Koumine Alleviates Lipopolysaccharide-Induced Intestinal Barrier Dysfunction in IPEC-J2 Cells by Regulating Nrf2/NF-kappa B Pathway
Koumine Alleviates Lipopolysaccharide-Induced Intestinal Barrier Dysfunction in IPEC-J2 Cells by Regulating Nrf2/NF-kappa B Pathway
复制标题
Koumine 通过调节 Nrf2/NF-kappa B 通路减轻脂多糖诱导的 IPEC-J2 细胞肠屏障功能障碍
DOI：
10.1142/s0192415x2050007x
复制
发表时间：
2020
影响因子：
5.7
通讯作者：
Sun Zhi-Liang
中科院分区：
文献类型：
--
作者：
Wu Jing;Yang Cheng-Lin;Sha Yuan-Kun;Wu Yong;Liu Zhao-Ying;Yuan Zhi-Hang;Sun Zhi-Liang
钩吻是一种传统中药，在动物体内具有良好的促生长作用，但其肌动蛋白的作用机制尚不清楚。在此，我们评价了狗舌草提取物的保护作用。雷公藤通过减轻炎症和氧化应激来对抗脂多糖(LPS)诱导的IPEC-J2细胞的肠屏障功能障碍。四甲基偶氮唑盐比色法和乳酸脱氢酶比色法显示，钩藤碱可显著降低脂多糖的细胞毒作用。跨皮细胞电阻(TEER)和细胞单层通透性分析显示，库明治疗可减轻内毒素诱导的肠屏障功能障碍，但对紧密连接蛋白ZO-1、Claudin-1和occludin的影响不明显。Koumine还能抑制LPS诱导的炎症反应，下调的炎症因子包括TNF-α、IL-6、IL-1、NO、iNOS和COX-2，这与抑制NF-B途径，减少iBand、NF-B的磷酸化和p-p65的核转位密切相关。Koumine还可通过激活Nrf2途径减少脂多糖诱导的ROS和丙二醛的产生，增加KEAP-1对Nrf2和HO-1的降解，从而促进超氧化物歧化酶(SOD)和过氧化氢酶(CAT)等抗氧化剂的产生。综上所述，Koumine-通过调节Nrf2/NF-B信号通路，预防肠屏障功能障碍，减轻了内毒素引起的氧化应激和炎症反应。
Gelsemium elegans Benth.(G. elegans), a traditional Chinese medicine, has great potential as an effective growth promoter in animals, however, the mechanism of its actin remains unclear. Here, we evaluated the protective effects of koumine extract fromG. elegansagainst lipopolysaccharide (LPS)-induced intestinal barrier dysfunction in IPEC-J2 cells through alleviation of inflammation and oxidative stress. MTT and LDH assays revealed that koumine significantly reduced LPS cytotoxicity. Transepithelial electrical resistance (TEER) and cell monolayer permeability assays showed that koumine treatment attenuated the LPS-induced intestinal barrier dysfunction with no particularly different effects in tight junction proteins such as ZO-1, claudin-1, and occludin. LPS-triggered inflammatory response was also suppressed by koumine, as evidenced by the downregulated inflammatory factors, including TNF-, IL-6, IL-1, NO, iNOS, and COX-2, which was closely connected with the inhibition of NF-B pathway for the decrease of phosphorylation of IBand NF-B and nuclear translocation of p-p65. Amount of reactive oxygen species (ROS) and MDA induced by LPS was also reduced by koumine through activation of Nrf2 pathway, and increased in the levels of Nrf2 and HO-1 degradation of keap-1 to promote anti-oxidants, including superoxide dismutase (SOD) and catalase (CAT). To summarize, koumine-reduced the oxidative stress and inflammatory reaction triggered by LPS through regulation of the Nrf2/NF-B signaling pathway and preventing intestinal barrier dysfunction.