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小檗碱通过调控 NF-κB/IRF7/JAK-STAT 信号通路和细胞凋亡抑制传染性支气管炎病毒的作用。

Antiviral effect of palmatine against infectious bronchitis virus through regulation of NF-κB/IRF7/JAK-STAT signalling pathway and apoptosis.

机构信息

Natural Medicine Research Center, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

College of Animal Science and Technology, Sichuan Agricultural University, Chengdu, China.

出版信息

Br Poult Sci. 2024 Apr;65(2):119-128. doi: 10.1080/00071668.2023.2296929. Epub 2024 Jan 26.

Abstract
  1. Infectious bronchitis virus (IBV), a gamma-coronavirus, can infect chickens of all ages and leads to an acute contact respiratory infection. This study evaluated the anti-viral activity of palmatine, a natural non-flavonoid alkaloid, against IBV in chicken embryo kidney (CEK) cells.2. The half toxic concentration (CC) of palmatine was 672.92 μM, the half inhibitory concentration (IC) of palmatine against IBV was 7.76 μM and the selection index (SI) was 86.74.3. Mode of action assay showed that palmatine was able to directly inactivate IBV and inhibited the adsorption, penetration and intracellular replication of IBV.4. Palmatine significantly upregulated , and compared with the IBV-infected group, leading to the increased expressions of pro-inflammatory cytokines and in the downstream NF-κB signalling pathway.5. Palmatine significantly up-regulated the levels of MDA5, MAVS, IRF7, IFN-α and IFN-β in the IRF7 pathway, inducing type I interferon production. It up-regulated the expression of 2'5'-oligoadenylate synthase (OAS) in the JAK-STAT pathway.6. IBV infection induced cell apoptosis and palmatine-treatment delayed the process of apoptosis by regulation of the expression of apoptosis-related genes (, , and ).7. Palmatine could exert anti-IBV activity through regulation of NF-κB/IRF7/JAK-STAT signalling pathways and apoptosis, providing a theoretical basis for the utilisation of palmatine to treat IBV infection.
摘要
  1. 传染性支气管炎病毒(IBV)是一种γ冠状病毒,可感染所有年龄段的鸡,导致急性接触性呼吸道感染。本研究评估了天然非黄酮类生物碱黄连碱对鸡胚肾(CEK)细胞中 IBV 的抗病毒活性。

  2. 黄连碱的半毒性浓度(CC)为 672.92 μM,黄连碱对 IBV 的半抑制浓度(IC)为 7.76 μM,选择指数(SI)为 86.74。

  3. 作用方式测定表明,黄连碱能够直接灭活 IBV,并抑制 IBV 的吸附、穿透和细胞内复制。

  4. 与 IBV 感染组相比,黄连碱显著上调 、 和 ,导致下游 NF-κB 信号通路中促炎细胞因子 和 的表达增加。

  5. 黄连碱显著上调 IRF7 通路中 MDA5、MAVS、IRF7、IFN-α和 IFN-β的水平,诱导 I 型干扰素的产生。它上调 JAK-STAT 通路中 2'5'-寡腺苷酸合成酶(OAS)的表达。

  6. IBV 感染诱导细胞凋亡,黄连碱处理通过调节凋亡相关基因( 、 、 和 )的表达来延缓凋亡过程。

  7. 黄连碱可以通过调节 NF-κB/IRF7/JAK-STAT 信号通路和细胞凋亡发挥抗 IBV 活性,为利用黄连碱治疗 IBV 感染提供了理论依据。

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