2. Academic Validation
  3. 1,8-cineole ameliorates experimental diabetic angiopathy by inhibiting NLRP3 inflammasome-mediated pyroptosis in HUVECs via SIRT2

1,8-cineole ameliorates experimental diabetic angiopathy by inhibiting NLRP3 inflammasome-mediated pyroptosis in HUVECs via SIRT2

  • Biomed Pharmacother. 2024 Aug:177:117085. doi: 10.1016/j.biopha.2024.117085.
Jian Zhang 1,  Xinlin Li 1,  Wenqing Cui 1,  Dingchun Lu 1,  Yanyan Zhang 1,  Jiajia Liao 1,  Linlin Guo 1,  Chunen Jiao 1,  Ling Tao 2,  Yini Xu 3,  Xiangchun Shen 4
Affiliations

Affiliations

  • 1 The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, No.6 Ankang Avenue,Guiyang city and Guian New District, Guizhou 561113, China; The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province (The high educational key laboratory of Guizhou province for natural medicianl Pharmacology and Druggability), School of Pharmaceutical Sciences, Guizhou Medical University, No.6 Ankang Avenue, Guiyang city and Guian New District, Guizhou 561113, China; The Key Laboratory of Optimal Utilization of Natural Medicine Resources,The Department of Pharmacology of Materia Medica, School of Pharmaceutical Sciences, Guizhou Medical University, No.6 Ankang Avenue, Guiyang city and Guian New District, Guizhou 561113, China.
  • 2 The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, No.6 Ankang Avenue,Guiyang city and Guian New District, Guizhou 561113, China; The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province (The high educational key laboratory of Guizhou province for natural medicianl Pharmacology and Druggability), School of Pharmaceutical Sciences, Guizhou Medical University, No.6 Ankang Avenue, Guiyang city and Guian New District, Guizhou 561113, China.
  • 3 The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, No.6 Ankang Avenue,Guiyang city and Guian New District, Guizhou 561113, China; The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province (The high educational key laboratory of Guizhou province for natural medicianl Pharmacology and Druggability), School of Pharmaceutical Sciences, Guizhou Medical University, No.6 Ankang Avenue, Guiyang city and Guian New District, Guizhou 561113, China; The Key Laboratory of Optimal Utilization of Natural Medicine Resources,The Department of Pharmacology of Materia Medica, School of Pharmaceutical Sciences, Guizhou Medical University, No.6 Ankang Avenue, Guiyang city and Guian New District, Guizhou 561113, China. Electronic address: 605446623@qq.com.
  • 4 The State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, No.6 Ankang Avenue,Guiyang city and Guian New District, Guizhou 561113, China; The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province (The high educational key laboratory of Guizhou province for natural medicianl Pharmacology and Druggability), School of Pharmaceutical Sciences, Guizhou Medical University, No.6 Ankang Avenue, Guiyang city and Guian New District, Guizhou 561113, China; The Key Laboratory of Optimal Utilization of Natural Medicine Resources,The Department of Pharmacology of Materia Medica, School of Pharmaceutical Sciences, Guizhou Medical University, No.6 Ankang Avenue, Guiyang city and Guian New District, Guizhou 561113, China. Electronic address: shenxiangchun@126.com.
PMID: 38972150 DOI: 10.1016/j.biopha.2024.117085
Abstract

Accumulating evidence strongly support the key role of NLRP3-mediated Pyroptosis in the pathogenesis and progression of vascular endothelial dysfunction associated with diabetes mellitus. Various studies have demonstrated that the activation or upregulation of Silent Information Regulation 2 homolog 2 (SIRT2) exerts inhibitory effect on the expression of NLRP3. Although 1,8-cineole has been found to protect against endothelial dysfunction and cardiovascular diseases, its role and mechanism in diabetic angiopathy remain unknown. Therefore, the aim of this study was to investigate the ameliorative effect of 1,8-cineole through SIRT2 on Pyroptosis associated with diabetic angiopathy in human umbilical vein endothelial cells (HUVECs) and to elucidate the underlying mechanism. The findings revealed that 1,8-cineole exhibited a protective effect against vascular injury and ameliorated pathological alterations in the thoracic aorta of diabetic mice. Moreover, it effectively mitigated Pyroptosis induced by palmitic acid-high glucose (PA-HG) in HUVECs. Treatment with 1,8-cineole effectively restored the reduced levels of SIRT2 and suppressed the elevated expression of pyroptosis-associated proteins. Additionally, our findings demonstrated the occurrence of NLRP3 deacetylation and the physical interaction between NLRP3 and SIRT2. The SIRT2 Inhibitor AGK2 and siRNA-SIRT2 effectively attenuated the effect of 1,8-cineole on NLRP3 deacetylation in HUVECs and compromised its inhibitory effect against Pyroptosis in HUVECs. However, overexpression of SIRT2 inhibited PA-HG-induced Pyroptosis in HUVECs. 1,8-Cineole inhibited the deacetylation of NLRP3 by regulating SIRT2, thereby reducing Pyroptosis in HUVECs. In conclusion, our findings suggest that PA-HG-induced Pyroptosis in HUVECs plays a crucial role in the development of diabetic angiopathy, which can be mitigated by 1,8-cineole.

Keywords

1; 8-cineole; Diabetic angiopathy; NLRP3; Pyroptosis; SIRT2.

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