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Pharmacokinetics-Based Identification of Potential Therapeutic Phthalides from XueBiJing, a Chinese Herbal Injection Used in Sepsis Management

文献类型：期刊论文

作者Zhang, Nating4,5; Cheng, Chen5; Olaleye, Olajide E.5; Sun, Yan2,5; Li, Li5; Huang, Yuhong1; Du, Feifei5; Yang, Junling5; Wang, Fengqing5; Shi, Yanhong5
刊名DRUG METABOLISM AND DISPOSITION
出版日期2018-06-01
卷号46期号:6页码:823-834
ISSN号0090-9556
DOI10.1124/dmd.117.079673
文献子类Article
英文摘要XueBiJing, an injectable five-herb preparation, has been incorporated into routine sepsis care in China. Phthalides, originating from XueBiJing's component herbs Ligusticum chuanxiong rhizomes and Angelica sinensis roots, are believed to contribute to its therapeutic effects due to their presence in the preparation and antisepsis-related properties. This investigation aimed to identify potential therapeutic phthalides that are bioavailable to act on XueBiJing's therapeutic targets and that could serve as pharmacokinetic markers to supplement classic biomarkers for sepsis care. Among 10 phthalides detected in XueBiJing, senkyunolides I and G were the major circulating phthalides in human subjects, but their different pharmacokinetics might influence their contribution to XueBiJing's therapeutic action. Senkyunolide I exhibited a large distribution volume (1.32 l/kg) and was moderately bound in plasma (54% unbound), whereas senkyunolide G exhibited a small distribution volume (0.10 l/kg) and was extensively bound in plasma (3% unbound). Clearance of senkyunolide I from the systemic circulation was governed by UGT2B15-mediated hepatic glucuronidation; the resulting electrophilic glucuronides were conjugated with glutathione in the liver. Senkyunolide G was selectively bound to albumin (99%) in human plasma. To our knowledge, the human pharmacokinetic data of XueBiJing's phthalides are reported here for the first time. Based on this investigation and such investigations of the other component herbs, follow-up pharmacodynamic assessments of bioavailable herbal compounds are planned to elucidate XueBiJing's chemical basis responsible for its therapeutic action. Senkyunolides I and G, having the preceding disposition characteristics that could be detectably altered by septic pathophysiology, could serve as pharmacokinetic markers for sepsis care.
WOS关键词UDP-GLUCURONOSYLTRANSFERASES ; DRUG-METABOLISM ; RATS ; PLASMA ; CONSTITUENTS ; INFLAMMATION ; MULTICENTER ; DISPOSITION ; BIOMARKERS ; MEDICINE
资助项目National Science and Technology Major Project of China "Key New Drug Creation and Manufacturing Program"[2009ZX09304-002] ; National Science and Technology Major Project of China "Key New Drug Creation and Manufacturing Program"[2011ZX09201-201-23] ; National Science and Technology Major Project of China "Key New Drug Creation and Manufacturing Program"[2017ZX09301012006] ; National Science Foundation of China[30925044] ; National Basic Research Program of China[2012CB518403] ; National Natural Science Foundation of China[81503345] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12050306]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000439228300007
出版者AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
源URL[http://119.78.100.183/handle/2S10ELR8/279716]  
专题上海药物代谢研究中心
中科院受体结构与功能重点实验室
新药研究国家重点实验室
科研与新药推进处
通讯作者Li, Chuan
作者单位1.Tianjin Univ Tradit Chinese Med, Affiliated Hosp 2, Tianjin, Peoples R China;
2.Fudan Univ, Shanghai Canc Ctr, Lab Phase Clin Trials 1, Shanghai, Peoples R China;
3.Hainan Med Univ, Haikou, Hainan, Peoples R China
4.Univ Chinese Acad Sci, Beijing, Peoples R China;
5.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China;
推荐引用方式
GB/T 7714		 Zhang, Nating,Cheng, Chen,Olaleye, Olajide E.,et al. Pharmacokinetics-Based Identification of Potential Therapeutic Phthalides from XueBiJing, a Chinese Herbal Injection Used in Sepsis Management[J]. DRUG METABOLISM AND DISPOSITION,2018,46(6):823-834.
APA Zhang, Nating.,Cheng, Chen.,Olaleye, Olajide E..,Sun, Yan.,Li, Li.,...&Li, Chuan.(2018).Pharmacokinetics-Based Identification of Potential Therapeutic Phthalides from XueBiJing, a Chinese Herbal Injection Used in Sepsis Management.DRUG METABOLISM AND DISPOSITION,46(6),823-834.
MLA Zhang, Nating,et al."Pharmacokinetics-Based Identification of Potential Therapeutic Phthalides from XueBiJing, a Chinese Herbal Injection Used in Sepsis Management".DRUG METABOLISM AND DISPOSITION 46.6(2018):823-834.

入库方式： OAI收割

来源：上海药物研究所

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