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Research Paper|Volume 15, Issue 1|pp 261—275

The protective effect of luteolin on the depression-related dry eye disorder through Sirt1/NF-κB/NLRP3 pathway

Mingxia Xie1,3,5, Hanqing Wang2, Tiantian Gao2, Jun Peng4, Pan Meng5, Xi Zhang3, Dongwei Guo3, Guangya Liu3, Jian Shi1,4, Qinghua Peng1,4
  • 1College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410007, P.R. China
  • 2College of Pharmacy, Ningxia Medical University, Yinchuan, Ningxia 750004, P.R. China
  • 3College of Clinical Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410007, P.R. China
  • 4The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, P.R. China
  • 5National Key Laboratory Cultivation Base of Chinese Medicinal Powder and Innovative Medicinal Jointly Established by Province and Ministry, Hunan University of Chinese Medicine, Changsha, Hunan 410007, P.R. China
Received: August 23, 2022Accepted: December 29, 2022Published: January 11, 2023
https://doi.org/10.18632/aging.204479

Copyright: © 2023 Xie et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Luteolin has been reported to exhibit therapeutic effect on depressive-like behaviors in mice. Nevertheless, the therapeutic effect of luteolin on the depression-related dry eye disorder remains inconclusive. In this study, C57 mice were subjected to chronic unpredictable mild stress in a dry environment (relative humidity in the cage <40%). The behavioral test and phenol red cotton thread test were employed to select the mice with both dry eye and depression-like behavior. The mechanism of luteolin on depression-related dry eye disorder was assessed by the Sirt1 selective inhibitor EX-527. Luteolin alleviated depressive-like behaviors induced by CUMS, increased tear secretion and restored corneal defects in mice. The secretions of pro-inflammatory factors IL-1β, IL-6, IL-18 and TNF-α were decreased in hippocampi and corneal tissues by Luteolin treatment. Luteolin treatment up-regulated Sirt1 expression and down-regulated Ac-NF-κB, NLRP3, Ac-Caspase-1, GSDMD-N, Cleaved IL-1β, and Cleaved IL-18 expressions. In addition, the selective inhibition of Sirt1 could weaken the therapeutic effect of luteolin on depression-related dry eye disorder. The beneficial effect of luteolin through Sirt1/NF-κB/NLRP3 signaling pathway might be a therapeutic strategy for the depression-related dry eye disorder.