Funk Janet L, Frye Jennifer B, Oyarzo Janice N, Kuscuoglu Nesrin, Wilson Jonathan, McCaffrey Gwen, Stafford Gregory, Chen Guanjie, Lantz R Clark, Jolad Shivanand D, Sólyom Aniko M, Kiela Pawel R, Timmermann Barbara N
University of Arizona, Tucson, USA.
Arthritis Rheum. 2006 Nov;54(11):3452-64. doi: 10.1002/art.22180.
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).
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.
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.
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.
目前缺乏科学证据证明用于治疗关节炎的姜黄膳食补充剂具有抗关节炎功效。因此，我们开展了研究，以确定一种特征明确的姜黄提取物在类风湿性关节炎（RA）动物模型中的抗关节炎功效及作用机制。
采用高效液相色谱法测定市售姜黄膳食补充剂的成分。分离出一种成分与这些补充剂相似的含姜黄素的姜黄提取物，并在链球菌细胞壁诱导的关节炎发作之前或之后腹腔注射给雌性Lewis大鼠。通过临床、组织学检查以及测量骨密度来确定预防关节肿胀和破坏的功效。通过分析姜黄对关节转录因子激活的影响、关节基因表达的微阵列分析以及对基因表达改变的生理效应验证来阐明作用机制。
一种去除了精油的姜黄组分以剂量依赖的方式显著抑制关节炎症和关节周围破坏。体内治疗可防止NF-κB的局部激活以及随后介导关节炎症和破坏的NF-κB调节基因的表达，包括趋化因子、环氧化酶2和RANKL。与这些发现一致，姜黄提取物治疗可抑制炎症细胞浸润、关节中前列腺素E2的水平以及关节周围破骨细胞的形成。
这些转化研究证明了体内功效，并确定了一种特征明确的姜黄提取物的作用机制，这支持对姜黄膳食补充剂治疗RA进行进一步的临床评估。
