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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

Oral B401 treatment prolongs life and maintains body weight of R6/2 (HD) mice.Notes: (A) Survival duration of R6/2 mice given the oral B401 treatment was longer than those given the sham treatment. (B) Averaged body weight of R6/2 mice given the oral B401 treatment was significantly higher when compared with those given the sham treatment from 10 weeks of age and thereafter. The number of R6/2 mice under oral B401 and sham treatments were 22 and 20, respectively. Values are mean ± SEM (*P<0.05, **P<0.01, one-way ANOVA followed by a Student–Newman–Keuls multiple comparison posttest).Abbreviations: HD, Huntington’s disease; ANOVA, analysis of variance; SEM, standard error of the mean.
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f2-cia-10-1825: Oral B401 treatment prolongs life and maintains body weight of R6/2 (HD) mice.Notes: (A) Survival duration of R6/2 mice given the oral B401 treatment was longer than those given the sham treatment. (B) Averaged body weight of R6/2 mice given the oral B401 treatment was significantly higher when compared with those given the sham treatment from 10 weeks of age and thereafter. The number of R6/2 mice under oral B401 and sham treatments were 22 and 20, respectively. Values are mean ± SEM (*P<0.05, **P<0.01, one-way ANOVA followed by a Student–Newman–Keuls multiple comparison posttest).Abbreviations: HD, Huntington’s disease; ANOVA, analysis of variance; SEM, standard error of the mean.

Mentions: A total of 42 male R6/2 mice (22 R6/2 mice received oral B401 treatment and 20 R6/2 mice received sham treatment) were observed in this study. We compared the life span and body weight of R6/2 mice with and without oral B401 treatment. Our results had shown that oral B401 treatment lengthened life span and assisted in maintaining the body weight of R6/2 mice (Figure 2). The survival duration of the R6/2 mice given the oral B401 treatment was greater than the mice having received the sham treatment (Figure 2A). The R6/2 mice given the oral B401 treatment all died having reached 21 weeks of age (Figure 2A, solid line), whereas R6/2 mice given the sham treatment all died at 17 weeks of age (Figure 2A, dotted line). We compared the body weight of R6/2 mice given both the oral B401 and sham treatments. The body weights of R6/2 mice given the oral B401 treatment were significantly higher than those of R6/2 mice given the sham treatment from 10 weeks of age and thereafter (Figure 2B, P<0.01–0.05). We compared stride lengths of R6/2 mice with and without oral B401 treatment by using gait analysis (Figure 3A). Stride lengths of paw placement records of 10-week-old R6/2 mice given the oral B401 treatment were significantly longer than those of mice given the sham treatment (Figure 3B, P<0.01). Hindlimb gait abnormalities were apparent from 8 weeks and were followed at later ages by dragging of the hind legs. At 10 weeks of age, R6/2 mice given the oral B401 treatment placed their hind paws in almost the same spots as those occupied by the preceding forepaws during walking, whereas the steps of R6/2 mice given the sham treatment were irregular (Figure 3B).


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)

Oral B401 treatment prolongs life and maintains body weight of R6/2 (HD) mice.Notes: (A) Survival duration of R6/2 mice given the oral B401 treatment was longer than those given the sham treatment. (B) Averaged body weight of R6/2 mice given the oral B401 treatment was significantly higher when compared with those given the sham treatment from 10 weeks of age and thereafter. The number of R6/2 mice under oral B401 and sham treatments were 22 and 20, respectively. Values are mean ± SEM (*P<0.05, **P<0.01, one-way ANOVA followed by a Student–Newman–Keuls multiple comparison posttest).Abbreviations: HD, Huntington’s disease; ANOVA, analysis of variance; SEM, standard error of the mean.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4644183&req=5

f2-cia-10-1825: Oral B401 treatment prolongs life and maintains body weight of R6/2 (HD) mice.Notes: (A) Survival duration of R6/2 mice given the oral B401 treatment was longer than those given the sham treatment. (B) Averaged body weight of R6/2 mice given the oral B401 treatment was significantly higher when compared with those given the sham treatment from 10 weeks of age and thereafter. The number of R6/2 mice under oral B401 and sham treatments were 22 and 20, respectively. Values are mean ± SEM (*P<0.05, **P<0.01, one-way ANOVA followed by a Student–Newman–Keuls multiple comparison posttest).Abbreviations: HD, Huntington’s disease; ANOVA, analysis of variance; SEM, standard error of the mean.
Mentions: A total of 42 male R6/2 mice (22 R6/2 mice received oral B401 treatment and 20 R6/2 mice received sham treatment) were observed in this study. We compared the life span and body weight of R6/2 mice with and without oral B401 treatment. Our results had shown that oral B401 treatment lengthened life span and assisted in maintaining the body weight of R6/2 mice (Figure 2). The survival duration of the R6/2 mice given the oral B401 treatment was greater than the mice having received the sham treatment (Figure 2A). The R6/2 mice given the oral B401 treatment all died having reached 21 weeks of age (Figure 2A, solid line), whereas R6/2 mice given the sham treatment all died at 17 weeks of age (Figure 2A, dotted line). We compared the body weight of R6/2 mice given both the oral B401 and sham treatments. The body weights of R6/2 mice given the oral B401 treatment were significantly higher than those of R6/2 mice given the sham treatment from 10 weeks of age and thereafter (Figure 2B, P<0.01–0.05). We compared stride lengths of R6/2 mice with and without oral B401 treatment by using gait analysis (Figure 3A). Stride lengths of paw placement records of 10-week-old R6/2 mice given the oral B401 treatment were significantly longer than those of mice given the sham treatment (Figure 3B, P<0.01). Hindlimb gait abnormalities were apparent from 8 weeks and were followed at later ages by dragging of the hind legs. At 10 weeks of age, R6/2 mice given the oral B401 treatment placed their hind paws in almost the same spots as those occupied by the preceding forepaws during walking, whereas the steps of R6/2 mice given the sham treatment were irregular (Figure 3B).

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