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Discovery, synthesis, and functional characterization of a novel neuroprotective natural product from the fruit of alpinia oxyphylla for use in Parkinson's disease through LC/MS-based multivariate data analysis-guided fractionation
Guohui Li1,2; Zaijun Zhang2,3; Quan Quan1; Renwang Jiang4; Samuel S.W. Szeto1; Shuai Yuan2; Wing-tak Wong5; Herman H. C. Lam1; Simon Ming-Yuen Lee2; Ivan K. Chu1
2016-08-05
Source PublicationJournal of Proteome Research
ISSN15353907 15353893
Volume15Issue:8Pages:2595-2606
Abstract

Herein we report the discovery of a novel lead compound, oxyphylla A [(R)-4-(2-hydroxy-5-methylphenyl)-5-methylhexanoic acid] (from the fruit of Alpinia oxyphylla), which functions as a neuroprotective agent against Parkinson's disease. To identify a shortlist of candidates from the extract of A. oxyphylla, we employed an integrated strategy combining liquid chromatography/mass spectrometry, bioactivity-guided fractionation, and chemometric analysis. The neuroprotective effects of the shortlisted candidates were validated prior to scaling up the finalized list of potential neuroprotective constituents for more detailed chemical and biological characterization. Oxyphylla A has promising neuroprotective effects: (i) it ameliorates in vitro chemical-induced primary neuronal cell damage and (ii) alleviates chemical-induced dopaminergic neuron loss and behavioral impairment in both zebrafish and mice in vivo. Quantitative proteomics analyses of oxyphylla A-treated primary cerebellar granule neurons that had been intoxicated with 1-methyl-4-phenylpyridinium revealed that oxyphylla A activates nuclear factor-erythroid 2-related factor 2 (NRF2) - a master redox switch - and triggers a cascade of antioxidative responses. These observations were verified independently through western blot analyses. Our integrated metabolomics, chemometrics, and pharmacological strategy led to the efficient discovery of novel bioactive ingredients from A. oxyphylla while avoiding the nontargeting, labor-intensive steps usually required for identification of bioactive compounds. Our successful development of a synthetic route toward oxyphylla A should lead to its availability on a large scale for further functional development and pathological studies.

KeywordNatural Products Neuroprotective Nrf2 Parkinson's Disease Proteomics
DOI10.1021/acs.jproteome.6b00152
URLView the original
Indexed BySCIE
Language英语
WOS Research AreaBiochemistry & Molecular Biology
WOS SubjectBiochemical Research Methods
WOS IDWOS:000381235900022
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Cited Times [WOS]:16   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorSimon Ming-Yuen Lee; Ivan K. Chu
Affiliation1.Department of Chemistry, The University of Hong Kong, Hong Kong, China
2.State Key Laboratory of Quality Research in Chinese Medicine and Institute of Chinese Medical Sciences, University of Macau, Avenue Padre Tomás Pereira S.J., Taipa, Macao, China
3.Institute of New Drug Research, Guangdong Province Key Laboratory of Pharmacodynamic, Constituents of Traditional Chinese Medicine & New Drug Research, College of Pharmacy, Jinan University, Guangdong, China
4.Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, P. R. China
5.Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, China
First Author AffilicationInstitute of Chinese Medical Sciences
Corresponding Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Guohui Li,Zaijun Zhang,Quan Quan,et al. Discovery, synthesis, and functional characterization of a novel neuroprotective natural product from the fruit of alpinia oxyphylla for use in Parkinson's disease through LC/MS-based multivariate data analysis-guided fractionation[J]. Journal of Proteome Research,2016,15(8):2595-2606.
APA Guohui Li.,Zaijun Zhang.,Quan Quan.,Renwang Jiang.,Samuel S.W. Szeto.,...&Ivan K. Chu.(2016).Discovery, synthesis, and functional characterization of a novel neuroprotective natural product from the fruit of alpinia oxyphylla for use in Parkinson's disease through LC/MS-based multivariate data analysis-guided fractionation.Journal of Proteome Research,15(8),2595-2606.
MLA Guohui Li,et al."Discovery, synthesis, and functional characterization of a novel neuroprotective natural product from the fruit of alpinia oxyphylla for use in Parkinson's disease through LC/MS-based multivariate data analysis-guided fractionation".Journal of Proteome Research 15.8(2016):2595-2606.
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