In vitro Mechanistic Assays of Tetracyclic Iridoid Compounds Isolated from Morinda lucida Benth in Leishmania species

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dc.contributor.authorAzerigyik, Faustus Akankperiwenen_US
dc.contributor.authorAmoa-Bosompem, Michaelen_US
dc.contributor.authorTetteh, Thelmaen_US
dc.contributor.authorAyertey, Fredericken_US
dc.contributor.authorAntwi, Ama Nyamekyeen_US
dc.contributor.authorOwusu, Kofi Baffour-Awuahen_US
dc.contributor.authorDadzie, Kofi Kwofieen_US
dc.contributor.authorDjameh, Georgina Isabellaen_US
dc.contributor.authorTetteh-Tsifoanya, Marken_US
dc.contributor.authorIwanaga, Shiroen_US
dc.contributor.authorAppiah, Alfred Ampomahen_US
dc.contributor.authorOhta, Tomoeen_US
dc.contributor.authorUto, Takuhiroen_US
dc.contributor.authorShoyama, Yukihiroen_US
dc.contributor.authorOhta, Nobuoen_US
dc.contributor.authorGwira, Theresa Manfulen_US
dc.contributor.authorOhashi, Mitsukoen_US
dc.date.accessioned2020-01-02T06:14:12Z
dc.date.available2020-01-02T06:14:12Z
dc.date.issued2018-11
dc.description.abstractAims: This study investigates the activity of tetracyclic iridoid compounds against Leishmania spp. and the mechanism(s) of action. Study Design: An experimental study. Place and Duration: Department of Parasitology, Noguchi Memorial Institute for Medical Research, between September 2017 and July 2018. Methodology: The 50 % inhibitory concentration (IC50) of compounds against Leishmania donovani and L. major promastigotes were determined after 48 hours of incubation using the Alamar blue. Cytotoxicity of compounds was determined against cell lines using MTT assay. The anti-amastigote activity of compounds was further assessed by DAPI (4′,6-diamidino-2-phenylindole) staining. The mechanism of cell death induced by compounds was determined using nexin assay. Mitosis, cytokinesis and morphometry were monitored by DAPI and Kinetoplastid Membrane Protein (KMP) staining. Cell cycle arrest induced by compounds was analyzed by FACS. Results: Molucidin and ML-F52 inhibited the growth of promastigote in L. donovani (Molucidin; IC50 = 2.94±0.60 µM, ML-F52; IC50 = 0.91±0.50 µM) and L. major (Molucidin; IC50 = 1.85± 0.20 µM, ML-F52; IC50 = 1.77± 0.20 µM). ML-F52 had a 10-fold cytotoxic effect on parasites relative to normal cell lines. Against intracellular forms, Molucidin and ML-F52 inhibited intracellular amastigote replication and infectivity. Amphotericin B, Molucidin and ML-F52, induced a dose-dependent apoptotic effect on promastigotes. Although no change in KMP-11 expression was observed, iridoids inhibited cell division and morphological changes in promastigote cultures. Molucidin and ML-F52 induced apoptotic mechanism of cell death, inhibited cytokinesis and induced phenotypic changes in promastigotes. Molucidin further induced ‘’nectomonad-like’’ forms and loss of kDNA, ML-F52 induced ‘cell-rounding’ with loss of flagellum. Molucidin also induced cell growth arrest at G2-M phase (54.5 %). A significant induction of apoptosis (P = .05) was shown by an enhanced peak in the sub-G1 confirming the apoptotic inducing properties of iridoids. Conclusion: This study shows the anti-leishmania activity of tetracyclic iridoids which could be further investigated for the development of new chemotherapy against Leishmaniasis.en_US
dc.identifier.affiliationsWest African Centre for Cell Biology and Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Biology (DBCMB), University of Ghana, Legon, Ghana and Noguchi Memorial Institute for Medical Research (NMIMR), College of Health Sciences, University of Ghana, P.O.Box LG 581, Legon, Ghanaen_US
dc.identifier.affiliationsNoguchi Memorial Institute for Medical Research (NMIMR), College of Health Sciences, University of Ghana, P.O.Box LG 581, Legon, Ghana and Section of Environmental Parasitology, Faculty of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japanen_US
dc.identifier.affiliationsNoguchi Memorial Institute for Medical Research (NMIMR), College of Health Sciences, University of Ghana, P.O.Box LG 581, Legon, Ghanaen_US
dc.identifier.affiliationsCentre for Plant Medicine Research, P.O.Box 73, Mampong - Akuapem, Ghanaen_US
dc.identifier.affiliationsNoguchi Memorial Institute for Medical Research (NMIMR), College of Health Sciences, University of Ghana, P.O.Box LG 581, Legon, Ghanaen_US
dc.identifier.affiliationsNoguchi Memorial Institute for Medical Research (NMIMR), College of Health Sciences, University of Ghana, P.O.Box LG 581, Legon, Ghanaen_US
dc.identifier.affiliationsSection of Environmental Parasitology, Faculty of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japanen_US
dc.identifier.affiliationsNoguchi Memorial Institute for Medical Research (NMIMR), College of Health Sciences, University of Ghana, P.O.Box LG 581, Legon, Ghanaen_US
dc.identifier.affiliationsNoguchi Memorial Institute for Medical Research (NMIMR), College of Health Sciences, University of Ghana, P.O.Box LG 581, Legon, Ghanaen_US
dc.identifier.affiliationsSection of Environmental Parasitology, Faculty of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japanen_US
dc.identifier.affiliationsCentre for Plant Medicine Research, P.O.Box 73, Mampong - Akuapem, Ghanaen_US
dc.identifier.affiliationsFaculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japanen_US
dc.identifier.affiliationsFaculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japanen_US
dc.identifier.affiliationsFaculty of Pharmaceutical Sciences, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki 859-3298, Japanen_US
dc.identifier.affiliationsSection of Environmental Parasitology, Faculty of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japanen_US
dc.identifier.affiliationsWest African Centre for Cell Biology and Infectious Pathogens (WACCBIP), Department of Biochemistry, Cell and Molecular Biology (DBCMB), University of Ghana, Legon, Ghana.en_US
dc.identifier.affiliationsNoguchi Memorial Institute for Medical Research (NMIMR), College of Health Sciences, University of Ghana, P.O.Box LG 581, Legon, Ghana.en_US
dc.identifier.citationAzerigyik Faustus Akankperiwen, Amoa-Bosompem Michael, Tetteh Thelma, Ayertey Frederick, Antwi Ama Nyamekye, Owusu Kofi Baffour-Awuah, Dadzie Kofi Kwofie, Djameh Georgina Isabella, Tetteh-Tsifoanya Mark, Iwanaga Shiro, Appiah Alfred Ampomah, Ohta Tomoe, Uto Takuhiro, Shoyama Yukihiro, Ohta Nobuo, Gwira Theresa Manful, Ohashi Mitsuko. In vitro Mechanistic Assays of Tetracyclic Iridoid Compounds Isolated from Morinda lucida Benth in Leishmania species. European Journal of Medicinal Plants. 2018 Nov; 25(4): 1-14en_US
dc.identifier.issn2231-0894
dc.identifier.placeIndiaen_US
dc.identifier.urihttps://imsear.searo.who.int/handle/123456789/189430
dc.languageenen_US
dc.publisherScience Domain Internationalen_US
dc.relation.issuenumber4en_US
dc.relation.volume25en_US
dc.source.urihttps://doi.org/10.9734/EJMP/2018/44972en_US
dc.subjectLeishmania donovanien_US
dc.subjectLeishmania majoren_US
dc.subjectIn vitro screeningen_US
dc.subjectmedicinal plantsen_US
dc.subjectTetracyclic iridoidsen_US
dc.subjectMorinda lucidaen_US
dc.subjectApoptosisen_US
dc.titleIn vitro Mechanistic Assays of Tetracyclic Iridoid Compounds Isolated from Morinda lucida Benth in Leishmania speciesen_US
dc.typeJournal Articleen_US
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