Journal
BRAIN SCIENCES
Volume 12, Issue 10, Pages -Publisher
MDPI
DOI: 10.3390/brainsci12101376
Keywords
isofraxidin; depression; CUMS; HPA axis; neuroinflammation; NF-kappa B-NLRP3 inflammasomes
Categories
Funding
- National Natural Science Foundation of China [82104374, 82003615, 62003094]
- Guangdong Basic and Applied Basic Research Foundation [2020A1515110899]
- Natural Science Foundation of Guangdong Province [2019A1515011377]
- Science and Technology Projects in Guangzhou [2020A1515110899, 202201010147, 202102020573]
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Isofraxidin has antidepressant-like effects in CUMS-induced mice, accompanied by inhibition of hyperactivity of the HPA axis and NF-kappa B /NLRP3 inflammasomes pathways.
Isofraxidin is an active component of several traditional and functional plants that have beneficial properties for neurodegenerative diseases. In this study, we examined whether isofraxidin exhibited antidepressant-like effects in chronic unpredictable mild stress (CUMS)-induced mice. Firstly, isofraxidin could reverse CUMS-induced decrease in body weight gain in mice. Additionally, in the sucrose preference test (SPT), isofraxidin reversed the decrease in sucrose consumption due to CUMS-induced depressive-like behavior. Isofraxidin also increased locomotor activity in the open field test (OFT) and alleviated immobility duration in the forced swimming test (FST) and tail-suspension test (TST). Furthermore, isofraxidin decreased levels of corticosterone (CORT), adrenocorticotropic hormone (ACTH), and hypothalamus corticotrophin-releasing hormone (CRH) in the serum after CUMS-induced hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. Also, isofraxidin suppresses tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, and IL-6 expression in the hippocampus of CUMS mice. Further investigations demonstrated that isofraxidin inhibited CUMS-induced activation of nuclear factor kappa B (NF-kappa B) and NOD-like receptor protein 3 (NLRP3) inflammasomes in the hippocampus. Summarily, in CUMS-induced mice, isofraxidin reduced depressive-like behaviors, accompanied by its inhibitory effects on hyperactivity of the HPA axis and NF-kappa B /NLRP3 inflammasomes pathways.
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