Effect of geranylated dihydrochalcone from Artocarpus altilis leaves extract on Plasmodium falciparum ultrastructural changes and mitochondrial malate: Quinone oxidoreductase
Nearly half of the world's population is at risk of being infected by Plasmodium falciparum, the pathogen of malaria. Increasing resistance to common antimalarial drugs has encouraged investigations to find compounds with different scaffolds. Extracts of Artocarpus altilis leaves have previousl...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-04-01
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| Series: | International Journal for Parasitology: Drugs and Drug Resistance |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211320722000343 |
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| author | Agriana Rosmalina Hidayati Melinda Hilkatul Ilmi Takaya Sakura Miako Sakaguchi Junko Ohmori Endah Dwi Hartuti Lidya Tumewu Daniel Ken Inaoka Mulyadi Tanjung Eri Yoshida Fuyuki Tokumasu Kiyoshi Kita Mihoko Mori Kazuyuki Dobashi Tomoyoshi Nozaki Din Syafruddin Achmad Fuad Hafid Danang Waluyo Aty Widyawaruyanti |
| author_facet | Agriana Rosmalina Hidayati Melinda Hilkatul Ilmi Takaya Sakura Miako Sakaguchi Junko Ohmori Endah Dwi Hartuti Lidya Tumewu Daniel Ken Inaoka Mulyadi Tanjung Eri Yoshida Fuyuki Tokumasu Kiyoshi Kita Mihoko Mori Kazuyuki Dobashi Tomoyoshi Nozaki Din Syafruddin Achmad Fuad Hafid Danang Waluyo Aty Widyawaruyanti |
| author_sort | Agriana Rosmalina Hidayati |
| collection | DOAJ |
| description | Nearly half of the world's population is at risk of being infected by Plasmodium falciparum, the pathogen of malaria. Increasing resistance to common antimalarial drugs has encouraged investigations to find compounds with different scaffolds. Extracts of Artocarpus altilis leaves have previously been reported to exhibit in vitro antimalarial activity against P. falciparum and in vivo activity against P. berghei. Despite these initial promising results, the active compound from A. altilis is yet to be identified. Here, we have identified 2-geranyl-2′, 4′, 3, 4-tetrahydroxy-dihydrochalcone (1) from A. altilis leaves as the active constituent of its antimalarial activity. Since natural chalcones have been reported to inhibit food vacuole and mitochondrial electron transport chain (ETC), the morphological changes in food vacuole and biochemical inhibition of ETC enzymes of (1) were investigated. In the presence of (1), intraerythrocytic asexual development was impaired, and according to the TEM analysis, this clearly affected the ultrastructure of food vacuoles. Amongst the ETC enzymes, (1) inhibited the mitochondrial malate: quinone oxidoreductase (PfMQO), and no inhibition could be observed on dihydroorotate dehydrogenase (DHODH) as well as bc1 complex activities. Our study suggests that (1) has a dual mechanism of action affecting the food vacuole and inhibition of PfMQO-related pathways in mitochondria. |
| first_indexed | 2024-04-09T20:20:54Z |
| format | Article |
| id | doaj.art-6b134f392fa14e72bc9716284882d2dc |
| institution | Directory Open Access Journal |
| issn | 2211-3207 |
| language | English |
| last_indexed | 2024-04-09T20:20:54Z |
| publishDate | 2023-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | International Journal for Parasitology: Drugs and Drug Resistance |
| spelling | doaj.art-6b134f392fa14e72bc9716284882d2dc2023-03-31T05:53:17ZengElsevierInternational Journal for Parasitology: Drugs and Drug Resistance2211-32072023-04-01214050Effect of geranylated dihydrochalcone from Artocarpus altilis leaves extract on Plasmodium falciparum ultrastructural changes and mitochondrial malate: Quinone oxidoreductaseAgriana Rosmalina Hidayati0 Melinda1Hilkatul Ilmi2Takaya Sakura3Miako Sakaguchi4Junko Ohmori5Endah Dwi Hartuti6Lidya Tumewu7Daniel Ken Inaoka8Mulyadi Tanjung9Eri Yoshida10Fuyuki Tokumasu11Kiyoshi Kita12Mihoko Mori13Kazuyuki Dobashi14Tomoyoshi Nozaki15Din Syafruddin16Achmad Fuad Hafid17Danang Waluyo18Aty Widyawaruyanti19Doctoral Program, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia; Department of Pharmacy, Faculty of Medicine, Universitas Mataram, Mataram, IndonesiaResearch Center for Genetic Engineering, National Research and Innovation Agency (BRIN), Bogor, IndonesiaCenter of Natural Product Medicine Research and Development, Institute of Tropical Disease, Universitas Airlangga, Surabaya, IndonesiaDepartment of Molecular Infection Dynamics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan; School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, JapanCentral Laboratory, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, JapanSchool of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, JapanResearch Center for Genetic Engineering, National Research and Innovation Agency (BRIN), Bogor, Indonesia; Graduate School of Biomedical Science, Nagasaki University, Nagasaki, JapanCenter of Natural Product Medicine Research and Development, Institute of Tropical Disease, Universitas Airlangga, Surabaya, IndonesiaDepartment of Molecular Infection Dynamics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, Japan; School of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan; Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, JapanDepartment of Chemistry, Faculty of Science and Technology, Universitas Airlangga, Surabaya, IndonesiaDepartment of Molecular Infection Dynamics, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, JapanDepartment of Cellular Architecture Studies, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, JapanSchool of Tropical Medicine and Global Health, Nagasaki University, Nagasaki, Japan; Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Japan; Department of Host-Defense Biochemistry, Institute of Tropical Medicine (NEKKEN), Nagasaki University, Nagasaki, JapanKitasato Institute for Life Science, Kitasato University, Tokyo, JapanKitasato Institute for Life Science, Kitasato University, Tokyo, JapanDepartment of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, JapanDepartment of Parasitology, Faculty of Medicine, Hasanudin University, Makassar, IndonesiaCenter of Natural Product Medicine Research and Development, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, IndonesiaResearch Center for Genetic Engineering, National Research and Innovation Agency (BRIN), Bogor, IndonesiaCenter of Natural Product Medicine Research and Development, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia; Department of Pharmaceutical Sciences, Faculty of Pharmacy, Universitas Airlangga, Surabaya, Indonesia; Corresponding author. Center of Natural Product Medicine Research and Development, Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia.Nearly half of the world's population is at risk of being infected by Plasmodium falciparum, the pathogen of malaria. Increasing resistance to common antimalarial drugs has encouraged investigations to find compounds with different scaffolds. Extracts of Artocarpus altilis leaves have previously been reported to exhibit in vitro antimalarial activity against P. falciparum and in vivo activity against P. berghei. Despite these initial promising results, the active compound from A. altilis is yet to be identified. Here, we have identified 2-geranyl-2′, 4′, 3, 4-tetrahydroxy-dihydrochalcone (1) from A. altilis leaves as the active constituent of its antimalarial activity. Since natural chalcones have been reported to inhibit food vacuole and mitochondrial electron transport chain (ETC), the morphological changes in food vacuole and biochemical inhibition of ETC enzymes of (1) were investigated. In the presence of (1), intraerythrocytic asexual development was impaired, and according to the TEM analysis, this clearly affected the ultrastructure of food vacuoles. Amongst the ETC enzymes, (1) inhibited the mitochondrial malate: quinone oxidoreductase (PfMQO), and no inhibition could be observed on dihydroorotate dehydrogenase (DHODH) as well as bc1 complex activities. Our study suggests that (1) has a dual mechanism of action affecting the food vacuole and inhibition of PfMQO-related pathways in mitochondria.http://www.sciencedirect.com/science/article/pii/S2211320722000343Geranylated dihydrochalconeArtocarpus altilisPlasmodium falciparumUltrastructural changesPfMQO |
| spellingShingle | Agriana Rosmalina Hidayati Melinda Hilkatul Ilmi Takaya Sakura Miako Sakaguchi Junko Ohmori Endah Dwi Hartuti Lidya Tumewu Daniel Ken Inaoka Mulyadi Tanjung Eri Yoshida Fuyuki Tokumasu Kiyoshi Kita Mihoko Mori Kazuyuki Dobashi Tomoyoshi Nozaki Din Syafruddin Achmad Fuad Hafid Danang Waluyo Aty Widyawaruyanti Effect of geranylated dihydrochalcone from Artocarpus altilis leaves extract on Plasmodium falciparum ultrastructural changes and mitochondrial malate: Quinone oxidoreductase International Journal for Parasitology: Drugs and Drug Resistance Geranylated dihydrochalcone Artocarpus altilis Plasmodium falciparum Ultrastructural changes PfMQO |
| title | Effect of geranylated dihydrochalcone from Artocarpus altilis leaves extract on Plasmodium falciparum ultrastructural changes and mitochondrial malate: Quinone oxidoreductase |
| title_full | Effect of geranylated dihydrochalcone from Artocarpus altilis leaves extract on Plasmodium falciparum ultrastructural changes and mitochondrial malate: Quinone oxidoreductase |
| title_fullStr | Effect of geranylated dihydrochalcone from Artocarpus altilis leaves extract on Plasmodium falciparum ultrastructural changes and mitochondrial malate: Quinone oxidoreductase |
| title_full_unstemmed | Effect of geranylated dihydrochalcone from Artocarpus altilis leaves extract on Plasmodium falciparum ultrastructural changes and mitochondrial malate: Quinone oxidoreductase |
| title_short | Effect of geranylated dihydrochalcone from Artocarpus altilis leaves extract on Plasmodium falciparum ultrastructural changes and mitochondrial malate: Quinone oxidoreductase |
| title_sort | effect of geranylated dihydrochalcone from artocarpus altilis leaves extract on plasmodium falciparum ultrastructural changes and mitochondrial malate quinone oxidoreductase |
| topic | Geranylated dihydrochalcone Artocarpus altilis Plasmodium falciparum Ultrastructural changes PfMQO |
| url | http://www.sciencedirect.com/science/article/pii/S2211320722000343 |
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