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Web End = Mol Neurobiol (2016) 53:61556168 DOI 10.1007/s12035-015-9519-1
http://crossmark.crossref.org/dialog/?doi=10.1007/s12035-015-9519-1&domain=pdf
Web End = The Dietary Components Carnosic Acid and Carnosol as Neuroprotective Agents: a Mechanistic View
Marcos Roberto de Oliveira1
Received: 21 August 2015 /Accepted: 28 October 2015 /Published online: 9 November 2015 # Springer Science+Business Media New York 2015
Abstract Carnosic acid (CA) and carnosol are the major diterpenes found in Rosmarinus officinalis (rosemary), a culinary spice. CA and carnosol account for over 90 % of its anti-oxidant activity in rosemary leaves. The diterpenes exert anti-oxidant, anti-inflammatory, and anti-carcinogenic activities, and present neuroprotective effects in both in vitro and in vivo experimental models. In some cases, CA exerted protective effects upon neuronal cells more intensely than resveratrol or sulforaphane. Therefore, CA and carnosol demonstrate a potential pharmacological role for rosemary diterpenes in ameliorating mammalian brain redox status, among other parameters, as for instance the modulation of neuroinflammation. The aim of this review is to discuss the biological effects of CA and carnosol on neuronal and glial cells with focus on the mechanism of action of such diterpenes.
Keywords Carnosic acid . Carnosol . Brain . Neuron . Glia
Introduction
Carnosic acid (CA; C20H28O4, MW 332.43392 g/mol), an ortho-diphenolic diterpene containing an abietane carbon
skeleton, is found in Rosmarinus officinalis (rosemary) and exerts several protective effects on mammalian cells, as demonstrated in both in vitro and in vivo experimental models [1]. CA is an anti-oxidant molecule and possesses anti-inflammatory and anti-carcinogenic properties [28].
CA is an ortho-dihydroquinone-type of compound that becomes electrophilic (an ortho-quinone form) when reacts with free radicals produced in biological systems. Therefore, CA is a pro-electrophilic molecule that becomes electrophilic after oxidative conversion to a quinone form, which is able to activate the nuclear factor erythroid 2-related factor 2 (Nrf2) transcription factor, the major regulator of the cellular redox homeostasis in mammalian animals [9]. Moreover, the direct CA anti-oxidant effects associated to its chemical structure (due to two O-phenolic hydroxyl moieties present at C11 and C12 the so-called catechol moiety) were seen in different in vitro experimental models [4, 10]. In this context, CA has been viewed as a potent neuroprotective agent due to its ability to modulate glutathione (GSH) synthesis and to downregulate the levels of neurotrophins (as for instance...