title: Multifunction of Chrysin in Parkinson's Model: Anti-Neuronal Apoptosis, Neuroprotection via Activation of MEF2D, and Inhibition of Monoamine Oxidase-B.
abstract: Chrysin, a flavonoid compound existing in several plants, is applied as a dietary supplement because of its beneficial effects on general human health and alleviation of neurological disorders. However, mechanisms underlying neuroprotection of chrysin has not been fully elucidated, and the effects of chrysin on the Parkinson's disease (PD) model in vivo have not been investigated. It is here shown that chrysin protects primary granular neurons against 1-methyl-4-phenylpyridinium ion insult via antiapoptosis by reversing the dysregulated expression of Bcl-2, Bax, and caspase 3. The mechanisms also involved activating transcriptional factor myocyte enhancer factor 2D (MEF2D) via regulation of AKT-GSK3β signaling. In this in vivo model of PD, chrysin rescued the dopaminergic neurons loss and alleviated the decrease in dopamine level induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine in mice. Moreover, chrysin markedly inhibited monoamine oxidase-B activity in vitro and in vivo. In conclusion, chrysin exerts beneficial effects to PD, possibly through multitarget mechanisms including antineuronal apoptosis, activation of the AKT-GSK3β/MEF2D pathway, and inhibition of the MAO-B activity.
authors.affiliation: Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University College of Pharmacy , Guangzhou, 510632 China.
authors.forename: Baojian
authors.initials: B
authors.lastname: Guo
authors.affiliation: Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University College of Pharmacy , Guangzhou, 510632 China.
authors.forename: Chengyou
authors.initials: C
authors.lastname: Zheng
authors.affiliation: Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University College of Pharmacy , Guangzhou, 510632 China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
authors.affiliation: Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University College of Pharmacy , Guangzhou, 510632 China.
authors.forename: Jiehong
authors.initials: J
authors.lastname: Cheng
authors.affiliation: Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University College of Pharmacy , Guangzhou, 510632 China.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Quality Research of Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau , Taipa, Macao, China.
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.affiliation: Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University College of Pharmacy , Guangzhou, 510632 China.
authors.forename: Yewei
authors.initials: Y
authors.lastname: Sun
authors.affiliation: School of Medicine, Ningbo University , Zhejiang, 315211 China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.affiliation: Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University College of Pharmacy , Guangzhou, 510632 China.
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Applied Biology and Chemical Technology, Institute of Modern Chinese Medicine, The Hong Kong Polytechnic University , Hung Hom, Hong Kong, China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Han
authors.affiliation: State Key Laboratory of Quality Research of Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau , Taipa, Macao, China.
authors.forename: Simon Ming-Yuen
authors.initials: SM
authors.lastname: Lee
authors.affiliation: Institute of New Drug Research and Guangzhou Key Laboratory of Innovative Chemical Drug Research in Cardio-cerebrovascular Diseases, Jinan University College of Pharmacy , Guangzhou, 510632 China.
authors.forename: Zaijun
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005419:Flavonoids / Q000008:administration & dosage*; D006801:Humans; D064326:MEF2 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D005419:Flavonoids; D064326:MEF2 Transcription Factors; C043561:chrysin; D008995:Monoamine Oxidase
keywords: MAO-B; MEF2D; Parkinson’s disease; chrysin; neuroprotection