Geniposide Plays an Anti-inflammatory Role via Regulating TLR4 and Downstream Signaling Pathways in Lipopolysaccharide-Induced Mastitis in Mice
Geniposide Plays an Anti-inflammatory Role via Regulating TLR4 and Downstream Signaling Pathways in Lipopolysaccharide-Induced Mastitis in Mice
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京尼平苷通过调节 TLR4 和下游信号通路在脂多糖诱导的小鼠乳腺炎中发挥抗炎作用
DOI：
10.1007/s10753-014-9885-2
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发表时间：
2014-10-01
期刊：
影响因子：
5.1
通讯作者：
Zhang, Naisheng
中科院分区：
文献类型：
--
作者：
Song, Xiaojing;Zhang, Wen;Zhang, Naisheng
京尼平苷是从栀子中分离出来的一种药物，栀子是一种传统的中国草药，在亚洲被广泛用于治疗炎症，脑部疾病和肝脏疾病。乳腺炎是一种高度流行的重要传染病。本研究采用脂多糖（LPS）诱导的小鼠乳腺炎模型和LPS刺激的原代小鼠乳腺上皮细胞（mMEC），探讨京尼平苷的抗炎作用及其作用机制。采用乳管内注射LPS的小鼠乳腺炎模型，我们发现京尼平苷显著减少炎症细胞的浸润，并下调肿瘤坏死因子-α（TNF-α）、白细胞介素-1 β（IL-1β）和白细胞介素-6（IL-6）的产生。为了进一步研究抗炎机制，我们使用LPS刺激的mMEC作为体外乳腺炎模型。酶联免疫吸附试验（ELISA）和实时定量聚合酶链反应（qRT-PCR）结果显示，京尼平苷可抑制TNF-α、IL-1β和IL-6的表达，并呈剂量依赖性。Western blot分析显示，京尼平苷可抑制抑制性κ B（IκBα）、核因子-κB（NF-κB）、p38、细胞外信号调节激酶（ERK）和c-Jun N末端激酶（JNK）的磷酸化。京尼平苷还抑制LPS刺激的mMEC中Toll样受体4（TLR 4）的表达。结论：京尼平苷通过调节TLR 4表达，影响下游NF-κB和丝裂原活化蛋白激酶（MAPK）信号通路发挥抗炎作用。因此，京尼平苷可能是一种潜在的乳腺炎治疗药物。
Geniposide is a medicine isolated fromGardenia jasminoidesEllis, which is a traditional Chinese herb that is widely used in Asia for the treatment of inflammation, brain diseases, and hepatic disorders. Mastitis is a highly prevalent and important infectious disease. In this study, we used a lipopolysaccharide (LPS)-induced mouse mastitis model and LPS-stimulated primary mouse mammary epithelial cells (mMECs) to explore the anti-inflammatory effect and the mechanism of action of geniposide. Using intraductal injection of LPS as a mouse model of mastitis, we found that geniposide significantly reduced the infiltration of inflammatory cells and downregulated the production of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). To further investigate the anti-inflammatory mechanism, we used LPS-stimulated mMECs as anin vitromastitis model. The results of enzyme-linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR) showed that geniposide inhibited the expression of TNF-α, IL-1β, and IL-6 in a dose-dependent manner. Western blot analysis demonstrated that geniposide could suppress the phosphorylation of inhibitory kappa B (IκBα), nuclear factor-κB (NF-κB), p38, extracellular signal-regulated kinase (ERK), and c-Jun N-terminal kinase (JNK). Geniposide also inhibited the expression of toll-like receptor 4 (TLR4) in the LPS-stimulated mMECs. In conclusion, geniposide exerted its anti-inflammatory effect by regulating TLR4 expression, which affected the downstream NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways. Thus, geniposide may be a potential drug for mastitis therapy.