Turmeric extracts containing curcuminoids prevent experimental rheumatoid arthritis

Abstract

Turmeric has been used for centuries in Ayurvedic medicine as a treatment for inflammatory disorders including arthritis. On the basis of 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 antiarthritic 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 antiarthritic efficacy of an essential oil-depleted turmeric fraction and (2) suggest that the three major curcuminoids are responsible for this antiarthritic effect, while the remaining compounds in the crude turmeric extract may inhibit this protective effect.

Figure 1

Chemical structures of curcumin (1), demethoxycurcumin (2) and bis-demethoxycurcumin (3).

Figure 2

Effect of purified curcuminoids on joint inflammation. Female Lewis rats were injected on day 0 with SCW (25 μg/g) or vehicle. Joint swelling was assessed by daily calculation of the arthritic index (mean ± SEM) with statistical significance was determined by Students’ T test as described in methods. (A) Purified curcuminoids (4 mg curcuminoids/kg/d) or vehicle alone ip injections were begun 4 days prior to SCW administration (n=11 animals/group) and continued on a daily basis until 10 days after SCW injection at which time treatment frequency decreased to 5 days/week. * p < 0.02. (B) Purified curcuminoids (4 mg/kg/d) or vehicle alone ip injections were begun 4 days prior to SCW administration (n=5 animals/group) and continued daily for only 5 days with last dose 6 hours prior to SCW administration. * p < 0.01. (C) Purified curcuminoids (117 mg/kg/d) or vehicle alone were administered orally 4 days prior to SCW administration (n=10–11 animals/group) and continued on a daily basis until 10 days after SCW injection at which time treatment frequency decreased to 5 days/week. * p < 0.05.

Figure 2

Effect of purified curcuminoids on joint inflammation. Female Lewis rats were injected on day 0 with SCW (25 μg/g) or vehicle. Joint swelling was assessed by daily calculation of the arthritic index (mean ± SEM) with statistical significance was determined by Students’ T test as described in methods. (A) Purified curcuminoids (4 mg curcuminoids/kg/d) or vehicle alone ip injections were begun 4 days prior to SCW administration (n=11 animals/group) and continued on a daily basis until 10 days after SCW injection at which time treatment frequency decreased to 5 days/week. * p < 0.02. (B) Purified curcuminoids (4 mg/kg/d) or vehicle alone ip injections were begun 4 days prior to SCW administration (n=5 animals/group) and continued daily for only 5 days with last dose 6 hours prior to SCW administration. * p < 0.01. (C) Purified curcuminoids (117 mg/kg/d) or vehicle alone were administered orally 4 days prior to SCW administration (n=10–11 animals/group) and continued on a daily basis until 10 days after SCW injection at which time treatment frequency decreased to 5 days/week. * p < 0.05.

Figure 2

Effect of purified curcuminoids on joint inflammation. Female Lewis rats were injected on day 0 with SCW (25 μg/g) or vehicle. Joint swelling was assessed by daily calculation of the arthritic index (mean ± SEM) with statistical significance was determined by Students’ T test as described in methods. (A) Purified curcuminoids (4 mg curcuminoids/kg/d) or vehicle alone ip injections were begun 4 days prior to SCW administration (n=11 animals/group) and continued on a daily basis until 10 days after SCW injection at which time treatment frequency decreased to 5 days/week. * p < 0.02. (B) Purified curcuminoids (4 mg/kg/d) or vehicle alone ip injections were begun 4 days prior to SCW administration (n=5 animals/group) and continued daily for only 5 days with last dose 6 hours prior to SCW administration. * p < 0.01. (C) Purified curcuminoids (117 mg/kg/d) or vehicle alone were administered orally 4 days prior to SCW administration (n=10–11 animals/group) and continued on a daily basis until 10 days after SCW injection at which time treatment frequency decreased to 5 days/week. * p < 0.05.

Figure 3

Comparison of effect of turmeric fraction (TF) vs. purified curcuminoids (CURC) on incidence of arthritis vs. hepatic granuloma formation. Female Lewis rats were injected on day 0 with SCW (25 μg/g) or vehicle. Botanical extracts or vehicle alone ip injections were begun 4 days prior to SCW administration and continued on a daily basis until 10 days after SCW injection at which time treatment frequency decreased to 5 days/week. Incidence of joint swelling at day 28 was assessed by calculation of the arthritic index (n=11–34 animals/group). The incidence of granuloma formation was assessed histologically as described in methods (n=11–23 animals/group). Statistical significance was determined by Fisher’s Exact Testing. * p < 0.05 vs. untreated. ** p <.007 vs. untreated.