P-Coumaric Acid Reverses Depression-Like Behavior and Memory Deficit Via Inhibiting AGE-RAGE-Mediated Neuroinflammation

Autor: Xu-Dong Yu, Dan Zhang, Chu-Li Xiao, Yu Zhou, Xing Li, Le Wang, Zhiming He, James Reilly, Zhi-Yong Xiao, Xinhua Shu
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Cells, Vol 11, Iss 10, p 1594 (2022)
Druh dokumentu: article
ISSN: 2073-4409
DOI: 10.3390/cells11101594
Popis: Depression, a mood disorder, affects one in fifteen adults, has multiple risk factors and is associated with complicated underlying pathological mechanisms. P-coumaric acid (p-CA), a phenolic acid, is widely distributed in vegetables, fruits and mushrooms. P-CA has demonstrated a protective role against oxidative stress and inflammation in various diseases, including cardiovascular disease, diabetes and cancer. In the current study, we investigated the protection of p-CA against depression and memory impairment in a corticosterone (CORT)-induced chronic depressive mouse model. CORT administration resulted in depression-like behaviors and memory impairment. P-CA treatment alleviated CORT-induced depression-related behaviors and memory impairment. Network pharmacology predicted that p-CA had multiple targets and mediated various signaling pathways, of which inflammation-associated targets and signaling pathways are predominant. Western blotting showed CORT-induced activation of the advanced glycation end product (AGE)-receptor of AGE (RAGE) (AGE-RAGE) signaling and increased expression of the proinflammatory cytokines interleukin-1 beta (IL-1β) and tumor necrosis factor-alpha (TNFα) in the hippocampus, while p-CA treatment inactivated AGE-RAGE signaling and decreased the levels of IL-1β and TNFα, suggesting that protection against depression and memory impairment by p-CA is mediated by the inhibition of inflammation, mainly via the AGE-RAGE signaling pathway. Our data suggest that p-CA treatment will benefit patients with depression.
Databáze: Directory of Open Access Journals
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