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Neuroprotection Comparison of Rosmarinic Acid and Carnosic Acid in Primary Cultures of Cerebellar Granule Neurons

1
Department of Biological Sciences, University of Denver, 2199 S. University Blvd., Denver, CO 80208, USA
2
Knoebel Institute for Healthy Aging, University of Denver, 2155 E. Wesley Ave., Denver, CO 80208, USA
*
Author to whom correspondence should be addressed.
These authors contributed equally to this paper.
Molecules 2018, 23(11), 2956; https://doi.org/10.3390/molecules23112956
Received: 31 August 2018 / Revised: 1 November 2018 / Accepted: 7 November 2018 / Published: 13 November 2018
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Abstract

Neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), Alzheimer’s disease, and Parkinson’s disease, are characterized by the progressive loss of neurons in specific regions of the brain and/or spinal cord. Neuronal cell loss typically occurs by either apoptotic or necrotic mechanisms. Oxidative stress and nitrosative stress, along with excitotoxicity and caspase activation, have all been implicated as major underlying causes of neuronal cell death. Diverse nutraceuticals (bioactive compounds found in common foods) have been shown to have neuroprotective effects in a variety of in vitro and in vivo disease models. In the current study, we compared the neuroprotective effects of two polyphenolic compounds, rosmarinic acid and carnosic acid, which are both found at substantial concentrations in the herb rosemary. The capacity of these compounds to rescue primary cultures of rat cerebellar granule neurons (CGNs) from a variety of stressors was investigated. Both polyphenols significantly reduced CGN death induced by the nitric oxide donor, sodium nitroprusside (nitrosative stress). Rosmarinic acid uniquely protected CGNs from glutamate-induced excitotoxicity, while only carnosic acid rescued CGNs from caspase-dependent apoptosis induced by removal of depolarizing extracellular potassium (5K apoptotic condition). Finally, we found that carnosic acid protects CGNs from 5K-induced apoptosis by activating a phosphatidylinositol 3-kinase (PI3K) pro-survival pathway. The shared and unique neuroprotective effects of these two compounds against diverse modes of neuronal cell death suggest that future preclinical studies should explore the potential complementary effects of these rosemary polyphenols on neurodegenerative disease progression. View Full-Text
Keywords: nutraceuticals; rosemary; neuronal apoptosis; antioxidants; polyphenols nutraceuticals; rosemary; neuronal apoptosis; antioxidants; polyphenols
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Taram, F.; Ignowski, E.; Duval, N.; Linseman, D.A. Neuroprotection Comparison of Rosmarinic Acid and Carnosic Acid in Primary Cultures of Cerebellar Granule Neurons. Molecules 2018, 23, 2956.

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