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

• DOI: 10.1021/acs.jproteome.6b00152
• Publication Date: 2016-06-01T07:09:18Z
• Authors: Guohui Li; Zaijun Zhang; Quan Quan; Renwang Jiang; Samuel S.W. Szeto; Shuai Yuan; Wing-tak Wong; Herman H. C. Lam; Simon Ming-Yuen Lee; Ivan K. Chu
• Keywords: Alpinia; Natural product

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