Turmeric Curry May Keep Alzheimer's at Bay

A spice used for thousands of years, curry, may be a powerful new weapon in fighting Alzheimer's Disease, researchers said.

Researchers from UCLA and the Department of Veterans Affairs said their study of curcumin, the yellow pigment in curry, found it broke up existing beta amyloid on rats' brains and helped prevent accumulation of the destructive plaque.

Reporting in the Journal of Biological Chemistry, the team said curcumin is more effective in stopping the protein fragments from forming than many other drugs being tested to treat the disease that affects 4 million Americans and millions more worldwide. "The prospect of finding a safe and effective new approach to both prevention and treatment of Alzheimer's disease is tremendously exciting," said Gregory Cole, the main UCLA investigator.

"Curcumin has been used for thousands of years as a safe anti-inflammatory in a variety of ailments as part of Indian traditional medicine," Cole said. Recent animal studies "support a growing interest in its possible use for diseases of aging involving oxidative damage and inflammation like Alzheimer's, cancer and heart disease."

Cole called for human trials of curcumin to establish safe and effective doses.

Curcumin inhibits formation of Abeta oligomers and fibrils and binds plaques and reduces amyloid in vivo

By GRECC (VA Medical) and Medicine, University of California Los Angeles

Alzheimer's disease 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 Alzheimer's disease 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. Alzheimer'sdisease 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 Alzheimer's disease.

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.

Curcumin, the activeconstituent of turmeric, inhibits amyloid peptide-induced cytochemokinegene expression and CCR5-mediated chemotaxis of THP-1 monocytes by modulating early growth response-1 transcription factor.

Epidemiological studies show reduced risk of Alzheimer's disease among patients usingnon-steroidal inflammatory drugs (NSAID) indicating the role of inflammation in Alzheimer's disease. Studies have shown a chronic CNS inflammatory response associated with increased accumulation of amyloid peptide and activated microglia in Alzheimer's disease. Our previous studies showed that interaction of Abeta1-40 or fibrilar Abeta1-42 caused activation of nuclear transcription factor, early growth response-1 (Egr-1), which resulted in increased expression of cytokines (TNF-alpha and IL-1beta) and chemokines (MIP-1beta, MCP-1 and IL-8) in monocytes. We determined whether curcumin, a natural product known to have anti-inflammatory properties, suppressed Egr-1 activation and concomitant expression of cytochemokines. We show that curcumin (12.5-25 microm) suppresses the activation of Egr-1 DNA-binding activity in THP-1 monocytic cells. Curcuminabrogated Abeta1-40-induced expression of cytokines (TNF-alpha and IL-1beta)and chemokines (MIP-1beta, MCP-1 and IL-8) in both peripheral blood monocytesand THP-1 cells. We found that curcumin inhibited Abeta1-40-induced MAPkinase activation and the phosphorylation of ERK-1/2 and its downstream target Elk-1. We observed that curcumin inhibited Abeta1-40-induced expressionof CCR5 but not of CCR2b in THP-1 cells. This involved abrogation of Egr-1DNA binding in the promoter of CCR5 by curcumin as determined by: (i) electrophoretic mobility shift assay, (ii) transfection studies with truncated CCR5 gene promoter constructs, and (iii) chromatin immunoprecipitation analysis. Finally, curcumin inhibited chemotaxis of THP-1 monocytes inresponse to chemoattractant. The inhibition of Egr-1 by curcumin may represent a potential therapeutic approach to ameliorate the inflammation and progression of Alzheimer's disease.

Giri RK, Rajagopal V, Kalra VK.

Department of Biochemistry and Molecular Biology, University of Southern California, Keck School of Medicine, Los Angeles, California 90033, USA.

Alzheimer's Research

Nutritional antioxidants and the heme oxygenase pathway of stress tolerance: novel targets for neuroprotection in Alzheimer's disease. PMID:15141484

Redox regulation of heat shock protein expression in aging and neurodegenerative disorders associated with oxidative stress: a nutritional approach. PMID:14661103

Nitric oxide and cellular stress response in brain aging andneurodegenerative disorders: the role of vitagenes. PMID:15341181

Oxidative stress in the pathogenesis of Alzheimer's disease and antioxidant neuroprotection PMID:9565761

Redox regulation in neurodegeneration and longevity: role of the heme oxygenase and HSP70 systems in brain stress tolerance. PMID:15345150

The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. PMID:11606625

Regional distribution of heme oxygenase, HSP70, and glutathione in brain: relevance for endogenous oxidant/antioxidant balance and stress tolerance. PMID:11933050

Evidence of oxidative stress and in vivo neurotoxicity of beta-amyloid in a transgenic mouse model of Alzheimer's disease: a chronic oxidative paradigm for testing antioxidant therapies in vivo. PMID:9546346

The heat shock/oxidative stress connection. Relevance to Alzheimer disease. PMID:8871938

Alzheimer's disease and oxidative stress: implications for novel therapeutic approaches. PMID:10096843

Curcumin, an antioxidant and anti-inflammatory agent, induces heme oxygenase-1 and protects endothelial cells against oxidative stress.

Heme oxygenase-1: function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury. PMID:8679227

Alzheimer's disease--synergistic effects of glucose deficit, oxidative stress and advanced glycation endproducts. PMID:9720973

Antioxidant strategies for Alzheimer's disease. PMID:12133201

Redox-active metals, oxidative stress, and Alzheimer's disease pathology. PMID:15105262

Oxidative stress hypothesis in Alzheimer's disease. PMID:9165306

Regulation of heme oxygenase expression by cyclopentenone prostaglandins. PMID:12709576

Vitamin E and other antioxidants in neuroprotection. PMID:10389030

Vitamin E as an antioxidant/free radical scavenger against amyloid beta-peptide-induced oxidative stress in neocortical synaptosomal membranes and hippocampal neurons in culture: insights into Alzheimer's disease. PMID:10658956

Decreased activity of the antioxidant heme oxygenase enzyme: implications in ischemia and in Alzheimer's disease. PMID:12057765

Homocysteine and B vitamins relate to brain volume and white-matter changes in geriatric patients with psychiatric disorders

Elevated homocysteine and low folate were associated with radiological markers of neuropathology. Since no patient had clinically deficient folate, it may be important to rethink what defines functionally significant micronutrient deficiency and explore what this means in different age- and health-status groups.

Am J Geriatr Psychiatry. 2004 PMID:15545331

Can cognitive deterioration associated with Down syndrome be reduced?

By Thiel R, Fowkes SW. Center for Natural Health Research, Down Syndrome-Epilepsy Foundation, 2005;64(3):524-32.

This paper suggests that essential nutrients such as folate, vitamin B6, vitamin C, vitamin E, selenium, and zinc, as well as alpha-lipoic acid and carnosine may be partially preventive. Continue

Standardized Curcumin (Turmeric)

Curcumin, the active constituent of the spice turmeric, is an antioxidant that may possess benefits for degenerative diseases. Curcumin has also shown a wide range of health-boosting properties, including support for inflammation relief and circulation.

In several studies, curcumin has shown increasing potential as an anti-cancer agent. Curcumin has previously displayed success in protecting against the development of colonic tumors in laboratory animals treated with colon cancer-inducing agents. In a study published in the Journal of Carcinogenesis, curcumin appeared to induce cellular arrest when added to human colon cancer cells. Other studies show that curcumin's anti-cancer effects appear to be due to its ability to induce apoptosis, a predetermined death of cells, as well as to arrest the cell cycle. Other published studies show that curcumin effectively inhibits cancer cell growth in human skin cancer, lung cancer, and prostate cancer cells. Large randomized, double-blind, placebo-controlled studies need to be conducted in humans to prove benefits in cancer patients.

Curcumin may hold anti-inflammatory properties, as studies have shown that it may benefit joint function, while reducing inflammation and pain. Curcumin has been shown to reduce inflammation by lowering histamine levels, while possibly increasing the production of natural cortisone by the adrenal glands. This antioxidant has been used in rheumatoid arthritis trials, and was shown to display some benefits for reducing inflammation and symptoms such as pain and stiffness. And in a study published in the International Journal of Clinical Pharmacology and Therapeutic Toxicology, curcumin was proven effective at easting post-surgical inflammation.

In studies, curcumin has displayed other health benefits. It has been shown to aid circulation, as it may reduce platelets from clumping together, and may defend against atherosclerosis.

Curcumin is also effective at shielding the liver from various toxic compounds. And one recent study showed that curcumin may have some benefit for cystic fibrosis.

Nutraceutical Research

A growing body of evidence shows how nutraceuticals may offer many advantages for the future of medicine.

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