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Amentoflavone protects dopaminergic neurons in MPTP-induced Parkinson's disease model mice through PI3K/Akt and ERK signaling pathways.
Toxicol Appl Pharmacol. 2017 03 15; 319:80-90.TA

Abstract

Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc). Mitochondrial dysfunction and cell apoptosis are suggested to be actively involved in the pathogenesis of PD. In the present study, the neuroprotective effect of amentoflavone (AF), a naturally occurring biflavonoid from Selaginella tamariscina, was examined in PD models both in vitro and in vivo. On SH-SY5Y cells, AF treatment dose-dependently reduced 1-methyl-4-phenylpyridinium (MPP+)-induced nuclear condensation and loss of cell viability without obvious cytotoxicity. It inhibited the activation of caspase-3 and p21 but increased the Bcl-2/Bax ratio. Further study disclosed that AF enhanced the phosphorylation of PI3K, Akt and ERK1/2 down-regulated by MPP+ in SH-SY5Y cells, the effect of which could be blocked by LY294002, the inhibitor of PI3K. Consistently, AF alleviated the behavioral deterioration in pole and traction tests and rescued the loss of dopaminergic neurons in SNpc and fibers in striatum in methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced mice. It also could enhance the activation of PI3K and Akt as well as Bcl-2/Bax ratio in SN. Moreover, AF alleviated gliosis as well as the gene expression levels of IL-1β and iNOS in SN. Collectively, these results suggested that AF protected dopaminergic neurons against MPTP/MPP+-induced neurotoxicity, which might be mediated through activation of PI3K/Akt and ERK signaling pathways in dopaminergic neurons and attenuation of neuroinflammation.

Authors+Show Affiliations

The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Complex Prescriptions, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, China.The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Complex Prescriptions, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, China.The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Complex Prescriptions, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, China. Electronic address: Fei_H@hotmail.com.The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Complex Prescriptions, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, China.The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Complex Prescriptions, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, China.The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Complex Prescriptions, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, China.The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Complex Prescriptions, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, China.The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Complex Prescriptions, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, China.The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Complex Prescriptions, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, China.The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Complex Prescriptions, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, China. Electronic address: xiaojunwu320@126.com.

Pub Type(s)

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

Language

eng

PubMed ID

28185818

Citation

Cao, Qin, et al. "Amentoflavone Protects Dopaminergic Neurons in MPTP-induced Parkinson's Disease Model Mice Through PI3K/Akt and ERK Signaling Pathways." Toxicology and Applied Pharmacology, vol. 319, 2017, pp. 80-90.
Cao Q, Qin L, Huang F, et al. Amentoflavone protects dopaminergic neurons in MPTP-induced Parkinson's disease model mice through PI3K/Akt and ERK signaling pathways. Toxicol Appl Pharmacol. 2017;319:80-90.
Cao, Q., Qin, L., Huang, F., Wang, X., Yang, L., Shi, H., Wu, H., Zhang, B., Chen, Z., & Wu, X. (2017). Amentoflavone protects dopaminergic neurons in MPTP-induced Parkinson's disease model mice through PI3K/Akt and ERK signaling pathways. Toxicology and Applied Pharmacology, 319, 80-90. https://doi.org/10.1016/j.taap.2017.01.019
Cao Q, et al. Amentoflavone Protects Dopaminergic Neurons in MPTP-induced Parkinson's Disease Model Mice Through PI3K/Akt and ERK Signaling Pathways. Toxicol Appl Pharmacol. 2017 03 15;319:80-90. PubMed PMID: 28185818.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Amentoflavone protects dopaminergic neurons in MPTP-induced Parkinson's disease model mice through PI3K/Akt and ERK signaling pathways. AU - Cao,Qin, AU - Qin,Liyue, AU - Huang,Fei, AU - Wang,Xiaoshuang, AU - Yang,Liu, AU - Shi,Hailian, AU - Wu,Hui, AU - Zhang,Beibei, AU - Chen,Ziyu, AU - Wu,Xiaojun, Y1 - 2017/02/07/ PY - 2016/07/05/received PY - 2017/01/23/revised PY - 2017/01/27/accepted PY - 2017/2/12/pubmed PY - 2017/6/1/medline PY - 2017/2/11/entrez KW - 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) KW - Amentoflavone KW - Flavonoids KW - Neuroinflammation KW - Parkinson's disease SP - 80 EP - 90 JF - Toxicology and applied pharmacology JO - Toxicol Appl Pharmacol VL - 319 N2 - Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc). Mitochondrial dysfunction and cell apoptosis are suggested to be actively involved in the pathogenesis of PD. In the present study, the neuroprotective effect of amentoflavone (AF), a naturally occurring biflavonoid from Selaginella tamariscina, was examined in PD models both in vitro and in vivo. On SH-SY5Y cells, AF treatment dose-dependently reduced 1-methyl-4-phenylpyridinium (MPP+)-induced nuclear condensation and loss of cell viability without obvious cytotoxicity. It inhibited the activation of caspase-3 and p21 but increased the Bcl-2/Bax ratio. Further study disclosed that AF enhanced the phosphorylation of PI3K, Akt and ERK1/2 down-regulated by MPP+ in SH-SY5Y cells, the effect of which could be blocked by LY294002, the inhibitor of PI3K. Consistently, AF alleviated the behavioral deterioration in pole and traction tests and rescued the loss of dopaminergic neurons in SNpc and fibers in striatum in methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced mice. It also could enhance the activation of PI3K and Akt as well as Bcl-2/Bax ratio in SN. Moreover, AF alleviated gliosis as well as the gene expression levels of IL-1β and iNOS in SN. Collectively, these results suggested that AF protected dopaminergic neurons against MPTP/MPP+-induced neurotoxicity, which might be mediated through activation of PI3K/Akt and ERK signaling pathways in dopaminergic neurons and attenuation of neuroinflammation. SN - 1096-0333 UR - https://www.unboundmedicine.com/medline/citation/28185818/Amentoflavone_protects_dopaminergic_neurons_in_MPTP_induced_Parkinson's_disease_model_mice_through_PI3K/Akt_and_ERK_signaling_pathways_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(17)30046-7 DB - PRIME DP - Unbound Medicine ER -