Letter to the Editor
Neuroprotective effects of resveratrol: Potential mechanisms
Dear Editor,
Neurochemistry International 57 (2010) 621622
Contents lists available at ScienceDirect
Neurochemistry
journa l homepage: www.e lVahl, C.F., 2007. Ischemia-reperfusion
injury: pathophysiology and clinicalimplications. Eur. J. Trauma
Emerg. Surg. 33, 600612.
Dustin, M.L., Rothlein, R., Bhan, A.K., Dinarello, C.A.,
Springer, T.A., 1986. Inductionby IL 1 and interferon-gamma: tissue
distribution, biochemistry, and function ofa natural adherence
molecule (ICAM-1). J. Immunol. 137, 245254.
Fukui, M., Choi, H.J., Zhu, B.T., 2010. Mechanism for the
protective effect ofresveratrol against oxidative stress-induced
neuronal death in HT22 cells. FreeRadic. Biol. Med. (June) (Epub
ahead of print).
Imler Jr., T.J., Petro, T.M., 2009. Decreased severity of
experimental autoimmuneencephalomyelitis during resveratrol
administration is associated with in-creased IL-17+IL-10+ T cells,
CD4-IFN-g+ cells, and decreased macrophageIL-6 expression. Int.
Immunopharmacol. 9, 134143.Fig. 1. Chemical structure of
resveratrol.
0197-0186/$ see front matter 2010 Elsevier Ltd. All rights
reserved.doi:10.1016/j.neuint.2010.06.014Resveratrol (Fig. 1) is a
natural dietary polyphenol with diversebiological and
pharmacological activities which is synthesized in awide variety of
about 70 plant species (Saiko et al., 2008), notablyskin of grapes,
raspberries, mulberries, pistachios and peanuts(Rocha-Gonzalez et
al., 2008). In recent years, there has beenconsiderable interest on
the neuroprotective properties ofresveratrol and its potential
benets against neurodegenerativediseases including Alzheimers
disease, Parkinsons disease and soforth (Rocha-Gonzalez et al.,
2008). However, the mechanismsresponsible for the neuroprotective
effects of resveratrol are notfully claried. In regard to the
proposed mechanisms, severalstudies have reported remarkable
inhibition of b-amyloidpolymerization and reduced plaque pathology
in a region specicmanner following dietary supplementation with
resveratrol(Karuppagounder et al., 2009). Moreover, resveratrol has
beenreported to inhibit the evoked glutamate release from
cerebro-cortical nerve terminals and thus could counteract the
excessiverelease of this excitatory neurotransmitter in a number
ofneurological disorders (Chang and Wang, 2009). Finally,
resvera-trol has antioxidant effects such as interference with the
NADPHoxidase pathway in astrocytes (Jensen et al., 2009) and
protectionagainst glutamate-induced oxidative neurotoxicity through
upre-gulation of mitochondrial superoxide dismutase (SOD2) (Fukuiet
al., 2010). The aforementioned properties represent somepossible
mechanisms underlying the observed neuroprotectiveactivities of
resveratrol.
In a recent interesting article by Li et al. (2009), the
authorsreported the neuroprotective effect of resveratrol against
cerebralischemia/reperfusion injury. Based on their detailed
analysis, theauthors concluded that the neuroprotective activity of
resveratrolcould be due to the modulating effects of this compound
on therelease of multiple neurotransmitters and
neuromodulatorsduring ischemia/reperfusion. Herewith, I would like
to add other[(Fig._1)TD$FIG]potential mechanisms by which
resveratrol may counteractischemia/reperfusion injury.
There is conclusive evidence indicating the involvement
ofproinammatory cytokines such as tumor necrosis factor (TNF)-aand
interleukin-1b in the postischemic response (Dorweiler et
al.,2007). In response to inammatory stimuli, endothelial
cellsmodify their phenotype and become activated through
upregula-tion of several surface adhesion molecules, thereby
promotingadhesion, activation and transmigration of neutrophils
(Olszaneckiet al., 2007). Neutrophils have a pivotal role in the
I/R injury(Welbourn et al., 1991) and their contribution is thought
to be dueto various mechanisms including generation ROS, release
ofproteolytic enzymes and proinammatory cytokines and
physicalobstruction of microvasculature (Lysiak et al., 2001;
Siemionowand Arslan, 2004). One of the most important endothelial
celladhesion molecules is intercellular adhesion molecule-1
(ICAM-1;CD54) which interacts with the integrin lymphocyte
function-associated antigen-1 (LFA-1; CD11a/CD18) on activated
neutro-phils (Dustin et al., 1986; Olszanecki et al., 2007). This
interactionis crucial for neutrophil transmigration across
endothelium.
Several previous studies have implied that resveratrol
coulddownregulate the expression of ICAM-1 and therefore
mightdecrease the LFA-1/ICAM-1 interaction (Park et al.,
2009a,b).Moreover, this polyphenol has been shown to exert
substantialreductions in the levels of proinammatory cytokines such
as TNF-a and IL-1b, which are involved in the postischemic response
andneutrophil activation (Kang et al., 2009; Sanchez-Fidalgo et
al.,2010). Finally, there is evidence that resveratrol is able to
decreasethe level of E-selectin (Yang et al., 2007; Imler and
Petro, 2009;Yang et al., 2010), another endothelia cell adhesion
moleculewhich is exclusively found on endothelial cells and has
animportant role in mediating neutrophil adhesion.
Along side the effects of resveratrol on neurotransmitters
andneuromodulators, the aforementioned activities should be
consid-ered as mechanisms that may, at least partly, account for
theobserved neuroprotective effects. However, additional studies
arerequired to conrm these mechanisms in the cerebral tissue.
References
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International
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Amirhossein Sahebkara,b,*aCardiovascular Research Center,
Avicenna Research Institute,
Mashhad University of Medical Sciences (MUMS),
Mashhad, IranbBiotechnology Research Center and School of
Pharmacy,
Mashhad University of Medical Sciences (MUMS),
Mashhad, Iran
*Correspondence address: Biotechnology Research Center andSchool
of Pharmacy,
Mashhad University of Medical Sciences (MUMS),P.O. Box:
91775-1365, Mashhad, Iran.
Tel.: +98 511 8823255; fax: +98 511 8823251E-mail address:
[email protected]
17 June 2010Available online 1 July 2010
Letter to the Editor / Neurochemistry International 57 (2010)
621622622
Neuroprotective effectsReferences
