Absorption, Disposition, and Pharmacokinetics of Saponins from Chinese Medicinal Herbs: What Do We Know and What Do We Need to Know More?

doi:10.2174/1389200211209050577

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	Absorption, Disposition, and Pharmacokinetics of Saponins from Chinese Medicinal Herbs: What Do We Know and What Do We Need to Know More?
	Yu, Ke ; Chen, Feng 1; Li, Chuan2
刊名	CURRENT DRUG METABOLISM
	2012-06
卷号	13 期号:5 页码:577-598
关键词	Panax ginsenoside saponin absorption disposition
ISSN号	1389-2002
DOI	10.2174/1389200211209050577
文献子类	Review
英文摘要	Saponins are a group of amphiphilic glycosides containing one or more sugar chains linked to a nonpolar triterpene or steroid aglycone skeleton, which are believed to be responsible for the pharmacological activities of many Chinese medicinal herbs. The purpose of this paper is to summarize the contemporary knowledge of the absorption, disposition, and pharmacokinetics of some important saponins, including ginsenosides, licorice saponins, dioscorea saponins, astragalosides, and saikosaponins. Poor intestinal absorption of saponins is mainly due to their unfavorable physicochemical traits, such as large molecular mass (>500 Da), high hydrogen-bonding capacity (>12), and high molecular flexibility (>10), that underlie poor membrane permeability. Rapid and extensive biliary excretion is another primary factor that limits the oral bioavailability of most saponins. However, several saponins, including ginsenosides Ra-3, Rb-1, Rc, and Rd, and dioscin, are excreted slowly into the bile and in turn have significantly long elimination half lives (7-25 h in rats). These long-circulating saponins may be used as pharmacokinetic markers to substantiate systemic exposure to the ingested herb extracts. In addition to biliary excretion for elimination of most saponins unchanged, renal excretion may also be important for certain saponins. Saponins can be hydrolyzed by the colonic microflora. After absorption, the deglycosylated aglycones undergo phase I and/or II metabolism by the host. In line with the poor permeability, saponin concentrations in most rat tissues are lower than the concurrent plasma level and the brain level is usually very low. However, the liver concentrations of many saponins, as well as the kidney levels of certain saponins, can be quite high, which involves transporter-mediated uptake mechanisms. Repeated p.o. ingestion of glycyrrhizin appears to be able to induce CYP3A in rodents and humans, while several deglycosylated products of ginsenosides can moderately inhibit CYP activities in vitro with IC50 values of 10-50 mu M. More research is required for elucidation of the absorption, disposition, and pharmacokinetics of multiple saponins to enhance understanding which saponins are most likely to exert pharmacological effects in vivo, as well as influence of complex herb matrix. In addition, research is also needed to characterize the microbiotal deglycosylation and the subsequent aglycone metabolism by the host for a broader range of saponins, as well as the hepatobiliary transporter phenotyping for and the interaction with saponins. Furthermore, in vitro and in vivo studies of saponin-based herb-drug interactions are also warranted.
资助项目	National Science Fund of China for Distinguished Young Scholars[30925044] ; National Science and Technology Major Project of China "Key New Drug Creation and Manufacturing Program"[2009ZX09304-002] ; Chinese Academy of Sciences[KSCX2-YW-R-191] ; National Basic Research Program of China[2012CB518403]
WOS关键词	PERFORMANCE LIQUID-CHROMATOGRAPHY ; TANDEM MASS-SPECTROMETRY ; HUMAN INTESTINAL BACTERIA ; BETA-D-GLUCURONIDASE ; DRUG-DRUG INTERACTION ; RAT-LIVER MICROSOMES ; CHRONIC HEPATITIS-C ; HUMAN-SERUM-ALBUMIN ; HUMAN CYTOCHROME-P450 ENZYMES ; SOLID-PHASE EXTRACTION
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy
语种	英语
出版者	BENTHAM SCIENCE PUBL LTD
WOS记录号	WOS:000304041700007
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/278070]
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.Hainan Med Univ, Haikou, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Lab DMPK Res Herbal Med, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Yu, Ke,Chen, Feng,Li, Chuan. Absorption, Disposition, and Pharmacokinetics of Saponins from Chinese Medicinal Herbs: What Do We Know and What Do We Need to Know More?[J]. CURRENT DRUG METABOLISM,2012,13(5):577-598.
APA	Yu, Ke,Chen, Feng,&Li, Chuan.(2012).Absorption, Disposition, and Pharmacokinetics of Saponins from Chinese Medicinal Herbs: What Do We Know and What Do We Need to Know More?.CURRENT DRUG METABOLISM,13(5),577-598.
MLA	Yu, Ke,et al."Absorption, Disposition, and Pharmacokinetics of Saponins from Chinese Medicinal Herbs: What Do We Know and What Do We Need to Know More?".CURRENT DRUG METABOLISM 13.5(2012):577-598.