X-Message-Number: 24378
Date: Sun, 11 Jul 2004 20:41:46 -0700 (PDT)
From: Doug Skrecky <>
Subject: curry versus Alzheimer's disease?

Neurobiol Aging. 2001 Nov-Dec;22(6):993-1005
Phenolic anti-inflammatory antioxidant reversal of Abeta-induced
cognitive deficits and neuropathology.
Both oxidative damage and inflammation have been implicated in
age-related neurodegenerative diseases including Alzheimer's Disease
(AD). The yellow curry spice, curcumin, has both antioxidant and
anti-inflammatory activities which confer significant protection against
neurotoxic and genotoxic agents. We used 22 month Sprague-Dawley (SD) rats
to compare the effects of the conventional NSAID, ibuprofen, and curcumin
for their ability to protect against amyloid beta-protein (Abeta)-induced
damage. Lipoprotein carrier-mediated, intracerebroventricular infusion of
Abeta peptides induced oxidative damage, synaptophysin loss, a microglial
response and widespread Abeta deposits. Dietary curcumin (2000 ppm), but
not ibuprofen, suppressed oxidative damage (isoprostane levels) and
synaptophysin loss. Both ibuprofen and curcumin reduced microgliosis in
cortical layers, but curcumin increased microglial labeling within and
adjacent to Abeta-ir deposits. In a second group of middle-aged female SD
rats, 500 ppm dietary curcumin prevented Abeta-infusion induced spatial
memory deficits in the Morris Water Maze and post-synaptic density
(PSD)-95 loss and reduced Abeta deposits. Because of its low side-effect
profile and long history of safe use, curcumin may find clinical
application for AD prevention.

J Neurosci. 2001 Nov 1;21(21):8370-7.
The curry spice curcumin reduces oxidative damage and amyloid pathology
in an Alzheimer transgenic mouse.
Inflammation in Alzheimer's disease (AD) patients is characterized by
increased cytokines and activated microglia. Epidemiological studies
suggest reduced AD risk associates with long-term use of nonsteroidal
anti-inflammatory drugs (NSAIDs). Whereas chronic ibuprofen suppressed
inflammation and plaque-related pathology in an Alzheimer transgenic APPSw
mouse model (Tg2576), excessive use of NSAIDs targeting cyclooxygenase I
can cause gastrointestinal, liver, and renal toxicity. One alternative
NSAID is curcumin, derived from the curry spice turmeric. Curcumin has an
extensive history as a food additive and herbal medicine in India and is
also a potent polyphenolic antioxidant. To evaluate whether it could
affect Alzheimer-like pathology in the APPSw mice, we tested a low (160
ppm) and a high dose of dietary curcumin (5000 ppm) on inflammation,
oxidative damage, and plaque pathology. Low and high doses of curcumin
significantly lowered oxidized proteins and interleukin-1beta, a
proinflammatory cytokine elevated in the brains of these mice. With
low-dose but not high-dose curcumin treatment, the astrocytic marker GFAP
was reduced, and insoluble beta-amyloid (Abeta), soluble
Abeta, and plaque burden were significantly decreased by 43-50%. However,
levels of amyloid precursor (APP) in the membrane fraction were not
reduced. Microgliosis was also suppressed in neuronal layers but not
adjacent to plaques. In view of its efficacy and apparent low toxicity,
this Indian spice component shows promise for the prevention of
Alzheimer's disease.

J Neurosci Res. 2004 Mar 15;75(6):742-50.
Curcumin has potent anti-amyloidogenic effects for Alzheimer's
beta-amyloid fibrils in vitro.
Inhibition of the accumulation of amyloid beta-peptide (Abeta) and the
formation of beta-amyloid fibrils (fAbeta) from Abeta, as well as the
destabilization of preformed fAbeta in the central nervous system, would
be attractive therapeutic targets for the treatment of Alzheimer's
disease (AD). We reported previously that nordihydroguaiaretic acid (NDGA)
and wine-related polyphenols inhibit fAbeta formation from Abeta(1-40)
and Abeta(1-42) and destabilize preformed fAbeta(1-40) and fAbeta(1-42)
dose-dependently in vitro. Using fluorescence spectroscopic analysis with
thioflavin T and electron microscopic studies, we examined the effects of
curcumin (Cur) and rosmarinic acid (RA) on the formation, extension, and
destabilization of fAbeta(1-40) and fAbeta(1-42) at pH 7.5 at 37 degrees
C in vitro. We next compared the anti-amyloidogenic activities of Cur and
RA with NDGA. Cur and RA dose-dependently inhibited fAbeta formation from
Abeta(1-40) and Abeta(1-42), as well as their extension. In addition,
they dose-dependently destabilized preformed fAbetas. The overall
activities of Cur, RA, and NDGA were similar. The effective
concentrations (EC(50)) of Cur, RA, and NDGA for the formation, extension,
and destabilization of fAbetas were in the order of 0.1-1 microM.
Although the mechanism by which Cur and RA inhibit fAbeta formation from
Abeta and destabilize preformed fAbeta in vitro remains unclear, they
could be a key molecule for the development of therapeutics for AD.

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