Auraptene-ameliorating depressive-like behaviors induced by lipopolysaccharide combined with chronic unpredictable mild stress in mice mitigate hippocampal neuroinflammation mediated by microglia

• Published in: International immunopharmacology Vol. 136; p. 112330
• Main Authors: Zhang, Lu-wen, Cui, Chun-ai, Liu, Chao, Sun, Lian-ping, Ouyang, Yi-nan, Li, Long-fei, Zhang, Dong-liang, Yu, Hai-ling
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 30.07.2024
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Anti-Inflammatory Agents - therapeutic use; Antidepressive Agents - pharmacology; Antidepressive Agents - therapeutic use; Auraptene; Behavior, Animal - drug effects; Coumarins - pharmacology; Coumarins - therapeutic use; Cytokines - metabolism; Depression - chemically induced; Depression - drug therapy; Depression - immunology; Disease Models, Animal; Hippocampus; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - pathology; Inflammation Mediators - metabolism; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Microglia; Microglia - drug effects; Neuroinflammation; Neuroinflammatory Diseases - drug therapy; Neuroinflammatory Diseases - immunology; Stress, Psychological - drug therapy; Stress, Psychological - immunology; Unpredictable chronic mild stress; Unpredictable chronic mild stress; Neuroinflammation; Mice; Auraptene; Hippocampus; Microglia
• ISSN: 1567-5769; 1878-1705; 1878-1705
• DOI: 10.1016/j.intimp.2024.112330

•LPS combined with uCMS exacerbated depression-like behaviors and inflammatory challenges.•Auraptene ameliorate the behavioral phenotype of mice induced by intermittent LPS injection combined with uCMS.•Auraptene can balance the expression of hippocampal inflammatory cytokines via the polarization phenotype transition from M1 to M2 in the microglia. An inflammatory response is one of the pathogeneses of depression. The anti-inflammatory and neuroprotective effects of auraptene have previously been confirmed. We established an inflammatory depression model by lipopolysaccharide (LPS) injection combined with unpredictable chronic mild stress (uCMS), aiming to explore the effects of auraptene on depressive-like behaviors in adult mice. Mice were divided into a control group, vehicle group, fluoxetine group, celecoxib group, and auraptene group. Then, behavioral tests were conducted to evaluate the effectiveness of auraptene in ameliorating depressive-like behavior. Cyclooxygenase-2 (COX-2), C-reactive protein (CRP), tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were examined by ELISA. Interleukin-10 (IL-10), interleukin-4 (IL-4), and transforming growth factor-β (TGF-β) were examined by protein chip technology. The morphology of microglia was observed by the immunohistochemical method. The data showed that, compared with the control group, the vehicle group mice exhibited a depressive-like behavioral phenotype, accompanied by an imbalance in inflammatory cytokines and the activation of microglia in the hippocampus. The depressive behaviors of the auraptene group’s mice were significantly alleviated, along with the decrease in pro-inflammatory factors and increase in anti-inflammatory factors, while the activation of microglia was inhibited in the hippocampus. Subsequently, we investigated the role of auraptene in vitro-cultured BV-2 cells treated with LPS. The analysis showed that auraptene downregulated the expression of IL-6, TNF-α, and NO, and diminished the ratio of CD86/CD206. The results showed that auraptene reduced the excessive phagocytosis and ROS production of LPS-induced BV2 cells. In conclusion, auraptene relieved depressive-like behaviors in mice probably via modulating hippocampal neuroinflammation mediated by microglia.