Polysaccharides from Dicliptera chinensis ameliorate liver disturbance by regulating TLR‐4/NF‐κB and AMPK/Nrf2 signalling pathways
Polysaccharides from Dicliptera chinensis ameliorate liver disturbance by regulating TLR‐4/NF‐κB and AMPK/Nrf2 signalling pathways
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双翅目多糖通过调节 TLR-4/NF-kappa B 和 AMPK/Nrf2 信号通路改善肝功能紊乱
DOI：
10.1111/jcmm.15286
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发表时间：
2020
影响因子：
5.3
通讯作者：
Ling Jin
中科院分区：
文献类型：
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作者：
Kefeng Zhang;Qiongmei Xu;Ya Gao;Houkang Cao;Jie Xu;Jianghui Dong;Ling Jin
本研究旨在通过应用狗肝菜多糖（DCP）作用于腺苷一磷酸活化蛋白激酶/核因子红细胞2相关因子2（NF-2）来减轻肝损害（AMPK/Nrf 2）氧化应激途径和Toll样受体4（TLR-4）/核因子κ B（NF-κB）炎症途径，并使用雄性C57 BL/Nrf 2建立体内肝脏障碍模型。6 J和TLR-4敲除（−/−）小鼠。为此，我们评估了使用siRNA技术沉默AMPK表达后SREBP-1和Nrf 2的表达水平。我们的研究结果表明，对于TLR-4/ NF-κB炎症通路，DCP抑制TLR-4，上调过氧化物酶体增殖物激活受体-γ（PPAR-γ）的表达，降低磷酸化（p）-NF-κB的表达，并导致下游炎症因子如肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-6和IL-1β的减少，从而抑制炎症反应。关于AMPK/Nrf 2氧化应激途径，DCP除了调节葡萄糖和脂质代谢、氧化应激和改善肝脏障碍症状外，还上调p-AMPK和Nrf 2的表达。综上所述，我们的研究表明，DCP通过抑制肝脏炎症和氧化应激抑制过程中使用的机制来减轻肝脏障碍，这为肝脏障碍的临床治疗提供了新的策略。
The purpose of this study was to alleviate liver disturbance by applying polysaccharides fromDicliptera chinensis(DCP) to act on the adenosine monophosphate–activated protein kinase/ nuclear factor erythroid 2‐related factor 2 (AMPK/ Nrf2) oxidative stress pathway and the Toll‐like receptor 4 (TLR‐4)/ nuclear factor kappa‐B (NF‐κB) inflammatory pathway and to establish an in vivo liver disturbance model using male C57BL/6J and TLR‐4 knockout (−/−) mice. For this, we evaluated the expression levels of SREBP‐1 and Nrf2 after silencing the expression of AMPK using siRNA technology. Our results show that with regard to the TLR‐4/ NF‐κB inflammatory pathway, DCP inhibits TLR‐4, up‐regulates the expression of peroxisome proliferator‐activated receptor‐γ (PPAR‐γ), reduces the expression of phospho(p)‐NF‐κB and leads to the reduction of downstream inflammatory factors, such as tumour necrosis factor‐α (TNF‐α), interleukin (IL)‐6 and IL‐1β, thereby inhibiting the inflammatory response. Regarding the AMPK/ Nrf2 oxidative stress pathway, DCP up‐regulates the expression of p‐AMPK and Nrf2, in addition to regulating glucose and lipid metabolism, oxidative stress and ameliorating liver disturbance symptoms. In summary, our study shows that DCP alleviates liver disturbances by inhibiting mechanisms used during liver inflammation and oxidative stress depression, which provides a new strategy for the clinical treatment of liver disturbance.