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Examining the neuroprotective effects of protocatechuic acid and chrysin on in vitro and in vivo models of Parkinson disease
Zhang Z.2,3; Li G.1; Szeto S.S.W.1; Chong C.M.3; Quan Q.1; Huang C.3; Cui W.4; Guo B.2; Wang Y.2; Han Y.4; Michael Siu K.W.5; Yuen Lee S.M.3; Chu I.K.1
2015
Source PublicationFree Radical Biology and Medicine
ISSN8915849
Volume84Pages:331
Abstract

Polypharmacology-based strategies using drug combinations with different mechanisms of action are gaining increasing attention as a novel methodology to discover potentially innovative medicines for neurodegenerative disorders. We used this approach to examine the combined neuroprotective effects of two polyphenols, protocatechuic acid (PCA) and chrysin, identified from the fruits of Alpinia oxyphylla. Our results demonstrated synergistic neuroprotective effects, with chrysin enhancing the protective effects of PCA, resulting in greater cell viability and decreased lactate dehydrogenase release from 6-hydroxydopamine-treated PC12 cells. Their combination also significantly attenuated chemically induced dopaminergic neuron loss in both zebrafish and mice. We examined the molecular mechanisms underlying these collective cytoprotective effects through proteomic analysis of treated PC12 cells, resulting in the identification of 12 regulated proteins. Two were further characterized, leading to the determination that pretreatment with PCA and chrysin resulted in (i) increased nuclear factor-erythroid 2-related factor 2 protein expression and transcriptional activity; (ii) modulation of cellular redox status with the upregulated expression of hallmark antioxidant enzymes, including heme oxygenase-1, superoxide dismutase, and catalase; and (iii) decreased levels of malondialdehyde, a known lipid peroxidation product. Treatment with PCA and chrysin also inhibited activation of nuclear factor-κB and expression of inducible nitric oxide synthase. Our findings suggest that natural products, when used in combination, can be effective potential therapeutic agents for treating diseases such as Parkinson disease. A therapy involving both PCA and chrysin exhibits its enhanced neuroprotective effects through a combination of cellular mechanisms: antioxidant cytoprotection and anti-inflammation. © 2015 Elsevier Inc. All rights reserved.

KeywordAnti-inflammation Freeradicals Neuroprotection Nrf2 Nf-κb Parkinsondisease Proteomics
DOI10.1016/j.freeradbiomed.2015.02.030
URLView the original
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS SubjectBiochemistry & Molecular Biology ; Endocrinology & Metabolism
WOS IDWOS:000355896500030
The Source to ArticleScopus
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Cited Times [WOS]:61   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorYuen Lee S.M.; Chu I.K.
Affiliation1.Department of Chemistry, The University of Hong Kong, Hong Kong, China
2.Institute of New Drug Research and Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine, College of Pharmacy, Jinan University, Guangdong, China
3.State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Taipa, Macao, China
4.Department of Applied Biology and Chemical Technology, Institute of Modern Medicine, The Hong Kong Polytechnic University, Hong Kong, China
5.Department of Chemistry and Biochemistry, University of Windsor, Windsor, ON, Canada
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Zhang Z.,Li G.,Szeto S.S.W.,et al. Examining the neuroprotective effects of protocatechuic acid and chrysin on in vitro and in vivo models of Parkinson disease[J]. Free Radical Biology and Medicine,2015,84:331.
APA Zhang Z..,Li G..,Szeto S.S.W..,Chong C.M..,Quan Q..,...&Chu I.K..(2015).Examining the neuroprotective effects of protocatechuic acid and chrysin on in vitro and in vivo models of Parkinson disease.Free Radical Biology and Medicine,84,331.
MLA Zhang Z.,et al."Examining the neuroprotective effects of protocatechuic acid and chrysin on in vitro and in vivo models of Parkinson disease".Free Radical Biology and Medicine 84(2015):331.
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