Yoichi Nakao - Academia.edu (original) (raw)

Papers by Yoichi Nakao

Journal of Agricultural and Food Chemistry, Mar 4, 2022

Plants in the genus Curcuma have been widely used as traditional medicines in Asian countries. Th... more Plants in the genus Curcuma have been widely used as traditional medicines in Asian countries. These plants contain bioactive compounds with neuroprotective properties or activities that increase neural stem cells (NSCs) and neurons. However, bioactive components in Curcuma that promote the differentiation of NSCs into astrocytes have not yet been reported. Here, the effects of Curcuma extracts on the in vitro differentiation of embryonic stem-cell-derived NSCs were evaluated. The extract of the wild turmeric, Curcuma aromatica, strongly promoted the differentiation of NSCs into astrocytes. Bioassay-guided isolation yielded coronarins C (1) and D (2), as well as (E)-labda-8(17),12-diene-15,16-dial (3) as the bioactive compounds. Coronarin D (2) markedly promoted the differentiation of NSCs into astrocytes up to approximately 4 times (3.64 ± 0.48) and increased the expression level of GFAP at the mRNA and protein level, while compounds 1 and 3 exhibited only weak effects, suggesting that the 15-hydroxy-Δ12-γ-lactone moiety is important for bioactivity. Moreover, compound 2 increased the number of pSTAT3-positive cells, suggesting that compound 2 promoted astrocytic differentiation through JAK/STAT signaling pathway.

Bioorganic & Medicinal Chemistry, Jul 1, 2018

The Molecular Biology Society of Japan, Nov 8, 2016

bioRxiv (Cold Spring Harbor Laboratory), May 30, 2021

Parasitology International, 2022

Plasmodium falciparum, the most virulent human malaria parasite, causes serious diseases among th... more Plasmodium falciparum, the most virulent human malaria parasite, causes serious diseases among the infected patients in the world and is particularly important in African regions. Although artemisinin combination therapy is recommended by the WHO for treatment of P. falciparum-malaria, the emergence of artemisinin-resistant parasites has become a serious issue which underscores the importance of sustained efforts to obtain novel chemotherapeutic agents against malaria. As a part of such efforts, thirty-nine herbal extracts from traditional Chinese medicine (TCM) were assayed for their anti-malarial activity using 3D7 strain of P. falciparum. Three herbal supplements appeared to possess higher specific anti-malarial activity than the others. One of them (D3) was separated by two sequential fractionations with reverse-phase (the first step) and normal-phase (the second step) liquid chromatography, in which some fractions resulted in higher specific activities than those of D3 or the previous fractions. Cell toxicity assay was performed with the fractions of the first fractionation and demonstrated no obvious cell toxicity. These results suggest that structure determination of the major compound for the anti-malarial activity in D3 may help the development of more potent chemicals in the future.

The Molecular Biology Society of Japan, 2016

Marine Drugs, 2021

Marine sponges are the most prolific marine sources for discovery of novel bioactive compounds. S... more Marine sponges are the most prolific marine sources for discovery of novel bioactive compounds. Sponge secondary metabolites are sought-after for their potential in pharmaceutical applications, and in the past, they were also used as taxonomic markers alongside the difficult and homoplasy-prone sponge morphology for species delineation (chemotaxonomy). The understanding of phylogenetic distribution and distinctiveness of metabolites to sponge lineages is pivotal to reveal pathways and evolution of compound production in sponges. This benefits the discovery rate and yield of bioprospecting for novel marine natural products by identifying lineages with high potential of being new sources of valuable sponge compounds. In this review, we summarize the current biochemical data on sponges and compare the metabolite distribution against a sponge phylogeny. We assess compound specificity to lineages, potential convergences, and suitability as diagnostic phylogenetic markers. Our study finds...

Chemical Science, 2021

The combination of a proapoptotic peptide with covalent tagging and a carrier-Ru-complex inhibite... more The combination of a proapoptotic peptide with covalent tagging and a carrier-Ru-complex inhibited tumor growth in mice after a single injection.

Journal of Cell Science, 2020

Post-translational modifications on histones can be stable epigenetic marks and transient signals... more Post-translational modifications on histones can be stable epigenetic marks and transient signals that can occur in response to internal and external stimuli. Levels of histone modifications fluctuate during the cell cycle and vary among different cell types. Here we describe a simple system to monitor the levels of multiple histone modifications in single cells by multicolor immunofluorescence using directly labeled modification-specific antibodies. We analyzed histone H3 and H4 modifications during the cell cycle. Levels of active marks, such as acetylation and H3K4 methylation, were increased during the S phase, in association with chromatin duplication. By contrast, levels of some repressive modifications gradually increased during the G2 and the next G1 phases. We applied this method to validate the target modifications of various histone demethylases in cells using a transient overexpression system. We also screened chemical compounds in marine organism extracts that affect hi...

Increasing evidence indicates that insecticides induce various diseases via DNA methylation. DNA ... more Increasing evidence indicates that insecticides induce various diseases via DNA methylation. DNA methylation plays an important role during cell differentiation and exhibits its greatest vulnerability to environmental factors during embryogenesis. Therefore, it is important to evaluate the effects on DNA methylation at the early stage of cell differentiation to understand developmental toxicity. However, DNA methylation induced by insecticides and the associated effects on cell differentiation are unclear. In this research, we introduced a high-content approach utilizing mouse embryonic stem cells harboring enhanced green fluorescent protein fused with methyl CpG-binding protein to evaluate global DNA methylation induced by various insecticides. DNA methylation was assessed in 22 genes after pesticide exposure to investigate the relationships with biological processes such as cell cycle, cell apoptosis, and cell differentiation. Exposure to acetamiprid, imidacloprid, carbaryl, and o...

Stem cell reports, Feb 13, 2018

Biochemical and biophysical research communications, Aug 5, 2017

EGR2 is a zinc finger transcription factor that regulates myelination in the peripheral nervous s... more EGR2 is a zinc finger transcription factor that regulates myelination in the peripheral nervous system and T cell anergy. The transcriptional activity of EGR2 is known to be regulated by its co-activators and/or co-repressors. Although the activity of transcription factors is generally regulated not only by interactions with co-regulators but also posttranslational modifications including acetylation, little is known about posttranslational modifications of EGR2. Here we show that EGR2 is a novel acetylated protein. Through immunoblotting analyses using an antibody that specifically recognizes the acetylated form of EGR2, CBP and p300 were identified as acetyltransferases, while HDAC6, 10 and SIRT1 were identified as deacetylases of EGR2. Although the NuRD complex containing HDAC1 and HDAC2 is known to associate with EGR2, the present study suggests that acetylation of EGR2 is regulated independently of NuRD.

Angewandte Chemie, 2017

Metal complex catalysis within biological systems is largely limited to cell and bacterial system... more Metal complex catalysis within biological systems is largely limited to cell and bacterial systems. In this work, a glycoalbumin–AuIII complex was designed and developed that enables organ‐specific, localized propargyl ester amidation with nearby proteins within live mice. The targeted reactivity can be imaged through the use of Cy7.5‐ and TAMRA‐linked propargyl ester based fluorescent probes. This targeting system could enable the exploitation of other metal catalysis strategies for biomedical and clinical applications.

Bioorganic & medicinal chemistry letters, Sep 1, 2016

The core structure of cristaxenicin A having trans-fused dihydropyran and nine membered ring has ... more The core structure of cristaxenicin A having trans-fused dihydropyran and nine membered ring has been synthesized and evaluated the antileishmanial activity. The dihydropyran ring was synthesized by [4+2] cycloaddition reaction between an unsaturated aldehyde and a β-alkoxy-α,β-unsaturated ketone. The nine membered ring possessing α,β-unsaturated aldehyde was constructed by the intramolecular NHK reaction followed by the Mitsunobu rearrangement. The racemic core structure of cristaxenicin A was evaluated the anti-leishmanial activity with an IC50 value of 2.4μM.

The Journal of Organic Chemistry, 2012

Journal of Natural Products, 2007

Marine invertebrates are rich sources of small molecules with unique chemical skeletons and poten... more Marine invertebrates are rich sources of small molecules with unique chemical skeletons and potent bioactivities. Historically, such compounds were discovered mainly through the use of assays for phenotype-oriented activities, such as cytotoxicity or antimicrobial effects. More recently, target-oriented searches for bioactive substances, as exemplified by enzyme inhibitors, have become much more common, given a growing need for small-molecule inhibitors essential for studies of complex processes at the interface of chemistry and biology. In this review, selected enzyme inhibitors from marine invertebrates are presented.

Journal of Natural Products, 1997

Journal of Medicinal Chemistry, 2011