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      Isolation and Identification of Potent Antidiabetic Compounds from Antrodia cinnamomea—An Edible Taiwanese Mushroom

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          Abstract

          Antrodia cinnamomea (AC), an edible Taiwanese mushroom, has been recognized as a valuable natural resource with vast biological and medicinal benefits. Recently, the hypoglycemic and anti-diabetic effects of AC were mentioned in several studies. However, no studies have investigated α-glucosidase inhibitors from AC fruiting bodies (ACFB) as they relate to type 2 diabetes (T2D) treatment. The purpose of this study was to gain evidence of potent α-glucosidase inhibitory effects, as well as isolate, identify and characterize the active compounds of ACFB. The MeOH extract of ACFB demonstrated potent α-glucosidase inhibitory activity, and possessed high pH stability (pH 2–11) and thermostable properties at 40–50 °C. Further purification led to the isolation of eight constituents from ACFB, identified as: 25 S-antcin K ( 1), 25 R-antcin K ( 2), dehydrosulphurenic acid ( 3), 25 S-antcin I ( 4), 25 S-antcin B ( 5), 25 R-antcin B ( 6), dehydroeburicoic acid ( 7) and eburicoic acid ( 8). Notably, the ACFB extract and its identified compounds, except 1, 4, and 6 demonstrated a greater effect (EC 50 = 0.025–0.21 mg/mL) than acarbose (EC 50 = 0.278 mg/mL). As such, these active compounds were determined to be new potent mushroom α-glucosidase inhibitors. These active compounds were also identified on the HPLC fingerprints of ACFB.

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          Medicinal mushroom science: Current perspectives, advances, evidences, and challenges.

          The main target of the present review is to draw attention to the current perspectives, advances, evidences, challenges, and future development of medicinal mushroom science in the 21 st century. Medicinal mushrooms and fungi are thought to possess approximately 130 medicinal functions, including antitumor, immunomodulating, antioxidant, radical scavenging, cardiovascular, anti-hypercholesterolemic, antiviral, antibacterial, anti-parasitic, antifungal, detoxification, hepatoprotective, and antidiabetic effects. Many, if not all, higher Basidiomycetes mushrooms contain biologically active compounds in fruit bodies, cultured mycelium, and cultured broth. Special attention is paid to mushroom polysaccharides. The data on mushroom polysaccharides and different secondary metabolites are summarized for approximately 700 species of higher hetero- and homobasidiomycetes. Numerous bioactive polysaccharides or polysaccharide-protein complexes from the medicinal mushrooms described appear to enhance innate and cell-mediated immune responses, and exhibit antitumor activities in animals and humans. Whilst the mechanism of their antitumor actions is still not completely understood, stimulation and modulation of key host immune responses by these mushroom compounds appear central. Polysaccharides and low-molecular-weight secondary metabolites are particularly important due to their antitumor and immunostimulating properties. Several of the mushroom compounds have been subjected to Phase I, II, and III clinical trials, and are used extensively and successfully in Asia to treat various cancers and other diseases. Special attention is given to many important unsolved problems in the study of medicinal mushrooms.
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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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              Antroquinonol from ethanolic extract of mycelium of Antrodia cinnamomea protects hepatic cells from ethanol-induced oxidative stress through Nrf-2 activation.

              In recent years, the medicinal mushroom Antrodia cinnamomea, known as "niu-chang chih" has received much attention with regard to its possible health benefits; especially its hepatoprotective effects against various drugs, toxins, and alcohol induced liver diseases. However, the molecular mechanism underlying this protective effect of Antrodia cinnamomea and its active compound antroquinonol was poorly understood. In the present study we evaluated to understand the hepatoprotective efficacy of antroquinonol and ethanolic extracts of mycelia of Antrodia cinnamomea (EMAC) in vitro and in vivo. The protective mechanism of antroquinonol and EMAC against ethanol-induced oxidative stress was investigated in cultured human hepatoma HepG2 cells and ICR mice model, respectively. HepG2 cells were pretreated with antroquinonol (1-20μM) and oxidative stress was induced by ethanol (100mM). Meanwhile, male ICR mice were pretreated with EMAC for 10 days and hepatotoxicity was generated by the addition of ethanol (5g/kg). Hepatic enzymes, cytokines and chemokines were determined using commercially available assay kits. Western blotting and real-time PCR were subjected to analyze HO-1 and Nr-2 expression. EMSA was performed to monitor Nrf-2 ARE binding activity. Possible changes in hepatic lesion were observed using histopathological analysis. Antroquinonol pretreatment significantly inhibited ethanol-induced AST, ALT, ROS, NO, MDA production and GSH depletion in HepG2 cells. Western blot and RT-PCR analysis showed that antroquinonol enhanced Nrf-2 activation and its downstream antioxidant gene HO-1 via MAPK pathway. This mechanism was then confirmed in vivo in an acute ethanol intoxicated mouse model: serum ALT and AST production, hepatocellular lipid peroxidation and GSH depletion was prevented by EMAC in a dose-dependent manner. EMAC significantly enhanced HO-1 and Nrf-2 activation via MAPKs consistent with in vitro studies. Ethanol-induced hepatic swelling and hydropic degeneration of hepatocytes was significantly inhibited by EMAC in a dose-dependent manner. These results provide a scientific basis for the hepatoprotective effects of Antrodia cinnamomea. Data also imply that antroquinonol, a potent bioactive compound may be responsible for the hepatoprotective activity of Antrodia cinnamomea. Moreover, the present study highly supported our traditional knowledge that Antrodia cinnamomea as a potential candidate for the treatment of alcoholic liver diseases. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.
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                Author and article information

                Journal
                Molecules
                Molecules
                molecules
                Molecules
                MDPI
                1420-3049
                02 November 2018
                November 2018
                : 23
                : 11
                : 2864
                Affiliations
                [1 ]Department of Biochemical Science and Technology, National Taiwan University, Taipei 106, Taiwan; kk49310953@ 123456nricm.edu.tw
                [2 ]Division of Chinese Materia Medica Development, National Research Institute of Chinese Medicine, Taipei 11221, Taiwan
                [3 ]Department of Chemistry, Tamkang University, New Taipei City 25137, Taiwan
                [4 ]Life Science Development Center, Tamkang University, New Taipei City 25137, Taiwan
                [5 ]Institute of Research and Development, Duy Tan University, Da Nang 550000, Vietnam
                [6 ]Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung 40402, Taiwan
                [7 ]Ph.D. Program for Clinical Drug Development of Chinese Herbal Medicine, College of Pharmacy, Taipei Medical University, Taipei 11031, Taiwan
                Author notes
                [* ]Correspondence: sabulo@ 123456mail.tku.edu.tw (S.-L.W.); bondhtn@ 123456gmail.com (V.B.N.); kuoyh@ 123456nricm.edu.tw (Y.-H.K.); Tel.: +886-2-2621-5656 (S.-L.W.); Fax: +886-2-2620-9924 (S.-L.W.)
                Author information
                https://orcid.org/0000-0002-1384-3731
                https://orcid.org/0000-0002-2666-9584
                Article
                molecules-23-02864
                10.3390/molecules23112864
                6278467
                30400247
                37daa4ec-ce2a-433a-9410-efbf71845076
                © 2018 by the authors.

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

                History
                : 16 September 2018
                : 01 November 2018
                Categories
                Article

                antrodia cinnamomea,antidiabetic,edible mushroom,α-glucosidase inhibitor,antcin k,dehydrosulphurenic acid,dehydroeburicoic acid,eburicoic acid

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