2. Academic Validation
  3. Aucubin improves chronic unpredictable mild stress-induced depressive behavior in mice via the GR/NF-κB/NLRP3 axis

Aucubin improves chronic unpredictable mild stress-induced depressive behavior in mice via the GR/NF-κB/NLRP3 axis

  • Int Immunopharmacol. 2023 Oct:123:110677. doi: 10.1016/j.intimp.2023.110677.
Ping Liu 1,  Shiyuan Song 2,  Ping Yang 3,  Xiuming Rao 4,  Yuqi Wang 5,  Xinyu Bai 6
Affiliations

Affiliations

  • 1 Department of Clinical Pharmacy, Key Laboratory of Clinical Pharmacy in Zunyi City, Zunyi Medical University, Zunyi 563000, China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, China. Electronic address: [email protected].
  • 2 Department of Clinical Pharmacy, Key Laboratory of Clinical Pharmacy in Zunyi City, Zunyi Medical University, Zunyi 563000, China. Electronic address: [email protected].
  • 3 Department of Clinical Pharmacy, Key Laboratory of Clinical Pharmacy in Zunyi City, Zunyi Medical University, Zunyi 563000, China. Electronic address: [email protected].
  • 4 Department of Clinical Pharmacy, Key Laboratory of Clinical Pharmacy in Zunyi City, Zunyi Medical University, Zunyi 563000, China. Electronic address: [email protected].
  • 5 Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, China. Electronic address: [email protected].
  • 6 Department of Clinical Pharmacy, Key Laboratory of Clinical Pharmacy in Zunyi City, Zunyi Medical University, Zunyi 563000, China; Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi 563000, China. Electronic address: [email protected].
PMID: 37523973 DOI: 10.1016/j.intimp.2023.110677
Abstract

Eucommia ulmoides Oliv (EUO) is a traditional therapeutic drug that tonifies the liver and kidney and may improve depression. However, the mechanism of action of the main component, aucubin (AU), is unknown. To study the therapeutic effect of AU, we constructed a chronic unpredictable mild stress (CUMS) depression model in mice. Depression-like behaviors, pathological damage, hormonal changes, inflammation, intranuclear expression of glucocorticoidreceptor (GR), and hippocampal protein expression were assessed. Immunofluorescence staining of the hippocampus showed that CUMS decreased neuronal regeneration, and axons were observed to be reduced and broken. Intracellular GR expression decreased in the hippocampus and hypothalamus, and serum levels of stress Hormones increased. Furthermore, molecular changes indicative of Pyroptosis were observed. AU administration reversed these changes and significantly improved the depression-like behavior induced by CUMS. Our results suggested that AU improves depression by promoting the intranuclear expression of GR and inhibiting nuclear factor-kappa B-mediated inflammatory activation-driven cell Pyroptosis.

Keywords

Aucubin; Chronic unpredictable mild stress; Hypothalamic–pituitary–adrenal axis; Inflammation; Pyroptosis.

Figures
Products