Ishiwa J, Sato T, Mimaki Y, Sashida Y, Yano M, Ito A
Department of Biochemistry and Molecular Biology, School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan.
J Rheumatol. 2000 Jan;27(1):20-5.
Flavonoids including nobiletin are known to exert many biological actions in vitro. We investigated the chondroprotective effect of citrus flavonoids, especially nobiletin, using cultured rabbit synovial fibroblasts and articular chondrocytes.
We examined the effects of citrus flavonoids on the production and gene expression of matrix metalloproteinases (MMP) and prostaglandin E2 (PGE2)production in rabbit synovial fibroblasts.
Six flavonoids isolated from Citrus depressa Rutaceae including tangeretin, 6-demethoxytangeretin, nobiletin, 5-demethylnobiletin, 6-demethoxynobiletin, and sinensetin suppressed the interleukin 1 (IL-1) induced production of proMMP-9/progelatinase B in rabbit synovial cells in a dose dependent manner (<64 microM); nobiletin most effectively suppressed proMMP-9 production along with the decrease in its mRNA. Nobiletin also reduced IL-1 induced production of PGE2 in the synovial cells, but did not modify the synthesis of total protein. These suppressive effects of nobiletin were also observed in rabbit articular chondrocytes. Nobiletin inhibited proliferation of rabbit synovial fibroblasts in the growth phase.
These results suggest nobiletin is a novel antiinflammatory candidate that has the potential to inhibit PGE2 production, matrix degradation of the articular cartilage, and pannus formation in osteoarthritis and rheumatoid arthritis.
包括川陈皮素在内的类黄酮在体外具有多种生物学作用。我们使用培养的兔滑膜成纤维细胞和关节软骨细胞，研究了柑橘类黄酮尤其是川陈皮素的软骨保护作用。
我们检测了柑橘类黄酮对兔滑膜成纤维细胞中基质金属蛋白酶（MMP）的产生、基因表达以及前列腺素E2（PGE2）产生的影响。
从芸香科的温州蜜柑中分离出的六种类黄酮，包括橘红素、6-去甲氧基橘红素、川陈皮素、5-去甲基川陈皮素、6-去甲氧基川陈皮素和甜橙黄酮，以剂量依赖方式（<64 microM）抑制白细胞介素1（IL-1）诱导的兔滑膜细胞中前MMP-9/前明胶酶B的产生；川陈皮素最有效地抑制前MMP-9的产生及其mRNA的减少。川陈皮素还减少了IL-1诱导的滑膜细胞中PGE2的产生，但不改变总蛋白的合成。在兔关节软骨细胞中也观察到了川陈皮素的这些抑制作用。川陈皮素在生长期抑制兔滑膜成纤维细胞的增殖。
这些结果表明川陈皮素是一种新型抗炎候选物，具有抑制骨关节炎和类风湿关节炎中PGE2产生、关节软骨基质降解和血管翳形成的潜力。
