Combinatorial Metabolism Notably Affects Human Systemic Exposure to Ginsenosides from Orally Administered Extract of Panax notoginseng Roots (Sanqi)

doi:10.1124/dmd.113.051391

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	Combinatorial Metabolism Notably Affects Human Systemic Exposure to Ginsenosides from Orally Administered Extract of Panax notoginseng Roots (Sanqi)
	Hu, Zheyi 2; Yang, Junling2 ; Cheng, Chen 2; Huang, Yuhong 1; Du, Feifei 2; Wang, Fengqing 2; Niu, Wei 2; Xu, Fang 2; Jiang, Rongrong 2; Gao, Xiumei 1
刊名	DRUG METABOLISM AND DISPOSITION
	2013-07
卷号	41 期号:7 页码:1457-1469
ISSN号	0090-9556
DOI	10.1124/dmd.113.051391
文献子类	Article
英文摘要	Ginsenosides are medicinal ingredients of the cardiovascular herb Panax notoginseng roots (Sanqi). Here, we implemented a human study (ChiCTR-ONC-09000603; www.chictr.org) to characterize pharmacokinetics and metabolism of ginsenosides from an orally ingested Sanqi-extract (a 1: 10 water extract of Sanqi) and the human plasma and urine samples were analyzed by liquid chromatography-mass spectrometry. Plasma and urinary compounds derived from ginsenosides included: 1) intestinally absorbed ginsenosides Ra-3, Rb-1, Rd, F-2, Rg(1), and notoginsenoside R-1; and 2) the deglycosylated products compound-K, 20(S)-protopanaxadiol, 20(S)-protopanaxatriol, and their oxidized metabolites. The systemic exposure levels of the first group compounds increased as the Sanqi-extract dose increased, but those of the second group compounds were dose-independent. The oxidized metabolites of 20(S)-protopanaxadiol and 20(S)-protopanaxatriol represented the major circulating forms of ginsenosides in the bloodstream, despite their large interindividual differences in exposure level. The metabolites were formed via combinatorial metabolism that consisted of a rate-limiting step of ginsenoside deglycosylation by the colonic microflora and a subsequent step of sapogenin oxidation by the enterohepatic cytochrome P450 enzymes. Significant accumulation of plasma ginsenosides and metabolites occurred in the human subjects receiving 3-week sub-chronic treatment with the Sanqi-extract. Plasma 20(S)-protopanaxadiol and 20(S)-protopanaxatriol could be used as pharmacokinetic markers to reflect the subjects' microbial activities, as well as the timely-changes and interindividual differences in plasma levels of their respective oxidized metabolites. The information gained from the current study is relevant to pharmacology and therapeutics of Sanqi.
资助项目	National Science Fund of China for Distinguished Young Scholars[30925044] ; National Basic Research Program of China[2012CB518403] ; 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"[2012ZX09304007] ; National Science and Technology Major Project of China "Key New Drug Creation and Manufacturing Program"[2012ZX09303010] ; Knowledge Innovation Program of the Chinese Academy of Sciences[KSCX2-YW-R-191]
WOS关键词	HERBAL MEDICINES ; DRUGS ; PHARMACOKINETICS ; ABSORPTION ; RAT
WOS研究方向	Pharmacology & Pharmacy
语种	英语
出版者	AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
WOS记录号	WOS:000320307100018
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/277570]
专题	上海药物代谢研究中心科研与新药推进处
通讯作者	Li, Chuan
作者单位	1.Tianjin Univ Tradit Chinese Med, Tianjin, Peoples R China; 2.Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China; 3.China Acad Chinese Med Sci, Inst Chinese Mat Med, Beijing, Peoples R China
推荐引用方式 GB/T 7714	Hu, Zheyi,Yang, Junling,Cheng, Chen,et al. Combinatorial Metabolism Notably Affects Human Systemic Exposure to Ginsenosides from Orally Administered Extract of Panax notoginseng Roots (Sanqi)[J]. DRUG METABOLISM AND DISPOSITION,2013,41(7):1457-1469.
APA	Hu, Zheyi.,Yang, Junling.,Cheng, Chen.,Huang, Yuhong.,Du, Feifei.,...&Li, Chuan.(2013).Combinatorial Metabolism Notably Affects Human Systemic Exposure to Ginsenosides from Orally Administered Extract of Panax notoginseng Roots (Sanqi).DRUG METABOLISM AND DISPOSITION,41(7),1457-1469.
MLA	Hu, Zheyi,et al."Combinatorial Metabolism Notably Affects Human Systemic Exposure to Ginsenosides from Orally Administered Extract of Panax notoginseng Roots (Sanqi)".DRUG METABOLISM AND DISPOSITION 41.7(2013):1457-1469.