start-ver=1.4
cd-journal=joma
no-vol=15
cd-vols=
no-issue=13
article-no=
start-page=7238
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=20250627
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Protective Effects of the Ethyl Acetate Fraction of Distylium racemosum Against Metabolic Dysfunction-Associated Steatohepatitis
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Metabolic dysfunction-associated steatohepatitis (MASH), previously referred to as non-alcoholic steatohepatitis (NASH), which is a progressive non-alcoholic fatty liver disease, is accompanied by hepatic steatosis, inflammation, and fibrosis. Despite its increasing prevalence, available treatment options for MASH are limited. Here, we investigated the protective effects of the Distylium racemosum ethyl acetate fraction (DRE) using MASH models and explored its key physiologically active components. Palmitic acid (PA)-induced AML12 hepatocytes and high-fat methionine- and choline-deficient-fed C57BL/6 mice were used as MASH models. Lipid accumulation was evaluated via triglyceride measurement, oil red O staining, and histological analysis. Lipid accumulation, inflammation, and fibrosis-associated gene expression were evaluated via real-time polymerase chain reaction. The physiologically active components of DRE were identified via high-performance liquid chromatography. Lipid accumulation and triglyceride levels were significantly reduced in PA-treated AML12 cells following DRE treatment. Additionally, DRE inhibited the expression of genes involved in lipogenesis (FAS and SREBP1c), inflammation (CD68, IL-6, and MCP-1), and fibrosis (COL1A1, COL1A2, and TIMP1). DRE reduced the liver weight, liver-to-body weight ratio, and hepatic steatosis in MASH model mice. It increased carnitine palmitoyltransferase-1 levels and decreased CD36 and transforming growth factor-β levels in the MASH mouse liver. High-performance liquid chromatography revealed that the extract contained rutin flavonoid family members. Overall, DRE was involved in lipid metabolism, inflammation, and fibrosis regulation, exerting potent hepatoprotective effects partly attributed to rutin and serving as a potential preventive candidate for MASH.
en-copyright=
kn-copyright=

en-aut-name=LeeYoung-Hyeon
en-aut-sei=Lee
en-aut-mei=Young-Hyeon
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=YeoMin-Ho
en-aut-sei=Yeo
en-aut-mei=Min-Ho
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=ChangKyung-Soo
en-aut-sei=Chang
en-aut-mei=Kyung-Soo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=YoonWeon-Jong
en-aut-sei=Yoon
en-aut-mei=Weon-Jong
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KimHye-Sook
en-aut-sei=Kim
en-aut-mei=Hye-Sook
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KimJongwan
en-aut-sei=Kim
en-aut-mei=Jongwan
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=KimHye-Ran
en-aut-sei=Kim
en-aut-mei=Hye-Ran
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

affil-num=1
en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan
kn-affil=

affil-num=2
en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan
kn-affil=

affil-num=3
en-affil=Department of Clinical Laboratory Science, Catholic University of Pusan
kn-affil=

affil-num=4
en-affil=Clean Bio Business Division, Biodiversity Research Institute (JBRI), Jeju Technopark (JTP)
kn-affil=

affil-num=5
en-affil=Department of International Infectious Diseases Control, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Anatomy, College of Medicine, Dongguk University
kn-affil=

affil-num=7
en-affil=Department of Biomedical Laboratory Science, Dong-Eui Institute of Technology
kn-affil=
en-keyword=metabolic dysfunction-associated steatohepatitis
kn-keyword=metabolic dysfunction-associated steatohepatitis
en-keyword=Distylium racemosum
kn-keyword=Distylium racemosum
en-keyword=ethyl acetate fraction
kn-keyword=ethyl acetate fraction
en-keyword=extract
kn-keyword=extract
END

start-ver=1.4
cd-journal=joma
no-vol=106
cd-vols=
no-issue=
article-no=
start-page=103026
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2025
dt-pub=202506
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=The antimalarial activity of transdermal N-89 mediated by inhibiting ERC gene expression in P. Berghei-infected mice
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=Through studies of new antimalarial drugs, we identified 1,2,6,7-tetraoxaspiro[7.11]nonadecane (N-89) as a potential drug candidate. Here, we analyzed the antimalarial action of a transdermal formulation (td) of N-89, designed for easy use by children, using Plasmodium berghei-infected mice as a model for malaria patients. The td N-89 or artemisinin (ART) formulation was transdermally administered to P. berghei-infected mice with 0.2?0.4 % parasitemia, twice daily for four days, at an effective dose of 90 % for malaria. Parasitemia was decreased in td N-89 and td ART groups during the drug treatment; then, three of the eight mice in td N-89 group were completely cured without relapse. Additionally, abnormal trophozoites in td N-89 group were observed 8 h after administration and increased up to 24 h. To study the change in endoplasmic reticulum-resident calcium-binding protein (ERC) gene expression with td N-89, we investigated the gene expression of P. berghei ERC (PbERC) after td N-89 treatment. PbERC gene expression was increased time-dependently in control group, and was statistically decreased at 4 and 8 h and then increased similar to that of control group at 12 h in td ART group. In contrast, the expression in td N-89 group was almost steady starting from 0 h. We also studied parasite egress-related genes expression after td N-89 treatment, plasmepsin X, subtilisin-like protease 1 and merozoite surface protein 1, were suppressed at 12 h compared to control group. These results suggest that N-89 affects function of endoplasmic reticulum via regulating gene suppression and subsequently parasite growth is inhibited.
en-copyright=
kn-copyright=

en-aut-name=MatsumoriHiroaki
en-aut-sei=Matsumori
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=DinhThi Quyen
en-aut-sei=Dinh
en-aut-mei=Thi Quyen
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MiyoshiShin-ichi
en-aut-sei=Miyoshi
en-aut-mei=Shin-ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=MoritaMasayuki
en-aut-sei=Morita
en-aut-mei=Masayuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=KimHye-Sook
en-aut-sei=Kim
en-aut-mei=Hye-Sook
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

affil-num=1
en-affil=Division of International Infectious Diseases Control, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Division of International Infectious Diseases Control, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Research Center for Intestinal Health Science, Okayama University
kn-affil=

affil-num=4
en-affil=Department of Anatomy, Kawasaki Medical School
kn-affil=

affil-num=5
en-affil=Division of International Infectious Diseases Control, Faculty of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Synthetic antimalarial endoperoxide
kn-keyword=Synthetic antimalarial endoperoxide
en-keyword=Transdermal N-89
kn-keyword=Transdermal N-89
en-keyword=Artemisinin
kn-keyword=Artemisinin
en-keyword=In vivo
kn-keyword=In vivo
en-keyword=Abnormal trophozoite
kn-keyword=Abnormal trophozoite
en-keyword=Endoplasmic reticulum-resident calcium-binding protein (ERC)
kn-keyword=Endoplasmic reticulum-resident calcium-binding protein (ERC)
en-keyword=Parasite egress-related gene
kn-keyword=Parasite egress-related gene
END

start-ver=1.4
cd-journal=joma
no-vol=61
cd-vols=
no-issue=1
article-no=
start-page=33
end-page=41
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2023
dt-pub=20230222
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=Antimalarial effect of synthetic endoperoxide on synchronized Plasmodium chabaudi infected mice
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=The discovery of new antimalarial drugs can be developed using asynchronized Plasmodium berghei malaria parasites in vivo in mice. Studies on a particular stage are also required to assess the effectiveness and mode of action of drugs. In this report, we used endoperoxide 6-(1,2,6,7-tetraoxaspiro [7.11] nonadec-4-yl) hexan-1-ol (N-251) as a model antimalarial compound on P. chabaudi parasites. We examined the antimalarial effect of N-251 against ring-stage- and trophozoite-stage-rich P. chabaudi parasites and asynchronized P. berghei parasites using the 4-day suppressive test. The ED50 values were 27, 22, and 22 mg/kg, respectively, and the antimalarial activity of N-251 was verified in both rodent malaria parasites. To assess the stage-specific effect of N-251 in vivo, we evaluated the change of parasitemia and distribution of parasite stages using ring-stage- and trophozoite-stage-rich P. chabaudi parasites with one-day drug administration for one life cycle. We discovered that the parasitemias decreased after 13 and 9 hours post-treatment in the ring-stage- and trophozoite-stage-rich groups, respectively. Additionally, in the ring-stage-rich N-251 treated group, the ring-stage parasites hindered trophozoite parasite development. For the trophozoite-stage-rich N-251 treated group, the distribution of the trophozoite stage was maintained without a change in parasitemia until 9 hours. Because of these findings, it can be concluded that N-251 suppressed the trophozoite stage but not the ring stage. We report for the first time that N-251 specifically suppresses the trophozoite stage using P. chabaudi in mice. The results show that P. chabaudi is a reliable model for the characterization of stage-specific antimalarial effects.
en-copyright=
kn-copyright=

en-aut-name=AlyNagwa S. M.
en-aut-sei=Aly
en-aut-mei=Nagwa S. M.
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=MatsumoriHiroaki
en-aut-sei=Matsumori
en-aut-mei=Hiroaki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=DinhThi Quyen
en-aut-sei=Dinh
en-aut-mei=Thi Quyen
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=SatoAkira
en-aut-sei=Sato
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=MiyoshiShin-Ichi
en-aut-sei=Miyoshi
en-aut-mei=Shin-Ichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=ChangKyung-Soo
en-aut-sei=Chang
en-aut-mei=Kyung-Soo
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=YuHak Sun
en-aut-sei=Yu
en-aut-mei=Hak Sun
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=KobayashiFumie
en-aut-sei=Kobayashi
en-aut-mei=Fumie
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=KimHye-Sook
en-aut-sei=Kim
en-aut-mei=Hye-Sook
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

affil-num=1
en-affil=Division of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=2
en-affil=Division of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=3
en-affil=Division of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=4
en-affil=Division of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=5
en-affil=Department of Sanitary Microbiology, Faculty of Pharmaceutical Sciences, Okayama University
kn-affil=

affil-num=6
en-affil=Department of Clinical Laboratory Science, College of Health Sciences, Catholic University of Pusan
kn-affil=

affil-num=7
en-affil=Department of Parasitology and Tropical Medicine, School of Medicine, Pusan National University
kn-affil=

affil-num=8
en-affil=Department of Environmental Science, School of Life Environmental Science, Azabu University
kn-affil=

affil-num=9
en-affil=Division of International Infectious Diseases Control, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University
kn-affil=
en-keyword=Plasmodium chabaudi
kn-keyword=Plasmodium chabaudi
en-keyword=synchronization
kn-keyword=synchronization
en-keyword=stage-specific activity
kn-keyword=stage-specific activity
en-keyword=antimalarial N-251
kn-keyword=antimalarial N-251
END

start-ver=1.4
cd-journal=joma
no-vol=8
cd-vols=
no-issue=8
article-no=
start-page=e72519
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2013
dt-pub=20130830
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=New Preclinical Antimalarial Drugs Potently Inhibit Hepatitis C Virus Genotype 1b RNA Replication
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=BACKGROUND: 

Persistent hepatitis C virus (HCV) infection causes chronic liver diseases and is a global health problem. Although new triple therapy (pegylated-interferon, ribavirin, and telaprevir/boceprevir) has recently been started and is expected to achieve a sustained virologic response of more than 70% in HCV genotype 1 patients, there are several problems to be resolved, including skin rash/ageusia and advanced anemia. Thus a new type of anti-HCV drug is still needed. 　

METHODOLOGY/PRINCIPAL FINDINGS: 　
　
Recently developed HCV drug assay systems using HCV-RNA-replicating cells (e.g., HuH-7-derived OR6 and Li23-derived ORL8) were used to evaluate the anti-HCV activity of drug candidates. During the course of the evaluation of anti-HCV candidates, we unexpectedly found that two preclinical antimalarial drugs (N-89 and its derivative N-251) showed potent anti-HCV activities at tens of nanomolar concentrations irrespective of the cell lines and HCV strains of genotype 1b. We confirmed that replication of authentic HCV-RNA was inhibited by these drugs. Interestingly, however, this anti-HCV activity did not work for JFH-1 strain of genotype 2a. We demonstrated that HCV-RNA-replicating cells were cured by treatment with only N-89. A comparative time course assay using N-89 and interferon-α demonstrated that N-89-treated ORL8 cells had more rapid anti-HCV kinetics than did interferon-α-treated cells. This anti-HCV activity was largely canceled by vitamin E. In combination with interferon-α and/or ribavirin, N-89 or N-251 exhibited a synergistic inhibitory effect.　
　
CONCLUSIONS/SIGNIFICANCE:　
　
We found that the preclinical antimalarial drugs N-89 and N-251 exhibited very fast and potent anti-HCV activities using cell-based HCV-RNA-replication assay systems. N-89 and N-251 may be useful as a new type of anti-HCV reagents when used singly or in combination with interferon and/or ribavirin.
en-copyright=
kn-copyright=

en-aut-name=UedaYouki
en-aut-sei=Ueda
en-aut-mei=Youki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=1
ORCID=

en-aut-name=TakedaMidori
en-aut-sei=Takeda
en-aut-mei=Midori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=2
ORCID=

en-aut-name=MoriKyoko
en-aut-sei=Mori
en-aut-mei=Kyoko
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=3
ORCID=

en-aut-name=DansakoHiromichi
en-aut-sei=Dansako
en-aut-mei=Hiromichi
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=4
ORCID=

en-aut-name=WakitaTakaji
en-aut-sei=Wakita
en-aut-mei=Takaji
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=5
ORCID=

en-aut-name=KimHye-Sook
en-aut-sei=Kim
en-aut-mei=Hye-Sook
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=6
ORCID=

en-aut-name=SatoAkira
en-aut-sei=Sato
en-aut-mei=Akira
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=7
ORCID=

en-aut-name=WatayaYusuke
en-aut-sei=Wataya
en-aut-mei=Yusuke
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=8
ORCID=

en-aut-name=IkedaMasanori
en-aut-sei=Ikeda
en-aut-mei=Masanori
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=9
ORCID=

en-aut-name=KatoNobuyuki
en-aut-sei=Kato
en-aut-mei=Nobuyuki
kn-aut-name=
kn-aut-sei=
kn-aut-mei=
aut-affil-num=10
ORCID=

affil-num=1
en-affil=
kn-affil=Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences

affil-num=2
en-affil=
kn-affil=Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences

affil-num=3
en-affil=
kn-affil=Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences

affil-num=4
en-affil=
kn-affil=Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences

affil-num=5
en-affil=
kn-affil=Department of Virology II, National Institute of Infectious Disease

affil-num=6
en-affil=
kn-affil=Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Okayama University

affil-num=7
en-affil=
kn-affil=Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Okayama University

affil-num=8
en-affil=
kn-affil=Department of Drug Informatics, Faculty of Pharmaceutical Sciences, Okayama University

affil-num=9
en-affil=
kn-affil=Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences

affil-num=10
en-affil=
kn-affil=Department of Tumor Virology, Okayama University Graduate School of Medicine, Dentistry, and Pharmaceutical Sciences
END

start-ver=1.4
cd-journal=joma
no-vol=127
cd-vols=
no-issue=3
article-no=
start-page=231
end-page=235
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=2015
dt-pub=20151201
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=New antimalarial endoperoxides for drug-resistant Plasmodium falciparumn : The current situation
kn-title=薬剤耐性マラリアに有望な新規抗マラリア薬開発の現況
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=KimHye-Sook
en-aut-sei=Kim
en-aut-mei=Hye-Sook
kn-aut-name=金惠淑
kn-aut-sei=金
kn-aut-mei=惠淑
aut-affil-num=1
ORCID=

en-aut-name=KatamotoAkane
en-aut-sei=Katamoto
en-aut-mei=Akane
kn-aut-name=片本茜
kn-aut-sei=片本
kn-aut-mei=茜
aut-affil-num=2
ORCID=

en-aut-name=SatoAkira
en-aut-sei=Sato
en-aut-mei=Akira
kn-aut-name=佐藤聡
kn-aut-sei=佐藤
kn-aut-mei=聡
aut-affil-num=3
ORCID=

en-aut-name=WatayaYusuke
en-aut-sei=Wataya
en-aut-mei=Yusuke
kn-aut-name=綿矢有佑
kn-aut-sei=綿矢
kn-aut-mei=有佑
aut-affil-num=4
ORCID=

en-aut-name=DoiHiroyuki
en-aut-sei=Doi
en-aut-mei=Hiroyuki
kn-aut-name=土居弘幸
kn-aut-sei=土居
kn-aut-mei=弘幸
aut-affil-num=5
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科

affil-num=2
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科

affil-num=3
en-affil=
kn-affil=東京理科大学薬学部

affil-num=4
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科

affil-num=5
en-affil=
kn-affil=岡山大学大学院医歯薬学総合研究科
en-keyword=薬剤耐性マラリア
kn-keyword=薬剤耐性マラリア
en-keyword=ACT療法（artemisinin-based combination therapy）
kn-keyword=ACT療法（artemisinin-based combination therapy）
en-keyword=新薬開発
kn-keyword=新薬開発
en-keyword=環状過酸化物
kn-keyword=環状過酸化物
en-keyword=標的分子
kn-keyword=標的分子
END

start-ver=1.4
cd-journal=joma
no-vol=
cd-vols=
no-issue=
article-no=
start-page=
end-page=
dt-received=
dt-revised=
dt-accepted=
dt-pub-year=1998
dt-pub=19980325
dt-online=
en-article=
kn-article=
en-subject=
kn-subject=
en-title=
kn-title=ヌクレオシド構造を基本骨格とする新規抗マラリア剤の開発およびその作用機序に関する研究
en-subtitle=
kn-subtitle=
en-abstract=
kn-abstract=
en-copyright=
kn-copyright=

en-aut-name=
en-aut-sei=
en-aut-mei=
kn-aut-name=金惠淑
kn-aut-sei=金
kn-aut-mei=惠淑
aut-affil-num=1
ORCID=

affil-num=1
en-affil=
kn-affil=岡山大学
END