Clinical Interventions in Aging (Nov 2015)
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
Abstract
Sheue-Er Wang,1,2 Ching-Lung Lin,1 Chih-Hsiang Hsu,1 Shuenn-Jyi Sheu,3 Chung-Hsin Wu1 1Department of Life Science, National Taiwan Normal University, Taipei, 2Department of Pathological Inspection, Saint Paul’s Hospital, Taoyuan, 3Brion Research Institute of Taiwan, Taipei, Taiwan 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. Keywords: neuroprotection, reactive oxygen species, superoxide dismutase 2, B-cell lymphoma 2, Bcl-2-associated X protein, calpain, caspase-3, transgenic mouse model, Huntington’s disease
