11 results on '"Toshihiro Hashimoto"'
Search Results
2. In vitro antitrypanosomal activity of some phenolic compounds from propolis and lactones from Fijian Kawa (Piper methysticum)
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Toshihiro Hashimoto, Kazuhiko Otoguro, Hiroaki Kiyohara, Haruki Yamada, Miyuki Namatame, Aki Nishihara-Tsukashima, Yoshinori Asakawa, Satoshi Ōmura, Aki Ishiyama, and Masato Iwatsuki
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Dihydrokawain ,biology ,Traditional medicine ,Chemistry ,Piper methysticum ,Stereochemistry ,Suramin ,Trypanosoma brucei brucei ,Pharmacology toxicology ,Trypanosoma brucei ,Propolis ,biology.organism_classification ,Trypanocidal Agents ,In vitro ,Lactones ,Pyrones ,parasitic diseases ,medicine ,Molecular Medicine ,Kava ,medicine.drug - Abstract
During our search to discover new antitrypanosomal compounds, eight known plant compounds (three phenolic compounds and five kawa lactones) were evaluated for in vitro activity against Trypanosoma brucei brucei. Among them, we found two phenolic compounds and three kawa lactones possessing an α-pyrone influenced antitrypanosomal property. In particular, β-phenethyl caffeate, farnesyl caffeate and dihydrokawain exhibited high or moderate selective and potent antitrypanosomal activity in vitro. We detail here the antitrypanosomal activity and cytotoxicities of the compounds, in comparison with two commonly used antitrypanosomal drugs (eflornithine and suramin). Our findings represent the first report of the promising trypanocidal activity of these compounds.
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- 2011
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3. In vitro antitrypanosomal activity of bis(bibenzyls)s and bibenzyls from liverworts against Trypanosoma brucei
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Kazuhiko Otoguro, Aki Ishiyama, Aki Nishihara-Tukashima, Toshihiro Hashimoto, Yoshinori Asakawa, Miyuki Namatame, Satoshi Omura, Masato Iwatsuki, Haruki Yamada, and Hiroaki Kiyohara
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Hepatophyta ,Molecular Structure ,biology ,Stereochemistry ,Suramin ,Trypanosoma brucei brucei ,Pharmacology toxicology ,Trypanosoma brucei ,biology.organism_classification ,Trypanocidal Agents ,In vitro ,Eflornithine ,Bibenzyls ,medicine ,Molecular Medicine ,Marchantin A ,Mode of action ,medicine.drug - Abstract
During the course of our screening program to discover new antitrypanosomal compounds, 17 known plant aromatic compounds [12 bis(bibenzyls)s and 5 bibenzyls] were evaluated for in vitro activity against Trypanosoma brucei brucei. Sixteen compounds were found to exhibit antitrypanosomal activity. In particular, three compounds, marchantin A (1), plagiochin A (5) and 2(R)-2-isopropenyl-6,7-dihydroxy-4-(2-phenylethyl)dihydrobenzofuran (16) demonstrated moderate selective and potent antitrypanosomal activities in vitro. We detail here the antitrypanosomal properties and cytotoxicities of the compounds in comparison with two commonly used therapeutic drugs, eflornithine and suramin. Our finding represents the first report of the promising trypanocidal activity of these compounds. The research also provides valuable insight into structure-activity relationships and the possible mode of action of the compounds.
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- 2011
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4. Triterpene esters from Uncaria rhynchophylla drive potent IL-12-dependent Th1 polarization
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Toshihiro Hashimoto, Ayaka Uda, Minori Okada, Masao Takei, Akemi Umeyama, Noboru Shoji, Je-Jung Lee, Yoshinori Yahisa, and Eriko Okayama
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Stereochemistry ,medicine.medical_treatment ,HL-60 Cells ,Cancer immunotherapy ,Triterpene ,Immunity ,medicine ,Humans ,chemistry.chemical_classification ,biology ,Plant Extracts ,Uncaria rhynchophylla ,Cell Polarity ,Esters ,Th1 Cells ,biology.organism_classification ,Acquired immune system ,Interleukin-12 ,Triterpenes ,Cytokine ,Uncaria ,chemistry ,Interleukin 12 ,Molecular Medicine ,Plant Structures - Abstract
Dendritic cells (DC) are key antigen-presenting cells that link innate and adaptive immunity and ultimately activate antigen-specific T cells. In the current study, we demonstrated that two triterpene esters, uncarinic acid C (1) and uncarinic acid D (2), which are isolated from the hooks of Uncaria rhynchophylla, activate phenotypic and cytokine production alterations in DC. We also show that 1 and 2 modulate human DC function in a fashion that favors Th1 cell polarization. The effect of 1 (E configuration at the 2' position) was approximately 20 times more potent than that of 2 (Z configuration at 2'). These results indicated that the configuration of the 2' double bond greatly effects activity. Thus, 1 and 2 may prove useful as DC-based vaccines for cancer immunotherapy.
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- 2010
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5. Polyacetylene diols with antiproliferative and driving Th1 polarization effects from the marine sponge Callyspongia sp
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Noboru Shoji, Shigenobu Arihara, Toshihiro Hashimoto, Miwa Matsui, Eri Arimoto, Akemi Nakata, Masao Takei, Nanae Matsuoka, Rieko Mine, and Akemi Umeyama
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Polymers ,Stereochemistry ,Diol ,Antineoplastic Agents ,Apoptosis ,HL-60 Cells ,Fractionation ,Th1 polarization ,Inhibitory Concentration 50 ,Polyacetylene ,chemistry.chemical_compound ,Leukemia, Promyelocytic, Acute ,Animals ,Humans ,Cell Proliferation ,biology ,Acetylene ,Cell Polarity ,Polyynes ,Cell Differentiation ,Dendritic Cells ,Th1 Cells ,biology.organism_classification ,Callyspongia ,Sponge ,Biochemistry ,chemistry ,Molecular Medicine ,Drug Screening Assays, Antitumor ,Callyspongiidae - Abstract
A screening of 30 crude extracts of marine sponges against human promyelocytic leukemia cells (HL-60) yielded an EtOAc extract of the sponge Callyspongia sp. (Callyspongiidae) with significant activity. Further bioassay-guided fractionation of the EtOAc extract led to the isolation of three polyacetylene metabolites: a new polyacetylene diol, callyspongidiol (1), along with two known compounds, siphonodiol (2) and 14,15-dihydrosiphonodiol (3). Their structures were determined by a combination of spectroscopic analyses. Compounds 1-3 exhibited antiproliferative activity against HL-60 with IC(50) values of 6.5, 2.8, and 6.5 microg/ml, respectively. These metabolites induce apoptosis in HL-60 cells. Dendritic cells (DC) differentiated with 1-3 enhance the differentiation of naïve T cells towards the Th1 type.
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- 2009
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6. Novel selective ligands for free fatty acid receptors GPR120 and GPR40
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Toshihiro Hashimoto, Gozoh Tsujimoto, Akira Hirasawa, Tetsuya Adachi, Takafumi Hara, Qi Sun, Tomoyo Iga, Keiko Sadakane, Yoshinori Asakawa, Taka-aki Koshimizu, and Chisato Itsubo
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Pharmacology ,chemistry.chemical_classification ,endocrine system ,Terpenes ,GPR120 ,Fatty acid ,Enteroendocrine cell ,Palmitic Acids ,General Medicine ,Biology ,Ligands ,Cell Line ,Receptors, G-Protein-Coupled ,Mice ,Biochemistry ,chemistry ,Cell culture ,Free fatty acid receptor 1 ,Free fatty acid receptor ,Animals ,Humans ,Calcium ,Extracellular Signal-Regulated MAP Kinases ,Receptor ,G protein-coupled receptor - Abstract
GPR120 and GPR40 are G-protein-coupled receptors whose endogenous ligands are medium- and long-chain free fatty acids, and they are thought to play an important physiological role in insulin release. Despite recent progress in understanding their roles, much still remains unclear about their pharmacology, and few specific ligands for GPR120 and GPR40 besides medium- to long-chain fatty acids have been reported so far. To identify new selective ligands for these receptors, more than 80 natural compounds were screened, together with a reference compound MEDICA16, which is known to activate GPR40, by monitoring the extracellular regulated kinase (ERK) and [Ca(2+)](i) responses in inducible and stable expression cell lines for GPR40 and GPR120, respectively. MEDICA16 selectively activated [Ca(2+)](i) response in GPR40-expressing cells but not in GPR120-expressing cells. Among the natural compounds tested, grifolin derivatives, grifolic acid and grifolic acid methyl ether, promoted ERK and [Ca(2+)](i) responses in GPR120-expressing cells, but not in GPR40-expressing cells, and inhibited the alpha-linolenic acid (LA)-induced ERK and [Ca(2+)](i) responses in GPR120-expressing cells. Interestingly, in accordance with the pharmacological profiles of these compounds, similar profiles of glucagon-like peptide-1 secretion were seen for mouse enteroendocrine cell line, STC-1 cells, which express GPR120 endogenously. Taken together, these studies identified a selective GPR40 agonist and several GPR120 partial agonists. These compounds would be useful probes to further investigate the physiological and pharmacological functions of GPR40 and GPR120.
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- 2009
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7. Valproic acid exerts anti-tumor as well as anti-angiogenic effects on myeloma
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Ayako Nakano, Shuji Ozaki, Takeshi Harada, Hiroe Amou, Toshio Matsumoto, Masahiro Abe, Kenichi Kitazoe, Asuka Oda, Toshihiro Hashimoto, Masahiro Hiasa, and Kyoko Takeuchi
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Melphalan ,medicine.medical_specialty ,Cell Survival ,medicine.drug_class ,Angiogenesis ,Osteoclasts ,Biology ,Bone Marrow ,immune system diseases ,hemic and lymphatic diseases ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Tumor Cells, Cultured ,medicine ,Humans ,Multiple myeloma ,Cell Proliferation ,Hematology ,Valproic Acid ,Histone deacetylase inhibitor ,Drug Synergism ,medicine.disease ,Coculture Techniques ,Thalidomide ,Histone Deacetylase Inhibitors ,medicine.anatomical_structure ,Apoptosis ,Cancer research ,lipids (amino acids, peptides, and proteins) ,Bone marrow ,Multiple Myeloma ,medicine.drug - Abstract
Multiple myeloma is still an incurable disease, most commonly occurring in the elderly. The myeloma-induced bone marrow microenvironment protects myeloma cells from drug-induced apoptosis. Therefore, the development of novel and tolerable therapeutic alternatives to overcome the drug resistance is an important clinical issue. Valproic acid (VPA), a safe and widely used anti-epileptic agent, is revisited as a class I- and IIa-specific histone deacetylase inhibitor. In the present study, we evaluated the effect as well as a mechanism of actions of VPA on myeloma cell growth and survival, with special reference to the myeloma-induced bone marrow microenvironment. VPA at therapeutic concentrations for epilepsy induced cell death in primary CD138-positive myeloma cells as well as myeloma cell lines, but not in CD138-negative bone marrow cells. VPA suppressed osteoclastogenesis as well as osteoclast-mediated myeloma cell growth. VPA also inhibited vascular tubule formation enhanced by co-cultures of myeloma cells and osteoclasts in concert with thalidomide. In addition, VPA induced both caspase-dependent and -independent cell death in myeloma cells, and potentiated the anti-myeloma effects of melphalan and dexamethasone. Collectively, VPA is suggested to exert multi-factorial anti-myeloma actions, and may serve as a safe adjuvant to be included in conventional chemotherapies against myeloma.
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- 2008
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8. Inhibitory activity of nitric oxide production in RAW 264.7 cells of daldinals A–C from the fungus Daldinia childiae and other metabolites isolated from inedible mushrooms
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Chie Kohchi, Takashi Nishizawa, Liva Harinantenaina, Yoshinori Asakawa, Toshihiro Hashimoto, Gen-Ichiro Soma, and Dang Ngoc Quang
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Messenger RNA ,Lipopolysaccharide ,biology ,Fungus ,biology.organism_classification ,law.invention ,Nitric oxide ,Nitric oxide synthase ,chemistry.chemical_compound ,chemistry ,Biochemistry ,law ,biology.protein ,Molecular Medicine ,Agarose ,Polymerase chain reaction ,RAW 264.7 Cells - Abstract
Three benzophenone derivatives, daldinals A–C, from the Japanese fungus Daldinia childiae were evaluated for their inhibitory activity of nitric oxide (NO) production stimulated by lipopolysaccharide (LPS) in RAW 264.7 cells. They strongly suppressed the LPS-induced production of NO with IC50 values of 15.2, 4.6 and 6.4 μM, respectively. To clarify the mechanism involved, total RNA extraction, followed by reverse-transcribed, polymerase chain reaction (PCR) for inducible nitric oxide synthase (iNOS) mRNA and finally electrophoresis on agarose gel were performed. These experimental results suggest that the inhibition of the LPS-induced NO production of daldinal B is due to the inhibition of iNOS mRNA synthesis. Further, their biological activities were compared with those of other metabolites obtained during our studies on biologically active substances from inedible fungi in recent years.
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- 2006
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9. Aromatic compounds and their antioxidant activity of Acer saccharum
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Shigenobu Arihara, Toshihiro Hashimoto, Yuki Kawahara, and Kazuko Yoshikawa
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Magnetic Resonance Spectroscopy ,Antioxidant ,Stereochemistry ,medicine.medical_treatment ,Acer ,Antioxidants ,Lignans ,Superoxide dismutase ,chemistry.chemical_compound ,Scopoletin ,medicine ,Organic chemistry ,Glycosides ,Lignan ,chemistry.chemical_classification ,Molecular Structure ,biology ,Phenylpropanoid ,Superoxide Dismutase ,Chemistry ,Glycoside ,Nuclear magnetic resonance spectroscopy ,biology.organism_classification ,Aceraceae ,biology.protein ,Molecular Medicine - Abstract
A new lignan glycoside, 5-(3″,4″-dimethoxy-phenyl)-3-hydroxy-3-(4'-hydroxy-3'-methoxybenzyl)-4-hydroxymethyl-dihydrofuran-2-one 4'-O-α-L: -rhamnopyranoside (1), with seven known compounds, compound 2, koaburside, icariside E(4), cleomiscosin C, cleomiscosin D, scopoletin, and 5'-demethylaquillochin, were isolated from the EtOH extract of the wood of Acer saccharum (Aceraceae). Their structures were determined by 1D and 2D nuclear magnetic resonance (NMR) and mass spectroscopy analysis. All of the isolated compounds, 1-8, were tested for their antioxidant activity in superoxide dismutase (SOD)-like assay.
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- 2010
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10. Erratum: In vitro antitrypanosomal activity of the cyclodepsipeptides, cardinalisamides A–C, from the insect pathogenic fungus Cordyceps cardinalis NBRC 103832
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Akemi Umeyama, Koichi Takahashi, Aleksandra Grudniewska, Mina Shimizu, Sayaka Hayashi, Masayuki Kato, Yasuko Okamoto, Midori Suenaga, Sayaka Ban, Toshio Kumada, Aki Ishiyama, Masato Iwatsuki, Kazuhiko Otoguro, Satoshi Ōmura, and Toshihiro Hashimoto
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Pharmacology ,Drug Discovery - Published
- 2014
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11. Production of IL1-beta by ovarian cancer cells induces mesothelial cell beta1-integrin expression facilitating peritoneal dissemination
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Steve Goodison, Takafumi Watanabe, Shu Soeda, Keiya Fujimori, Takashi Sugino, Hidekazu Yamada, Toshihiro Hashimoto, Hiroshi Nishiyama, and Yutaka Morimura
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Pathology ,medicine.medical_specialty ,endocrine system diseases ,Interleukin 1 family ,lcsh:Gynecology and obstetrics ,mesothelial cell ,β1 integrin ,Ovarian carcinoma ,Obstetrics and Gynaecology ,Medicine ,Beta (finance) ,lcsh:RG1-991 ,business.industry ,Research ,Obstetrics and Gynecology ,peritoneal dissemination ,Adhesion ,Beta1 Integrin ,medicine.disease ,ovarian cancer ,Oncology ,IL-1β ,Cell culture ,Cancer research ,business ,Ovarian cancer ,Mesothelial Cell - Abstract
Background A crucial step in the metastatic spread of ovarian cancer (OC) is the adhesion and implantation of tumor cells to the peritoneal mesothelium. In order to study this step in the cascade, we derived a pro-metastatic human ovarian carcinoma cell line (MFOC3) from the non-metastatic FOC3 line. Methods Molecular profiling of the isogeneic lines identified differentially expressed genes, and investigation for a role in dissemination for specific factors was achieved by development of a co-culture adhesion assay utilizing monolayers of human mesothelial cells. Results After murine intraperitoneal inoculation, the FOC3 cell line formed no metastases, but the MFOC3 subline formed metastases in > 80% of SCID mice. MFOC3 cells also adhered 2-3 times more avidly to mesothelial monolayers. This adhesion was inhibited by neutralizing antibodies to IL-1β and enhanced by recombinant IL-1β (p < 0.01). IL-1β induced mesothelial cell β1-integrin, and an antibody to this subunit also inhibited the adhesion of MFOC3 to mesothelial cells in vitro and significantly reduced metastases in vivo. Immunohistochemical analysis of a cohort of 96 ovarian cancer cases showed that negative IL-1β expression was significantly associated with an improved overall survival rate. Conclusions These results suggest that a IL-1β/β1-integrin axis plays a role in ovarian tumor cell adhesion to mesothelia, a crucial step in ovarian cancer dissemination.
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- 2012
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