Tehran University of Medical Sciences Iranian Journal of Allergy, Asthma and Immunology 1735-1502 0 0 2026 10 15 1 13 Zhaopeng Kang General Psychiatry Division I, Guangji Hospital of Suzhou, Suzhou, China Lin Zhang General Psychiatry Division I, Guangji Hospital of Suzhou, Suzhou, China Cheng Lian Department of Psychiatric Medicine, The Fourth Affiliated Hospital of Soochow University, Suzhou, China 2026 06 08 2026 07 03 This study aimed to investigate the effects and mechanisms of Chrysoeriol (CHR) in improving depression-like behavior in mice. Network pharmacology analysis was conducted to identify CHR-related targets and signaling pathways associated with depression and neuroinflammation. The chronic unpredictable mild stress (CUMS) method was used to construct a depression mouse model. After CHR intervention, behavioral changes were assessed using the elevated plus maze and open field tests. Cortical proinflammatory cytokine levels were measured using enzyme-linked immunosorbent assay (ELISA) kits, and pathological changes were examined by hematoxylin and eosin (H&E) and Nissl staining. Network pharmacology identified AKT1 among the core predicted targets of CHR. Elevated plus maze and open field test results indicated that CHR improved depression-like behavior in mice. CHR reduced neuroinflammatory cytokine levels and attenuated tissue and neuronal damage. CHR alleviated CUMS-induced depression-like behaviors and reduced neuroinflammation and neuronal damage. Network pharmacology identified predicted core targets, including AKT1. Further molecular verification and safety evaluation are required to validate its antidepressant potential. https://ijaai.tums.ac.ir/index.php/ijaai/article/view/4868 https://ijaai.tums.ac.ir/index.php/ijaai/article/download/4868/2443