School of Pharmacy, Taipei Medical University, Sinyi District, Taipei City 110, Taiwan, ROC.
Nutr Res. 2010 Jan;30(1):57-65. doi: 10.1016/j.nutres.2009.10.020.
Septic arthritis is an inflammatory arthropathy characterized by degeneration of articular cartilage. Icariin, the main active flavonoid glucoside isolated from Epimedium pubescens, is used as antirheumatics (or antiinflammatory), tonics, and aphrodisiacs in traditional Chinese medicine. In this study, we used lipopolysaccharide (LPS) to simulate the in vitro inflammatory response of chondrocytes during septic arthritis. Our hypothesis is that the icariin can protect chondrocytes from LPS-induced inflammation and extracellular matrix degradation. The inflammation of neonatal mice chondrocytes was induced by LPS and the antiinflammatory effects were examined. The synthesis of nitric oxide was analyzed, whereas the titer of glycosaminoglycan and total collagen were measured and the gene expressions (including inducible nitric oxide synthase [iNOS], matrix metalloproteinase [MMP]-1, MMP-3, and MMP-13) were evaluated. The results showed that the viability of chondrocytes, extracellular matrix synthesis, was significantly decreased, whereas nitric oxide synthesis was significantly increased in the presence of 10(-5) g/mL LPS. Icariin pretreatment can partially reverse these effects. The up-regulated expressions of MMP-1, 3, 13, cyclooxygenase-2 (COX-2), and iNOS genes by LPS treatment were also significantly down-regulated by the pretreatment of icariin to 1.8%, 0.056%, 7.7%, 3.1%, and 5.3% of the LPS-positive control sample, respectively. Our results demonstrate that icariin is a safe anabolic agent of chondrocytes. Icariin may exert its protective effects through inhibition of nitric oxide and MMP synthesis, and may then reduce the extracellular matrix destruction.
脓毒性关节炎是一种以关节软骨退化为特征的炎症性关节病。淫羊藿素是从淫羊藿中分离出的主要活性黄酮类糖苷，在中国传统医学中被用作抗风湿药（或抗炎药）、滋补剂和壮阳药。在本研究中，我们使用脂多糖（LPS）模拟脓毒性关节炎时软骨细胞的体外炎症反应。我们的假设是，淫羊藿素可以保护软骨细胞免受 LPS 诱导的炎症和细胞外基质降解。通过 LPS 诱导新生小鼠软骨细胞的炎症，并检测其抗炎作用。分析一氧化氮的合成，测量糖胺聚糖和总胶原的含量，并评估基因表达（包括诱导型一氧化氮合酶（iNOS）、基质金属蛋白酶（MMP）-1、MMP-3 和 MMP-13）。结果表明，在 10(-5) g/mL LPS 存在的情况下，软骨细胞的活力、细胞外基质合成显著降低，而一氧化氮的合成显著增加。淫羊藿素预处理可以部分逆转这些作用。LPS 处理上调的 MMP-1、3、13、环氧化酶-2（COX-2）和 iNOS 基因的表达也被淫羊藿素预处理分别显著下调至 LPS 阳性对照组的 1.8%、0.056%、7.7%、3.1%和 5.3%。我们的结果表明，淫羊藿素是软骨细胞的一种安全的合成代谢剂。淫羊藿素可能通过抑制一氧化氮和 MMP 的合成发挥其保护作用，从而减少细胞外基质的破坏。
