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Neuroprotective Effects of Baicalein on Acrolein-induced Neurotoxicity in the Nigrostriatal Dopaminergic System of Rat Brain

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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 and Affiliations

  1. Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan

    Wei-Zhong Zhao, Hsiang-Tsui Wang, Yu-Li Lo & Anya Maan-Yuh Lin

  2. Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan

    Hui-Ju Huang & Anya Maan-Yuh Lin

  3. Faculty of Pharmacy, National Yang-Ming University, Taipei, Taiwan

    Anya Maan-Yuh Lin

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  1. Wei-Zhong Zhao
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  2. Hsiang-Tsui Wang
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  3. Hui-Ju Huang
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  4. Yu-Li Lo
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  5. Anya Maan-Yuh Lin
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Correspondence to Yu-Li Lo or Anya Maan-Yuh Lin.

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The use of animals has been approved by the Institutional Animal Care and Use Committee of Taipei Veterans General Hospital, Taipei, Taiwan, R.O.C. All experiments were performed in accordance with the approved guidelines. The approval number is IACUC2014-186.

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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 55, 130–137 (2018). https://doi.org/10.1007/s12035-017-0725-x

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