导语
前沿科研成果
紫檀茋抗血管性痴呆作用的发现及基于Triad3A依赖性TLR4泛素化降解的机制研究
Figure 1. Pterostilbene prevents working memory impairment in BCCAO mice(来源:J Agric Food Chem)
Figure 2. Pterostilbene prevents spatial memory impairment in BCCAO mice(来源:J Agric Food Chem)
作者通过免疫荧光实验和实时定量PCR实验,发现紫檀茋能够保护神经元,抑制小胶质细胞活化(Figure 3和Figure 4,J Agric Food Chem,2022,70,5896-5910)。
Figure 3. Pterostilbene alleviates neuronal damage in the hippocampus of BCCAO mice(来源:J Agric Food Chem)
Figure 4. Pterostilbene inhibits microglial activation in the hippocampus of BCCAO mice(来源:J Agric Food Chem)
作者进一步在细胞和整体水平发现紫檀茋对于经典炎症信号通路TLR4/NF-κB信号通路的活化具有抑制作用(Figure 5和Figure 6,J Agric Food Chem,2022,70,5896-5910)。
Figure 5. Pterostilbene inhibits the TLR4 pathway in microglia of BCCAO mice(来源:J Agric Food Chem)
Figure 6. Pterostilbene inhibits the TLR4 pathway in OGD/R BV-2 Cells(来源:J Agric Food Chem)
通过慢病毒包装的过表达TLR4基因质粒,作者在细胞水平进一步确认紫檀茋通过调控TLR4抑制下游NF-κB信号通路及下游炎症因子的表达(Figure 7,J Agric Food Chem,2022,70,5896-5910)。
Figure 7. Pterostilbene suppresses the NF-κB pathway by modulating TLR4(来源:J Agric Food Chem)
通过考察紫檀茋对TLR4表达水平的影响,发现紫檀茋对TLR4表达的抑制是通过促进其降解实现的(Figure 8,J Agric Food Chem,2022,70,5896-5910)。
Figure 8. Pterostilbene promotes TLR4 ubiquitination(来源:J Agric Food Chem)
最后,通过对TLR4与其泛素化蛋白Triad3A蛋白结合情况进行免疫共沉淀实验,并通过慢病毒包装的Triad3A基因质粒,进一步发现紫檀茋对TLR4及其下游炎症信号通路的抑制作用依赖于Triad3A介导的TLR4泛素化降解(Figure 9和Figure 10,J Agric Food Chem,2022,70,5896-5910)。
Figure 9. Pterostilbene promotes the binding of Triad3A to TLR4(来源:J Agric Food Chem)
Figure 10. Pterostilbene regulates the TLR4 pathway by modulating Triad3A(来源:J Agric Food Chem)
总结:
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