文献类型：期刊文献

中文题名：Synthesis,and anti-inflammatory activities of gentiopicroside derivatives

英文题名：Synthesis, and anti-inflammatory activities of gentiopicroside derivatives

作者：Zhang Qi-Li[1];Xia Peng-Fei[1,2,3];Peng Xue-Jing[1,2,3];Wu Xiao-Yu[1,2,3];Jin Hua[1];Zhang Jian[1,2,3];Zhao Lei[1,2,3]

第一作者：Zhang Qi-Li

通信作者：Zhang, J[1];Zhao, L[1];Zhang, J[2];Zhao, L[2];Zhang, J[3];Zhao, L[3]

机构：[1]Gansu Univ Chinese Med, Lanzhou 730000, Peoples R China;[2]Key Lab Chem & Qual TCM Coll Gansu Prov, Lanzhou 730000, Peoples R China;[3]Gansu Prov Engn Lab TCM Standardizat Technol & Po, Lanzhou 730000, Peoples R China

第一机构：甘肃中医药大学

通信机构：[1]corresponding author), Gansu Univ Chinese Med, Lanzhou 730000, Peoples R China;[2]corresponding author), Key Lab Chem & Qual TCM Coll Gansu Prov, Lanzhou 730000, Peoples R China;[3]corresponding author), Gansu Prov Engn Lab TCM Standardizat Technol & Po, Lanzhou 730000, Peoples R China.|[10735]甘肃中医药大学;

年份：2022

卷号：20

期号：4

起止页码：309

中文期刊名：Chinese Journal of Natural Medicines

外文期刊名：CHINESE JOURNAL OF NATURAL MEDICINES

收录：CSTPCD;;Scopus;WOS:【SCI-EXPANDED(收录号:WOS:000798292700007)】；CSCD:【CSCD2021_2022】；PubMed;

基金：This work was supported by the National Natural Science Foundation of China (Nos. 82160457 and 81660577) and the Natural Science Foundation of Gansu Province (No. 21JR7RA564).

语种：英文

中文关键词：Gentiopicroside derivatives;Structural modification;Anti-inflammatory activity;Selective inhibitors

外文关键词：Gentiopicroside derivatives; Structural modification; Anti-inflammatory activity; Selective inhibitors

摘要：A series of 26 novel derivatives have been synthesized through structural modification of gentiopicroside,a lead COX-2 inhibitor.And their in vivo and in vitro anti-inflammatory activities have been investigated.The in vitro anti-inflammatory activities were evaluated against NO,PGE2,and IL-6 production in the mouse macrophage cell line RAW264.7 stimulated by LPS.Results showed that most compounds had good inhibitory activity.The in vivo inhibitory activities were further tested against xylene-induced mouse ear swelling.Results demonstrated that several compounds were more active than the parent compound gentiopicroside.The inhibition rate of the most active compound P23(57.26%)was higher than positive control drug celecoxib(46.05%)at dose 0.28 mmol-kg-1.Molecular docking suggested that these compounds might bind to COX-2 and iNOS.Some of them,e.g P7,P14,P16,P21,P23,and P24,had high docking scores in accordance with their potency of the anti-inflammatory activitiy,that downregulation of the inflammatory factors,NO,PGE2,and IL-6,was possibly associated with the suppression of iNOS and COX-2.Therefore,these gentiopicroside derivatives may represent a novel class of COX-2 and iNOS inhibitors.
[ABSTRACT] A series of 26 novel derivatives have been synthesized through structural modification of gentiopicroside, a lead COX2 inhibitor. And their in vivo and in vitro anti-inflammatory activities have been investigated. The in vitro anti-inflammatory activities were evaluated against NO, PGE2, and IL-6 production in the mouse macrophage cell line RAW264.7 stimulated by LPS. Results showed that most compounds had good inhibitory activity. The in vivo inhibitory activities were further tested against xylene-induced mouse ear swelling. Results demonstrated that several compounds were more active than the parent compound gentiopicroside. The inhibition rate of the most active compound P23 (57.26%) was higher than positive control drug celecoxib (46.05%) at dose 0.28 mmol??kg???1. Molecular docking suggested that these compounds might bind to COX-2 and iNOS. Some of them, e.g P7, P14, P16, P21, P23, and P24, had high docking scores in accordance with their potency of the anti-inflammatory activitiy, that downregulation of the inflammatory factors, NO, PGE2, and IL-6, was possibly associated with the suppression of iNOS and COX-2. Therefore, these gentiopicroside derivatives may represent a novel class of COX-2 and iNOS inhibitors. [CLC Number] R284;R965 [Document code] A [Article ID] 2095-6975(2022)04-0309-12