成川 佑次 (ナルカワ ユウジ)

Narukawa, Yuji

写真a

所属(所属キャンパス)

薬学部 薬学科 天然医薬資源学講座 (芝共立)

職名

専任講師

 

研究分野 【 表示 / 非表示

  • 天然資源系薬学

 

著書 【 表示 / 非表示

  • 薬用食品の開発.

    竹田忠紘*、成川佑次、浅野 孝., 東京/シーエムシー出版, 2007年02月

    担当範囲: 267-277

論文 【 表示 / 非表示

  • Preparation of menisdaurigenin and related compounds

    Shirakawa R., Ishikawa S., Takahasi M., Ueno Y., Uekusa Y., Narukawa Y., Sugai T., Kiuchi F.

    Journal of Natural Medicines (Journal of Natural Medicines)  73 ( 1 ) 236 - 243 2019年01月

    ISSN  13403443

     概要を見る

    © 2018, The Japanese Society of Pharmacognosy and Springer Japan KK, part of Springer Nature. Menisdaurin (1), a cyano glucoside, was first isolated in 1978 from Menispermum dauricum (Menispermaceae) and named after the plant. It has been also isolated from several plant sources. The stereochemistry of the aglycone part was first reported as (Z,4R,6S)-enantiomer of (4,6-dihydroxy-2-cyclohexen-1-ylidene)acetonitrile based on the CD spectrum of menisdaurilide (2), the α,β-unsaturated γ-lactone obtained by an acid hydrolysis of menisdaurin. Later, the absolute stereochemistry was revised as (Z,4S,6R) by X-ray crystal analysis of 1 isolated from Saniculiphyllum guangxiens. The aglycone part of menisdaurin (1) has not been obtained from 1, because an acid hydrolysis of 1 gave menisdaurilide (2), and enzymatic hydrolysis with emulsin did not give the aglycone. On the other hand, a compound named coculauril (3) was isolated from Cocculus lauriforius. This compound has the same planner structure corresponding to the aglycone of 1, but the stereochemistry was reported to be (E,4R,6S). Here, we confirmed the absolute stereochemistry of 1 by Mosher’s method to be (Z,4S,6R), and prepared the aglycone of 1, i.e., menisdaurigenin (4) by an enzymatic hydrolysis of 1. We also revealed that 4 is a different compound from 3 and unstable in water and MeOH.

  • Taxodione induces apoptosis in BCR-ABL-positive cells through ROS generation

    Uchihara Y., Tago K., Taguchi H., Narukawa Y., Kiuchi F., Tamura H., Funakoshi-Tago M.

    Biochemical Pharmacology (Biochemical Pharmacology)  154   357 - 372 2018年08月

    ISSN  00062952

     概要を見る

    © 2018 Elsevier Inc. Chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) are hematopoietic malignancies caused by the constitutive activation of BCR-ABL tyrosine kinase. Although direct BCR-ABL inhibitors, such as imatinib, were initially successful in the treatment of leukemia, many patients developed drug resistance over time due to the gatekeeper mutation of BCR-ABL T315I. In the present study, we found that taxodione, a quinone methide diterpene isolated from Taxodium distichum, significantly induced apoptosis in human myelogenous leukemia-derived K562 cells, which were transformed by BCR-ABL. Taxodione reduced the activities of mitochondrial respiratory chain (MRC) complexes III and V, which appeared to induce the production of reactive oxygen species (ROS). N-acetylcysteine (NAC), an antioxidant agent, canceled taxodione-induced ROS production, reductions in MRC activities, particularly complex V, and apoptotic cell death. Furthermore, in K562 cells treated with taxodione, BCR-ABL and its major signaling molecules, such as STAT5 and Akt were sequestered in mitochondrial fraction, and their localization changes decrease their abilities to stimulate cell proliferation, suggesting that these actions seem to be a mechanism how taxodione functions as an anti-tumor drug. Strikingly, NAC canceled these taxodione-caused anti-cancer effects. Taxodione induced apoptosis in transformed Ba/F3 cells induced not only by BCR-ABL, but also T315I-mutated BCR-ABL through the generation of ROS. Collectively, the present results suggest that in the treatment of leukemia, taxodione has potential as a compound with high efficacy to overcome BCR-ABL T315I mutation-mediated resistance in leukemia cells.

  • Quantitative analysis of the anti-inflammatory activity of orengedokuto II: berberine is responsible for the inhibition of NO production

    Oshima N., Shimizu T., Narukawa Y., Hada N., Kiuchi F.

    Journal of Natural Medicines (Journal of Natural Medicines)  72 ( 3 ) 706 - 714 2018年06月

    ISSN  13403443

     概要を見る

    © 2018, The Japanese Society of Pharmacognosy and Springer Japan KK, part of Springer Nature. Orengedokuto is a Kampo formula that has been used for removing “heat” and “poison” to treat inflammation, hypertension, gastrointestinal disorders, and liver and cerebrovascular diseases. We report here our analysis of the anti-inflammatory effect of the component crude drugs of orengedokuto and their constituents using the inhibition of nitric oxide (NO) production in the murine macrophage-like cell line J774.1. An initial comparison of NO production inhibitory activities of the extracts of the component crude drugs and their combinations revealed that the activity could be attributed to Phellodendron Bark and Coptis Rhizome. Berberine (1), the major constituent of these crude drugs, showed potent activity (IC50 4.73 ± 1.46 μM). Quantitative analysis of 1 in the extracts of all combinations of component crude drugs revealed that the amount of 1 in each extract of the combination of Scutellaria Root with either Phellodendron Bark and/or Coptis Rhizome was lower than that in the corresponding mixtures of the extracts of the individual crude drugs and that 1 was present in the precipitates formed during the decoction process. To the contrary, the differences in the amounts of 1 were smaller in the extracts containing Gardenia Fruit. These results indicated that the constituents of Scutellaria Root precipitated with 1 and that the constituents of Gardenia Fruit dissolved the precipitates. To identify the constituents affecting the solubility of 1, we fractionated the hot-water extracts of Scutellaria Root based on solubility tests of 1 to give baicalin (2), wogonin (3) and oroxyloside (4), which formed precipitates with 1.

  • Three new 5,6,7,8-tetrahydroxy-5,6,7,8-tetrahydrochromone derivatives enantiomeric to agarotetrol from agarwood

    Sugiyama T., Narukawa Y., Shibata S., Masui R., Kiuchi F.

    Journal of Natural Medicines (Journal of Natural Medicines)  72 ( 3 ) 667 - 674 2018年06月

    ISSN  13403443

     概要を見る

    © 2018, The Japanese Society of Pharmacognosy and Springer Japan KK, part of Springer Nature. Agarwood (jinkoh in Japanese) is a resinous wood from Aquilaria species of the family Thymelaeaceae and has been used as incense and in traditional medicines. Characteristic chromone derivatives such as agarotetrol have been isolated from agarwood. In previous study, we isolated two new 2-(2-phenylethyl)chromones together with six known compounds from MeOH extract of agarwood. Further chemical investigation of the MeOH extract led to isolation of eighteen 2-(2-phenylethyl)chromones, including three new 5,6,7,8-tetrahydroxy-5,6,7,8-tetrahydrochromones with stereochemistry enantiomeric to agarotetrol-type, viz. (5R,6S,7S,8R)-2-[2-(3′-hydroxy-4′-methoxyphenyl)ethyl]-5,6,7,8-tetrahydroxy-5,6,7,8-tetrahydrochromone (2), (5R,6S,7S,8R)-2-[2-(4′-methoxyphenyl)ethyl]-5,6,7,8-tetrahydroxy-5,6,7,8-tetrahydrochromone (6), and (5R,6S,7S,8R)-2-[2-(4′-hydroxy-3′- methoxyphenyl)ethyl]-5,6,7,8-tetrahydroxy-5,6,7,8-tetrahydrochromone (13). The absolute configurations of the new compounds were determined by exciton chirality method. All isolated compounds were tested for their phosphodiesterase (PDE) 3A inhibitory activity by fluorescence polarization method. Compounds 8, 12–15, 21–24 showed moderate PDE 3A inhibitory activity.

  • Synergistic effect of baicalein, wogonin and oroxylin A mixture: multistep inhibition of the NF-κB signalling pathway contributes to an anti-inflammatory effect of Scutellaria root flavonoids

    Shimizu T., Shibuya N., Narukawa Y., Oshima N., Hada N., Kiuchi F.

    Journal of Natural Medicines (Journal of Natural Medicines)  72 ( 1 ) 181 - 191 2018年01月

    ISSN  13403443

     概要を見る

    © 2017, The Japanese Society of Pharmacognosy and Springer Japan KK. Scutellaria root, the root of Scutellaria baicalensis Georgi, is a crude drug used for inflammatory diseases. In our previous report, the combination of flavonoids contained in Scutellaria root have been found to inhibit PGE2 production more strongly than individual flavonoids. Here, to investigate the mechanism of the synergistic effect, we examined the effects of an equimolar mixture (F-mix) of baicalein (1), wogonin (2) and oroxylin A (3) on the production of PGE2 in LPS-treated J774.1 cells. Although 1 and 3 inhibited COX-2 activity, the F-mix showed no synergistic effect on COX-2 inhibition. Therefore, we investigated the steps leading to the activation of COX-2 protein. Compounds 1–3 and F-mix inhibited the expression of COX-2 protein. However, only 2 inhibited the expression of COX-2 mRNA among the flavonoids, and the F-mix showed no synergistic effect. Only 1 inhibited NF-κB translocation into the nucleus, and the F-mix showed no synergistic effect. Although 2 did not affect NF-κB translocation, it strongly inhibited NF-κB-dependent transcriptional activity, and the F-mix inhibited the activity slightly more than 2. Compounds 1–3 also inhibited NO production, and the F-mix showed a synergistic effect. However, the effects of each flavonoid on the expression of iNOS mRNA were not consistent with those on COX-2 mRNA. Because the flavonoids inhibit different steps in the production of PGE2 and NO, and their mixture did not show apparent synergistic effects in each step, we conclude that the synergistic effect of the flavonoid mixture reflects the total effect of the flavonoids inhibiting different steps in the NF-κB signalling pathway.

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KOARA(リポジトリ)収録論文等 【 表示 / 非表示

研究発表 【 表示 / 非表示

  • ビャクジュツ成分の脂肪細胞分化への影響

    成川 佑次、鶴田 侑也、木内 文之

    日本薬学会第138会年会 (金沢) , 2018年03月, ポスター(一般), 日本薬学会

  • シンイ由来化合物のメラニン生成抑制活性について

    高嶋 杏奈、小路 麻梨恵、山内 理奈、成川 佑次、木内 文之

    第61回日本薬学会関東支部大会 (東京) , 2017年09月, ポスター(一般), 日本薬学会関東支部

  • キキョウ配合漢方処方の成分変化と抗炎症活性に関する研究

    三浦 麻由佳、成川 佑次、木内 文之

    第61回日本薬学会関東支部大会 (東京) , 2017年09月, ポスター(一般), 日本薬学会関東支部

  • ヤクモソウ由来のエストロゲン代謝に影響を及ぼす成分の探索

    鎗田 かおり、成川 佑次、木内 文之

    第61回日本薬学会関東支部大会 (東京) , 2017年09月, ポスター(一般), 日本薬学会関東支部

  • 抗糖化活性を有するソボクの成分探索

    田中 大河、成川 佑次、植野 壽夫、宮澤 利男、村西 修一、木内 文之

    日本生薬学会第64回年会 (千葉) , 2017年09月, ポスター(一般), 日本生薬学会

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競争的資金等の研究課題 【 表示 / 非表示

  • 漢方処方における生薬間相互作用の解析

    2018年04月
    -
    2021年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 成川 佑次, 基盤研究(C), 補助金,  代表

 

担当授業科目 【 表示 / 非表示

  • 課題研究(天然医薬資源学)

    2019年度

  • 演習(天然医薬資源学)

    2019年度

  • 卒業研究A

    2019年度

  • 生薬学実習

    2019年度

  • 薬学英語演習F

    2019年度

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