Open AccessKakonein restores diabetes‐induced endothelial junction dysfunction via promoting autophagy‐mediated NLRP 3 inflammasome degradation
Author(s) -
Lian Dawei,
Liu Jiaying,
Han Ruifang,
Jin Jiaqi,
Zhu Li,
Zhang Yanhong,
Huang Yi,
Wang Xiao,
Xian Shaoxiang,
Chen Yang
Publication year - 2021
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.16747
Subject(s) - inflammasome , autophagy , endothelial dysfunction , western blot , microbiology and biotechnology , chemistry , pharmacology , medicine , inflammation , biology , immunology , apoptosis , biochemistry , gene
In diabetes‐induced complications, inflammatory‐mediated endothelial dysfunction is the core of disease progression. Evidence shows that kakonein, an isoflavone common in Pueraria , can effectively treat diabetes and its complications. Therefore, we explored whether kakonein protects cardiovascular endothelial function by inhibiting inflammatory responses. In this study, C57BL/6J mice were injected with streptozocin to establish a diabetes model and treated with kakonein or metformin for 7 days. The protective effect of kakonein on cardiovascular endothelial junctions and NLRP3 inflammasome activation was verified through immunofluorescence and ELISA assay. In addition, the regulation of autophagy on the NLRP3 inflammasome was investigated through Western blot, immunofluorescence and RT‐qPCR. Results showed that kakonein restored the function of endothelial junctions and inhibited the assembly and activation of the NLRP3 inflammasome. Interestingly, kakonein decreased the expression of NLRP3 inflammasome protein by not reducing the transcriptional levels of NLRP3 and caspase‐1. Kakonein activated autophagy in an AMPK‐dependent manner, which reduced the activation of the NLRP3 inflammasome. In addition, kakonein inhibited both hyperglycaemia‐induced cardiovascular endothelial junction dysfunction and NLRP3 inflammasome activation, similar to autophagy agonist. Our findings indicated that kakonein exerts a protective effect on hyperglycaemia‐induced chronic vascular disease by regulating the NLRP3 inflammasome through autophagy.