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- Title
P-Coumaric Acid Reverses Depression-Like Behavior and Memory Deficit Via Inhibiting AGE-RAGE-Mediated Neuroinflammation.
- Authors
Yu, Xu-Dong; Zhang, Dan; Xiao, Chu-Li; Zhou, Yu; Li, Xing; Wang, Le; He, Zhiming; Reilly, James; Xiao, Zhi-Yong; Shu, Xinhua
- Abstract
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.
- Subjects
TUMOR necrosis factors; ADVANCED glycation end-products; RECEPTOR for advanced glycation end products (RAGE); MEMORY disorders; AFFECTIVE disorders; NEUROINFLAMMATION
- Publication
Cells (2073-4409), 2022, Vol 11, Issue 10, p1594
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells11101594