Masahiro Nagai

Hoshi University, Edo, Tōkyō, Japan

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Publications (56)97.6 Total impact

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    ABSTRACT: Forsythide (F1) isolated from the leaves of Forsythia viridissima (Oleaceae) showed vasorelaxant effects on norepinephrine (NE)-induced contraction of rat aorta with or without endothelium. This compound did not affect contraction induced by high concentration potassium (60 mM K(+)) and phorbol 12,13-diacetate, but inhibited NE-induced contraction in the presence of nicardipine. These results demonstrated the inhibitory effects of F1 on NE-induced vasocontraction presumably due to decrease of calcium influx from extracellular area, which was induced by NE.
    Phytomedicine: international journal of phytotherapy and phytopharmacology 12/2008; 16(4):386-90. DOI:10.1016/j.phymed.2008.09.011 · 2.88 Impact Factor
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    ABSTRACT: The organic extract of the heartwood of Acer nikoense Maxim. (Aceraceae) showed vasorelaxant activity on rat aorta with or without endothelium. Coumarin [scopoletin (1)] and coumarinolignans [cleomiscosin A (2) and aquillochin (3)] were isolated as major constituents from the organic extract of the heartwood of A. nikoense. Compounds 1-3 exhibited moderate vasorelaxant effects on rat aorta, while 2 and 3 showed vasorelaxant effects in the norepinephrine-stimulated and also in high K+-depolarized preparations.
    Biological & Pharmaceutical Bulletin 07/2007; 30(6):1164-6. DOI:10.1248/bpb.30.1164 · 1.78 Impact Factor
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    ABSTRACT: A platelet-aggregatory inhibitor was isolated from the 50% MeOH extract of Phyllanthus niruri L. leaf. Its structure was determined to be methyl brevifolincarboxylate on the basis of the 1H-, 13C-NMR, and high-resolution mass spectral data. We compared the antiplatelet aggregatory effects of the constituent with adenosine, a well-known inhibitor of platelet aggregation. Platelet aggregation was induced by collagen or adenosine 5'-diphosphate as an activating agent; the extent of inhibition was monitored with a platelet aggregometer employing a laser-scattering method. The inhibitory effects of methyl brevifolincarboxylate were found to be as potent as adenosine that is known to act on an A2A subtype receptor.
    Biological & Pharmaceutical Bulletin 03/2007; 30(2):382-4. DOI:10.1248/bpb.30.382 · 1.78 Impact Factor
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    ABSTRACT: In the course of our screening, we found that the methanolic extract of Sappan Lignum showed strong activity against lipopolysaccharide (LPS)-induced nitric oxide (NO) production by macrophages in vitro. As it was reported that Brazilin inhibited inducible NO gene, we conducted to similar tests for six known compounds isolated from Sappan Lignum, namely, brazilein, sappanchalcone, protosappanin A, protosappanin B, protosappanin C besides brazilin. And six compounds were also subjected to six tests to speculate their properties: (1) inhibition of NO production by cultured J774.1 (macrophage-like) cell line, (2) suppression of inducible NO synthase (iNOS) gene expression, (3) inhibition of NO production by murine peritoneal macrophages, (4) DPPH radical scavenging activity, (5) reduction of ferric ion and (6) antioxidant activity. Brazilein and sappanchalcone showed significant inhibition of lipopolysaccharide (LPS)-induced NO production by J774.1 cell line like Brazilin; 100% inhibition at 30 microM in test (1) and at 10 microM in test (3). The mechanisms underlying the inhibition of NO production by the compounds were investigated in test (2). As a result, brazilin was found to almost completely suppress iNOS gene expression at 100 microM as reported, and brazilein and sappanchalcone also suppressed iNOS gene expression. But strong activities were not observed for protosappanins A, B and C. So, we conducted tests (4), (5) and (6) to investigate other properties about six compounds. Protosappanin A and Brazilin demonstrated high antioxidant activity compared with Vitamin E in tests (4) and (5). Protosappanin A and B inhibited the oxidation of linoleic acid in test (6). Among the dibenzoxocin derivatives, only protosappanin C did not show significant activity in all the tests. We found that sappanchalcone showed same activity as brazilin, and six compounds isolated from Sappan Lignum showed various properties.
    Biological & Pharmaceutical Bulletin 02/2007; 30(1):193-6. DOI:10.1248/bpb.30.193 · 1.78 Impact Factor
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    Toru Iizuka, Hiroyoshi Moriyama, Masahiro Nagai
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    ABSTRACT: Methyl brevifolincarboxylate (1) isolated from the leaves of Phyllanthus niruri L. showed a vasorelaxant effect on rat aortic rings. Compound 1 exhibited slow relaxation activity against norepinephrine (NE)-induced contractions of rat aorta with or without endothelium. The compound did not affect contractions induced by a high concentration (60 mM) of K+, whereas it inhibited NE-induced vasocontraction in the presence of nicardipine. These results suggest that the inhibition of NE-induced vasocontraction by compound 1 is in part attributable to a decrease in [Ca2+]i through receptor-operated Ca2+ channels.
    Biological & Pharmaceutical Bulletin 02/2006; 29(1):177-9. DOI:10.1248/bpb.29.177 · 1.78 Impact Factor
  • Toru Iizuka, Masahiro Nagai
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    ABSTRACT: The vasorelaxant effects of forsythiaside (compound 1) from the fruits of Forsythia suspensa on isolated rat aortic rings were studied. Compound 1 showed a slow relaxation activity against norepinephrine (NE)-induced contractions of rat aorta with/without endothelium. This compound did not affect contractions induced by a high concentration of potassium (K(+) 60 mM), while it inhibited NE-induced vasocontraction in the presence of nicardipine. These results show that the inhibition by compound 1 of NE-induced vasocontraction is due to a decrease in calcium influx from the extracellular space caused by NE.
    Yakugaku zasshi journal of the Pharmaceutical Society of Japan 03/2005; 125(2):219-24. DOI:10.1248/yakushi.125.219 · 0.31 Impact Factor
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    ABSTRACT: In continuation of our previous report, cimigenol (1) and 15 related compounds were screened as potential antitumor promoters by using the in vitro short-term 12-O-tetradecanoylphorbol-13-acetate (TPA)--induced Epstein-Barr virus early antigen (EBV-EA) activation assay. Cimigenol-3,15-dione (2) displayed the greatest potency (100% inhibition at 1000 mol ratio/TPA) and consequently was further examined for antitumor-promoting activity in a two-stage carcinogenesis assay of mouse skin tumors (DMBA/TPA). In this assay, compound 2 showed significant activity, reducing the number of papillomas per mouse to 48% of the control group at 20 weeks. In addition, compounds 1 and 2 were examined for antitumor-initiating activity in a two-stage carcinogenesis assay of mouse skin tumors induced by peroxynitrite as an initiator and TPA as a promoter. Results showed that these two triterpenoids were almost equipotent with epigallocatechin gallate (EGCG) and slightly more potent than tocinol (group V), the positive controls. Thus, compounds 1 and 2 exhibited not only strong antitumor-promoting activity but also significant antitumor-initiating effect on mouse skin. These data suggest that both compounds might be valuable chemopreventors.
    Bioorganic & Medicinal Chemistry 03/2005; 13(4):1403-8. DOI:10.1016/j.bmc.2004.10.062 · 2.95 Impact Factor
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    ABSTRACT: Twelve N-caffeoylamino acids and N-cinnamoylamino acids were synthesized and their vasorelaxation activity against norepinephrine (NE)-induced contraction of rat aorta was examined. The following structure-activity relationships were found. 1) On the benzene ring, the caffeoyl structure is effective for vasorelaxation, while the cinnamoyl structure reduced vasorelaxation activity. 2) Four to six carbons are more effective as the carbon chain connecting the acylamino and carboxyl terminal groups. N-Caffeoyl-beta-alanine and N-caffeoyltranexamic acid were used to investigate the action mechanism of vasorelaxing activities. It is believed that these compounds antagonize NE-induced vasocontraction by inhibiting receptor-operated calcium channels.
    Yakugaku zasshi journal of the Pharmaceutical Society of Japan 12/2003; 123(11):963-71. DOI:10.1248/yakushi.123.963 · 0.31 Impact Factor
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    ABSTRACT: Adenine was isolated as a platelet aggregating inhibitor from the leaves of Cassia alata by HPLC using a triacontylsilyl silica (C(30)) column. The inhibitory effects of adenine and adenosine (positive control) on the platelet aggregation induced by collagen or adenosine 5'-diphosphate (ADP) as an aggregating agent was evaluated with a platelet aggregometer using a laser-scattering method. As a result, the inhibitory effect of adenine was observed in the platelet aggregation induced by collagen (1.0 microg/ml as the final concentration), but little inhibitory effect was noted in the aggregation induced by ADP (5.0 microM as the final concentration), whereas adenosine exhibited potent inhibitory effects on platelet aggregation induced both by collagen and ADP under the same experimental conditions.
    Biological & Pharmaceutical Bulletin 10/2003; 26(9):1361-4. DOI:10.1248/bpb.26.1361 · 1.78 Impact Factor
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    ABSTRACT: Kaempferol-3-O-gentiobioside, the major flavonoid glycoside in Indonesian Cassia alata was quantified in various parts of the plant. The mature leaf was found to contain the highest content of this metabolite. A decrease of the flavonoid content in the juvenile leaf during the period of October through December was also observed. The contents ranged from 2.0 to 5.0% and 1.0 to 4.0% in mature and juvenile leaves, respectively. The other parts studied were flower (sepal and petal), rachis, stem and seed. Kaempferol-3-O-gentiobioside was not detected in the seed.
    Fitoterapia 08/2003; 74(5):425-30. DOI:10.1016/S0367-326X(03)00058-3 · 2.22 Impact Factor
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    ABSTRACT: The vasorelaxant activities of chicoric acid (Compound 1) from Cichorium intybus and dicaffeoyl-meso-tartaric acid (Compound 2) from Equisetum arvense L. in isolated rat aorta strips were studied. Compound 1 is a diester composed of (S,S)-tartaric acid and caffeic acid, and 2 is composed of its meso type. Both 1 and 2 showed slow relaxation activity against norepinephrine (NE)-induced contraction of rat aorta with/without endothelium. These compounds did not affect contraction induced by a high concentration of potassium (60 mM K+), while they inhibited NE-induced vasocontraction in the presence of nicardipine. These results show that the inhibition by 1 and 2 of NE-induced vasocontraction is due to a decrease in calcium influx from the extracellular space caused by NE. In addition, dicaffeoyl tartaric acids showed vasorelaxant activity, regardless of their stereochemistry.
    Yakugaku zasshi journal of the Pharmaceutical Society of Japan 08/2003; 123(7):593-8. DOI:10.1248/yakushi.123.593 · 0.31 Impact Factor
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    ABSTRACT: Antiinflammatory activities of heat-treated Cassia alata leaf extract and kaempferol 3-O-gentiobioside (K3G) isolated from C. alata as an abundant flavonoid glycoside were studied by comparing their activities with the activities of sun-dried C. alata leaf extract. We observed strong inhibitory effects on Concanavalin A-induced histamine release from rat peritoneal exudate cells both in the extracts of heat-treated and sun-dried C. alata leaves. Furthermore, the heat-treated leaf extract exhibited stronger inhibitory effects than the effects of the sun-dried leaf extract at low concentrations in the studies of Concanavalin A-induced histamine release, 5-lipoxygenase inhibition, and also inhibition of cyclooxygenases (COX-1 and COX-2), whereas K3G showed weak inhibitory effects on Concanavalin A-induced histamine release, 5-lipoxygenase, and COX-1. No anti-hyaluronidase effect was detected in any of the materials tested.
    Yakugaku zasshi journal of the Pharmaceutical Society of Japan 08/2003; 123(7):607-11. DOI:10.1248/yakushi.123.607 · 0.31 Impact Factor
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    ABSTRACT: Cimigenol (1) and 39 related compounds were screened as potential antitumor promoters by examining the ability of the compounds to inhibit Epstein-Barr virus early antigen (EBV-EA) activation (induced by 12-O-tetradecanoylphorbol-13-acetate) in Raji cells. Structure-activity relationship analysis indicated that compound 1 showed the highest activity and also exhibited significant inhibitory effects on mouse skin tumor promotion in an in vivo two-stage carcinogenesis test. These data suggest that 1 and the related compounds might be valuable anti-tumor promoters.
    Bioorganic & Medicinal Chemistry 04/2003; 11(6):1137-40. DOI:10.1016/S0968-0896(02)00432-7 · 2.95 Impact Factor
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    ABSTRACT: Kaempferol-3-O-gentiobioside, the major flavonoid glycoside in Indonesian Cassia alata was quantified in various parts of the plant. The mature leaf was found to contain the highest content of this metabolite. A decrease of the flavonoid content in the juvenile leaf during the period of October through December was also observed. The contents ranged from 2.0 to 5.0% and 1.0 to 4.0% in mature and juvenile leaves, respectively. The other parts studied were flower (sepal and petal), rachis, stem and seed. Kaempferol-3-O-gentiobioside was not detected in the seed.
    Fitoterapia 01/2003; 74(5):425-430. · 2.22 Impact Factor
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    ABSTRACT: A number of curcumin analogues were prepared and evaluated as potential androgen receptor antagonists against two human prostate cancer cell lines, PC-3 and DU-145, in the presence of androgen receptor (AR) and androgen receptor coactivator, ARA70. Compounds 4 [5-hydroxy-1,7-bis(3,4-dimethoxyphenyl)-1,4,6-heptatrien-3-one], 20 [5-hydroxy-1,7-bis[3-methoxy-4-(methoxycarbonylmethoxy)phenyl]-1,4,6-heptatrien-3-one], 22 [7-(4-hydroxy-3-methoxyphenyl)-4-[3-(4-hydroxy-3-methoxyphenyl)acryloyl]-5-oxohepta-4,6-dienoic acid ethyl ester], 23 [7-(4-hydroxy-3-methoxyphenyl)-4-[3-(4-hydroxy-3-methoxyphenyl)acryloyl]5-oxohepta-4,6-dienoic acid], and 39 [bis(3,4-dimethoxyphenyl)-1,3-propanedione] showed potent antiandrogenic activities and were superior to hydroxyflutamide, which is the currently available antiandrogen for the treatment of prostate cancer. Structure-activity relationship (SAR) studies indicated that the bis(3,4-dimethoxyphenyl) moieties, the conjugated beta-diketone moiety, and the intramolecular symmetry of the molecules seem to be important factors related to antiandrogenic activity. The data further suggest that the coplanarity of the beta-diketone moiety and the presence of a strong hydrogen bond donor group were also crucial for the antiandrogenic activity, which is consistent with previous SAR results for hydroxyflutamide analogues. When the pharmacophoric elements of dihydrotestosterone (DHT) and compound 4 are superposed, the resulting construct implies that the curcumin analogues may function as a 17alpha-substituted DHT. Compounds 4, 20, 22, 23, and 39 have been identified as a new class of antiandrogen agents, and these compounds or their new synthetic analogues could be developed into clinical trial candidates to control androgen receptor-mediated prostate cancer growth.
    Journal of Medicinal Chemistry 12/2002; 45(23):5037-42. DOI:10.1021/jm020200g · 5.48 Impact Factor
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    ABSTRACT: Fifty-eight curcumin analogues were prepared and evaluated for in vitro cytotoxicity against a panel of human tumor cell lines. Compound was the most potent analogue against several cell lines, including HOS (bone cancer) and 1A9 (breast cancer), with ED50 values of 0.97 and <0.63 microg/mL, respectively.
    Bioorganic & Medicinal Chemistry 12/2002; 10(11):3481-7. DOI:10.1016/S0968-0896(02)00249-3 · 2.95 Impact Factor
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    ABSTRACT: Eleven cyclic diarylheptanoids and seven related compounds were screened as potential antitumor promoters by using the in vitro short-term 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus early antigen (EBV-EA) activation assay. In addition, the cyclic diarylheptanoid myricanone (2) was examined for antitumor initiating activity in a two-stage carcinogenesis assay of mouse skin tumors induced by peroxynitrite as an initiator and TPA as a promoter. Myricanone (2) exhibited significant antitumor-initiating effect on mouse skin. These data suggest that cyclic, as well as linear, diarylheptanoids might be valuable chemopreventors.
    Bioorganic & Medicinal Chemistry 11/2002; 10(10):3361-5. DOI:10.1016/S0968-0896(02)00164-5 · 2.95 Impact Factor
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    Hiroyoshi Moriyama, Toru Iizuka, Masahiro Nagai
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    ABSTRACT: Heat-treated leaves of Cassia alata were studied for any change in chemical constituents using sun dried leaves as the reference standard. A high concentration of a constituent was observed in the heat-treated leaves. Spectroscopic studies revealed the structure of the constituent as kaempferol 3-gentiobioside, which has not yet been detected in the Cassia species. In a stability study disappearance of kaempferol 3-gentiobioside was noted in the sun dried leaves while there was little or no change in the kaempferol 3-gentiobioside concentration in the heat-treated leaves when incubated in an aqueous solution, suggesting a possible presence of enzymatic activities in the sun dried leaves. Therefore, heat-treatment may be a good method to stabilize kaempferol 3-gentiobioside in Cassia alata leaves.
    Yakugaku zasshi journal of the Pharmaceutical Society of Japan 12/2001; 121(11):817-20. DOI:10.1248/yakushi.121.817 · 0.31 Impact Factor
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    ABSTRACT: The inhibitory collagenolytic activity (47-64% inhibition in 0.22-0.24 microM) of fukinolic acid and cimicifugic acids A, B, and C, which are esters of fukiic acid (3',4'-dihydroxybenzyl tartaric acid) was more potent than that (20-37% inhibition in 0.23-0.24 microM) of cimicifugic acids D, E, F, which are esters of pscidic acid (4'-hydroxybenzyl tartaric acid). Since fukiic acid showed weaker inhibition, and caffeic acid, ferulic acid, isoferulic acid, and p-coumaric acid showed far weaker activities, the entire structures of fukinolic acid and cimicifugic acids A, B, and C proved to be responsible for the inhibitory activities. Trypsin and pronase E hydrolyzed collagen nonselectively alone or in addition to collagenase. These collagenolytic activities were also inhibited by fukinolic acid. These results show that fukinolic acid may inhibit either the collagenolytic activities specific to collagenase or nonspecific to other emzymes. The present studies suggest the potential effect of fukinolic acid and cimicifugic acids of Cimicifuga rhizomes in preventing collagen degradation by collagenases or collagenolytic enzymes under pathological conditions, wound healing, or inflammation.
    Biological & Pharmaceutical Bulletin 11/2001; 24(10):1198-201. DOI:10.1248/bpb.24.1198 · 1.78 Impact Factor
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    ABSTRACT: ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
    ChemInform 03/2001; 32(11). DOI:10.1002/chin.200111177

Publication Stats

668 Citations
97.60 Total Impact Points

Institutions

  • 1989–2007
    • Hoshi University
      • • Faculty of Pharmaceutical Sciences
      • • Institute of Medicinal Chemistry
      Edo, Tōkyō, Japan
  • 2003
    • Tokushima Bunri University
      • Faculty of Pharmaceutical Sciences
      Edo, Tōkyō, Japan
  • 1997
    • Kyoto Pharmaceutical University
      Kioto, Kyōto, Japan