7Bi, Bii, and 9Bi, Bii, P<0.01). Calpain and caspases-3 levels in the 10-week-old R6/2 mice given the oral B401 treatment were not significant when compared with those of their WT (Figures 7Bi, Bii, and 9Bi, 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)

Expressions of ER-stress-related calpain in the brain tissue of the R6/2 (HD) mice were reduced under oral B401 treatment.Notes: (A) IHC staining shows that the expressions of calpain 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 had shown no difference in their WT. Scale bars: 30 µm. Western blotting analysis shows the following: (Ba) expression levels of calpain in whole brain tissue of the 10-week-old R6/2 mice given both oral B401 and sham treatments, and their WT and (Bb) quantified brain calpain levels of the 10-week-old R6/2 mice were significantly higher than their WT and significantly lower 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<0.01, two-way ANOVA followed by a Student–Newman–Keuls multiple comparison posttest).Abbreviations: ER, endoplasmic reticulum; HD, Huntington’s disease; IHC, immunohistochemistry; WT, wild-type littermate; ANOVA, analysis of variance; SEM, standard error of the mean.
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f7-cia-10-1825: Expressions of ER-stress-related calpain in the brain tissue of the R6/2 (HD) mice were reduced under oral B401 treatment.Notes: (A) IHC staining shows that the expressions of calpain 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 had shown no difference in their WT. Scale bars: 30 µm. Western blotting analysis shows the following: (Ba) expression levels of calpain in whole brain tissue of the 10-week-old R6/2 mice given both oral B401 and sham treatments, and their WT and (Bb) quantified brain calpain levels of the 10-week-old R6/2 mice were significantly higher than their WT and significantly lower 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<0.01, two-way ANOVA followed by a Student–Newman–Keuls multiple comparison posttest).Abbreviations: ER, endoplasmic reticulum; HD, Huntington’s disease; IHC, immunohistochemistry; WT, wild-type littermate; ANOVA, analysis of variance; SEM, standard error of the mean.
Mentions: Apoptosis is believed to be involved in the pathogenesis and progression of HD.16 We examined whether the Chinese herbal formula B401 alleviates apoptosis in the brain of R6/2 mice. As observed from IHC staining of the brain, expressions of endoplasmic reticulum (ER) stress-related calpain were obvious in the stratum, hippocampus, and medulla of R6/2 mice given the sham treatment, but were not obvious in those of R6/2 mice given the oral B401 treatment, and their WT (Figure 7A). Furthermore, expressions of anti-apoptosis-related Bcl-2 were not obvious in the stratum, hippocampus, and medulla of R6/2 mice given the sham treatment, but were obvious in those of R6/2 mice given the oral B401 treatment, and their WT (Figure 8Ai and Aii). On the contrary, expressions of mitochondrial dysfunction-related Bax and caspases-3 were obvious in the stratum, hippocampus, and medulla of R6/2 mice given the sham treatment, but were not obvious in those of R6/2 mice given the oral B401 treatment, and their WT (Figures 8Ai, Aii, and 9A). As analyzed from Western blotting analysis of the brain, the quantified ratio of Bcl-2/Bax of the 10-week-old R6/2 mice given the sham treatment was significantly reduced when compared with those of the 10-week-old R6/2 mice given the oral B401 treatment, and their WT (Figure 8Bi and Bii, P<0.01). Quantified brain calpain and caspases-3 levels in the 10-week-old R6/2 mice given the sham treatment significantly increased beyond those of the 10-week-old R6/2 mice given the oral B401 treatment, and their WT (Figures 7Bi, Bii, and 9Bi, Bii, P<0.01). Calpain and caspases-3 levels in the 10-week-old R6/2 mice given the oral B401 treatment were not significant when compared with those of their WT (Figures 7Bi, Bii, and 9Bi, 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