Next Article in Journal
Phenolic Profiles, Antioxidant Capacities, and Inhibitory Effects on Digestive Enzymes of Different Kiwifruits
Next Article in Special Issue
Nutritional Regulators of Bcl-xL in the Brain
Previous Article in Journal
Prediction of the Formation of Reactive Metabolites by A Novel Classifier Approach Based on Enrichment Factor Optimization (EFO) as Implemented in the VEGA Program
Previous Article in Special Issue
Mitigation Effects of a Novel Herbal Medicine, Hepad, on Neuroinflammation, Neuroapoptosis, and Neuro-Oxidation
Article Menu
Issue 11 (November) cover image

Export Article

Open AccessArticle

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

Department of Biological Sciences, University of Denver, 2199 S. University Blvd., Denver, CO 80208, USA
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;
Received: 31 August 2018 / Revised: 1 November 2018 / Accepted: 7 November 2018 / Published: 13 November 2018
PDF [1816 KB, uploaded 13 November 2018]


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

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

  • Externally hosted supplementary file 1
    Doi: N/A
    Link: http://N/A
    Description: N/A

Share & Cite This Article

MDPI and ACS Style

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.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top