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4-O-methylhonokiol attenuated memory impairment through modulation of oxidative damage of enzymes involving amyloid-β generation and accumulation in a mouse model of Alzheimer's disease.
J Alzheimers Dis. 2011; 27(1):127-41.JA

Abstract

Accumulations of amyloid-β (Aβ) and oxidative damage are critical pathological mechanisms in the development of Alzheimer's disease (AD). We previously found that 4-O-methylhonokiol, a compound extracted from Magnolia officinalis, improved memory dysfunction in Aβ-injected and presenilin 2 mutant mice through the reduction of accumulated Aβ. To investigate mechanisms of the reduced Aβ accumulation, we examined generation, degradation, efflux and aggregation of Aβ in Swedish AβPP AD model (AβPPsw) mice pre-treated with 4-O-methylhonokiol (1.0 mg/kg) for 3 months. 4-O-methylhonokiol treatment recovered memory impairment and prevented neuronal cell death. This memory improving activity was associated with 4-O-methylhonokiol-induced reduction of Aβ1-42 accumulation in the brains of AβPPsw mice. According to the reduction of Aβ1-42 accumulation, 4-O-methylhonkiol modulated oxidative damage sensitive enzymes. 4-O-methylhonkiol decreased expression and activity of brain beta-site AβPP cleaving enzyme (BACE1), but increased clearance of Aβ in the brain through an increase of expressions and activities of Aβ degradation enzymes; insulin degrading enzyme and neprilysin. 4-O-methylhonkiol also increased expression of Aβ transport molecule, low density lipoprotein receptor-related protein-1 in the brain and liver. 4-O-methylhonkiol decreased carbonyl protein and lipid peroxidation, but increased glutathione levels in the brains of AβPPsw mice suggesting that oxidative damage of protein and lipid is critical in the impairment of those enzyme activities. 4-O-methylhonokiol treatment also prevented neuronal cell death in the AβPPsw mousee brain through inactivation of caspase-3 and BAX. These results suggest that 4-O-methylhonokiol might prevent the development and progression of AD by reducing Aβ accumulation through an increase of clearance and decrease of Aβ generation via antioxidant mechanisms.

Authors+Show Affiliations

College of Pharmacy, Chungbuk National University, Heungduk-gu, Cheongju, Chungbuk, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21799245

Citation

Choi, Im Seop, et al. "4-O-methylhonokiol Attenuated Memory Impairment Through Modulation of Oxidative Damage of Enzymes Involving Amyloid-β Generation and Accumulation in a Mouse Model of Alzheimer's Disease." Journal of Alzheimer's Disease : JAD, vol. 27, no. 1, 2011, pp. 127-41.
Choi IS, Lee YJ, Choi DY, et al. 4-O-methylhonokiol attenuated memory impairment through modulation of oxidative damage of enzymes involving amyloid-β generation and accumulation in a mouse model of Alzheimer's disease. J Alzheimers Dis. 2011;27(1):127-41.
Choi, I. S., Lee, Y. J., Choi, D. Y., Lee, Y. K., Lee, Y. H., Kim, K. H., Kim, Y. H., Jeon, Y. H., Kim, E. H., Han, S. B., Jung, J. K., Yun, Y. P., Oh, K. W., Hwang, D. Y., & Hong, J. T. (2011). 4-O-methylhonokiol attenuated memory impairment through modulation of oxidative damage of enzymes involving amyloid-β generation and accumulation in a mouse model of Alzheimer's disease. Journal of Alzheimer's Disease : JAD, 27(1), 127-41. https://doi.org/10.3233/JAD-2011-110545
Choi IS, et al. 4-O-methylhonokiol Attenuated Memory Impairment Through Modulation of Oxidative Damage of Enzymes Involving Amyloid-β Generation and Accumulation in a Mouse Model of Alzheimer's Disease. J Alzheimers Dis. 2011;27(1):127-41. PubMed PMID: 21799245.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 4-O-methylhonokiol attenuated memory impairment through modulation of oxidative damage of enzymes involving amyloid-β generation and accumulation in a mouse model of Alzheimer's disease. AU - Choi,Im Seop, AU - Lee,Young-Jung, AU - Choi,Dong-Young, AU - Lee,Yong Kyung, AU - Lee,Yeun Hee, AU - Kim,Ki Ho, AU - Kim,Young Heui, AU - Jeon,Young Ho, AU - Kim,Eun Hee, AU - Han,Sang Bae, AU - Jung,Jae Kyung, AU - Yun,Yeo Pyo, AU - Oh,Ki-Wan, AU - Hwang,Dae Youn, AU - Hong,Jin Tae, PY - 2011/7/30/entrez PY - 2011/7/30/pubmed PY - 2012/3/1/medline SP - 127 EP - 41 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 27 IS - 1 N2 - Accumulations of amyloid-β (Aβ) and oxidative damage are critical pathological mechanisms in the development of Alzheimer's disease (AD). We previously found that 4-O-methylhonokiol, a compound extracted from Magnolia officinalis, improved memory dysfunction in Aβ-injected and presenilin 2 mutant mice through the reduction of accumulated Aβ. To investigate mechanisms of the reduced Aβ accumulation, we examined generation, degradation, efflux and aggregation of Aβ in Swedish AβPP AD model (AβPPsw) mice pre-treated with 4-O-methylhonokiol (1.0 mg/kg) for 3 months. 4-O-methylhonokiol treatment recovered memory impairment and prevented neuronal cell death. This memory improving activity was associated with 4-O-methylhonokiol-induced reduction of Aβ1-42 accumulation in the brains of AβPPsw mice. According to the reduction of Aβ1-42 accumulation, 4-O-methylhonkiol modulated oxidative damage sensitive enzymes. 4-O-methylhonkiol decreased expression and activity of brain beta-site AβPP cleaving enzyme (BACE1), but increased clearance of Aβ in the brain through an increase of expressions and activities of Aβ degradation enzymes; insulin degrading enzyme and neprilysin. 4-O-methylhonkiol also increased expression of Aβ transport molecule, low density lipoprotein receptor-related protein-1 in the brain and liver. 4-O-methylhonkiol decreased carbonyl protein and lipid peroxidation, but increased glutathione levels in the brains of AβPPsw mice suggesting that oxidative damage of protein and lipid is critical in the impairment of those enzyme activities. 4-O-methylhonokiol treatment also prevented neuronal cell death in the AβPPsw mousee brain through inactivation of caspase-3 and BAX. These results suggest that 4-O-methylhonokiol might prevent the development and progression of AD by reducing Aβ accumulation through an increase of clearance and decrease of Aβ generation via antioxidant mechanisms. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/21799245/4_O_methylhonokiol_attenuated_memory_impairment_through_modulation_of_oxidative_damage_of_enzymes_involving_amyloid_β_generation_and_accumulation_in_a_mouse_model_of_Alzheimer's_disease_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-2011-110545 DB - PRIME DP - Unbound Medicine ER -