Pharmacokinetics, anti-rheumatoid arthritis activity, and active ingredient contents of Eucommia ulmoides Oliv

被引:9
|
作者
Yang, Ruo-yan [1 ]
Liu, Kun [1 ]
Wang, Jian-ying [2 ]
Zhang, Lei [2 ]
Zhang, Bao-jun [2 ]
Yuan, Ying [1 ,3 ]
机构
[1] Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai 201203, Peoples R China
[2] Shanghai Univ Tradit Chinese Med, Shanghai Innovat Ctr TCM Hlth Serv, Shanghai 201203, Peoples R China
[3] Shanghai Univ Tradit Chinese Med, Sch Pharm, 1200 Cailun Rd,Zhangjiang Hitech Pk, Shanghai 201203, Peoples R China
基金
美国国家科学基金会;
关键词
Pharmacokinetics; Eucommia ulmoides Oliv; Rheumatoid arthritis; Chemical ingredient contents; BETULINIC ACID; EXTRACT; CORTEX;
D O I
10.1016/j.fitote.2023.105667
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Eucommia ulmoides Oliv. is a deciduous tree which contains various chemical ingredients. The main objective was to document the active chemical ingredients of Eucommia ulmoides Oliv. and their metabolic profiles in vivo, with a view to providing an experimental and theoretical basis for clarifying the mechanisms underlying the pharmacological activity of Eucommia ulmoides Oliv. against rheumatoid arthritis. Eight main active constituents of Eucommia ulmoides Oliv. bark (pinoresinol glucopyranoside, aucubin, geniposidic acid, geniposide, genipin, chlorogenic acid, quercetin and betulinic acid) were quantified using high-performance liquid chromatography (HPLC). This paper additionally identified and characterized prototype metabolites via ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) combined with the Human Metabolome Database (HMDB) and literature comparisons. Ultra pressure liquid chromatography-mass spectrometry/ mass spectrometry (UPLC-MS/MS) was subsequently employed to quantify these components in blood over time and evaluate their pharmacokinetic characteristics. The anti-rheumatoid arthritis effects of genipin, pinoresinol glucopyranoside and their combinations were assessed using in vitro cellular assays. We identified and characterized a total of 53 ingredients from Eucommia ulmoides Oliv. bark and plasma samples, among which 20 were confirmed as prototype metabolites. Meanwhile, this paper derived and analyzed the metabolic cleavage pathway of 8 index ingredients. Six of these compounds displayed rapid entry into blood, with high plasma exposure and fast elimination rates. Data from the in vitro cellular assay showed that aucubin, pinoresinol glucopyranoside, genipin, and combinations of these compounds effectively inhibit MH7A cell proliferation, reduce NO release, and decrease inflammatory factor levels.
引用
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页数:13
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