期刊
FRONTIERS IN PHARMACOLOGY
卷 13, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fphar.2022.984475
关键词
dry eye disease; depression; NLRP3 ubiquitination; gp78; acacetin
资金
- China Postdoctoral Science Foundation [2021M690990]
- Academician Liu Liang Workstation guidance project [21YS002]
- Disciplinary Reveal System project [22JBZ024]
- Scientific Research Project of Hunan Administration of traditional Chinese Medicine [D2022053]
- Scientific Research Project of Hunan Provincial Health Commission [202107021634]
- Hunan Provincial Department of Science and Technology, Hunan Clinical Medical Research Center [2021SK4022]
- Key Projects of Hunan Provincial Department of Education [21A0238]
The natural flavone acacetin has beneficial effects in depression-associated dry eye disease by improving depressive behaviors and relieving dry eye symptoms through inhibition of NLRP3 inflammasome expression levels and enhanced NLRP3 ubiquitination mediated by gp78.
Dry eye disease (DED) is a multifactorial syndrome that commonly occurs with depression. However, therapies targeting depression-related dry eye disease are rare. In the current study, we studied the beneficial effect of a natural flavone, acacetin, in depression-associated dry eye disease by utilizing the chronic unpredictable mild stress (CUMS) depression model. Our data showed that acacetin improved the depressive behaviors in sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST); relieved the dry eye symptoms including corneal epithelial impairments, tear production decrease and goblet cell loss in CUMS mice. Acacetin also inhibited NOD-like receptor protein 3 (NLRP3) inflammasome expression levels and suppressed inflammatory responses via enhancing glycoprotein 78 (gp78)/Insulin induced gene-1 (Insig-1)-controlled NLRP3 ubiquitination in CUMS mice. Furthermore, knockdown of gp78 compromised acacetin-conferred protective efficacy in depression-related dry eye disease. In summary, our findings indicated that acacetin exerts beneficial effect in depression-associated dry eye disease, which is tightly related to gp78-mediated NLRP3 ubiquitination.
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