Narukawa, Yuji



Faculty of Pharmacy, Department of Pharmacy 天然医薬資源学講座 (Shiba-Kyoritsu)


Assistant Professor/Senior Assistant Professor


Research Areas 【 Display / hide

  • Natural medicines


Books 【 Display / hide

  • 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, 2007.02

    Scope: 267-277

Papers 【 Display / hide

  • LC–MS analysis of saponins of Achyranthes root in the Japanese market

    Kuwada K., Kawase S., Nakata K., Shinya N., Narukawa Y., Fuchino H., Kawahara N., Kiuchi F.

    Journal of Natural Medicines (Journal of Natural Medicines)  74 ( 1 ) 135 - 141 2020.01

    ISSN  13403443

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    © 2019, The Japanese Society of Pharmacognosy. LC–MS analyses of saponin fractions of Achyranthes roots in the Japanese market revealed that there were three patterns for the saponin fraction of their water extracts, i.e., the saponins with a sugar moiety at position 28 [achyranthosides B (3), C (4) and D (5)] were the major constituents, the saponins without sugar moiety at position 28 [betavulgarosides II (10) and IV (11)] were the major constituents, and mixtures of these saponins. In a decoction prepared from the sample which contained 10 and 11 as the major saponins, their amounts were largely decreased compared with those of the water extract. As large amounts of these saponins were found in the precipitates formed by heating of the water extract, these saponins were seemed to precipitate out under heating. When hot water was used for the extraction, 3, 4 and 5 were detected even from the samples whose water extract did not contain these saponins. This was attributed to inhibition of endogenous esterase which hydrolyzes the ester linkage at position 28. When saponins were extracted with reagent grade 1-butanol, in addition to the decrease of the amounts of highly polar saponins, oxidative decarboxylation of 3 and 10 occurred resulting in formation of achyranthoside E (6) and spinacoside D (12), respectively. As these changes were not observed with HPLC grade 1-butanol, which contain not more than 5 ppm of peroxide impurities, the change was attributable to the peroxide impurities contained in the reagent grade 1-butanol.

  • 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 2019.01

    ISSN  13403443

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    © 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 2018.08

    ISSN  00062952

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    © 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 2018.06

    ISSN  13403443

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    © 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 2018.06

    ISSN  13403443

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    © 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.

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Papers, etc., Registered in KOARA 【 Display / hide

Presentations 【 Display / hide

  • 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) , 2018.03, Poster (general), 日本薬学会

  • 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) , 2017.09, Poster (general), 日本薬学会関東支部

  • 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) , 2017.09, Poster (general), 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) , 2017.09, Poster (general), 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) , 2017.09, Poster (general), 日本生薬学会

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 漢方処方における生薬間相互作用の解析


    MEXT,JSPS, Grant-in-Aid for Scientific Research, 成川 佑次, Grant-in-Aid for Scientific Research (C), Principal Investigator


Courses Taught 【 Display / hide











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