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APS Newsroom: April 17-21, 2004
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New Research An Important New Step In Determining Whether
Curry Can Protect Against Alzheimer’s
Curcumin, which provides the
yellow color in curry, may activate a key enzyme with antioxidative
properties
Washington, DC -- A new study has found that
curry, a common and popular cooking additive, could be an effective enhancer
of an enzyme that protects the brain against oxidative conditions. This
research is an important first step in determining whether curry could be
preventive agent against acute neurodegenerative conditions, or reducing the
progression of chronic and age associated neurodegenerative disorders, such
as Alzheimer’s disease.
Free Radicals and Neurodegenerative Disease
One of the most prominent current
theories of aging is the “free radical theory.” According to this theory,
free radical molecules generated through mitochondrial metabolism can act as
causative factor of abnormal function and cell death. Various toxins in the
environment can injure mitochondrial enzymes, leading to increased
generation of free radicals and oxidative stress, that over the life-span
would eventually play a major role in aging. Free radical’s oxidative
damage to key intracellular targets such as DNA or proteins has been shown
to be a major cause of the degenerative diseases related to aging such as
cancer and Alzheimer’s disease.
Luckily, mammalian cells have developed highly
protective systems against including oxidative challenges over time. When
properly activated, each one of these cell systems has the possibility to
restore cellular homeostasis and resume the ability to fight off oxidation.
Activation of antioxidant pathways is particularly important for tissue with
relatively weak antioxidant defenses, such as the brain. In fact, increasing
evidence points to the notion that reduced cellular expression and activity
of antioxidant proteins and the consequent oxidative stress are fundamental
causes for brain aging processes and neurodegenerative diseases.
HO-1 and Curcumin
There are a variety of genes encoding proteins that
possess anti-oxidant properties. Of particular interest in the central
nervous system (CNS) is the hemeoxygenase-1 (HO-1), which has been reported
to operate as a fundamental defensive mechanism for neurons exposed to an
oxidant challenge.
At the same time, a number of studies have supported
the beneficial effects of some commonly used natural products in preventing
various pathologic conditions. Spices and herbs often contain phenolic
substances with potent antioxidative and chemopreventive properties. Among
them is curcumin, a natural phenolic agent, extracted from the rhizome of
Curcuma Longa, and the yellow pigment in curry, strongly induced HO-1
expression and activity in rat astrocytes.
In recent years, there has been an unprecedented
interest in identifying new pharmacological strategies to increase defense
mechanisms by activating multiple antioxidant defense genes, a process that
has been referred to as programmed cell life. Previous studies have shown
that induction of HO-1 can represent an efficient antioxidant system and a
potential pharmacological target in a variety of oxidant- and
inflammatory-mediated diseases, including brain aging and neurodegenerative
disorders.
A New Study
A new study extends previous findings examining the
neuroprotective effects of curcumin and its ability to induce HO-1 on
cultured hippocampal neurons. This research effort investigated the effects
of curcumin on the expression profiles of other genes involved in the
cellular stress response. The study also explored subcellular localization
of HO-1 protein in one of the large cells of
nervous tissue after treatment with curcumin.
The investigators of a study entitled “Curcumin
Cytoprotective Effect in Rat Astrocytes and Neurons is Mediated by Specific
Induction of HO-1,” will present their findings at the American
Physiological Society’s (APS) (www.the-aps.org)
annual scientific conference, Experimental Biology 2003, being held
April 17-21, 2004, at the Washington, D.C. Convention Center. The research
team represents two countries. The Italian researchers are Giovanni
Scapagnini from the Institute of Neurological Sciences, CNR,
Catania, Claudia Colombrita and Vittorio Calabrese at the Dipartimento di
Scienze Chimiche, Universita' di Catania, and Alessia Pascale, at the
Department of Experimental and Applied Pharmacology, Universita' di Pavia,
Pavia. In the United States, the researchers are Michael L. Schwartzman and
Nader G. Abraham from the Department of Pharmacology, New York Medical
College, Valhalla, NY.
Methodology
Rat type 1 astrocytes and rat hippocampal neurons were
exposed to various concentrations of curcumin. After each treatment (six or
24 hours), cells were harvested for the determination of heme oxygenase
activity and protein expression. The researchers also measured the
expression of HO-1 and Phase II detoxification enzymes mRNAs by real time
quantitative RT-PCR.
Neurons growing in 24 wells were also exposed to
different concentrations of curcumin, and cell viability was determined at
24 hours. Other neurons were pretreated for 18 hours with curcumin 15mM
or curcumin 15mM + zinc
protoporphyrin IX (ZnPP IX) 10mM
and then exposed for two hours to 50 mu/ml glucose-oxidase (GOX), before
cell viability was determined.
Results
Treatment of astrocytes with curcumin increased
expression of HO-1 protein at both cytoplasmatic and nuclear level, as shown
by immunofluorescence analysis under laser-scanning confocal microscope.
The researchers also found a significant expression of quinone reductase and
glutathione S-transferase, two members of Phase II detoxification enzymes,
in astrocytes exposed to 5-15 µM curcumin. With exploration of the effects
of curcumin on HO-1 activity in cultured hippocampal neurons the researchers
found elevated expression of HO-1 mRNA and protein. Higher concentrations
of curcumin (50-100 µM) caused a substantial cytotoxic effect with no change
in HO-1 protein expression. Interestingly, pre-incubation (18 h) with
curcumin 15 µM resulted in an enhanced cellular resistance to GOX mediated
oxidative damage; this cytoprotective effect was considerably attenuated by
ZnPP IX, a specific inhibitor of heme oxygenase activity.
Conclusions
This study identifies a novel compound that could be
used for therapeutic purposes as potent inducers of HO-1 for protecting
brain cells against oxidative conditions. The researchers believe that
additional in vitro and in vivo studies are necessary to
determine whether curcumin can be used as preventive agent against acute
neurodegenerative conditions that affect an increasingly aged population.
- end -
The
American Physiological Society (APS) was founded in 1887 to foster basic and
applied science, much of it relating to human health. The Bethesda, MD-based
Society has more than 11,000 members and publishes 3,800 articles in its 14
peer-reviewed journals every year.
***
Editor’s
Note: For further information or to schedule an interview with a member of
the research team, please contact Donna Krupa at 703.967.2751 (cell),
703.527.7357 (office) or at
djkrupa1@aol.com. Or contact the APS newsroom at 202.249.4009 between
9:00 AM and 6:00 PM EDT April 17-21, 2004.
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