The Curry Spice Curcumin Reduces Oxidative Damage and Amyloid Pathology in an Alzheimer Transgenic Mouse
Giselle P. Lim1, 3, Teresa Chu1, 3, Fusheng Yang1, 3, Walter Beech1, 3, Sally A. Frautschy1, 2, 3, and Greg M. Cole1, 2, 3
Departments of 1 Medicine and 2 Neurology, University of California, Los Angeles, Los Angeles, California 90095, and 3 Greater Los Angeles Veterans Affairs Healthcare System, Geriatric Research, Education and Clinical Center, Sepulveda, California 91343
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-1, 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 -amyloid (A), soluble A, 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.
Key words: Alzheimer’s disease; inflammation; oxidative damage; anti-oxidant; microglia; plaque; interleukin-1; Tg2576; APPswedish
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By Shane Starling
August 22, 2008 – An eight-week clinical trial has found consumption of curcumin can benefit advanced pancreatic cancer sufferers.
Twenty five participants were administered supplements incorporating a patented curcumin ingredient manufactured by New Jersey-based herbals specialist, Sabinsa, which was found to advantage pancreatic cancer sufferers despite the supplements demonstrating “poor oral bioavailability”.
The study, published in the American Association for Cancer Research’s Clinical Cancer Research, was conducted by researchers at the University of Texas – MD Anderson Cancer Center.
They found, despite the limited absorption potential, the ingredient, Curcumin, had anti-cancer potential albeit in a small number of participants.
“A key question related to treatment with curcumin is its poor bioavailability after being taken orally. Our results also indicated that only low levels of curcumin are detectable in plasma (steady-state level at day 3 is f22-41 ng/mL),” the researchers wrote.
“Nevertheless, some of the patients had biological activity of curcumin as evidenced by the anti-tumor effects in two patients and by effects on cytokine levels and on NF-nB, COX-2, and pSTAT.”
The researchers posited that the reason curcumin could have an effect in the body despite its bioavailability “issues” may be due to the fact it largely consists in conjugated forms such as glucoronide in human (and rodent) plasma and is therefore cloaked in the blood supply.
Because of this factor, the researchers noted, “further investigations are needed to elucidate the relationship between the form of curcumin, its relative pharmacologic activity, and circulating versus tumor tissue levels.”
They concluded: “Our current study shows that oral curcumin is tolerated without toxicity at doses of 8 g/d for up to 18 months. Although this molecule is poorly absorbed, with low nanogram levels of circulating curcumin detected at steady-state, biological activity is evident. Preclinical data suggest that curcumin has potent activity against pancreatic cancer, but higher levels of exposure need to
Curcumin is a natural pigment that gives the spice turmeric its yellow colour. Recent studies have investigated its potential to lower cholesterol levels, improve cardiovascular health, reduce the risk of Alzheimer’s and diabetes as well as cancer-fighting properties.
Sabinsa’s Curcumin is an extract of turmeric roots standardized for 95 percent of phenolic compounds called curcuminoids.
One of the researchers, Vladimir Badmaev, is the vice president of scientific and medical affairs.
Clinical Cancer Research
2008:14(14), July 15, 2008
“Phase II Trial of Curcumin in Patients with Advanced Pancreatic Cancer”
Authors: Navneet Dhillon, Bharat B Aggarwal, Robert A Newman, Robert A.Wolff, Ajaikumar B Kunnumakkara, James L Abbruzzese, Chaan S Ng, Vladimir Badmaev, Razelle Kurzrock