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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

Chromatographic fingerprint analysis and cell viability assay for the herbal formula B401.Notes: HPLC fingerprint of the herbal formula B401. Characteristic peaks of B401, ie, (Aa) ginsenosides Rb1 (from Panax ginseng) and oleanolic acid (from Ligustri fructus), (Ab) formononetin (from Astragalus membranaceus), (Ac) 5-HMF (from Rehmannia glutinosa), (Ad) ferulic acid (from L. fructus), (Ae) wedelolactone (from Eclipta prostrata), were identified and marked at the corresponding peaks in the fingerprint. (B) Cell viabilities of RA-induced SH-SY5Y cells in the absence (Ctrl) or presence of the B401 at indicated doses. The herbal formula B401 has no cytotoxicity in SH-SY5Y cells under treatment at a dose of less than 80 mg/mL.Abbreviations: AU, arbitrary unit; IC50, half maximal inhibitory concentration; 5-HMF, 5-hydroxymethylfurfural; RA, retinoic acid; Ctrl, control group.
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f1-cia-10-1825: Chromatographic fingerprint analysis and cell viability assay for the herbal formula B401.Notes: HPLC fingerprint of the herbal formula B401. Characteristic peaks of B401, ie, (Aa) ginsenosides Rb1 (from Panax ginseng) and oleanolic acid (from Ligustri fructus), (Ab) formononetin (from Astragalus membranaceus), (Ac) 5-HMF (from Rehmannia glutinosa), (Ad) ferulic acid (from L. fructus), (Ae) wedelolactone (from Eclipta prostrata), were identified and marked at the corresponding peaks in the fingerprint. (B) Cell viabilities of RA-induced SH-SY5Y cells in the absence (Ctrl) or presence of the B401 at indicated doses. The herbal formula B401 has no cytotoxicity in SH-SY5Y cells under treatment at a dose of less than 80 mg/mL.Abbreviations: AU, arbitrary unit; IC50, half maximal inhibitory concentration; 5-HMF, 5-hydroxymethylfurfural; RA, retinoic acid; Ctrl, control group.

Mentions: The herbal formula B401 (US patent, No 7838048B2, November 23, 2010) was supplied by Sun-Ten Pharmaceutical Company (New Taipei City, Taiwan). B401 contains six herbal ingredients, including extracts from Panax ginseng, Astragalus membranaceus, Angelica sinensis, Rehmannia glutinosa, Ligustri fructus, and Eclipta prostrata in specific ratios, and has been developed as a health supplement. High-performance liquid chromatography (HPLC) charts with different wavelengths in Figure 1Ai–Av show the six ingredients of B401. The charts include ginsenosides Rb1 (molecular formula: C54H92O23; molecular weight: 1,109.3 g/mol; extracts from P. ginseng), oleanolic acid (molecular formula: C30H48O3; molecular weight: 456.7 g/mol; extracts from L. fructus), formononetin (molecular formula: C16H12O4; molecular weight: 268.3 g/mol; extracts from A. membranaceus), 5-hydroxymethylfurfural (molecular formula: C6H6O3; molecular weight: 126.1 g/mol; extracts from R. glutinosa), ferulic acid (molecular formula: C10H10O4; molecular weight: 194.2 g/mol; extracts from L. fructus), and wedelolactone (molecular formula: C16H10O7; molecular weight: 314.3 g/mol; extracts from E. prostrata). HPLC-grade acetonitrile was purchased from Burdick & Jackson (Gyeonggi-do, Korea), along with methanol from Avantor (Center Valley, PA, USA). Water was purified by a Milli-Q water purification system (EMD Millipore, Billerica, MA, USA). All chemicals used were of analytical grade and solubilized in distilled H2O/MeOH. The half maximal inhibitory concentration (IC50) of the herbal formula B401 was evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay.


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)

Chromatographic fingerprint analysis and cell viability assay for the herbal formula B401.Notes: HPLC fingerprint of the herbal formula B401. Characteristic peaks of B401, ie, (Aa) ginsenosides Rb1 (from Panax ginseng) and oleanolic acid (from Ligustri fructus), (Ab) formononetin (from Astragalus membranaceus), (Ac) 5-HMF (from Rehmannia glutinosa), (Ad) ferulic acid (from L. fructus), (Ae) wedelolactone (from Eclipta prostrata), were identified and marked at the corresponding peaks in the fingerprint. (B) Cell viabilities of RA-induced SH-SY5Y cells in the absence (Ctrl) or presence of the B401 at indicated doses. The herbal formula B401 has no cytotoxicity in SH-SY5Y cells under treatment at a dose of less than 80 mg/mL.Abbreviations: AU, arbitrary unit; IC50, half maximal inhibitory concentration; 5-HMF, 5-hydroxymethylfurfural; RA, retinoic acid; Ctrl, control group.
© Copyright Policy
Related In: Results  -  Collection

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

f1-cia-10-1825: Chromatographic fingerprint analysis and cell viability assay for the herbal formula B401.Notes: HPLC fingerprint of the herbal formula B401. Characteristic peaks of B401, ie, (Aa) ginsenosides Rb1 (from Panax ginseng) and oleanolic acid (from Ligustri fructus), (Ab) formononetin (from Astragalus membranaceus), (Ac) 5-HMF (from Rehmannia glutinosa), (Ad) ferulic acid (from L. fructus), (Ae) wedelolactone (from Eclipta prostrata), were identified and marked at the corresponding peaks in the fingerprint. (B) Cell viabilities of RA-induced SH-SY5Y cells in the absence (Ctrl) or presence of the B401 at indicated doses. The herbal formula B401 has no cytotoxicity in SH-SY5Y cells under treatment at a dose of less than 80 mg/mL.Abbreviations: AU, arbitrary unit; IC50, half maximal inhibitory concentration; 5-HMF, 5-hydroxymethylfurfural; RA, retinoic acid; Ctrl, control group.
Mentions: The herbal formula B401 (US patent, No 7838048B2, November 23, 2010) was supplied by Sun-Ten Pharmaceutical Company (New Taipei City, Taiwan). B401 contains six herbal ingredients, including extracts from Panax ginseng, Astragalus membranaceus, Angelica sinensis, Rehmannia glutinosa, Ligustri fructus, and Eclipta prostrata in specific ratios, and has been developed as a health supplement. High-performance liquid chromatography (HPLC) charts with different wavelengths in Figure 1Ai–Av show the six ingredients of B401. The charts include ginsenosides Rb1 (molecular formula: C54H92O23; molecular weight: 1,109.3 g/mol; extracts from P. ginseng), oleanolic acid (molecular formula: C30H48O3; molecular weight: 456.7 g/mol; extracts from L. fructus), formononetin (molecular formula: C16H12O4; molecular weight: 268.3 g/mol; extracts from A. membranaceus), 5-hydroxymethylfurfural (molecular formula: C6H6O3; molecular weight: 126.1 g/mol; extracts from R. glutinosa), ferulic acid (molecular formula: C10H10O4; molecular weight: 194.2 g/mol; extracts from L. fructus), and wedelolactone (molecular formula: C16H10O7; molecular weight: 314.3 g/mol; extracts from E. prostrata). HPLC-grade acetonitrile was purchased from Burdick & Jackson (Gyeonggi-do, Korea), along with methanol from Avantor (Center Valley, PA, USA). Water was purified by a Milli-Q water purification system (EMD Millipore, Billerica, MA, USA). All chemicals used were of analytical grade and solubilized in distilled H2O/MeOH. The half maximal inhibitory concentration (IC50) of the herbal formula B401 was evaluated by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay.

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