Identification and Pharmacokinetics of Multiple Potential Bioactive Constituents after Oral Administration of Radix Astragali on Cyclophosphamide-Induced Immunosuppression in Balb/c Mice

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Abstract

Radix Astragali (RA) is one of the commonly-used traditional Chinese medicines (TCMs) with an immunomodulatory effect confirmed in the clinic. In order to better understand the material basis for the therapeutic effects, this study was to investigate the absorbed components and their pharmacokinetic profile after oral administration of RA on cyclophosphamide-induced immunosuppression in Balb/c mice. As a result, 51 compounds in RA extract and 31 prototype compounds with nine metabolites were detected in mice plasma by the ultra-fast liquid chromatography (UFLC)-DAD-Q-TOF-MS/MS method. The pharmacokinetic parameters of five main constituents, including calycosin-7- O-glucoside, ononin, calycosin, formononetin and astragaloside IV, were obtained using HPLC-MS/MS. These results offered useful information for research on the pharmacological mechanism of RA and for its further development.

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Review of the botanical characteristics, phytochemistry, and pharmacology of Astragalus membranaceus (Huangqi).

Juan Juan Fu, Zenghui Wang, Linfang Huang … (2014)

Astragalus membranaceus is one of the most widely used traditional Chinese herbal medicines. It is used as immune stimulant, tonic, antioxidant, hepatoprotectant, diuretic, antidiabetic, anticancer, and expectorant. The current paper reviews the botanical characteristics, phytochemistry, and pharmacology of Astragali Radix. Information on Astragali Radix was gathered via the Internet (using Google Scholar, Baidu Scholar, Elsevier, ACS, Medline Plus, CNKI, and Web of Science) as well as from libraries and local books. More than 100 compounds, including flavonoids, saponins, polysaccharides, and amino acids, have so far been identified, and the various biological activities of the compounds have been reported. As an important traditional Chinese medicine, further studies on Astragali Radix can lead to the development of new drugs and therapies for various diseases. The improvement of its utilization should be studied further.

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Bioavailability of dietary flavonoids and phenolic compounds.

Daniele Del Buono, John N. Clifford, Alan Crozier (2010)

This paper reviews recent human studies on the bioavailability of dietary flavonoids and related compounds, including chlorogenic acids and ellagitannins, in which the identification of metabolites, catabolites and parent compounds in plasma, urine and ileal fluid was based on mass spectrometric methodology. Compounds absorbed in the small intestine appear in the circulatory system predominantly as glucuronide, sulfate and methylated metabolites which seemingly are treated by the body as xenobiotics as they are rapidly removed from the bloodstream. As a consequence, while analysis of plasma provides valuable information on the identity and pharmacokinetic profiles of circulating metabolites after acute supplementation, it does not provide accurate quantitative assessments of uptake from the gastrointestinal tract. Urinary excretion, of which there are great variations with different classes of flavonoids, provides a more realistic figure but, as this does not include the possibility of metabolites being sequestered in body tissues, this too is an under estimate of absorption, but to what degree remains to be determined. Even when absorption occurs in the small intestine, feeding studies with ileostomists reveal that substantial amounts of the parent compounds and some of their metabolites appear in ileal fluid indicating that in volunteers with a functioning colon these compounds will pass to the large intestine where they are subjected to the action of the colonic microflora. A diversity of colonic-derived catabolites is absorbed into the bloodstream and passes through the body prior to excretion in urine. There is growing evidence that these compounds, which were little investigated until recently, are produced in quantity in the colon and form a key part of the bioavailability equation of dietary flavonoids and related phenolic compounds. Copyright © 2010 Elsevier Ltd. All rights reserved.

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The profiling and identification of the absorbed constituents and metabolites of Paeoniae Radix Rubra decoction in rat plasma and urine by the HPLC-DAD-ESI-IT-TOF-MS(n) technique: a novel strategy for the systematic screening and identification of absorbed constituents and metabolites from traditional Chinese medicines.

Jing Liang, Feng Xu, Ya-Zhou Zhang … (2013)

Paeoniae Radix Rubra (PRR, the dried roots of Paeonia lactiflora) is a commonly used traditional Chinese medicine (TCM). A clear understanding of the absorption and metabolism of TCMs is very important in their rational clinical use and pharmacological research. To find more of the absorbed constituents and metabolites of TCMs, a novel strategy was proposed. This strategy was characterized by the following: the establishment and utilization of the databases of parent compounds, known metabolites and characteristic neutral losses; the comparison of base peak chromatograms and ClogPs; and the use of the HPLC-DAD-ESI-IT-TOF-MS(n) technique. This strategy was first applied to screen and identify the absorbed constituents and metabolites of PRR decoction and paeoniflorin in rats. In total, 13 new absorbed constituents and 90 new metabolites of PRR decoction were detected. Among these metabolites, the structures of 70 metabolites were identified, and the conjugation types and structure skeletons of the other 20 metabolites were preliminarily determined. Moreover, 35 new metabolites of some constituents of PRR, i.e., 22 new metabolites of paeoniflorin, 10 new metabolites of gallic acid-related compounds, 1 new metabolite of (epi)catechin-related compounds, and 2 new metabolites of other compounds, were reported for the first time. The results also indicated that (epi)catechin-related compounds, gallic acid-related compounds and paeoniflorin were the main precursors of these metabolites. Phase I reactions (dehydroxylation, decarboxylation, dehydrogenation) and phase II reactions (sulfation, glucuronidation and methylation) were observed as the main metabolic pathways of PRR. According to the literature, the 11 absorbed constituents and 11 metabolites have various bioactivities. This study is the first to explore the absorption and metabolism of PRR decoction, and the result also is a notable improvement in the discovery of paeoniflorin metabolites in vivo. These findings enhance our understanding of the metabolism and Effective forms (the truly active structures) of PRR decoction and paeoniflorin.

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Author and article information

Contributors

Maurizio Battino: Role: Academic Editor

Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 05 March 2015

Publication date Collection: March 2015

Volume: 16

Issue: 3

Pages: 5047-5071

Affiliations

[1 ]Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China; E-Mail: wuhuanxian37@ 123456163.com

[2 ]State Key Laboratory of Organ Failure Research, Guangdong Provincial Institute of Nephrology, Southern Medical University, Guangzhou 510515, China

[3 ]Guangzhou Quality R&D Center of Traditional Chinese Medicine, Guangdong Key Laboratory of Plant Resources, School of Life Sciences, Sun Yat-Sen University, Guangzhou 510275, China; E-Mails: lipanlin@ 123456gmail.com (P.L.); zengx6@ 123456mail2.sysu.edu.cn (X.Z.); lssswwhk@ 123456gmail.com (W.S.)

[4 ]Guangzhou Institute of Advanced Technology, Chinese Academy of Sciences, Guangzhou 511458, Guangdong, China

Author notes

[* ]Authors to whom correspondence should be addressed; E-Mails: menghua_liu@ 123456hotmail.com (M.L.); jy.he@ 123456giat.ac.cn (J.H.); Tel.: +86-20-6164-8597 (M.L.); +86-20-2291-2733 (J.H.); Fax: +86-20-6164-8533 (M.L.); +86-20-2291-2525 (J.H.).

Article

Publisher ID: ijms-16-05047

DOI: 10.3390/ijms16035047

PMC ID: 4394464

PubMed ID: 25751722

SO-VID: 86e287a9-4788-4422-82b2-9b5e02df2c8a

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This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

Identification and Pharmacokinetics of Multiple Potential Bioactive Constituents after Oral Administration of Radix Astragali on Cyclophosphamide-Induced Immunosuppression in Balb/c Mice

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Most cited references 39

Review of the botanical characteristics, phytochemistry, and pharmacology of Astragalus membranaceus (Huangqi).

Bioavailability of dietary flavonoids and phenolic compounds.

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