Anti-Inflammatory Effect of Geniposide on Osteoarthritis by Suppressing the Activation of p38 MAPK Signaling Pathway.
Anti-Inflammatory Effect of Geniposide on Osteoarthritis by Suppressing the Activation of p38 MAPK Signaling Pathway.
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DOI：
10.1155/2018/8384576
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发表时间：
2018
影响因子：
--
通讯作者：
Bao T
中科院分区：
文献类型：
--
作者：
Chen Y;Shou K;Gong C;Yang H;Yang Y;Bao T
有研究表明，p38丝裂原活化蛋白激酶（MAPK）信号通路的激活通过导致人骨关节炎软骨细胞中促炎细胞因子、趋化因子和信号酶的过度表达在OA的进展中起着重要作用。然而，大多数应用于OA的p38 MAPK抑制剂由于其潜在的长期毒性而被认为是有限的。京尼平苷（GE）是从栀子果实中提取的一种环烯醚萜苷类化合物，在传统医学中被广泛用于治疗多种慢性炎症性疾病。在这项研究中，我们评估了京尼平苷对手术诱导的骨关节炎的炎症进展的抑制作用，以及京尼平苷对OA的保护作用是否与抑制p38 MAPK信号通路有关。京尼平苷可抑制兔骨关节炎软骨细胞中IL-1、TNF-α、NO和MMP-13的表达。此外，京尼平苷还能显著抑制骨关节炎关节液中IL-1、TNF-α、NO和MMP-13的表达。更重要的是，我们的研究结果清楚地表明，京尼平苷对骨关节炎手术诱导的炎症介质表达的抑制作用与抑制p38 MAPK信号通路密切相关。我们的研究表明，京尼平苷可能作为一种替代药物的p38 MAPK抑制剂治疗OA，由于其固有的生物活性和低毒性的传统中药的特点，具有治疗潜力。
It has been suggested that the activation of the p38 mitogen activated protein kinases (MAPKs) signaling pathway plays a significant role in the progression of OA by leading to the overexpression of proinflammatory cytokines, chemokines, and signaling enzymes in human osteoarthritis chondrocytes. However, most p38 MAPK inhibitors applied for OA have been thought to be limited due to their potential long-term toxicities. Geniposide (GE), an iridoid glycoside purified from the fruit of the herb, has been widely used in traditional medicine for the treatment of a variety of chronic inflammatory diseases. In this study, we evaluated the inhibition effect of geniposide on the inflammatory progression of the surgically induced osteoarthritis and whether the protective effect of geniposide on OA is related to the inhibition of the p38 MAPK signaling pathway. In vitro, geniposide attenuated the expression of inflammatory cytokines including interleukin-1 (IL-1), tumor necrosis factor (TNF-α), and nitric oxide (NO) production as well as matrix metalloproteinase- (MMP-) 13 in chondrocytes isolated from surgically induced rabbit osteoarthritis model. Additionally, geniposide markedly suppressed the expression of IL-1, TNF-α, NO, and MMP-13 in the synovial fluid from the rabbits with osteoarthritis. More importantly, our results clearly demonstrated that the inhibitory effect of geniposide on surgery-induced expression of inflammatory mediators in osteoarthritis was closely associated with the suppression of the p38 MAPK signaling pathways. Our study demonstrates that geniposide may have therapeutic potential to serve as an alternative agent for the p38 MAPK inhibition for the treatment of OA due to its inherent features of biological activities and low toxicity as a traditional Chinese medicine.
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影响因子：
5.6
作者：
Kühn, K;Shikhman, AR;Lotz, M
通讯作者：
Lotz, M
影响因子：
2.9
作者：
GREEN, LC;WAGNER, DA;TANNENBAUM, SR
通讯作者：
TANNENBAUM, SR
影响因子：
5.7
作者：
Joos, Helga;Albrecht, Wolfgang;Brenner, Rolf E.
通讯作者：
Brenner, Rolf E.
DOI：
10.3109/17453677008991540
发表时间：
1970-01-01
期刊：
ACTA ORTHOPAEDICA SCANDINAVICA
影响因子：
--
作者：
HULTH, A;LINDBERG, L;TELHAG, H
通讯作者：
TELHAG, H
影响因子：
2.3
作者：
Neogi, Tuhina;Zhang, Yuqing
通讯作者：
Zhang, Yuqing