Efficacy and mechanism of action of turmeric supplements in the treatment of experimental arthritis.
OBJECTIVE
Scientific evidence is lacking for the antiarthritic efficacy of turmeric dietary supplements that are being promoted for arthritis treatment. Therefore, we undertook studies to determine the antiarthritic efficacy and mechanism of action of a well-characterized turmeric extract using an animal model of rheumatoid arthritis (RA).


METHODS
The composition of commercial turmeric dietary supplements was determined by high-performance liquid chromatography. A curcuminoid-containing turmeric extract similar in composition to these supplements was isolated and administered intraperitoneally to female Lewis rats prior to or after the onset of streptococcal cell wall-induced arthritis. Efficacy in preventing joint swelling and destruction was determined clinically, histologically, and by measurement of bone mineral density. Mechanism of action was elucidated by analysis of turmeric's effect on articular transcription factor activation, microarray analysis of articular gene expression, and verification of the physiologic effects of alterations in gene expression.


RESULTS
A turmeric fraction depleted of essential oils profoundly inhibited joint inflammation and periarticular joint destruction in a dose-dependent manner. In vivo treatment prevented local activation of NF-kappaB and the subsequent expression of NF-kappaB-regulated genes mediating joint inflammation and destruction, including chemokines, cyclooxygenase 2, and RANKL. Consistent with these findings, inflammatory cell influx, joint levels of prostaglandin E(2), and periarticular osteoclast formation were inhibited by turmeric extract treatment.


CONCLUSIONS
These translational studies demonstrate in vivo efficacy and identify a mechanism of action for a well-characterized turmeric extract that supports further clinical evaluation of turmeric dietary supplements in the treatment of RA.
Funk
Janet L
JL
University of Arizona, Tucson, USA. jfunk@u.arizona.edu
Frye
Jennifer B
JB
Oyarzo
Janice N
JN
Kuscuoglu
Nesrin
N
Wilson
Jonathan
J
McCaffrey
Gwen
G
Stafford
Gregory
G
Chen
Guanjie
G
Lantz
R Clark
RC
Jolad
Shivanand D
SD
Sólyom
Aniko M
AM
Kiela
Pawel R
PR
Timmermann
Barbara N
BN
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D001425:Bacterial Outer Membrane Proteins / Q000494:pharmacology; D030024:Curcuma; D019587:Dietary Supplements; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006099:Granuloma / Q000188:drug therapy / Q000473:pathology; D007596:Joints / Q000378:metabolism / Q000473:pathology; D008099:Liver / Q000473:pathology; D009000:Monocytes / Q000187:drug effects / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D051381:Rats; D011917:Rats, Inbred Lew; D027343:Rhizome / Q000737:chemistry; D013154:Spleen / Q000473:pathology; D013291:Streptococcus
D000975:Antioxidants; D001425:Bacterial Outer Membrane Proteins; D016328:NF-kappa B; D010936:Plant Extracts; C012596:turmeric extract; D015232:Dinoprostone