Tabersonine, a natural NLRP3 inhibitor, suppresses inflammasome activation in macrophages and attenuate NLRP3-driven diseases in mice
Tabersonine, a natural NLRP3 inhibitor, suppresses inflammasome activation in macrophages and attenuate NLRP3-driven diseases in mice
复制标题
Tabersonine 是一种天然 NLRP3 抑制剂，可抑制巨噬细胞中的炎症小体激活并减轻小鼠中 NLRP3 驱动的疾病
DOI：
10.1038/s41401-022-01040-z
复制
发表时间：
2023-01
影响因子：
8.2
通讯作者：
Hao-wen Xu;Wei-feng Li;Shanshan Hong;Ji Shao;Jiahui Chen;N. Chattipakorn;Di Wu;Wu Luo
中科院分区：
文献类型：
--
作者：
Hao-wen Xu;Wei-feng Li;Shanshan Hong;Ji Shao;Jiahui Chen;N. Chattipakorn;Di Wu;Wu Luo
Aberrant activation of NLRP3 inflammasome causes the progression of various inflammation-related diseases, but the small-molecule inhibitors of NLRP3 are not currently available for clinical use. Tabersonine (Tab) is a natural product derived from a traditional Chinese herbCatharanthus roseusthat is usually used as an anti-tumor agent. In this study we investigated the anti-inflammatory effects and molecular targets of Tab. We first screened 151 in-house natural compounds for their inhibitory activity against IL-1β production in BMDMs. We found that Tab potently inhibited NLRP3-mediated IL-1β production with an IC50value of 0.71 μM. Furthermore, we demonstrated that Tab suppressed the assembly of NLRP3 inflammasome, especially the interaction between NLRP3 and ASC. Interestingly, we found that Tab directly bound to NLRP3 NACHT domain, thereby reducing the self-oligomerization of NLRP3. In addition, we showed that administration of Tab significantly ameliorated NLRP3-driven diseases, such as peritonitis, acute lung injury, and sepsis in mouse models. The preventive effects of Tab were not observed in the models of NLRP3 knockout mouse. In conclusion, we have identified Tab as a natural NLRP3 inhibitor and a lead compound for the design and discovery of novel NLRP3 inhibitors.
