title: Neuroprotection comparison of chlorogenic acid and its metabolites against mechanistically distinct cell death-inducing agents in cultured cerebellar granule neurons.
abstract: While the number of patients diagnosed with neurodegenerative disorders like Alzheimer's disease, amyotrophic lateral sclerosis, and Parkinson's disease is increasing, there are currently no effective treatments that significantly limit the neuronal cell death underlying these diseases. Chlorogenic acid (CGA), a polyphenolic compound found in high concentration in coffee, is known to possess antioxidant and free radical scavenging activity. In this study, we investigated the neuroprotective effects of CGA and its major metabolites in primary cultures of rat cerebellar granule neurons. We show that CGA and caffeic acid displayed a dramatic protective effect against the nitric oxide donor, sodium nitroprusside. In marked contrast, ferulic acid and quinic acid had no protective effect against this nitrosative stress. While CGA and quinic acid had no protective effect against glutamate-induced cell death, caffeic acid and ferulic acid significantly protected neurons from excitotoxicity. Finally, caffeic acid was the only compound to display significant protective activity against hydrogen peroxide, proteasome inhibition, caspase-dependent intrinsic apoptosis, and endoplasmic reticulum stress. These results indicate that caffeic acid displays a much broader profile of neuroprotection against a diverse range of stressors than its parent polyphenol, CGA, or the other major metabolites, ferulic acid and quinic acid. We conclude that caffeic acid is a promising candidate for testing in pre-clinical models of neurodegeneration.
authors.affiliation: Department of Biological Sciences, University of Denver, Denver, CO, USA. Electronic address: faten.taram@du.edu.
authors.forename: Faten
authors.initials: F
authors.lastname: Taram
authors.affiliation: Department of Biological Sciences, University of Denver, Denver, CO, USA. Electronic address: aimee.winter@du.edu.
authors.forename: Aimee N
authors.initials: AN
authors.lastname: Winter
authors.affiliation: Department of Biological Sciences, University of Denver, Denver, CO, USA; Eleanor Roosevelt Institute, University of Denver, Denver, CO, USA; Knoebel Institute for Healthy Aging, University of Denver, Denver, CO, USA. Electronic address: daniel.linseman@du.edu.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Linseman
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002109:Caffeic Acids / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D002726:Chlorogenic Acid / Q000627:therapeutic use*; D003069:Coffee / Q000378:metabolism; D003373:Coumaric Acids / Q000378:metabolism / Q000627:therapeutic use; D003594:Cytoplasmic Granules / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D066128:Gray Matter / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D000066829:Neuroprotection / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology; D009599:Nitroprusside; D010300:Parkinson Disease / Q000378:metabolism; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000975:Antioxidants; D002109:Caffeic Acids; D003069:Coffee; D003373:Coumaric Acids; D018696:Neuroprotective Agents; D009599:Nitroprusside; D002726:Chlorogenic Acid; D018698:Glutamic Acid; C004999:ferulic acid; D006861:Hydrogen Peroxide; C040048:caffeic acid
keywords: Apoptosis; Caffeic acid; Excitotoxicity; Neuroprotection; Nitrosative stress; Oxidative stress