Hesperidin may improve depressive symptoms by binding NLRP3 and influencing the pyroptosis pathway in a rat model

Hui Cao; Dong Yang; Kechao Nie; Ruoheng Lin; Luqi Peng; Xuhui Zhou; Mei Zhang; Ying Zeng; Lini Liu; Wei Huang

doi:10.1016/j.ejphar.2023.175670

Hesperidin may improve depressive symptoms by binding NLRP3 and influencing the pyroptosis pathway in a rat model

Eur J Pharmacol. 2023 Aug 5:952:175670. doi: 10.1016/j.ejphar.2023.175670. Epub 2023 May 9.

Authors

Hui Cao¹, Dong Yang¹, Kechao Nie², Ruoheng Lin³, Luqi Peng⁴, Xuhui Zhou¹, Mei Zhang⁴, Ying Zeng⁴, Lini Liu¹, Wei Huang⁵

Affiliations

¹ Department of Psychiatry, Brain Hospital of Hunan Province, The Second People's Hospital of Hunan Province, Changsha, China.
² Department of Integrated Traditional Chinese & Western Internal Medicine, The Second Xiangya Hospital, Central South University, Changsha, China.
³ Department of Psychiatry, The Second Xiangya Hospital of Central South University, Changsha, China.
⁴ Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, China.
⁵ Department of Integrated Traditional Chinese and Western Medicine, Xiangya Hospital, Central South University, Changsha, China. Electronic address: huangweidavid@csu.edu.cn.

PMID: 37169143
DOI: 10.1016/j.ejphar.2023.175670

Abstract

Objective: Major depressive disorder (MDD) is a debilitating psychiatric disorder which is common and endangers human physical and mental health. Studies have shown that hesperidin could improve the symptoms of depression with unclear mechanisms.

Method: In this study, hesperidin was administered to chronic unpredictable mild stress (CUMS) depressed mice before behavioral test, network pharmacology analysis, RNA expression microarray analysis, pathway validation and molecular docking experiments.

Results: we found that hesperidin intervention could significantly improve the depressive symptoms and downregulate the expression level of pyroptosis pathway including caspase 1 (Casp1), interleukin 18 (IL18), interleukin-1β (IL-1β) and NOD-like receptor thermal protein domain associated protein 3 (NLRP3). In addition, we found that hesperidin could possibly bind to NLRP3.

Conclusions: Our study demonstrated that hesperidin had huge potential as anti-depressive neuroprotectant, and may play a role in treating MDD by regulating NLRP3-mediated pyroptosis.

Keywords: Hesperidin; Major depressive disorder; NLRP3; Pyroptosis.

MeSH terms

Animals
Caspase 1
Depression / drug therapy
Depressive Disorder, Major*
Hesperidin* / pharmacology
Hesperidin* / therapeutic use
Humans
Inflammasomes / metabolism
Molecular Docking Simulation
NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
Pyroptosis
Rats

Substances

Caspase 1
Hesperidin
Inflammasomes
NLR Family, Pyrin Domain-Containing 3 Protein