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Mechanism of ligusticum cycloprolactam against neuroinflammation based on network pharmacology and experimental verification

神经炎症 药理学 NF-κB 信号转导 化学 炎症 体内 促炎细胞因子 背景(考古学) 下调和上调 IκB激酶 医学 生物 免疫学 生物化学 基因 生物技术 古生物学 有机化学
作者
Juan Gao,Gang Su,Wei Chen,Qionghui Wu,Junxi Liu,Jifei Liu,Miao Chai,Ying Dong,He Wang,Lixia Chen,Zhenchang Zhang,Manxia Wang
出处
期刊:Clinical and Experimental Pharmacology and Physiology [Wiley]
卷期号:50 (8): 647-663
标识
DOI:10.1111/1440-1681.13784
摘要

Ligustilide, a natural phthalide mainly derived from chuanxiong rhizomes and Angelica Sinensis roots, possesses anti-inflammatory activity, particularly in the context of the nervous system. However, its application is limited because of its unstable chemical properties. To overcome this limitation, ligusticum cycloprolactam (LIGc) was synthesized through structural modification of ligustilide. In this study, we combined network pharmacological methods with experimental verification to investigate the anti-neuroinflammatory effects and mechanisms of ligustilide and LIGc. Based on our network pharmacology analysis, we identified four key targets of ligustilide involved in exerting an anti-inflammatory effect, with the nuclear factor (NF)-κB signal pathway suggested as the main signalling pathway. To verify these results, we examined the expression of inflammatory cytokines and inflammation-related proteins, analysed the phosphorylation level of NF-κB, inhibitor of κBα (IκBα) and inhibitor of κB kinase α and β (IKKα+β), and evaluated the effect of BV2 cell-conditioned medium on HT22 cells in vitro. Our results, demonstrate for the first time that LIGc can downregulate the activation of the NF-κB signal pathway in BV2 cells induced by lipopolysaccharide, suppress the production of inflammatory cytokines and reduce nerve injury in HT22 cells mediated by BV2 cells. These findings suggest that LIGc inhibits the neuroinflammatory response mediated by BV2 cells, providing strong scientific support for the development of anti-inflammatory drugs based on natural ligustilide or its derivatives. However, there are some limitations to our current study. In the future, further experiments using in vivo models may provide additional evidence to support our findings.
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