Turmeric has been used for centuries in Ayurvedic medicine as a treatment for inflammatory disorders including arthritis. Based on this traditional usage, dietary supplements containing turmeric rhizome and turmeric extracts are also being used in the western world for arthritis treatment and prevention. However, to our knowledge, no data are available regarding anti-arthritic efficacy of complex turmeric extracts similar in composition to those available for use as dietary supplements. Therefore, the studies described here were undertaken to determine the in vivo efficacy of well characterized curcuminoid-containing turmeric extracts in the prevention or treatment of arthritis using streptococcal cell wall (SCW) induced arthritis, a well-described animal model of rheumatoid arthritis (RA). Arthritic index, a clinical measure of joint swelling, was used as the primary endpoint for assessing the effect of extracts on joint inflammation. An essential oil-depleted turmeric fraction containing 41% of the three major curcuminoids was efficacious in preventing joint inflammation when treatment was started before, but not after, the onset of joint inflammation. A commercial sample containing 94% of the three major curcuminoids was more potent in preventing arthritis than the essential oil-depleted turmeric fraction when compared by total curcuminoid dose per body weight. In conclusion, these data (1) document the in vivo anti-arthritic efficacy of an essential oil-depleted turmeric fraction and (2) suggest that the three major curcuminoids are responsible for this anti-arthritic effect, while the remaining compounds in the crude turmeric extract may inhibit this protective effect.
Turmeric (Curcuma longa L. [Zingiberaceae]) is a perennial native to Asia where its rhizome is used as a spice (being responsible for the yellow color of curry), a pigment dye for textiles or for skin in religious ceremonies, and a traditional medicine, primarily used for the treatment of inflammatory disorders.1 Typical dietary intake of turmeric is estimated to be as high as 2.5 g/d (approximately 100 mg curcumin/d) in some countries,2 while up to 8 g/d of curcumin, one of the three major curcuminoids (curcumin , demethoxycurcumin  and bis-demethoxycurcumin , see Figure 1) that constitute 3% of the total rhizome, is without evidence of side effects in Phase I clinical trials.3
Organic extracts of the rhizomes of turmeric have previously been shown to have anti-inflammatory effects in vitro.4–8 However, analysis of these published reports is confounded by the use of extracts that are neither well characterized nor uniform in their composition. Most of these studies have evaluated the effects of various uncharacterized extracts designated as “curcumin” that inhibit production of TNF-α and IL-1β, as well as PGE2.4–8. The major site of action of these curcumin extracts is thought to be inhibition of transcription factor activation, including activation of NF-κB.4,5,9 NF-κB activation during inflammation leads to increased gene expression of cytokines (TNF-α, IL-1β), chemokines (MCP-1) and other inflammatory proteins (COX-2) that are critical mediators of joint inflammation in rheumatoid arthritis (RA).4,10–12
Analysis of the scant number of publications in the literature investigating the anti-arthritic efficacy of turmeric in animal or human studies is again confounded by the lack of characterization of the extracts tested, as well as the variety of models studied. In rodents, an uncharacterized curcumin extract (10–80 mg/kg orally) has been reported to reduce carrageenin-induced paw edema, a model of acute inflammation rather than actual destructive arthritis,13 as well as paw swelling in adjuvant-induced arthritis (100–300 mg/kg/d orally).14,15 In humans, one small double blind crossover study evaluating a single dose of an uncharacterized curcumin extract (1.2g/day) or phenylbutazone in RA (n=18 patients) reported some success in decreasing disease symptoms.16 In none of these reports was a chemical analysis of what one would assume to be curcumin-enriched extracts presented. In addition, to our knowledge, there are no reports on the anti-arthritic effect of unpurified, chemically complex turmeric extracts more analogous in composition to dietary turmeric supplements available for over-the-counter use.
Previous evaluation by our group of randomly chosen, over-the-counter turmeric dietary supplements (n=9), demonstrated that the majority of these extracts do not contain essential-oils but are still very complex extracts that are composed of less than 50% curcuminoids (median value, 19.3%).17 We therefore prepared, chemically characterized, and then tested the in vitro anti-inflammatory efficacy, followed by the in vivo anti-arthritic efficacy, of a complex turmeric extract depleted in essential oils and containing less than 50% curcuminoids which we isolated from a commercial source of ground turmeric rhizome. The efficacy of this chemically complex turmeric extract was compared to that of a commercially available curcumin product (greater than 90% curcuminoids by HPLC analysis). The animal model used, streptococcal cell wall (SCW)-induced arthritis, is a well-characterized animal model of rheumatoid arthritis.18–20 In this model, over a 28 day course, female Lewis rats develop an initial acute phase of joint swelling followed by a chronic phase of inflammation that is associated with actual joint destruction. Joint histopathology in this model is very similar to that seen in rheumatoid arthritis (RA), a disease typified by recurrent cycles of joint inflammation and gradual joint destruction.21,22 In addition, a granulomatous inflammatory response, similar to that responsible for inactivating tuberculosis bacilli by walling off the invading bacteria, occurs in the liver and spleen of these animals at sites of SCW deposition.18–20