|
|||||
|
|
Kakonein restores diabetes-induced endothelial junction dysfunction via promoting autophagy-mediated NLRP3 inflammasome degradation |
|
| Authors: | Dawei Lian Jiaying Liu Ruifang Han Jiaqi Jin Li Zhu Yanhong Zhang Yi Huang Xiao Wang Shaoxiang Xian Yang Chen |
| Affiliation: | 1. The First Affiliated Hospital and Postdoctoral Research Station, Guangzhou University of Chinese Medicine, Guangzhou, China School of Pharmaceutical, Guangzhou University of Chinese Medicine, Guangzhou, China Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal), Methodology (equal), Writing - original draft (equal);2. Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, China Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal), Writing - original draft (equal);3. School of Pharmaceutical, Guangzhou University of Chinese Medicine, Guangzhou, China Contribution: Investigation (supporting), Methodology (supporting);4. School of Pharmaceutical, Guangzhou University of Chinese Medicine, Guangzhou, China;5. Department of Traditional Chinese Medicine, School of Medicine, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, China Contribution: Funding acquisition (supporting), Resources (supporting);6. Department of Stomatology, The School of Dental Medicine, Jinan University First Affiliated Hospital, Guangzhou, China Contribution: Methodology (supporting), Resources (supporting);7. Laboratory Animal Center, Guangzhou University of Chinese Medicine, Guangzhou, China;8. The First Affiliated Hospital and Postdoctoral Research Station, Guangzhou University of Chinese Medicine, Guangzhou, China |
| Abstract: | 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. |
| Keywords: | autophagy diabetes endothelial dysfunction kakonein NLRP3 inflammasome |