Curcumin

The immune system has evolved to protect the host from microbial infection; nevertheless, a breakdown in the immune system often results in infection, cancer, and autoimmune diseases. Multiple sclerosis, rheumatoid arthritis, type 1 diabetes, inflammatory bowel disease, myocarditis, thyroiditis, uveitis, systemic lupus erythromatosis, and myasthenia gravis are organ-specific autoimmune diseases that afflict more than 5% of the population worldwide.

Although the etiology is not known and a cure is still wanting, the use of herbal and dietary supplements is on the rise in patients with autoimmune diseases, mainly because they are effective, inexpensive, and relatively safe. Curcumin is a polyphenolic compound isolated from the rhizome of the plant Curcuma longa that has traditionally been used for pain and wound-healing.

Recent studies have shown that curcumin ameliorates multiple sclerosis, rheumatoid arthritis, psoriasis, and inflammatory bowel disease in human or animal models. Curcumin inhibits these autoimmune diseases by regulating inflammatory cytokines such as IL-1beta, IL-6, IL-12, TNF-alpha and IFN-gamma and associated JAK-STAT, AP-1, and NF-kappaB signaling pathways in immune cells.

Although the beneficial effects of nutraceuticals are traditionally achieved through dietary consumption at low levels for long periods of time, the use of purified active compounds such as curcumin at higher doses for therapeutic purposes needs extreme caution. A precise understanding of effective dose, safe regiment, and mechanism of action is required for the use of curcumin in the treatment of human autoimmune diseases.

Curcumin and autoimmune disease.: Adv Exp Med Biol. 2007;595:425-51 Authors: Bright JJ

PMID: 17569223 [PubMed - in process] (14/07/07)

Turmeric, the spice that flavours and gives its yellow color to many curries and other foods, has been used for centuries by practitioners of Ayurvedic medicine to treat inflammatory disorders. Turmeric extract containing the ingredient curcumin is marketed widely in the Western world as a dietary supplement for the treatment and prevention of a variety of disorders, including arthritis.

At the UA College of Medicine, Janet L. Funk, MD, working with Barbara N. Timmermann, PhD, then-director of the National Institutes of Health (NIH)-funded Arizona Center for Phytomedicine Research at the UA, set out to determine whether (and how) turmeric works as an anti-arthritic. They began by preparing their own extracts from the rhizome, or root, of the plant, providing themselves with well-characterised materials to test and to compare with commercially available products. (Dr. Timmermann since has joined the faculty of the University of Kansas, Lawrence, Kan.)

Dr. Funk and her colleagues then tested in animal models a whole extract of turmeric root, only the essential oils, and an oil-depleted extract containing the three major curcuminoids found in the rhizome. Of the three extracts, the one containing the major curcuminoids was most similar in chemical composition to commercially available turmeric dietary supplements. It also was the most effective, completely inhibiting the onset of rheumatoid arthritis.

Dr. Funk, an endocrinologist in the UA Department of Medicine, says this study provides several noteworthy "firsts." Completed with the researchers' own prepared, well-defined extracts, the study represents the first documentation of the chemical composition of a curcumin-containing extract tested in a living organism, in vivo, for anti-arthritic efficacy. It also provides the first evidence of anti-arthritic efficacy of a complex turmeric extract that is analogous in composition to turmeric dietary supplements.

The significance, she explains, is that translating the results of trials such as these to clinical use depends on accurate information about the chemical content and biological activity of the botanical supplements available for use. This work paves the way for the preclinical and clinical trials needed before turmeric supplements can be recommended for medicinal use in preventing or suppressing rheumatoid arthritis.

This study also provides the first in vivo documentation of a mechanism of action – how curcumin-containing extracts protect against arthritis. The researchers found that the curcuminoid extract inhibits a transcription factor called NF-KB from being activated in the joint. A transcription factor is a protein that controls when genes are switched on or off. Once the transcription factor NF-KB is activated, or turned on, it binds to genes and enhances production of inflammatory proteins, destructive to the joint. The finding that curcuminoid extract inhibits activation of NF-KB suggests that turmeric dietary supplements share the same mechanism of action as anti-arthritic pharmaceuticals under development that target NF-KB. It also suggests that turmeric may have a use in other inflammatory disorders, such as asthma, multiple sclerosis and inflammatory bowel disease.

In addition to preventing joint inflammation, Dr. Funk's study shows that the curcuminoid extract blocked the pathway that affects bone resorption. Noting that bone loss associated with osteoporosis in women typically begins before the onset of menopause, she has begun work on another NIH-funded study to determine whether turmeric taken as a dietary supplement during perimenopause can prevent bone loss and osteoporosis. Both of the studies are supported by the National Center for Complementary and Alternative Medicine (NCCAM) and the Office of Dietary Supplements (ODS), both of the NIH.

An initial publication of the rheumatoid arthritis study results in the Journal of Natural Products, which was among the most-accessed articles from April-June 2006 in this prestigious American Chemical Society journal, is being followed by more detailed study results, which will appear in the November 2006 issue of the American College of Rheumatology flagship journal, Arthritis and Rheumatism. The article, "Efficacy and Mechanism of Action of Turmeric Supplements in the Treatment of Experimental Arthritis," is scheduled to appear in the online issue of Arthritis and Rheumatism Monday, Oct. 30, 2006.

Contributors to the study include Janet L. Funk, MD; Jennifer B. Frye; Janice N. Oyarzo, MS; Nesrin Kuscuoglu, PhD; Jonathan Wilson; Gwen McCaffrey, PhD; Gregory Stafford; Guanjie Chen, MD; R. Clark Lantz, PhD; Shivanand D. Jolad, PhD; Aniko M. Soìlyom, PhD; Pawel R. Kiela, DVM, PhD; and Barbara N. Timmermann, PhD.

Source: University of Arizona Health Sciences Center (30/10/06) 

Studies in mice suggest that curcumin, a compound found in the curry spice tumeric, may block the progression of MS.

Dr. Chandramohan Natarajan, of Vanderbilt University in Nashville, Tennessee, found that mice injected with curcumin showed little or no disease symptoms, while untreated animals went on to develop severe paralysis.

Interest in the possible protective properties of curcumin arose after studies showed very low levels of neurological disease in elderly Indian people. Also, studies have already confirmed curcumin as a potent anti-inflammatory agent. Curcumin also appears to slow the progression of Alzheimer's disease in mice.

In their 30 day study, Dr. Natarajan’s team administered 50 and 100 microgram doses of curcumin, three times a week to a group of mice bred to develop experimental autoimmune encephalomyelitis, (EAE) the animal mode of MS. They then monitored the mice for signs of MS-like neurological impairment.

By day 15, those mice which had not received curcumin had a marked progression of EAE with complete paralysis of both hind limbs. In contrast, mice given the 50 microgram dose of the curry compound showed only minor symptoms, such as a temporarily stiff tail. And mice given the 100 microgram dose appeared completely unimpaired throughout the 30 days of the study.

The results did not surprise Dr. Natarajan. In Asian countries, such as India and China, where people eat more spicy foods and more yellow compounds like curcumin, reports of MS are “very, very rare”.

Just how curcumin might work to halt the progression of demyelination remains unclear. But the Nashville researchers believe it may interrupt the production of IL-12 , which plays a key role in signalling immune cells to attack the myelin sheath.