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      Intestinal Absorption of Ergostane and Lanostane Triterpenoids from Antrodia cinnamomea Using Caco-2 Cell Monolayer Model

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          Abstract

          Abstract

          Antrodia cinnamomea is a precious medicinal mushroom. It exhibits promising therapeutic effects on cancer, intoxication, hypertension, hepatitis, and inflammation. Its major bioactive constituents are ergostane and lanostane triterpenoids. In this study, we used intestinal Caco-2 cell monolayer model to reveal the intestinal absorption property of 14 representative triterpenoids from A. cinnamomea. The bidirectional transport through the monolayer at different time points was monitored by a fully validated LC/MS/MS method. In the case of pure compounds, ergostanes 5 (25 R-antcin H), 6 (25 S-antcin H) and 10 (25 R-antcin B) could readily pass through the Caco-2 cell layer, whereas lanostanes 13 (dehydroeburicoic acid) and 14 (eburicoic acid) could hardly pass through. When the cells were treated with A. cinnamomea extract, antcins A, B, C, H and K ( 16 and 911) were absorbed via passive transcellular diffusion, and showed high P AB and P BA values (> 2.5 × 10 −5 cm/s). Meanwhile, the lanostanes dehydrosulphurenic acid ( 8), 15 α-acetyldehydrosulphurenic acid ( 12), 13 and 14 exhibited poor permeability. Transport features of these compounds were consistent with their pharmacokinetic behaviors in rats. This study could also be helpful in predicting the intestinal absorption of A. cinnamomea in human.

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          The online version of this article (doi:10.1007/s13659-015-0072-4) contains supplementary material, which is available to authorized users.

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          The Caco-2 cell monolayer: usefulness and limitations.

          The Caco-2 monolayer has been used extensively for the high-throughput screening of drug permeability and identification of substrates, inhibitors, and inducers of intestinal transporters, especially P-glycoprotein (P-gp). Traditionally, the Caco-2 monolayer is viewed as a single barrier rather than a polarized cell monolayer consisting of metabolic enzymes that are sandwiched between two membrane barriers with distinctly different transporters. This review addressed the usefulness and limitations of the Caco-2 cell monolayer in drug discovery and mechanistic studies. This mini-review covered applications of the Caco-2 monolayer, clarified misconceptions, and critically addressed issues on data interpretation. The catenary model extends the usefulness of Caco-2 monolayer and provides proper mechanistic insight and data interpretation.
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            Caco-2 monolayers in experimental and theoretical predictions of drug transport

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              Recent research and development of Antrodia cinnamomea.

              Medicinal mushrooms have attracted much attention recently owing to their potent therapeutic activity, especially as chemopreventive and immunomodulatory agents. Antrodia cinnamomea is a treasured Taiwanese mushroom that has been used by aboriginal tribes for centuries to treat food intoxication and to enhance liver functions. It was included in Asian folk medicine in the last few decades with remarkable results in treating inflammatory disorders, cancers, hypertension and hepatitis. This myriad of therapeutic activities encouraged several research groups to subject A. cinnamomea to intensive biological and phytochemical investigation, leading to the isolation of different classes of pharmacologically active secondary metabolites. The in vitro and in vivo biological results of the mushroom extracts and its active components revealed their potent cytotoxic, anti-inflammatory and hepatoprotective activities. The aim of this study is to review recent reports on the biological activities of A. cinnamomea extracts and its active components; quality control protocols; synthetic methodologies for the preparation of active components; developed culture techniques; phylogenetic analysis and gene cloning. This study also tackles major challenges facing future expansion of A. cinnamomea production. Copyright © 2013 Elsevier Inc. All rights reserved.
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                Author and article information

                Contributors
                +86 10 82801516 , deminzhou@bjmu.edu.cn
                +86 10 82801516 , yemin@bjmu.edu.cn
                Journal
                Nat Prod Bioprospect
                Nat Prod Bioprospect
                Natural Products and Bioprospecting
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                2192-2195
                2192-2209
                28 September 2015
                28 September 2015
                October 2015
                : 5
                : 5
                : 237-246
                Affiliations
                [ ]State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing, 100191 China
                [ ]Institute of Biochemical Sciences and Technology, Chaoyang University of Technology, Taichung, 41349 Taiwan
                Article
                72
                10.1007/s13659-015-0072-4
                4607679
                26411834
                0ddac73a-b2f1-4c8a-87e0-10017343802f
                © The Author(s) 2015

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

                History
                : 11 August 2015
                : 10 September 2015
                Categories
                Original Article
                Custom metadata
                © The Author(s) 2015

                antrodia cinnamomea,ergostane,lanostane,triterpenoids,caco-2

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