Licochalcone A protects against LPS-induced inflammation and acute lung injury by directly binding with MD2.

doi:10.1111/bph.15999

科研成果详情

题名	Licochalcone A protects against LPS-induced inflammation and acute lung injury by directly binding with MD2.
作者	Zhu, Weiwei1,2; Wang, Minxiu1; Jin, Leiming1; Yang, Bin1; Bai, Bin1; Mutsinze, Rumbidzai Natasha 1; Zuo, Wei 3; Chattipakorn, Nipon 4; Huh, Joo Young 2; Liang, Guang1,5; Wang, Yi1,2,3
发表日期	2022-12-08
发表期刊	British journal of pharmacology 影响因子和分区
语种	英语
原始文献类型	Journal Article
关键词	acute lung injury inflammation licochalcone A myeloid differentiation factor 2
摘要	Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a challenging clinical syndrome that leads to various respiratory sequelae and even high mortality in patients with severe disease. The development of novel pharmacological strategies and therapeutic drugs are urgently needed. Natural products (NPs) have played a fundamental role and provided an abundant pool in drug discovery., A compound library containing 160 NPs was used to screen potential anti-inflammatory compounds. Mice with lipopolysaccharide (LPS)-induced ALI was then used to verify the preventive and therapeutic effects of the selected compounds., Licochalcone A (LA) was discovered from the anti-inflammatory screening of NPs in macrophages. A qPCR array validated the inflammation-regulatory effects of LA and indicated that the potential targets of LA may be the upstream proteins in LPS pro-inflammatory signaling. Further studies showed that LA directly binds to myeloid differentiation factor 2 (MD2), an assistant protein of toll-like receptor 4 (TLR4), to block both LPS-induced TRIF- and MYD88-dependent pathways. LEU61 and PHE151 in MD2 protein are the two key residues that contribute to the binding of MD2 to LA. In vivo, LA treatment alleviated ALI in LPS-challenged mice through significantly reducing immunocyte infiltration, suppressing activation of TLR4 pathway, and inflammatory cytokine induction., In summary, our study identified MD2 as a direct target of LA for its anti-inflammatory activity and suggested that LA might serve as a novel MD2 inhibitor and a potential drug for developing ALI/ARDS therapy.
ISSN	0007-1188
DOI	10.1111/bph.15999
收录类别	PUBMED
URL	查看原文
PubMed ID	36480410
自科自定义期刊分类	T3(B)类
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/171534
专题	药学院（分析测试中心）其他_附属萧山医院（杭州市萧山区第一人民医院）
作者单位	1.Chemical Biology Research Center, School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China.; 2.College of Pharmacy, Chonnam National University, Gwangju, 61186, Korea.; 3.Affiliated Xiangshan Hospital of Wenzhou Medical University (Xiangshan First People's Hospital Medical and Health Group), Xiangshan, Zhejiang, 315799, China.; 4.Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand.; 5.School of Pharmaceutical Sciences, Hangzhou Medical College, Hangzhou, Zhejiang, 311399, China.
第一作者单位	药学院（分析测试中心）; 生物有机与药物化学研究中心
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Zhu, Weiwei,Wang, Minxiu,Jin, Leiming,et al. Licochalcone A protects against LPS-induced inflammation and acute lung injury by directly binding with MD2.[J]. British journal of pharmacology,2022.
APA	Zhu, Weiwei., Wang, Minxiu., Jin, Leiming., Yang, Bin., Bai, Bin., ... & Wang, Yi. (2022). Licochalcone A protects against LPS-induced inflammation and acute lung injury by directly binding with MD2.. British journal of pharmacology.
MLA	Zhu, Weiwei,et al."Licochalcone A protects against LPS-induced inflammation and acute lung injury by directly binding with MD2.".British journal of pharmacology (2022).