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Neuroprotective Effects of Baicalein on Acrolein-induced Neurotoxicity in the Nigrostriatal Dopaminergic System of Rat Brain.
Mol Neurobiol. 2018 01; 55(1):130-137.MN

Abstract

Elevated levels of acrolein, an α,β-unsaturated aldehyde are detected in the brain of patients with Parkinson's disease (PD). In the present study, the neuroprotective effect of baicalein (a phenolic flavonoid in the dried root of Scutellaria baicalensis Georgi) on acrolein-induced neurodegeneration of nigrostriatal dopaminergic system was investigated using local infusion of acrolein in the substantia nigra (SN) of rat brain. Systemic administration of baicalein (30 mg/kg, i.p.) significantly attenuated acrolein-induced elevations in 4-hydroxy-2-noneal (a product of lipid peroxidation), N-(3-formyl-3,4-dehydropiperidino)lysine (a biomarker of acrolein-conjugated proteins), and heme-oxygenase-1 levels (a redox-regulated protein) in the infused SN, indicating that baicalein inhibited acrolein-induced oxidative stress and protein conjugation. Furthermore, baicalein reduced acrolein-induced elevations in glial fibrillary acidic protein (a biomarker of activated astrocytes), ED-1 (a biomarker of activated microglia), and mature cathepsin B levels (a cysteine lysosomal protease), suggesting that baicalein attenuated acrolein-induced neuroinflammation. Moreover, baicalein attenuated acrolein-induced caspase 1 activation (a pro-inflammatory caspase) and interleukin-1β levels, indicating that baicalein prevented acrolein-induced inflammasome activation. In addition, baicalein significantly attenuated acrolein-induced caspase 3 activation (a biomarker of apoptosis) as well as acrolein-induced elevation in receptor interacting protein kinase (RIPK) 3 levels (an initiator of necroptosis), indicating that baicalein attenuated apoptosis and necroptosis. At the same time, baicalein mitigated acrolein-induced reduction in dopamine levels in the striatum ipsilateral to acrolein-infused SN. In conclusion, our data suggest that baicalein is neuroprotective via inhibiting oxidative stress, protein conjugation, and inflammation. Furthermore, baicalein prevents acrolein-induced program cell deaths, suggesting that baicalein is therapeutically useful for slowing PD progression.

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Authors+Show Affiliations

Zhao WZ
Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
Wang HT
Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan.
Huang HJ
Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan.
Lo YL
Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan. yulilo@ym.edu.tw.
Lin AM
Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan. myelin@ym.edu.tw. Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan. myelin@ym.edu.tw. Faculty of Pharmacy, National Yang-Ming University, Taipei, Taiwan. myelin@ym.edu.tw.

MeSH

AcroleinAnimalsAntioxidantsCorpus StriatumDopaminergic NeuronsFlavanonesMaleNeuroprotective AgentsRatsRats, Sprague-DawleySubstantia Nigra

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28866823

Citation

Zhao, Wei-Zhong, et al. "Neuroprotective Effects of Baicalein On Acrolein-induced Neurotoxicity in the Nigrostriatal Dopaminergic System of Rat Brain." Molecular Neurobiology, vol. 55, no. 1, 2018, pp. 130-137.
Zhao WZ, Wang HT, Huang HJ, et al. Neuroprotective Effects of Baicalein on Acrolein-induced Neurotoxicity in the Nigrostriatal Dopaminergic System of Rat Brain. Mol Neurobiol. 2018;55(1):130-137.
Zhao, W. Z., Wang, H. T., Huang, H. J., Lo, Y. L., & Lin, A. M. (2018). Neuroprotective Effects of Baicalein on Acrolein-induced Neurotoxicity in the Nigrostriatal Dopaminergic System of Rat Brain. Molecular Neurobiology, 55(1), 130-137. https://doi.org/10.1007/s12035-017-0725-x
Zhao WZ, et al. Neuroprotective Effects of Baicalein On Acrolein-induced Neurotoxicity in the Nigrostriatal Dopaminergic System of Rat Brain. Mol Neurobiol. 2018;55(1):130-137. PubMed PMID: 28866823.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Neuroprotective Effects of Baicalein on Acrolein-induced Neurotoxicity in the Nigrostriatal Dopaminergic System of Rat Brain. AU - Zhao,Wei-Zhong, AU - Wang,Hsiang-Tsui, AU - Huang,Hui-Ju, AU - Lo,Yu-Li, AU - Lin,Anya Maan-Yuh, PY - 2017/9/4/pubmed PY - 2019/5/9/medline PY - 2017/9/4/entrez KW - Acrolein KW - Baicalein KW - Inflammasome formation KW - Necroptosis KW - Neurotoxicity SP - 130 EP - 137 JF - Molecular neurobiology JO - Mol Neurobiol VL - 55 IS - 1 N2 - Elevated levels of acrolein, an α,β-unsaturated aldehyde are detected in the brain of patients with Parkinson's disease (PD). In the present study, the neuroprotective effect of baicalein (a phenolic flavonoid in the dried root of Scutellaria baicalensis Georgi) on acrolein-induced neurodegeneration of nigrostriatal dopaminergic system was investigated using local infusion of acrolein in the substantia nigra (SN) of rat brain. Systemic administration of baicalein (30 mg/kg, i.p.) significantly attenuated acrolein-induced elevations in 4-hydroxy-2-noneal (a product of lipid peroxidation), N-(3-formyl-3,4-dehydropiperidino)lysine (a biomarker of acrolein-conjugated proteins), and heme-oxygenase-1 levels (a redox-regulated protein) in the infused SN, indicating that baicalein inhibited acrolein-induced oxidative stress and protein conjugation. Furthermore, baicalein reduced acrolein-induced elevations in glial fibrillary acidic protein (a biomarker of activated astrocytes), ED-1 (a biomarker of activated microglia), and mature cathepsin B levels (a cysteine lysosomal protease), suggesting that baicalein attenuated acrolein-induced neuroinflammation. Moreover, baicalein attenuated acrolein-induced caspase 1 activation (a pro-inflammatory caspase) and interleukin-1β levels, indicating that baicalein prevented acrolein-induced inflammasome activation. In addition, baicalein significantly attenuated acrolein-induced caspase 3 activation (a biomarker of apoptosis) as well as acrolein-induced elevation in receptor interacting protein kinase (RIPK) 3 levels (an initiator of necroptosis), indicating that baicalein attenuated apoptosis and necroptosis. At the same time, baicalein mitigated acrolein-induced reduction in dopamine levels in the striatum ipsilateral to acrolein-infused SN. In conclusion, our data suggest that baicalein is neuroprotective via inhibiting oxidative stress, protein conjugation, and inflammation. Furthermore, baicalein prevents acrolein-induced program cell deaths, suggesting that baicalein is therapeutically useful for slowing PD progression. SN - 1559-1182 UR - https://www.unboundmedicine.com/medline/citation/28866823/Neuroprotective_Effects_of_Baicalein_on_Acrolein_induced_Neurotoxicity_in_the_Nigrostriatal_Dopaminergic_System_of_Rat_Brain_ L2 - https://dx.doi.org/10.1007/s12035-017-0725-x DB - PRIME DP - Unbound Medicine ER -