Pharmacologically significant constituents collectively responsible for anti-sepsis action of XueBiJing,a Chinese herb-based intravenous formulation  

作　　者：Chen Cheng Chao Ren Mu-zi Li Yi-hui Liu Ren-qi Yao Yang Yu Xuan Yu Jian-li Wang Li-xue Wang Yu-chun Leng Hui Zhang Fei-fei Du Ning Dong Feng-qing Wang Yao Wu Fang Xu Xiao-mei Zhu Gui-ping Zhang Kai Dong Si Liu Xiao-qing Yao Chuan Li Yong-ming Yao 

机构地区：[1]State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai,201203,China [2]Translational Medicine Research Center,Medical Innovation Research Division and Fourth Medical Center of the Chinese PLA General Hospital,Beijing,100853,China [3]Department of Pulmonary and Critical Care Medicine,Beijing Chaoyang Hospital,Capital Medical University,Beijing,100020,China [4]School of Chinese Materia Medica,Nanjing University of Chinese Medicine,Nanjing,210023,China [5]Tianjin Chasesun Pharmaceutical Co.,Ltd,Tianjin,301700,China [6]School of Pharmacy,University of Chinese Academy of Sciences,Shanghai,201203,China [7]Zhongshan Institute for Drug Discovery,Zhongshan,528400,China [8]Haihe Laboratory of Modern Chinese Medicine,Tianjin,301617,China

出　　处：《Acta Pharmacologica Sinica》2024年第5期1077-1092,共16页中国药理学报（英文版）

基　　金：funded by National Natural Science Foundation of China(82192912,82074176,81801935,and 82272187);Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine(ZYYCXTD-C-202009);the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA12050306).

摘　　要：Sepsis,a life-threatening health issue,lacks effective medicine targeting the septic response.In China,treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response.In this study,we identified the combined active constituents that are responsible for the XueBiJing’s anti-sepsis action.Sepsis was induced in rats by cecal ligation and puncture(CLP).The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing.Furthermore,the identified compounds in combination were assessed,by comparing with XueBiJing,for levels of primary therapeutic outcome,pharmacokinetic equivalence,and pharmacokinetic compatibility.We showed that a total of 12 XueBiJing compounds,unchanged or metabolized,circulated with significant systemic exposure in CLP rats that received XueBiJing.Among these compounds,hydroxysafflor yellow A,paeoniflorin,oxypaeoniflorin,albiflorin,senkyunolide I,and tanshinol displayed significant anti-sepsis activities,which involved regulating immune responses,inhibiting excessive inflammation,modulating hemostasis,and improving organ function.A combination of the six compounds,with the same respective doses as in XueBiJing,displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing.Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds.The identification of XueBiJing’s pharmacologically significant constituents supports the medicine’s anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.

关 键 词：Traditional Chinese medicine XUEBIJING SEPSIS mortality pharmacokinetic compatibility POLYPHARMACOLOGY 

分 类 号：R285[医药卫生—中药学]