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      Identification of Licopyranocoumarin and Glycyrurol from Herbal Medicines as Neuroprotective Compounds for Parkinson's Disease

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          Abstract

          In the course of screening for the anti-Parkinsonian drugs from a library of traditional herbal medicines, we found that the extracts of choi-joki-to and daio-kanzo-to protected cells from MPP +-induced cell death. Because choi-joki-to and daio-kanzo-to commonly contain the genus Glycyrrhiza, we isolated licopyranocoumarin (LPC) and glycyrurol (GCR) as potent neuroprotective principals from Glycyrrhiza. LPC and GCR markedly blocked MPP +-induced neuronal PC12D cell death and disappearance of mitochondrial membrane potential, which were mediated by JNK. LPC and GCR inhibited MPP +-induced JNK activation through the suppression of reactive oxygen species (ROS) generation, thereby inhibiting MPP +-induced neuronal PC12D cell death. These results indicated that LPC and GCR derived from choi-joki-to and daio-kanzo-to would be promising drug leads for PD treatment in the future.

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          Review of Pharmacological Effects of Glycyrrhiza sp. and its Bioactive Compounds

          Marjan Nassiri Asl, Hossein Hosseinzadeh (2008)
          Abstract The roots and rhizomes of licorice (Glycyrrhiza) species have long been used worldwide as a herbal medicine and natural sweetener. Licorice root is a traditional medicine used mainly for the treatment of peptic ulcer, hepatitis C, and pulmonary and skin diseases, although clinical and experimental studies suggest that it has several other useful pharmacological properties such as antiinflammatory, antiviral, antimicrobial, antioxidative, anticancer activities, immunomodulatory, hepatoprotective and cardioprotective effects. A large number of components have been isolated from licorice, including triterpene saponins, flavonoids, isoflavonoids and chalcones, with glycyrrhizic acid normally being considered to be the main biologically active component. This review summarizes the phytochemical, pharmacological and pharmacokinetics data, together with the clinical and adverse effects of licorice and its bioactive components. Copyright © 2008 John Wiley & Sons, Ltd.
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            Complex I deficiency in Parkinson's disease frontal cortex.

            W Davis Parker, Janice K. Parks, Russell Swerdlow (2008)
            A study of complex I (NADH:ubiquinone oxidoreductase) activity in Parkinson's disease (PD) brain has identified loss of activity only in substantia nigra although loss of activity of this enzyme has been identified in a number of non-brain tissues. We investigated this paradox by studying complex I and other complexes of the mitochondrial electron transport chain in frontal cortex from PD and aged control brain using a variety of assay conditions and tissue preparations. We found increasingly significant losses of complex I activity in PD frontal cortex as increasingly pure mitochondria were studied. Complexes II, III, and IV were comparable in PD and controls. Inclusion of bovine serum albumin in the assay increased enzyme activity but lessened discrimination between PD and controls. Complex I deficiency in PD brain is not confined to substantia nigra. Methodological issues are critical in demonstrating this loss of activity.
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              A primate model of parkinsonism: selective destruction of dopaminergic neurons in the pars compacta of the substantia nigra by N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

              H. Ebert, C Chiueh, Andrew Burns … (1983)
              A syndrome similar to idiopathic parkinsonism developed after intravenous self-administration of an illicit drug preparation in which N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (NMPTP) might have been responsible for the toxicity. In the present study we show that intravenous administration of NMPTP to the rhesus monkey produces a disorder like parkinsonism (akinesia, rigidity, postural tremor, flexed posture, eyelid closure, drooling) that is reversed by the administration of L-dopa. NMPTP treatment decreases the release of dopamine and dopamine accumulates in swollen, distorted axons in the nigrostriatal pathway just above the substantia nigra, followed by severe nerve cell loss in the pars compacta of the substantia nigra and a marked reduction in the dopamine content of the striatum. The pathological and biochemical changes produced by NMPTP are similar to the well-established changes in patients with parkinsonism. Thus, the NMPTP-treated monkey provides a model that can be used to examine mechanisms and explore therapies of parkinsonism.
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                Author and article information

                Contributors
                Hiroyoshi Ariga: Role: Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, USA )
                ISSN (Electronic): 1932-6203
                Publication date Collection: 2014
                Publication date (Electronic): 24 June 2014
                Volume: 9
                Issue: 6
                Electronic Location Identifier: e100395
                Affiliations
                [1 ]Department of Biosciences and Informatics, Faculty of Science and Technology, Keio University, Yokohama, Japan
                [2 ]Department of Neurology, Juntendo University School of Medicine, Bunkyo, Tokyo
                Hokkaido University, Japan
                Author notes

                Competing Interests: The extract powder of 128 traditional herbal (kampo) medicines (The Kampo, TJ-1∼3, TJ-5∼12, TJ-14∼41, TJ-43, TJ-45∼48, TJ-50∼93, TJ-95∼128, TJ-133∼138) and powder of Glycyrrhiza were kindly donated from Tsumura Corporation (Tokyo, Japan). This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: NH MI. Performed the experiments: TF DY. Analyzed the data: TF MK. Contributed reagents/materials/analysis tools: TF SS ET MI. Wrote the paper: TF SS ET NH MI.

                Article
                Publisher ID: PONE-D-14-10350
                DOI: 10.1371/journal.pone.0100395
                PMC ID: 4069009
                PubMed ID: 24960051
                SO-VID: 19b82c18-f62a-4283-b436-b37d9f34bcc3
                Copyright statement: Copyright @ 2014
                License:

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Date received : 6 March 2014
                Date accepted : 19 May 2014
                Page count
                Pages: 12
                Funding
                This work was supported by Health Labour Sciences Research Grants from the Ministry of Health, Labour and Welfare of Japan. The extract powder of 128 traditional herbal (kampo) medicines (The Kampo, TJ-1∼3, TJ-5∼12, TJ-14∼41, TJ-43, TJ-45∼48, TJ-50∼93, TJ-95∼128, TJ-133∼138) and powder of Glycyrrhiza were kindly donated from Tsumura Corporation (Tokyo, Japan). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Subject: Biology and Life Sciences
                Subject: Biochemistry
                Subject: Neurochemistry
                Subject: Neuromodulation
                Subject: Antioxidants
                Subject: Chemical Biology
                Subject: Medicine and Health Sciences
                Subject: Complementary and Alternative Medicine
                Subject: Herbal Medicine
                Custom metadata
                Data Availability The authors confirm that all data underlying the findings are fully available without restriction. All data are included within the paper and its Supporting Information files.

                ScienceOpen disciplines: Uncategorized
                Data availability:
                ScienceOpen disciplines: Uncategorized

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