P-coumaric acid reverses depression-like behavior and memory deficit via inhibiting AGE-RAGE-Mediated neuroinflammation

Xu-Dong Yu, Dan Zhang, Chu-Li Xiao, Yu Zhou, Xing Li, Le Wang, Zhiming He, James Reilly, Zhi-Yong Xiao*, Xinhua Shu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)
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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.
Original languageEnglish
Article number1594
Number of pages14
Issue number10
Publication statusPublished - 10 May 2022


  • depression
  • p-coumaric acid
  • inflammation
  • AGE-RAGE signaling pathway
  • network pharmacology

ASJC Scopus subject areas

  • Medicine(all)


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