A target lipidomics approach to investigate the acute inflammatory irritation induced by indolealkylamines from Chansu water fraction in rats  

作　　者：YANG Xin CHEN Wu-Yue GONG Yan DI Liu-Qing DUAN Jin-Ao ZHOU Jing MA Hong-Yue 

机构地区：[1]Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization,and Jiangsu Key Laboratory for High Technology Research of TCM Formulae,College of Pharmacy,Nanjing University of Chinese Medicine,Nanjing 210023,China [2]Jiangsu Engineering Research Center for Efficient Delivery System of TCM,Nanjing University of Chinese Medicine,Nanjing 210023,China

出　　处：《Chinese Journal of Natural Medicines》2021年第11期856-867,共12页中国天然药物（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(Nos.82073975,81673563,81102762,and 2018YFC1706200);the Open Project Program of Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization/Jiangsu Key Laboratory for High Technology Research ofTCM Formulae(Nos.ZDXM-1-14,FJGJS-2015-15);the Fund of Quality Standardization of Liu-Shen-Wan(Nos.BA2016104,ZYBZH-C-JS-30),and Jiangsu Qing Lan Project for Young academic leaders.

摘　　要：Chansu has demonstrated adverse reactions in clinical settings,which is associated with its toxicity and limits its clinical applications.But there are methodological limitations for drug safety evaluation.In the current study,ultra-high performance liquid chromatography,lipidomic profiling,and molecular docking were used to systemically assess Chansu-induced acute inflammatory irritation and further identify the underlying drug targets.Compared with the EtOAc extract,Chansu water fraction containing indolealkylamines caused acute inflammatory irritation in rats,including acute pain(spontaneous raising foot reaction),and inflammation(paw edema).At the molecular level,lipids analysis revealed significantly higher levels of pro-inflammatory mediators of the COX and LOX pathways.However,anti-inflammatory mediators from the CYP 450,ALA,and DHA pathways markedly decreased after exposure to Chansu water fraction.Moreover,four indolealkylamines from Chansu showed a high theoretical affinity to a known irritation target,5-HT_(2A)R.These results suggest that Chansu-induced inflammatory irritation is related to the distinct dysregulation of inflammatory lipids,and peripheral 5-HT_(2A)R is a potential target for irritation therapy.The strategy used in this study can be a crucial approach in the safety evaluation of natural medicinal substances.

关 键 词：Chansu Acute inflammatory irritation LIPIDOMICS EICOSANOIDS Molecular docking 

分 类 号：R965[医药卫生—药理学]