姜黄素
尾部悬挂试验
PI3K/AKT/mTOR通路
蛋白激酶B
药理学
行为绝望测验
信号转导
LY294002型
神经炎症
医学
化学
内科学
炎症
抗抑郁药
生物化学
海马体
作者
Jing Guo,Meng Fang,Zhe Xiong,Ke Zhou,Peng Zeng
出处
期刊:Research Square - Research Square
日期:2023-01-03
标识
DOI:10.21203/rs.3.rs-2412991/v1
摘要
Abstract Growing evidence supports the involvement of neuroinflammation in the pathophysiology of depression. Administrating curcumin could revert the depressive-like symptoms and weakened microglial activation and increased the level of pro-inflammatory cytokine. This study aimed to identify potential anti-depression targets and mechanisms of curcumin (CUR) by an approach of network pharmacology. GSEA and KEGG pathways showed the most significantly enriched pathway of CUR against depression was the PI3K-Akt pathway. Moreover, 52 targets were significantly correlated with PI3K-Akt signaling pathway and CUR-related targets. In addition, among these top 50 targets which were ranked by degree in the PPI network, there were 23 targets involved in the 52 intersection targets. Thus, our findings suggest that CUR exerts its anti-depression effects through PI3K-Akt signaling pathway. Furthermore, we investigated the anti-depression effects of CUR using a mouse model of depression induced by lipopolysaccharide (LPS). Administration of LPS alone (2 mg/kg/day, i.p.) extended the immobility time in the open filed test (OFT) and tail suspension test (TST), decreased sucrose consumption in the sucrose preference test (SPT). Pretreatment with CUR (50 mg/kg/day, i.p.) for 7 consecutive days relieved LPS-induced changes in the behavior tests, the activity of PI3K-Akt signaling pathway, neuronal damage in the PFC and inflammatory response. Moreover, inhibition of the PI3K-Akt signaling pathway by LY294002 (7.5 mg/kg/day, i.p.) blocks the therapeutic effects of CUR. In conclusion, our study indicate that CUR may be an effective antidepressant agent for LPS-induced mouse model, in part because of its anti-inflammatory actin through PI3K-Akt signaling pathway.
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