Biochem Biophys Res Commun. 2008 Aug 22;373(2):181-5. Epub 2008 Jun 9.

Nobiletin, a citrus polymethoxy flavonoid, suppresses gene expression and production of aggrecanases-1 and -2 in collagen-induced arthritic mice.

Imada K, Lin N, Liu C, Lu A, Chen W, Yano M, Sato T, Ito A.

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Department of Biochemistry and Molecular Biology, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji-shi, Tokyo 192-0392, Japan. imadak@ps.toyaku.ac.jp <imadak@ps.toyaku.ac.jp>

Abstract

Aggrecanase-1/a disintegrin and metalloproteinase with thrombospondin-like motifs (ADAMTS)-4 and aggrecanase-2/ADAMTS-5 have been shown to play crucial roles in cartilage destruction in arthritic diseases, including rheumatoid arthritis and osteoarthritis. In this study, we examined the effects of nobiletin, a citrus polymethoxy flavone, on the expression and production of ADAMTS-4 and -5 in vitro and in vivo. Nobiletin (16-64muM) interfered with the interleukin (IL)-1beta-mediated ADAMTS-4 and -5 mRNA expression in cultured human synovial fibroblasts. Furthermore, intraperitoneal administration of nobiletin (15, 30, and 60mg/kg) also suppressed ADAMTS-4 and -5 mRNA expression in the joint tissues of collagen-induced arthritic (CIA) mice. Immunohistochemical analysis using an antibody against aggrecan neoepitope (NVTEGE(373)) revealed that aggrecanase-mediated degradation of aggrecan in cartilage was effectively inhibited by nobiletin. These results provide novel evidence that nobiletin effectively interferes with gene expression of ADAMTS-4 and -5, and thereby prevents cartilage destruction in CIA mice.

PMID:: 18541144; [PubMed - indexed for MEDLINE]

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