Song Xiaojing, Zhang Wen, Wang Tiancheng, Jiang Haichao, Zhang Zecai, Fu Yunhe, Yang Zhengtao, Cao Yongguo, Zhang Naisheng
College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, 130062, People's Republic of China.
Inflammation. 2014 Oct;37(5):1588-98. doi: 10.1007/s10753-014-9885-2.
Geniposide is a medicine isolated from Gardenia jasminoides Ellis, 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 an in vitro mastitis 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.
栀子苷是从栀子中分离出的一种药物，栀子是一种传统的中草药，在亚洲被广泛用于治疗炎症、脑部疾病和肝脏疾病。乳腺炎是一种高度普遍且重要的传染病。在本研究中，我们使用脂多糖（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（mMECs）来探究栀子苷的抗炎作用及其作用机制。通过导管内注射LPS作为小鼠乳腺炎模型，我们发现栀子苷显著减少了炎性细胞的浸润，并下调了肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（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mMECs作为体外乳腺炎模型。酶联免疫吸附测定（ELISA）和定量实时聚合酶链反应（qRT-PCR）结果表明，栀子苷以剂量依赖性方式抑制TNF-α、IL-1β和IL-6的表达。蛋白质免疫印迹分析表明，栀子苷可抑制抑制性κB（IκBα）、核因子-κB（NF-κB）、p38、细胞外信号调节激酶（ERK）和c-Jun氨基末端激酶（JNK）的磷酸化。栀子苷还抑制LPS刺激的mMECs中Toll样受体4（TLR4）的表达。总之，栀子苷通过调节TLR4表达发挥其抗炎作用，这影响了下游NF-κB和丝裂原活化蛋白激酶（MAPK）信号通路。因此，栀子苷可能是一种治疗乳腺炎的潜在药物。
