Curcumin and Na/K ATPase
tcar...@elp.rr.com
4: Br J Pharmacol. 2005 Mar 7; [Epub ahead of print] Related Articles,
Links
Curcumin modulation of Na,K-ATPase: phosphoenzyme accumulation,
decreased K(+) occlusion, and inhibition of hydrolytic activity.
Mahmmoud YA.
1Department of Biophysics, Institute of Physiology and Biophysics,
University of Aarhus, Ole Worms Alle 185, DK-8000 Aarhus C., Denmark.
Curcumin, the major constitute of tumeric, is an
important nutraceutical that has been shown to be useful in the
treatment of many diseases. As an inhibitor of the sarcoplasmic
reticulum Ca(2+)-ATPase, curcumin was shown to correct cystic fibrosis
(CF) defects in some model systems, whereas others have reported no or
little effects on CF after curcumin treatment, suggesting that curcumin
effect is not due to simple inhibition of the Ca(2+)-ATPase.We tested
the hypothesis that curcumin may modulate other members of the
P(2)-type ATPase superfamily by studying the effects of curcumin on the
activity and kinetic properties of the Na,K-ATPase.Curcumin treatment
inhibited Na,K-ATPase activity in a dose-dependent manner (K(0.5)
approximately 14.6 muM). Curcumin decreased the apparent affinity of
Na,K-ATPase for K(+) and increased it for Na(+) and ATP. Kinetic
analyses indicated that curcumin induces a three-fold reduction in the
rate of E1P --> E2P transition, thereby increasing the steady-state
phosphoenzyme level. Curcumin treatment significantly abrogated K(+)
occlusion to the enzyme as evidenced from kinetic and proteolytic
cleavage experiments. Curcumin also significantly decreased the
vanadate sensitivity of the enzyme.Thus, curcumin partially blocks the
K(+) occlusion site, and induces a constitutive shift in the
conformational equilibrium of the enzyme, towards the E1
conformation.The physiological consequences of curcumin treatment
previously reported in different epithelial model systems may, at least
in part, be related to the direct effects of curcumin on Na,K-ATPase
activity.British Journal of Pharmacology advance online publication, 7
March 2005; doi:10.1038/sj.bjp.0706185.PMID: 15753945
This is of course a large potential negative for curcumin and suggests
that the spice should be taken with potassium.
Thomas
tcar...@elp.rr.com
Here's another negative for curcumin. I have three now. They're
started to add up.
Thomas
8: Biochem Pharmacol. 2005 Apr 15;69(8):1205-13. Related Articles,
Links
Curcumin-induced histone hypoacetylation: The role of reactive oxygen
species.
Kang J, Chen J, Shi Y, Jia J, Zhang Y.
School of Life Sciences, Institute of Physics, Lanzou University,
Lanzou 730000, China; Shanghai Institute of Cell Biology, Chinese
Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China.
Curcumin (Cur), a well-known dietary pigment derived from
Curcuma longa, is a promising anticancer drug, but its in vivo target
molecules remain to be clarified. Here we report that exposure of human
hepatoma cells to Cur led to a significant decrease of histone
acetylation. Histone acetyltransferase (HAT) and histone deacetylase
(HDAC) are the enzymes controlling the state of histone acetylation in
vivo. Cur treatment resulted in a comparable inhibition of histone
acetylation in the absence or presence of trichostatin A (the specific
HDAC inhibitor), and showed no effect on the in vitro activity of HDAC.
In contrast, the domain negative of p300 (a most potent HAT protein)
could block the inhibition of Cur on histone acetylation; and the Cur
treatment significantly inhibited the HAT activity both in vivo and in
vitro. Thus, it is HAT, but not HDAC that is involved in Cur-induced
histone hypoacetylation. At the same time, exposure of cells to low or
high concentrations of Cur diminished or enhanced the ROS generation,
respectively. And the promotion of ROS was obviously involved in
Cur-induced histone hypoacetylation, since Cur-caused histone
acetylation and HAT activity decrease could be markedly diminished by
the antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT) or
their combination, but not by their heat-inactivated forms. The data
presented here prove that HAT is one of the in vivo target molecules of
Cur; through inhibiting its activity, Cur induces histone
hypoacetylation in vivo, where the ROS generation plays an important
role. Considering the critical roles of histone acetylation in
eukaryotic gene transcription and the involvement of histone
hypoacetylation in the lose of cell viability caused by high
concentrations of Cur, these results open a new door for us to further
understand the molecular mechanism involved in the in vivo function of
Cur.PMID: 15794941
--------------------------------------------------------------------------------
hancock
> Hi,
> Here's another negative for curcumin. I have three now. They're
> started to add up.
>
> Thomas
That is jumping to conclusions isn't it? SIR2 also works through hypoacetylation.
John
tcar...@elp.rr.com
Hi John,
It was the phrase, "promotion of ROS" that caused me to file
this with my other two negative curcumin papers. I've drawn no
conclusions and continue to take not only 1500 mg of tumeric but 25 mg
of piperine with it. This is a highly speculative combination which
could put my bioavailable curcumin levels at far more than has been
proven safe in humans. This is one of the more risky interventions I
use and for that reason I'm very concerned about its safety. I
diligently watch for, and save any negative information on substances I
take, and share much of this info on the premise that other savy life
extensionists in the group also want to know of such negative reports.
Curcumin shows a huge potential compared to many other
supplements and only for this reason will take even what I hope to be a
small risk with it. It's been a while since I posted my curcumin info.
Here's some of it. I see inclusion of all the refs is to long for
Google if anyone wants to see the rest just ask.
Thomas
These are the major effects of Curcumin
Induces HSP, but inhibits P53 without increasing cancer. (1) Inhibits
COX-2 (2) Is anti-inflammatory. (3) Synergistic with green tea. (4)
Lowers fibrinogin (5) Could slow @Alzheimer's at physiological
concentrations (6) Prevents colon cancer, other cancers and ulcers
and could be synergistic with resveratrol (7 many papers) Prevents
atherosclerosis (8) Increases lifespan (9) Attenuates diabetes (10)
Some minor effects are: Prevents eye enlargement (11) Antioxidant
and phase II enzyme induction (12) Potentiates beneficial effects of
alcohol and attenuates the detriments (13) Increases bone density
(14)
Any intervention with most of the above effects clearly has
a very basic antiaging mechanism if Occam's razor cuts at all.
(1) Medline search string: curcumin AND heat shock protein. Shows that
curcumin induces HSP70 at 5 to 18 microMole Below is one of the seven
abstracts.
Mol Carcinog 1996 Dec;17(4):224-34 Induction of HSP70 gene
expression by modulation of Ca(+2) ion and cellular p53 protein by
curcumin in colorectal carcinoma cells. Chen YC, Kuo TC, Lin-Shiau SY,
Lin JK. Institute of Biochemistry, College of Medicine, National
Taiwan University, Taipei, Republic of China.
Curcumin (diferuloyl
methane) is the major active yellow pigment of turmeric and curry.
Studies in recent years have indicated that curcumin is a potent
inhibitor of the initiation and promotion of chemical
carcinogen-induced skin carcinogenesis in mice. When COLO205
colorectal carcinoma cells were treated with curcumin (60 microM), the
appearance of apoptotic DNA ladders was delayed about 5 h, and G1
arrest was detected. Further analysis of the endonuclease activities
in these cells revealed that the activity of Ca(+2)-dependent
endonuclease in COLO205 cells was profoundly inhibited and that the
extent of inhibition depended on the degree of calcium depletion. The
reduction of p53 gene expression was accompanied by the induction of
HSP70 gene expression in the curcumin-treated cells. These findings
suggest that curcumin may induce the expression of the HSP70 gene
through the initial depletion of intracellular Ca(+2), followed by the
suppression of p53 gene function in the target cells. PMID: 8989916
XXXX
(2) Company says curry spice might prevent bowel cancer
LONDON, Jan 08 (Reuters Health) - A spice used in curry powder might
help prevent and treat bowel cancer, according to study results
released Monday by the UK botanicals' pharmaceutical company
Phytopharm.
The spice, turmeric (curcuma longa), a member of the ginger family, is
believed to have medicinal properties because it inhibits production
of the inflammation-related enzyme cyclo-oxygenase 2 (COX-2), levels
of which are abnormally high in certain inflammatory diseases and
cancers.
Phytopharm said in a news release that its natural product, P54, had
now been subjected to a study in 15 patients with advanced colorectal
cancer at the Leicester Royal Infirmary NHS Trust and the Medical
Research Council Centre for Mechanisms of Human Toxicology.
Five groups of patients were dosed orally once a day with 2, 4, 6, 8
or 10 capsules of P54, for up to 4 months. Anti-tumour activity was
assessed clinically, biochemically and radiologically every 28 days.
"No dose-limiting toxicity was identified and all of the patients
tolerated their allocated dose without any significant safety issues,"
the firm said. In addition, dose-related inhibition of COX-2 was
noted.
"We are all cautiously optimistic that inhibition of COX-2 may be an
important mechanism to reduce cancer risk. The results of this trial
appear to confirm that P54 is able to inhibit COX-2 and may have a
role in both the prevention of colon cancer and, possibly, could form
part of a treatment regimen for established disease," according to
lead investigator, Professor Will Steward from the University of
Leicester School of Medicine and Biological Sciences.
Dr. Richard Dixey, chief executive of Phytopharm, told Reuters Health
that the firm is discussing development opportunities with three
companies.
The firm was particularly interested in developing P54 as a food
product for chemo-prevention of bowel cancer--thereby bypassing the
normal pharmaceutical regulatory pathway.
This represents a huge potential market--300,000 people with colonic
polyps in the UK alone who could start chemo-prevention in their 40s
and 50s and continue for the rest of their lives.
Dixey said P54 works earlier in the chemical pathway than do
conventional COX-2 inhibitors and should therefore avoid their side
effects while still being as effective.
As a natural product, turmeric had been used in cooking for thousands
of years.
He stressed that P54 contains certain volatile oils, which greatly
increase the potency of the turmeric spice. "You would have to eat a
hell of a lot of curry to have the same effect."
Two major companies--American Home Products and Merck--have already
launched COX-2 inhibitors for arthritis and cancer indications may
follow.
Copyright © 2001 Reuters (Google Phytopharm to keep current. As of
2004 they have yet to complete a phase II trial)
XXXX
(3) Curcumin inhibition of inflammatory cytokine production by
human peripheral blood monocytes and alveolar macrophages.
Abe Y, Hashimoto S, Horie T. Pharmacol Res 1999;39:41-47.
Curcumin, a dietary pigment responsible for the yellow colour of
curry, has been used for the treatment of inflammatory diseases and
exhibits a variety of pharmacological effects such as
anti-inflammatory activity. The mechanism in anti-inflammatory
activity of curcumin has been investigated; however, little is known
about the effect of curcumin on cytokine production by human
peripheral blood monocytes and alveolar macrophages. In the present
study, we shed light on the effect of curcumin on inflammatory
cytokine production by human peripheral blood monocytes and alveolar
macrophages. To this end, we determined the concentrations of
interleukin-8 (IL-8), monocyte inflammatory protein-1 (MIP-1alpha),
monocyte chemotactic protein-1 (MCP-1), interleukin-1beta (IL-1beta),
and tumour necrosis factor-alpha (TNF-alpha) in the culture
supernatants from phorbor ester, 4beta phorbor
12beta-myristate-13alpha acetate (PMA)- or lipo-polysaccharide
(LPS)-stimulated monocytes and alveolar macrophages in the presence or
absence of curcumin. Curcumin inhibited the production of IL-8,
MIP-1alpha, MCP-1, IL-1beta, and TNF-alpha by PMA- or LPS-stimulated
monocytes and alveolar macrophages in a concentration- and a
time-dependent manner. These results show that curcumin exhibits an
inhibitory effect on the production of IL-8, MIP-1alpha, MCP-1,
IL-1beta, and TNF-alpha by PMA- or LPS-stimulated monocytes and
alveolar macrophages.
XXXX
(4) Quantitation of chemopreventive synergism between
(-)-epigallocatechin-3-gallate and curcumin in normal, premalignant
and malignant human oral epithelial cells.
Khafif A, Schantz SP, Chou TC, et al. Carcinogenesis 1998;19:419-424.
An in vitro model for oral cancer was used to examine the growth
inhibitory effects of chemopreventive agents when used singly and in
combination. The model consists of primary cultures of normal oral
epithelial cells, newly established cell lines derived from dysplastic
leukoplakia and squamous cell carcinoma. Two naturally occurring
substances, (-)-epigallocatechin-3-gallate (EGCG) from green tea and
curcumin from the spice turmeric were tested. Cells were treated
singly and in combination and effects on growth determined in 5-day
growth assays and by cell cycle analysis. Effective dose 50s and the
combination index were calculated with the computerized Chou-Talalay
method which is based on the median-effect principle. Agents were
shown to differ in their inhibitory potency. EGCG was less effective
with cell progression; the cancer cells were more resistant than
normal or dysplastic cells. In contrast, curcumin was equally
effective regardless of the cell type tested. Cell cycle analysis
indicated that EGCG blocked cells in G1, whereas curcumin blocked
cells in S/G2M. The combination of both agents showed synergistic
interactions in growth inhibition and increased sigmoidicity
(steepness) of the dose-effect curves, a response that was dose and
cell type dependent. Combinations allowed for a dose reduction of
4.4-8.5-fold for EGCG and 2.2-2.8-fold for curcumin at ED50s as
indicated by the dose reduction index (DRI). Even greater DRI values
were observed above ED50 levels. Our results demonstrate that this
model which includes normal, premalignant and malignant oral cells can
be used to analyse the relative potential of various chemopreventive
agents. Two such naturally-occurring agents, EGCG and curcumin, were
noted to inhibit growth by different mechanisms, a factor which may
account for their demonstrable interactive synergistic effect.
Curcumin helps tea
@tea............................................
3: Di Yi Jun Yi Da Xue Xue Bao. 2005 Jan;25(1):48-52. Related Articles,
Links
Effects of combined use of curcumin and catechin on cyclooxygenase-2
mRNA expression in dimethylhydrazine-induced rat colon carcinogenesis.
[Article in Chinese]
Xu G, Huang W, Zhang WM, Lai ZS, He MR, Wang YD, Zhang YL.
Institute for Digestive Diseases, Nanfang Hospital, Southern Medical
University, Guangzhou 510515, China.
OBJECTIVE: To examine the effect of combined use of curcumin
and catechin on the number of aberrant crypt foci (ACF) and expression
levels of cyclooxygenase-2 (COX-2) mRNA in rat colon carcinogenesis.
Methods Dimethylhydrazine (DMH)-induced rats colon carcinogenesis model
was used for evaluation of the synergistic inhibitory effect between
curcumin and catechin in light of ACF formation and tumor incidence.
COX-2 mRNA expression was also detected in rat colon carcinogenesis.
RESULTS: Curcumin, catechin and their co-treatment caused significant
inhibition of DMH-induced ACF and colon carcinogenesis as compared with
untreated DMH-induced rat models (P<0.01). Co-treatment with curcumin
and catechins caused greater inhibition of DMH-induced ACF and colon
carcinogenesis than the single use of curcumin or catechin (P<0.05). A
synergistic inhibitory effect between curcumin and catechin on the
expression of COX-2 mRNA was observed in the early stage of rat colon
carcinogenesis but not in colon tumor tissues. CONCLUSION: Curcumin and
catechin have synergistic effect on ACF and COX-2 mRNA expression in
rat colon carcinogenesis, suggesting their potential value in the
prevention of human colon cancers.PMID: 15683997
XXXX
(5) Turmeric Lowers Fibrinogen<O:P</O:P
It now appears, however, that there may be a more practical approach
to reduce fibrinogen levels, and the inherent risk of
hyper-fibrinogenemia-related diseases. It is with the common herb,
Curcuma longa (turmeric). Scientists in Spain have previously
demonstrated that turmeric is an extremely potent antioxidant, capable
of dramatically reducing blood levels of lipid peroxides and oxidized
lipoproteins (Ramirez-Bosca, et al, 1995, 1997).<O:P</O:P
In this most recent study, Ramirez-Bosca and her colleagues (2000)
selected eight subjects with elevated fibrinogen levels and treated
them with 20 mg of Curcuma longa (turmeric) extract per day. After
only 15 days, previously elevated levels of fibrinogen dropped like a
rock in all eight subjects (Fig. 4). No adverse effects were noted by
any of the subjects, nor were there any adverse changes in any other
blood chemistries. The safety of Turmeric is unquestioned, since some
people have been known to regularly consume as much as 3.8 grams
daily, without adverse effects.........................................
Arch Gerontol Geriatr. 2002 Feb;34(1):37-46. Related Articles, Links
The curcuma antioxidants: pharmacological effects and prospects for
future clinical use. A review.
Miquel J, Bernd A, Sempere JM, Diaz-Alperi J, Ramirez A.
Department of Biotechnology, University of Alicante, San Vicente,
E-03080, Alicante, Spain. as...@intertext.es
In agreement with the predictions of the oxygen-stress theory of aging
and age-related degenerative diseases, diet supplementation with a
number of phenolic or thiolic antioxidants has been able to increase
the life span of laboratory animals, protect against senescent immune
decline and preserve the respiratory function of aged mitochondria. In
addition to the above, more recent data reviewed here suggest that the
polyphenolic compound curcumin and related non-toxic antioxidants from
the rhizome of the spice plant Curcuma longa have a favorable effect on
experimental mouse tumorigenesis as well as on inflammatory processes
such as psoriasis and ethanol-caused hepatic injury. Our own research
has focused on the effects of diet supplementation with an
antioxidant-rich hydroalcoholic extract of the curcuma rhizome on key
risk factors of atherogenesis and related cardiovascular disease. Our
reviewed data show that, in human healthy subjects, the daily intake of
200 mg of the above extract results in a decrease in total blood lipid
peroxides as well as in HDL and LDL-lipid peroxidation. This
anti-atherogenic effect was accompanied by a curcuma
antioxidant-induced normalization of the plasma levels of fibrinogen
and of the apo B/apo A ratio, that may also decrease the cardiovascular
risk. The reviewed literature indicates that curcumin and related plant
co-antioxidants are powerful anti-inflammatory agents. Further, since
they potentiate the anti-atherogenic effect of alpha-tocopherol, more
extensive clinical testing of their probable usefulness in
cardiovascular risk reduction seems justified.PMID: 14764309
PHYTOTHERAPY RESEARCH, 2000, Vol 14, Iss 6, pp 443-447
XXXX
(6) J Biol Chem. 2004 Dec 7;
Curcumin inhibits formation of Abeta oligomers and fibrils and binds
plaques and reduces amyloid in vivo.
Yang F, Lim GP, Begum AN, Ubeda OJ, Simmons MR, Ambegaokar SS, Chen PP,
Kayed R, Glabe CG, Frautschy SA, Cole GM.
GRECC (VA Medical) and Medicine, University of California Los Angeles,
North Hills, CA 91343.
Alzheimer's disease (AD) involves amyloid (Abeta)
accumulation, oxidative damage and inflammation, and risk is reduced
with increased antioxidant and anti-inflammatory consumption. The
phenolic yellow curry pigment curcumin has potent anti-inflammatory and
antioxidant activities and can suppress oxidative damage, inflammation,
cognitive deficits, and amyloid accumulation. Since the molecular
structure of curcumin suggested potential Ass-binding, we investigated
whether its efficacy in AD models could be explained by effects on Ass
aggregation. Under aggregating conditions in vitro, curcumin inhibited
aggregation (IC(50) =0.8 microM) as well as disaggregated fibrillar
Ass40 (IC(50) =1 microM), indicating favorable stoichiometry for
inhibition. Curcumin was a better Abeta40 aggregation inhibitor than
ibuprofen and naproxen, and prevented Abeta42 oligomer formation and
toxicity between 0.1-1.0 muM. Under electron microscopy, curcumin
decreased dose-dependently Ass fibril formation beginning with 0.125
microM. Curcumin's effects did not depend on Abeta sequence but on
fibril-related conformation. AD and Tg2576 mice brain sections
incubated with curcumin revealed preferential labeling of amyloid
plaques. In vivo studies showed that curcumin injected peripherally
into aged Tg mice, crossed the blood brain barrier and bound plaques.
When fed to aged Tg2576 mice with advanced amyloid accumulation,
curcumin labeled plaques and reduced amyloid levels and plaque burden.
Hence, curcumin directly binds small ss-amyloid species to block
aggregation and fibril formation in vitro and in vivo. These data
suggest that low dose curcumin effectively disaggregates Ass as well as
prevents fibril and oligomer formation, supporting the rationale for
curcumin use in clinical trials preventing or treating AD.PMID:
15590663 from the full text.....................
They were fed 500 ppm, about 250 mg for me. Our previous
results demonstrated that chronic dietary curcumin lowered Aß
deposition in 16 month old APPsw transgenic mice (Tg2576) (12).
An efficacious drug must also be bioavailable and safe at
needed dose. We demonstrate
that curcumin can prevent Aß fibril formation at low doses in the
0.1-1 µM range which is
consistent with a recent in vitro report from Ono et al (Ono, K.,
Hasegawa, K., Naiki, H., and Yamada, M. (2004) J Neurosci Res 75,
742-750). These doses can likely be achieved
physiologically. Curcumin is rapidly glucuronidated after oral dosing
so plasma levels remain
low, despite high intake. However, high oral curcumin dosing appears
safe; for example, 4-8
gram doses in human patients produce no toxic effects, with peak serum
curcumin levels of 0.51-
1.77 µM (Cheng, A. L., Hu, C. H., Lin, J. K., Hsu, M. M., Ho, Y. F.,
Shen, T. S., Ko, J. Y., Lin, J.T., Lin, B. R., Ming-Shiang, W., Yu, H.
S., Jee, S. H., Chen, G. S., Chen, T. M., Chen, C.A., Lai, M. K., Pu,
Y. S., Pan, M. H., Wang, Y. J., Tsai, C. C., and Hsieh, C. Y.
(2001)Anticancer Res. 21(4B), 2895-2900). Mouse brain curcumin levels
of 0.41 µg/g (~1.1 µM) were measured one hour
after dosing that produced 0.6 µg/g (1.6 µM) in the plasma (56),
suggesting that achievable brain
levels may be close to blood levels. Curcumin-iron interaction reached
half-maximum at ~2.5-5
µM iron and exhibited negative cooperativity, with Kd1~0.5-1.6 µM and
Kd2~50-100 µM,
suggesting that some iron chelation may be achieved at brain curcumin
concentrations in the
submicromolar range (53). We have found that oral curcumin treatment
reduces CNS iNOS,
inflammatory cytokines and lipid peroxidation (57). Brain levels of
curcumin in the 0.1-1 µM
range are similar to those required to inhibit CNS AP-1 mediated
transcription in vivo (58) and
related suppression of iNOS (59) and antioxidant activities. Curcumin
can inhibit lipid
peroxidation better than vitamin E (60) and is a more potent
antioxidant. Its IC50 for Aß
aggregation is slightly below its IC50 for lipid peroxidation (1.3µM)
(61,62), indicating that
curcumin would be effective at concentrations required for desirable
antioxidant and antiinflammatory
activities. While higher (>5 µM) doses of curcumin have been reported
to inhibit
multiple kinases and enzyme activities and bind metals, these phenomena
are not likely to occur
in brain with oral dosing. On the other hand, in vitro efficacy may not
predict in vivo results. For
example, while curcumin and another polyphenolic, rosmarinic acid, were
found to inhibit Aß
aggregation in vitro (54), we find that @rosmarinic acid actually
increases Aß accumulation in Aß
22
Curcumin blocks amyloid aggregation infused rodent brain (63), which
was in sharp contrast to curcumin's effect in the same model
(41) and in our current in vivo results.
The final proof of any anti-amyloid effect is in vivo testing. Because
amyloid
accumulation begins decades before diagnosis, anti-amyloid therapy
would ideally begin prior to
clinical symptoms. Approaches that remain efficacious at advanced
stages of amyloid
accumulation are clearly needed; and our in vivo observations, suggest
curcumin may even be
beneficial even after the disease has developed.
23
Conclusion:
Curcumin is widely used at low doses as a yellow food dye and at higher
doses in traditional
Indian "Ayurvedic" medicine, typically as a turmeric extract. Because
of its use as a food
additive and its potential for cancer chemoprevention, curcumin has
undergone extensive
toxicological screening and pre-clinical investigation in rats, mice,
dogs and monkeys (11,64).
In clinical trials, cancer patients have not shown adverse effects with
doses from 2,000 to 8,000
mg per day (55). Thus, our data showing low dose inhibition of amyloid
oligomer and fibril
formation as well as suppression in aged animals combined with
published antioxidant, antiinflammatory
and anti-amyloid activities in two animals models (15,41), provide an
increasingly
compelling rationale for clinical trials for curcumin in the prevention
or even treatment of AD.
XXXX
Curry spice could slow Alzheimer's, study shows
By E. J. Mundell
NEW YORK, Nov 15 (Reuters Health) - Diets rich in curcumin--a compound
found in the curry spice turmeric--may help explain why rates of
Alzheimer's disease are much lower among the elderly in India compared
with their Western peers.
Alzheimer's disease is characterized by the buildup of amyloid
protein "plaques" within the brain. In studies in rats, curcumin "not
only reduces the amyloid, but also reduces the (brain's) response to
the amyloid," according to researcher Dr. Sally Frautschy of the
University of California, Los Angeles. She presented her findings
Thursday at the annual meeting of the Society for Neuroscience in San
Diego, California.
Previous studies have noted that elderly individuals living in Indian
villages appear to have the lowest incidence of Alzheimer's disease in
the world, with just 1% of those aged 65 and older developing the
degenerative brain condition. The reasons for this low incidence
remain unclear, however.
Frautschy speculated that curcumin found in curry could provide a clue
to this puzzle since the compound has "a long history of dietary and
herbal medicinal use" and is also a powerful antioxidant and
anti-inflammatory agent.
In her study, Frautschy fed middle-aged (9 months old) and aged (22
months old) rats diets rich in curcumin. All of the rats had received
brain injections of amyloid to mimic progressive Alzheimer's disease.
"Curcumin reduced the accumulation of beta-amyloid and the associated
loss of proteins" in the synapses, or gaps, between individual brain
cells, Frautschy reported.
"Synapses connect nerve cells and are crucial for memory," the
California researcher explained. Keeping synapses free of plaque is
important because "their loss correlates well with memory decline in
Alzheimer's."
This type of memory preservation may have been reflected in the fact
that rats fed curcumin also performed much better in memory-dependent
maze tests compared with rats on normal diets, according to Frautschy.
Curcumin also appeared to reduce Alzheimer's-related inflammation in
neurologic tissue.
Because "a combined anti-inflammatory and antioxidant approach will be
useful for Alzheimer's prevention or treatment," Frautschy speculates
that curcumin could be especially valuable in the fight against the
disease, especially in combination with anti-inflammatory drugs like
ibuprofen. Her team is hopeful they will soon receive funding for
clinical trials to investigate curcumin-ibuprofen combination therapy.
Curcumin may not be the only compound in the kitchen spice rack able
to ward off Alzheimer's. In an interview with Reuters Health,
Frautschy said that "chemicals from @rosemary (rosmarinic acid) and
@ginger (vanillin and zingerone, also high in Indian diets) have
similar structure and should be tested."
Copyright © 2001 see PMID: 11606625 with full
text.............................
Curry Could Save Brain Cells
Spice compound appears to enhance enzyme that protects neurons against
free radicals
By Betterhumans Staff
4/19/2004 · Hits: 11 · Comments: 0
Credit: Andrzej Burak
Spice of life: Curry and other spices might help fight such age-related
brain diseases as Alzheimer's
Curry may help fight brain diseases by enhancing an enzyme that
protects brain cells from oxidative damage.
Studying the effects of a compound in the spice on rat neurons, Italian
and American researchers have found that it might help protect against
such diseases as Alzheimer's.
The researchers-including Michael Schwartzman and Nader Abraham from
New York Medical College in Valhalla-think that the compound could
help prevent neurodegenerative conditions that affect the elderly,
although they say that much more research is needed. Oxygen damage
Neurodegenerative diseases are illnesses that involve progressive
nervous system dysfunction and damage to nervous system components.
Free radicals and oxidative stress are thought to play a role in many
neurodegenerative diseases by damaging cells of the nervous system.
Cells fight against oxidative damage with antioxidant proteins.
The brain, however, is considered to have relatively weak antioxidant
defenses, and this is thought to play a significant role in brain aging
and the development of neurodegenerative conditions.
Antioxidant genes
Several genes encode proteins that have antioxidant properties.
In the central nervous system, a gene called hemeoxygenase-1, HO-1 for
short, is thought to play an important role in protecting neurons from
free radicals.
Researchers have been looking for ways to activate genes such as HO-1
in order to prolong the life of neurons and in turn prevent the
development of brain diseases.
Curry has attracted attention for its possible brain-protecting
effects, and researchers have previously found that curcumin, the
yellow pigment in curry, reduces oxidative damage in the brains of mice
with a model of Alzheimer's disease.
Cellular protection
For its study, the two-country research team examined the effects of
curcumin on HO-1 and the expression of other genes involved in
responding to cellular stress.
They exposed rat neurons from the hippocampus as well as rat astrocytes
to different concentrations of curcumin.
After each treatment they checked the cells for hemeoxygenase activity
and protein expression.
They also pretreated some neurons with curcumin for 18 hours before
exposing them for two hours to an enzyme called glucose-oxidase.
Increased expression
The researchers found that astrocytes treated with curcumin had an
increased expression of hemeoxygenase.
They also found significant expression of two detoxification enzymes,
quinone reductase and glutathione S-transferase, in astrocytes exposed
to curcumin.
The pretreated neurons also had enhanced resistance to oxidative
damage.
The benefits were seen with low concentrations of curcumin, while high
concentrations had a substantially toxic effect.
More studies are necessary, the researchers say, to determine whether
curcumin should be used as a preventive agent against neurodegenerative
diseases.
The research was reported in Washington, DC at Experimental Biology
2004, the annual scientific conference of the American Physiological
Society.
XXXX
(7) A recent report in the medical journal, Cancer Research, shows that
colon cancer can be prevented by eating curry powder, a spice you add
to flavor food.
The chief ingredient in curry powder is curcumin (sir'qumin), the
pigment that gives turmeric spice its bright yellow-orange color.
Nutritional biochemist, Bandaru Reddy of the American Health
Foundation in Valhalla, N.Y., noted that people who live in certain
parts of Asia have a very low incidence of colon cancer. Her team
wanted to see if they could find something in their diets that helps
to prevent colon cancer. They know that aspirin and other antiswelling
drugs may help to prevent colon cancer in America, so they checked to
see what drugs or herbals were used by people who live in areas where
there is a very low incidence of colon cancer. They found that people
in India use turmeric in curry powder to treat traumatic aches and
sprains and also the pain of arthritis. They then fed huge amounts of
a chemical that is known to cause colon cancer to rats. Half of them
also ate large amounts of circumin,/ the active ingredient in curry
powder/ and they had half the rate of colon cancer of the rats who did
not receive the curry powder extract.
On the basis of this research, entrepreneurs will soon try to sell you
expensive supplements that contain circumin. Virtually all vegetables
contain phytochemicals that help to prevent cancers. You will get
maximum protection from cancer by eating large amounts of fruits and
vegetables, rather then spending extra money to supplement an
unhealthy diet with pills.
I'm Dr. Gabe Mirkin on Fitness.
Tumori. 1987 Feb 28;73(1):29-31. Related Articles, Links
Turmeric and curcumin as topical agents in cancer therapy.
Kuttan R, Sudheeran PC, Josph CD.
An ethanol extract of turmeric ("Curcuma longa") as well as an
ointment of curcumin (its active ingredient) were found to produce
remarkable symptomatic relief in patients with external cancerous
lesions. Reduction in smell were noted in 90% of the cases and
reduction in itching in almost all cases. Dry lesions were observed in
70% of the cases, and a small number of patients (10%) had a reduction
in lesion size and pain. In many patients the effect continued for
several months. An adverse reaction was noticed in only one of the 62
patients evaluated.PMID: 2435036
· Cancer Research January 15, 1995
Chemopreventive effect of curcumin, a naturally occurring
anti-inflammatory agent, during the promotion/progression stages of
colon cancer.
Kawamori T, Lubet R, Steele VE, et al. Cancer Res 1999;59:597-601.
Curcumin, derived from the rhizome of Curcuma longa L. and having both
antioxidant and anti-inflammatory properties, inhibits chemically
induced carcinogenesis in the skin, forestomach, and colon when it is
administered during initiation and/or postinitiation stages. This
study was designed to investigate the chemopreventive action of
curcumin when it is administered (late in the premalignant stage)
during the promotion/progression stage of colon carcinogenesis in male
F344 rats. We also studied the modulating effect of this agent on
apoptosis in the tumors. At 5 weeks of age, groups of male F344 rats
were fed a control diet containing no curcumin and an experimental
AIN-76A diet with 0.2% synthetically derived curcumin (purity, 99.9%).
At 7 and 8 weeks of age, rats intended for carcinogen treatment were
given s.c. injections of azoxymethane (AOM) at a dose rate of 15 mg/kg
body weight per week. Animals destined for the promotion/progression
study received the AIN-76A control diet for 14 weeks after the second
AOM treatment and were then switched to diets containing 0.2 and 0.6%
curcumin. Premalignant lesions in the colon would have developed by
week 14 following AOM treatment. They continued to receive their
respective diets until 52 weeks after carcinogen treatment and were
then sacrificed. The results confirmed our earlier study in that
administration of 0.2% curcumin during both the initiation and
postinitiation periods significantly inhibited colon tumorigenesis. In
addition, administration of 0.2% and of 0.6% of the synthetic curcumin
in the diet during the promotion/progression stage significantly
suppressed the incidence and multiplicity of noninvasive
adenocarcinomas and also strongly inhibited the multiplicity of
invasive adenocarcinomas of the colon. The inhibition of
adenocarcinomas of the colon was, in fact, dose dependent.
Administration of curcumin to the rats during the initiation and
postinitiation stages and throughout the promotion/progression stage
increased apoptosis in the colon tumors as compared to colon tumors in
the groups receiving AOM and the control diet. Thus, chemopreventive
activity of curcumin is observed when it is administered prior to,
during, and after carcinogen treatment as well as when it is given
only during the promotion/progression phase (starting late in
premalignant stage) of colon carcinogenesis.
The latest studies show that turmeric also protects the stomach lining
and helps prevent ulcers, says Alan R. Gaby, M.D., a Baltimore
physician who practices nutritional and natural medicine and is
president of the American Holistic Medical Association."Turmeric's
anti-ulcer effect should be cause for celebration among curry lovers
with Type-A personalities, like myself."
And several studies show that curcumin, an active chemicalin turmeric,
has anti-inflammatory action, lending credence to the herb's
traditional use in treating arthritis.
"Turmeric's anti-ulcer effect should be cause for celebration among
curry lovers with Type-A personalities, like myself." And several
studies show that curcumin, an active chemical in turmeric, has
anti-inflammatory action, lending credence to the herb's traditional
use in treating arthritis.
Caution: Large doses not recommended in cases of gallstones,
obstructive jaundice, acute bilious colic and toxic liver disorders
(7) Cancer Epidemiol Biomarkers Prev 2002 Jun;11(6):535-40
Chemopreventive efficacy and pharmacokinetics of curcumin in the min/+
mouse, a model of familial adenomatous polyposis. Perkins S,
Verschoyle RD, Hill K, Parveen I, Threadgill MD, Sharma RA, Williams
ML, Steward WP, Gescher AJ. Cancer Biomarkers and Prevention Group,
Department of Oncology, University of Leicester, Leicester, United
Kingdom. Curcumin, the major yellow pigment in turmeric, prevents the
development of adenomas in the intestinal tract of the C57Bl/6J Min/+
mouse, a model of human familial APC. To aid the rational development
of curcumin as a colorectal cancer-preventive agent, we explored the
link between its chemopreventive potency in the Min/+ mouse and levels
of drug and metabolites in target tissue and plasma. Mice received
dietary curcumin for 15 weeks, after which adenomas were enumerated.
Levels of curcumin and metabolites were determined by high-performance
liquid chromatography in plasma, tissues, and feces of mice after
either long-term ingestion of dietary curcumin or a single dose of
[(14)C]curcumin (100 mg/kg) via the i.p. route. Whereas curcumin at
0.1% in the diet was without effect, at 0.2 and 0.5%, it reduced
adenoma multiplicity by 39 and 40%, respectively, compared with
untreated mice. Hematocrit values in untreated Min/+ mice were
drastically reduced compared with those in wild-type C57Bl/6J mice.
Dietary curcumin partially restored the suppressed hematocrit. Traces
of curcumin were detected in the plasma. Its concentration in the
small intestinal mucosa, between 39 and 240 nmol/g of tissue, reflects
differences in dietary concentration. [(14)C]Curcumin disappeared
rapidly from tissues and plasma within 2-8 h after dosing. Curcumin
may be useful in the chemoprevention of human intestinal malignancies
related to Apc mutations. The comparison of dose, resulting curcumin
levels in the intestinal tract, and chemopreventive potency suggests
tentatively that a daily dose of 1.6 g of curcumin is required for
efficacy in humans. A clear advantage of curcumin over nonsteroidal
anti-inflammatory drugs is its ability to decrease intestinal bleeding
linked to adenoma maturation. PMID: 12050094
Phase I clinical trial of curcumin, a chemopreventive agent, in
patients with high-risk or pre-malignant lesions.
Cheng AL, Hsu CH, Lin JK, et al. Anticancer Res 2001;21:2895-2900.
Curcumin (diferuloylmethane), a yellow substance from the root of the
plant Curcuma longa Linn., has been demonstrated to inhibit
carcinogenesis of murine skin, stomach, intestine and liver. However,
the toxicology, pharmacokinetics and biologically effective dose of
curcumin in humans have not been reported. This prospective phase-I
study evaluated these issues of curcumin in patients with one of the
following five high-risk conditions: 1) recently resected urinary
bladder cancer; 2) arsenic Bowen's disease of the skin; 3) uterine
cervical intraepithelial neoplasm (CIN); 4) oral leucoplakia; and 5)
intestinal metaplasia of the stomach. Curcumin was taken orally for 3
months. Biopsy of the lesion sites was done immediately before and 3
months after starting curcumin treament. The starting dose was 500
mg/day. If no toxicity > or = grade II was noted in at least 3
successive patients, the dose was then escalated to another level in
the order of 1,000, 2,000, 4,000, 8,000, and 12,000 mg/day. The
concentration of curcumin in serum and urine was determined by high
pressure liquid chromatography (HPLC). A total of 25 patients were
enrolled in this study. There was no treatment-related toxicity up to
8,000 mg/day. Beyond 8,000 mg/day, the bulky volume of the drug was
unacceptable to the patients. The serum concentration of ~curcumin
usually peaked at 1 to 2 hours after oral intake of crucumin and
gradually declined within 12 hours. The average peak serum
concentrations after taking 4,000 mg, 6,000 mg and 8,000 mg of curcumin
were 0.51 +/- 0.11 microM, 0.63 +/- 0.06 microM and 1.77 +/- 1.87
microM, respectively. Urinary excretion of curcumin was undetectable.
One of 4 patients with CIN and 1 of 7 patients with oral leucoplakia
proceeded to develop frank malignancies in spite of curcumin treatment.
In contrast, histologic improvement of precancerous lesions was seen in
1 out of 2 patients with recently resected bladder cancer, 2 out of 7
patients of oral leucoplakia, 1 out of 6 patients of intestinal
metaplasia of the stomach, 1 out of 4 patients with CIN and 2 out of 6
patients with Bowen's disease. In conclusion, this study demonstrated
that curcumin is not toxic to humans up to 8,000 mg/day when taken by
mouth for 3 months. Our results also suggest a biologic effect of
curcumin in the chemoprevention of cancer.
@cancer
Clin Immunol 1999 Nov;93(2):152-61 Curcumin causes the growth arrest
and apoptosis of B cell lymphoma by downregulation of egr-1, c-myc,
bcl-XL, NF-kappa B, and p53. Han SS, Chung ST, Robertson DA, Ranjan D,
Bondada S. Department of Microbiology and Immunology, Department of
General Surgery, Lexington, Kentucky 40536, USA. It has been well
known that curcumin is a powerful inhibitor of proliferation of
several tumor cells. However, the molecular basis of the
anti-proliferative effect of curcumin has not been investigated in
detail. In this paper, we present evidence to show that curcumin
inhibited proliferation of a variety of B lymphoma cells. At low
concentrations curcumin inhibited the proliferation of BKS-2, an
immature B cell lymphoma, more effectively than that of normal B
lymphocytes and caused the apoptosis of BKS-2 cells in a dose- and
time-dependent manner. Furthermore, curcumin downregulated the
expression of survival genes egr-1, c-myc, and bcl-X(L) as well as the
tumor suppressor gene p53 in B cells. In addition, NF-kappaB binding
activity was also downregulated almost completely by curcumin.
Stimulation with CpG oligonucleotides or anti-CD40 overcame growth
inhibition induced by low concentrations of curcumin. Our results
suggest that curcumin caused the growth arrest and apoptosis of BKS-2
immature B cell lymphoma by downregulation of growth and survival
promoting genes. Copyright 1999 Academic Press. PMID: 10527691
Evidence from a recent study, a human trial in smokers, makes this herb
look even more beneficial. Smokers' urine contains substances
(mutagens) that cause genetic mutation. Mutagens are often carcinogens,
or cancer causers. Indian researchers added 1.5 grams of turmeric a day
(about a teaspoon) to the diet of 16 smokers for a month. The result
was a significant reduction in urinary mutagens
beni
tcar...@elp.rr.com wrote:
> Hi John,
> Hi John,
> It was the phrase, "promotion of ROS" that caused me to file
> this with my other two negative curcumin papers. I've drawn no
> conclusions and continue to take not only 1500 mg of tumeric but 25
mg
> of piperine with it. This is a highly speculative combination which
> could put my bioavailable curcumin levels at far more than has been
> proven safe in humans. This is one of the more risky interventions I
> use and for that reason I'm very concerned about its safety. I
> diligently watch for, and save any negative information on substances
I
> take, and share much of this info on the premise that other savy life
> extensionists in the group also want to know of such negative
reports.
> Curcumin shows a huge potential compared to many other
> supplements and only for this reason will take even what I hope to be
a
> small risk with it. It's been a while since I posted my curcumin
info.
> Here's some of it. I see inclusion of all the refs is to long for
> Google if anyone wants to see the rest just ask.
Thank you for the list.
I take 500mg of curcumin+piperine a day to inhibit cox2 because of a
nose allergy I have.So naturally I am concerned about the ROS dangers
of it.
does somebody know wether taking curcumin with other vitamins lessen or
cancel the danger of it being a ROS producer?
beni.
hancock
> Hi John,
> Hi John,
> It was the phrase, "promotion of ROS" that caused me to file
> this with my other two negative curcumin papers.
Fair enough. One could also read this article as being remarkably
positive. Remember that exercise also promotes ROS. The really
interesting thing for me in this article is that there are many
studies that show that Curcumin has many of the same effects as SIRT1
(SIR2): promotes HSP70, reduces P53, extends life span. I was
speculating to myself that Curcumin may activate SIRT1 (SIR2). SIRT1
is an HDAC. But this paper says, no, Curcumin activates HAT. We may
find out then that SIRT1 and HAT result in the similar patterns of
histone deacetylation. That would be pretty remarkable.
As long as we're speculating, I'm willing to bet that Resveratrol also
activates HAT. Have you ever counted the number of similar observed
effects of Curcumin and Resveratrol:
both activate:
PPAR Gamma, P53, HSP70, ARE, ...
both inhibit:
COX2, Cytokines, ...
both extend life span
both have low bioavailability
And I have never found a single instance where Resveratrol and
Curcumin are observed to have opposite effects.
One interesting thing, though, SIRT1 is supposed to inhibit PPAR Gamma
and Curcumin and Resveratrol promote PPAR Gamma.
John
timo...@my-deja.com
If you read my abstracts on garlic Groups C (250 mg/kg) and Groupd D
(500 mg/kg) appear to be the optimal levels at least regarding the
induction of endogenous antioxidants. Whereas in Group F (2000 mg/kg)
caused a 55% mortality rate at 15 days. We know garlic has
neuroprotective and other beneficial properties in post-mitotic tissue.
However the induction of ROS in tumor cells that Thomas posted is no
doubt a beneficial result. In normal cells this doesn't seem to happen
at least at proper dosages, that is augmentation of endogenous
antioxidants in normal cells and induction of ROS in malfunctioning
cells.
Tim
timo...@my-deja.com
intake or by bodyweight? I would guess it must be referring to
bodyweight.
Tim
timo...@my-deja.com
In the abstract I posted on garlic at least as far as antioxidant
levels in the heart, group C (250 mg/kg) or groups D (300 mg/kg) appear
to be an optimal intake of garlic homogenate. Whereas 55% mortality in
the 2000 mg/kg at fifteen days appears to be detrimental to say the
least. I assume the dosage is referring to dry weight food intake or is
it bodyweight? But noticing Thomas posts wouldn't an increase in ROS in
cancerous cells be a good thing as it's a trigger for apoptosis?
Tim
timo...@my-deja.com
a while back Ian?
Phytother Res. 2003 Feb;17(2):97-106. Related Articles, Links
Garlic as an antioxidant: the good, the bad and the ugly.
Banerjee SK, Mukherjee PK, Maulik SK.
Department of Pharmacology, All India Institute of Medical Sciences,
New Delhi 110029, India.
Garlic has played an important dietary and medicinal role throughout
the history of mankind. In some Western countries, the sale of garlic
preparations ranks with those of leading prescription drugs. The
therapeutic efficacy of garlic encompasses a wide variety of ailments,
including cardiovascular, cancer, hepatic and microbial infections to
name but a few. However, the elucidation of its mechanism for
therapeutic action has proved to be more elusive and a unifying theory,
which could account for its reported multifarious activities, is yet to
emerge. Reactive oxygen species (ROS) seem to be at the core of many
disease processes and it is an attractive and convenient hypothesis
that garlic might exert its activities through modulatory effects on
ROS. A literature search on garlic and its antioxidant potential
churned up a surprisingly large amount of data, some of it good, some
bad and some of its definitely ugly.Various preparations of garlic,
mainly aged garlic extract (AGE), have been shown to have promising
antioxidant potential. However, the presence of more than one compounds
in garlic, with apparently opposite biological effects, has added to
the complexity of the subject. Raw garlic homogenate has been reported
to exert antioxidant potential but higher doses have been shown to be
toxic to the heart, liver and kidney.So where do we stand today on this
issue of garlic? Is garlic always good for health? How safe is it? Is
it necessary to isolate the antioxidant compounds for its medicinal use
in a more effective way? These issues are addressed in this review.
Copyright 2003 John Wiley & Sons, Ltd.
Publication Types:
Review
Review, Tutorial
PMID: 12601669 [PubMed - indexed for MEDLINE]