Structure-activity relationship analysis of antioxidant ability and neuroprotective effect of gallic acid derivatives.
Gallic acid and its derivatives are a group of naturally occurring polyphenol antioxidants which have recently been shown to have potential healthy effects. In order to understand the relationship between the structures of gallic acid derivatives, their antioxidant activities, and neuroprotective effects, we examined their free radical scavenging effects in liposome and anti-apoptotic activities in human SH-SY5Y cell induced by 6-hydrodopamine autooxidation. It was found that these polyphenol antioxidants exhibited different hydrophobicity and could cross through the liposome membrane to react with 1,1-diphenyl-2-picryl-hydrazyl (DPPH) free radical in a time and dose-dependent manner. At the same time, the structure-antioxidant activity relationship of gallic acid derivatives on scavenging DPPH free radical in the liposome was also analyzed based on theoretical investigations. Analysis of cell apoptosis, intracellular GSH levels, production of ROS and the influx of Ca(2+) indicated that the protective effects of gallic acid derivatives in cell systems under oxidative stress depend on both their antioxidant capacities and hydrophobicity. However, the neuroprotective effects of gallic acid derivatives seem to depend more on their molecular polarities rather than antioxidant activities in the human SH-SY5Y cell line. In conclusion, these results reveal that compounds with high antioxidant activity and appropriate hydrophobicity are generally more effective in preventing the injury of oxidative stress in neurodegenerative diseases.
Lu
Zhongbing
Z
State Key Laboratory of Brain and Recognition Laboratory, Institute of Biophysics, The Chinese Academy of Sciences, Beijing 100101, PR China.
Nie
Guangjun
G
Belton
Peter S
PS
Tang
Huiru
H
Zhao
Baolu
B
D000975:Antioxidants / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004563:Electrochemistry; D004578:Electron Spin Resonance Spectroscopy; D016166:Free Radical Scavengers / Q000737:chemistry / Q000494:pharmacology; D005707:Gallic Acid / Q000737:chemistry* / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D018696:Neuroprotective Agents / Q000737:chemistry* / Q000494:pharmacology*; D016627:Oxidopamine / Q000037:antagonists & inhibitors; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship
D000975:Antioxidants; D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D005707:Gallic Acid; D016627:Oxidopamine; D005978:Glutathione