Reversing ROS-mediated neurotoxicity by chlorogenic acid involves its direct antioxidant activity and activation of Nrf2-ARE signaling pathway.

Abstract

Chlorogenic acid (CA), the ester of caffeic acid and quinic acid, is one of the most abundant polyphenols in coffee, and has multiple pharmacological functions. The present study is designed to explore the protection provided by CA against hydrogen peroxide (H2 O2 )-induced oxidative damages in the rat pheochromocytoma cells, and the underlying mechanisms engaged in this process. CA displays robust free radical-scavenging activity in vitro. More importantly, CA strikingly rescues the cells from the H2 O2 -mediated oxidative insults. Mechanistic studies revealed that CA upregulates a panel of phase II cytoprotective species, such as heme oxygenase-1, NAD(P)H: quinone oxidoreductase 1, glutathione, thioredoxin reductase 1, and thioredoxin 1. This neuroprotection is dependent on the activation of the transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2), as knockdown of Nrf2 abolishes such effect. Our results demonstrate that CA provides dual neuroprotection via directly neutralizing free radicals and indirectly inducing expression of Nrf2-driven cytoprotective enzymes, and suggest a potential therapeutic usage of CA as a neuroprotective agent. Coffee is one of the most popular drinks in the world, and our discovery may also contribute to understanding the beneficial effects of regular coffee consumption. © 2019 BioFactors, 45 (4):616-626, 2019.

• Authors: Juan Yao, Shoujiao Peng, Jianqiang Xu, Jianguo Fang
• Journal: BioFactors (Oxford, England) (Biofactors) Vol. 45 Issue 4 Pg. 616-626 (Jul 2019) ISSN: 1872-8081 [Electronic] Netherlands
• PMID: 30951611 (Publication Type: Journal Article)
• Copyright: © 2019 International Union of Biochemistry and Molecular Biology.

Chemical References

• Antioxidants
• Benzothiazoles
• Biphenyl Compounds
• NF-E2-Related Factor 2
• Neuroprotective Agents
• Nfe2l2 protein, rat
• Picrates
• RNA, Small Interfering
• Reactive Oxygen Species
• Sulfonic Acids
• Txn1 protein, rat
• 2,2'-azino-di-(3-ethylbenzothiazoline)-6-sulfonic acid
• Chlorogenic Acid
• Thioredoxins
• Hydrogen Peroxide
• 1,1-diphenyl-2-picrylhydrazyl
• Heme Oxygenase (Decyclizing)
• Hmox1 protein, rat
• NAD(P)H Dehydrogenase (Quinone)
• NQO1 protein, rat
• Thioredoxin Reductase 1
• Txnrd1 protein, rat
• Glutathione

Topics

• Animals
• Antioxidant Response Elements (drug effects)
• Antioxidants (pharmacology)
• Benzothiazoles (antagonists & inhibitors)
• Biphenyl Compounds (antagonists & inhibitors)
• Cell Differentiation (drug effects)
• Chlorogenic Acid (pharmacology)
• Gene Expression Regulation
• Glutathione (agonists, metabolism)
• Heme Oxygenase (Decyclizing) (genetics, metabolism)
• Hydrogen Peroxide (antagonists & inhibitors, pharmacology)
• NAD(P)H Dehydrogenase (Quinone) (genetics, metabolism)
• NF-E2-Related Factor 2 (antagonists & inhibitors, genetics, metabolism)
• Neurons (cytology, drug effects, metabolism)
• Neuroprotective Agents (pharmacology)
• Oxidative Stress (drug effects)
• PC12 Cells
• Picrates (antagonists & inhibitors)
• RNA, Small Interfering (genetics, metabolism)
• Rats
• Reactive Oxygen Species (antagonists & inhibitors, metabolism)
• Signal Transduction
• Sulfonic Acids (antagonists & inhibitors)
• Thioredoxin Reductase 1 (genetics, metabolism)
• Thioredoxins (genetics, metabolism)