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Stereoselective metabolism of (+/-)-praeruptorin A, a calcium channel blocker from Peucedani Radix, in pooled liver microsomes of rats and humans
Song, YL (Song, Y. L.)1; ing, WH (Jing, W. H.)1; Zhao, HY (Zhao, H. Y.)1; Yan, R (Yan, R.)1; Li, PT (Li, P. T.)2; Wang, YT (Wang, Y. T.)1,3
2012-03
Source PublicationXENOBIOTICA
ISSN0049-8254
Volume42Issue:3Pages:221-237
Abstract

1. (+/-)-Praeruptorin A (PA) is the major component of Peucedani Radix. The present study investigated stereoselectivity in PA metabolism in liver microsomes of rats (RLMs) and humans (HLMs), for the first time. 

2. PA was enantioseparated by semi-preparative chiral HPLC. Metabolic profiles of the dextrorotatory (dPA) and the levorotatory (/PA) forms in HLMs and RLMs were determined using LC-MS/MS. (-)-cis-Khellactone (D1) prepared from basic hydrolysis of dPA, and (3'R, 4'R)-4'-angeloyl-khellactone (L8) and (3'R, 4'R)-3'-angeloyl-khellactone (L9) isolated from a scale-up incubation of /PA with rat plasma were unambiguously identified by LC-MS/MS and NMR analysis. Other metabolites were tentatively identified using LC-MS/MS. 

3. In the absence of NADPH-regenerating system, dPA remained intact, however, lPA yielded L8 and L9 via a carboxylesterase(s)-mediated process. In the presence of NADPH-regenerating system, lPA produced 9 (L1-9) metabolites in both species, while dPA generated 12 (D1-12) and 6 (D1-3, 6, 9 and 10) metabolites in RLMs and HLMs, respectively. Hydrolysis, oxidation and acyl migration were demonstrated to be the predominant pathways for both enantiomers. Both enantiomers were eliminated faster in RLMs than in HLMs, while lPA showed greater species difference. 

4. PA enantiomers exhibited stereoselective metabolism in RLMs and HLMs, implying chiral discrimination in their actions

KeywordAninitric-oxide Production Caco-2 Cell Monolayers Anti-aids Agents Angelica-furcijuga In-vitro Inhibitory-activities Human Cytochrome-p450 Species-differences Cancer-cells Qian-hu
DOI10.3109/00498254.2011.609250
Indexed BySCI
Language英语
WOS Research AreaPharmacology & Pharmacy ; Toxicology
WOS SubjectPharmacology & Pharmacy ; Toxicology
WOS IDWOS:000299696900001
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被引频次[WOS]:17   [WOS记录]     [WOS相关记录]
Document TypeJournal article
专题Institute of Chinese Medical Sciences
Affiliation1.Univ Macau, Inst Chinese Med Sci, State Key Lab Qual Res Chinese Med, Taipa, Macao Sar, Peoples R China
2.Beijing Univ Chinese Med, Dongzhimen Hosp, Beijing, Peoples R China
3.Beijing Univ Chinese Med, Sch Chinese Mat Med, Beijing, Peoples R China
First Author AffilicationUniversity of Macau
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Song, YL ,ing, WH ,Zhao, HY ,et al. Stereoselective metabolism of (+/-)-praeruptorin A, a calcium channel blocker from Peucedani Radix, in pooled liver microsomes of rats and humans[J]. XENOBIOTICA,2012,42(3):221-237.
APA Song, YL ,ing, WH ,Zhao, HY ,Yan, R ,Li, PT ,&Wang, YT .(2012).Stereoselective metabolism of (+/-)-praeruptorin A, a calcium channel blocker from Peucedani Radix, in pooled liver microsomes of rats and humans.XENOBIOTICA,42(3),221-237.
MLA Song, YL ,et al."Stereoselective metabolism of (+/-)-praeruptorin A, a calcium channel blocker from Peucedani Radix, in pooled liver microsomes of rats and humans".XENOBIOTICA 42.3(2012):221-237.
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