Research Achievements - Original paper -
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乳がんFEC100療法におけるホスアプレピタント注とアプレピタントカプセルの有効性と安全性の比較
渡邊 桂子, 菊地 正史, 木皿 重樹, 小笠原 喜美代, 久道 周彦, 石田 孝宣, 鈴木 直人, 村井 ユリ子, 島田 美樹, 富岡 佳久, 石岡 千加史, 眞野 成康
医薬品相互作用研究 ( 医薬品相互作用研究会 ) 39 ( 1 ) 29 - 35 2015.08 [Refereed]
Research paper (journal)
乳がんFEC100療法におけるホスアプレピタント注(FOS)とアプレピタントカプセル(APR)の有効性と安全性について比較検討した.乳がんFEC100療法を施行し,FOSを末梢静脈から投与,またはAPRを内服し,制吐療法を施行した32例を対象とした.FOSを投与したFOS群19例,APRを内服したAPR群13例であった.急性および遅発性悪心は,それぞれFOS群7例,APR群5例およびFOS群13例,APR群6例に発現し,重症度は最大でgrade 2であった.急性嘔吐は,両群ともに0例で,遅発性嘔吐はFOS群の2例に発現し,重症度は最大でgrade 2であった.CR率は,FOS群36.8%,APR群76.9%で有意差を認めた.注射部位反応はFOS群の17例で発現し,血管痛や静脈炎が有意に高値であった.
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PTX療法におけるラニチジン注とファモチジン注のアレルギー発現率の後方視的コホート研究
片岡 佑太, 菊地 正史, 中川 直人, 木皿 重樹, 高橋 哉子, 小笠原 喜美代, 我妻 恭行, 久道 周彦, 鈴木 直人, 村井 ユリ子, 富岡 佳久, 石岡 千加史, 島田 美樹, 眞野 成康
日本病院薬剤師会雑誌 ( (一社)日本病院薬剤師会 ) 49 ( 10 ) 1091 - 1095 2013.10 [Refereed]
Research paper (journal)
パクリタキセル注(以下,PTX)を用いるがん化学療法においては,アレルギー予防のためH2受容体拮抗薬のラニチジン注またはファモチジン注が前投薬されるが,ラニチジン注を用いた場合にしばしばそう痒感,蕁麻疹などが発現し,東北大学病院のがん化学療法に関するプロトコル審査委員会で問題提起された.そこで,ラニチジン注投与群175例(以下,R群)とファモチジン注投与群97例(以下,F群)について,両群間のアレルギー発現率を後方視的に比較検討した.その結果,前投薬中に発現したアレルギーはR群が12例(6.9%),F群が0例(0%)であり,R群において有意に高頻度に発現していた(p<0.01).一方,PTX投与中に発現したアレルギーは,R群で1例(0.6%),F群で2例(2.1%)であり,両群に有意差は認められなかった.以上より,PTXの前投薬にはラニチジン注よりもファモチジン注のほうが安全に使用できることが示唆された.(著者抄録)
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Structure and Cytotoxic Activity of Enzymatic Hydrolysis Products of Secoiridoid Glucosides, Isoligustroside and Isooleuropein
Masafumi Kikuchi, Yasunori Yaoita, Nariyasu Mano, Masao Kikuchi
CHEMISTRY & BIODIVERSITY ( WILEY-BLACKWELL ) 8 ( 4 ) 651 - 657 2011.04 [Refereed]
Research paper (journal)
Hydrolysis of isoligustroside (1) and isooleuropein (2), secoiridoid glucosides, in the presence of beta-glucosidase provided 2-(4-hydroxyphenyl)methyl (2R,3S,4S)-3-formyl-3,4-dihydro-4-(2-methoxy-2-oxoethyl)-2-methyl-2H-pyran-5-carboxylate (3) and 2-(3,4-dihydroxyphenyl)methyl (2R,3S,4S)-3-formyl-3,4-dihydro-4-(2-methoxy-2-oxoethyl)-2-methyl-2H-pyran-5-carboxylate (4), respectively. The structures of 3 and 4 were elucidated on the basis of extensive spectral analyses, including 2D-NMR experiments. Compounds 3 and 4 were found to be new rearrangement products of the aglycones of 1 and 2. The cytotoxic activities of 3 and 4 were evaluated using a disease-oriented panel of 39 human cancer cell lines and showed moderate cytotoxic activity for 4, while 3 exhibited weaker activity compared to that of 4.
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Cytotoxic and EGFR tyrosine kinase inhibitory activities of aglycone derivatives obtained by enzymatic hydrolysis of oleoside-type secoiridoid glucosides, oleuropein and ligustroside
Masafumi Kikuchi, Nariyasu Mano, Yoshimasa Uehara, Koichi Machida, Masao Kikuchi
JOURNAL OF NATURAL MEDICINES ( SPRINGER JAPAN KK ) 65 ( 1 ) 237 - 240 2011.01 [Refereed]
Research paper (journal)
Hydrolysis of oleoside-type secoiridoid glucosides, oleuropein (1) and ligustroside (2), in the presence of beta-glucosidase provided their aglycones, named (5S,8R,9S)-7-3,4-dihydroxyphenethyl elenolate (3) and (5S,8R,9S)-7-4-hydroxyphenethyl elenolate (4), respectively. The structures of 3 and 4 were identified by spectroscopic means and optical rotation measurements. Evaluation of the cytotoxic and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitory activities of compounds 1-4 showed that compounds 3 and 4 exhibited moderate cytotoxicity against a disease-oriented panel of 39 human cancer cell lines in vitro, whereas compound 3 inhibited the enzyme.
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Masafumi Kikuchi, Yasunori Yaoita Nariyasu Mano, Masao Kikuchi
Shoyakugaku Zasshi ( 日本生薬学会 ) 64 ( 2 ) 104 - 105 2011.01 [Refereed]
Research paper (journal)
From the leaves of Syringa vulgaris L. (Oleaceae), nine known glycosides were isolated and identified: 3,4-dihydroxyphenethyl β-D-glucopyranoside (1), acteoside (2), echinacoside (3), oleoacteoside (4), oleoechinacoside (5), isooleoacteoside (6), syringopicroside B (7), syringalactone B (8), and 2"-epi-frameroside (9). This is the first time that compounds 6, 7 and 9 have been isolated from the leaves of S. vulgaris. The growth inhibitory activity of compounds 1-9 against 39 human cancer cell lines was evaluated.
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New physiological function of secoiridoids: neuritogenic activity in PC12h cells
Kenzo Chiba, Matsumi Yamazaki, Masafumi Kikuchi, Rie Kakuda, Masao Kikuchi
JOURNAL OF NATURAL MEDICINES ( SPRINGER TOKYO ) 65 ( 1 ) 186 - 190 2011.01 [Refereed]
Research paper (journal)
Previously, we have reported that geniposide isolated from an extract of Gardenia fructus has neuritogenic activity in PC12h cells, a subclone of rat pheochromocytoma cells. Furthermore, we have indicated that several geniposide-related iridoid compounds also had similar potent neuritogenic activity. In this study, we have examined the effects of various secoiridoid compounds [K-1, sweroside; K-2, swertiamarin; K-3, gentiopicroside; K-4, 6'-O-beta-d-glucopyranosylsweroside; K-5, 6'-O-beta-d-glucopyranosylgentiopicroside; K-6, 6'-O-beta-d-glucopyranosylswertiamarin; K-7, 5'-O-beta-d-glucopyranosylamarogentin; K-8, 5'-O-beta-d-glucopyranosylamaroswertin; H-1, n-butyl vogeloside; H-2, n-butyl epivogeloside; H-3, (7S)-secologanin butyl methyl acetal; H-4, (7R)-secologanin butyl methyl acetal; H-5, secologanin dimethyl acetal] isolated from various medicinal herbs. The secoiridoids H-1, H-2, H-3, H-4, and H-5 induced significant neurite outgrowth. Among these H-series compounds, H-2 was the most potent neuritogenic compound. Among the K-series compounds, K-1, K-2, K-3, and K-8 showed the most potent activity. These results suggest that secoiridoids have neuritogenic activity in PC12h cells and that these secoiridoid compounds are promising starting compounds for the development of neurotrophic factor-like and iridoid compounds.
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ムラサキハシドイの葉のセコイリドイド配糖体の構造並びにヒトがん細胞株に対する増殖阻害活性について
八百板 康範, 菊地 正史, 菊地 正雄
東北薬科大学研究誌 ( 東北医科薬科大学 ) ( 57 ) 47 - 50 2010.12 [Refereed]
Research paper (journal)
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Three new glycosides from the leaves of Hydrangea macrophylla subsp serrata (THUNB.) MAKINO
Masao Kikuchi, Rie Kakuda, Masafumi Kikuchi, Yasunori Yaoita
CHEMICAL & PHARMACEUTICAL BULLETIN ( PHARMACEUTICAL SOC JAPAN ) 56 ( 4 ) 610 - 611 2008.04 [Refereed]
Research paper (journal)
Three new glycosides, 7-deoxyloganic acid beta-D-glueopyranosyl ester (1), (3R)-hydrangenol 8,4'-di-O-beta-D-glu-copyranoside (2), and (6R,7E,9R)-megastigma-4,7-dien-3-one 9,13-di-O-beta-D-glueopyranoside (3), have been isolated from the leaves of Hydrangea macrophylla subsp. serrata (THUNB.) MAKINO (Saxifragaceae). The structures of 1-3 were elucidated on the basis of spectral data and chemical evidence.
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Monohydroxy-Substituted Polyunsaturated Fatty Acids from Swertia japonica
Masafumi Kikuchi, Yasunori Yaoita, Masao Kiknchi
HELVETICA CHIMICA ACTA ( WILEY-V C H VERLAG GMBH ) 91 ( 10 ) 1857 - 1862 2008 [Refereed]
Research paper (journal)
Fourteen monohydroxy-substituted polyunsaturated fatty acids, including two new compounds. (9Z,12S,13E,15Z)-12-hydroxyoetadeca-9,13,15-trienoic acid (10) and (9Z,12Z,14E,16R)-16-hydroxyoctadeca-9,12,14-trienoic acid acid (13), and 12 known ones. i.e., 1-9, 11, 12, and 14, were isolated from the whole plants of Swertia japonica MAKINO, and characterized as the corresponding methyl esters 1a- 14a. Their structures were elucidated by analysis of the corresponding spectroscopic data, and the absolute configurations of 10a and 13a were determined by the Mosher-ester method. The CD spectra (Table) of compounds 1a-14a are briefly discussed. This IS the first report oil the isolation of monohydroxy-substituted polyunsaturated fatty acids from the Swertia genus in Gentianaceae.
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New secoiridoid glucosides from Swertia japonica
Masafumi Kikuchi, Rie Kakuda, Yasunori Yaoita, Masao Kikuchi
HELVETICA CHIMICA ACTA ( WILEY-V C H VERLAG GMBH ) 91 ( 7 ) 1236 - 1243 2008 [Refereed]
Research paper (journal)
Four new secoiridoid glucosides, swertiajaposides C-F (1-4, resp.), were isolated from the whole plant of Swertia japonica MAKINO together with two known compounds, 8-hydroxy-10-hydrosweroside (5) and senburiside IV (6). The structures of 1-4 were elucidated on the basis of spectroscopic, chemical, and physicochemical evidence.
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Neuritogenesis of herbal geniposide-related compounds in PC12h cells
Kenzo Chiba, Matsumi Yamazaki, Masafumi Kikuchi, Koichi Machida, Masao Kikuchi
JOURNAL OF HEALTH SCIENCE ( PHARMACEUTICAL SOC JAPAN ) 52 ( 6 ) 743 - 747 2006.12 [Refereed]
Research paper (journal)
Previously, we have reported that geniposide, a compound isolated from an extract of Gardenia fructus, has neuritogenic activity in PC12h cells, a subclone of the rat pheochromocytoma cell. In this study, we have examined the effects of seven geniposide-related compounds (S-1, 6 alpha-hydroxygeniposide; S-2, 6 beta-hydroxygeniposide; S-3, 6 alpha-methoxygeniposide; S-4, 6 beta-methoxygeniposide; S-5, loganin; S-6, 7-ketologanin; and S-7, syringopicroside) isolated from various medicinal herbs. The geniposide-type iridoids S-1, S-2, S-3, and S-4, and S-7 induced neurite outgrowth that was similar or more potent to that of geniposide. S-2 and S-4, which are optical isomers of S-1 and S-3, respectively, were particularly potent. The 2 loganin-type iridoids, S-5 and S-6, showed less activity than geniposide. The neuritogenic activity of geniposide-type iridoids appears to be not necessarily correlated directly to their hydrophobicity. These results suggest that geniposide-type iridoids have potent neuritogenic activity and that specific configurations for the interactions between iridoid compounds and the target molecule are necessary for neuritogenic function.
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A new iridoid diglycoside from Gentianae Scabrae Radix
Tomoko Kyoya, Masafumi Kikuchi, Rie Kakuda, Yasunori Yaoita, Masao Kikuchi
Natural Medicines ( 日本生薬学会 ) 59 ( 4 ) 178 - 180 2005.08 [Refereed]
Research paper (journal)
A new iridoid diglycoside, gentianaside (1), was isolated together with two known compounds, 6'-O-β-D-glucopyranosylloganic acid (2) and 8-epikingiside (3), from Gentianae Scabrae Radix. The structure of the new compound was elucidated on the basis of spectral data.
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Secoiridoid glycosides from Gentiana scabra
M Kikuchi, R Kakuda, M Kikuchi, Y Yaoita
JOURNAL OF NATURAL PRODUCTS ( AMER CHEMICAL SOC ) 68 ( 5 ) 751 - 753 2005.05 [Refereed]
Research paper (journal)
Six new secoiridoid glycosides, gentiascabraside A (1), 6 beta-hydroxyswertiajaposide A (2), 1-O-beta-D-glucopyranosyl-4-epiamplexine (3), and scabrans G(3) (4), G(4) (5), and G(5) (6), have been isolated from the rhizomes and roots of Gentiana scabra together with a known compound, swertiajaposide A (7). The structures of the new Compounds were determined by spectroscopic (NMR, MS) and chemical means.
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Studies on the constituents of Swertia japonica MAKINO II.(1)) - On the structures of new glycosides
M Kikuchi, M Kikuchi
CHEMICAL & PHARMACEUTICAL BULLETIN ( PHARMACEUTICAL SOC JAPAN ) 53 ( 1 ) 48 - 51 2005.01 [Refereed]
Research paper (journal)
Two new secoiridoid glycosides, swertiajaposide A (1) and swertiajaposide B (2), a new unsaturated alcohol glycoside, 3-butenyl 6'-O-alpha-L-arabinopyranosyl-beta-D-glucopyranoside (3), and a new lignan glycoside, 7R,7'R,8S,8'S-(+)-neo-olivil-4-O-beta-D-glucopyranoside (4), were isolated together with six known compounds from the whole plants of Swertia japonica MAKINO. The structures of the new compounds were elucidated on the basis of chemical and spectroscopic evidence.
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Studies on the constituents of Swertia japonica MAKINO I. On the structures of new secoiridoid diglycosides
M Kikuchi, M Kikuchi
CHEMICAL & PHARMACEUTICAL BULLETIN ( PHARMACEUTICAL SOC JAPAN ) 52 ( 10 ) 1210 - 1214 2004.10 [Refereed]
Research paper (journal)
Eight new secoiridoid diglycosides, 6'-O-alpha-L-arabinopyranosylswertiamarin (1), 3'-O-P-D-glUeopyranosylswertiamarin (2), 4'-O-beta-D-glucopyranosylswertiamarin (3), 3'-O-beta-D-galactopyranosylswertiamarin (4), 6'-O-alpha-D-galactopyranosylswertiamarin (5), 6'-O-beta-D-mannopyranosylswertiamarin (6), 6'-O-beta-D-fructofuranosylswertiamarin (7) and 5"-O-beta-D-glucopyranosylamaroswerin (12), were isolated, together with five known compounds from the whole plants of Swertia japonica MAKINO. The structures of the new compounds were elucidated on the basis of chemical and spectroscopic evidence. Compounds 6 and 7 are the first naturally occuring iridoid diglycosides having an alpha-D-mannopyranosyl unit and beta-D-fructofuranosyl unit, respectively.
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Triterpenoids from Gentianae Scabrae Radix and Gentianae Radix
Rie Kakuda, Chie Ueno, Nagisa Kobayashi, Masafumi Kikuchi, Yasunori Yaoita, Masao Kikuchi
Natural Medicines ( 日本生薬学会 ) 58 ( 1 ) 22 - 26 2004.02 [Refereed]
Research paper (journal)
For new triterpenoids, uvaol 3-O-linoleate (1), uvaol 3-O-stearate (2), erythrodiol 3-O-linoleate (3) and erythrodiol 3-O-stearate (4), were isolated from Gentianae Scabrae Radix. Compounds 1 and 2, and an inseparable mixture of the new triterpenoids, α-amyrin 3-O-coriolate (5) and α-amyrin 3-O-dimorphecolate (6), were obtained from Gentianae Radix. The structures of the new compounds were elucidated on the basis of spectral data.
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Studies on the Constituents of Swertia japonica MAKINO III. On the Triterpenoids and Phenol Glucoside
菊地正史, 菊地正雄
東北薬科大学研究誌 ( 51 ) 49 - 53 2004
Research paper (journal)
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Studies on the constituents of Gentiana species. II. A new triterpenoid, and (S)-(+)- and (R)-(-)-gentiolactones from Gentiana lutea
R Kakuda, K Machida, Y Yaoita, M Kikuchi, M Kikuchi
CHEMICAL & PHARMACEUTICAL BULLETIN ( PHARMACEUTICAL SOC JAPAN ) 51 ( 7 ) 885 - 887 2003.07 [Refereed]
Research paper (journal)
A new triterpenoid, 12-ursene-3beta, 11alpha-diol 3-O-palmitate (1), has been isolated from the rhizomes and roots of Gentiana lutea, together with the artificial diene derivative, 9 (11), 12-ursadien-3beta-ol 3-O-palmitate (1a) and five known compounds (3-7). Their structures were established on the basis of spectral analysis. In addition, (+/-)-gentiolactone [(+/-)-2], isolated from this plant, was successfully separated into its enantiomers [(+)-2, (-)-2] for the first time, and the absolute configurations at C-9 of (+)-2, (-)-2 were assigned as S and R, respectively, from the optical rotations and the circular dichroism (CD) spectral data.
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New triterpenoids from Gentiana lutea
Y Toriumi, R Kakuda, M Kikuchi, Y Yaoita, M Kikuchi
CHEMICAL & PHARMACEUTICAL BULLETIN ( PHARMACEUTICAL SOC JAPAN ) 51 ( 1 ) 89 - 91 2003.01 [Refereed]
Research paper (journal)
Three new triterpenoids, 2,3-seco-3-oxours-12-en-2-oic acid, 2,3-seco-3-oxoolean-12-en-2-oic acid, and betulin 3-O-palmitate, have been isolated from the rhizomes and roots of Gentiana lutea, together with five known ones. The structures of the new compounds were determined by spectral and chemical methods.
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On the Chemical Constituents of Gentianae Radix, III
上野稚恵, 角田利枝, 菊地正史, 八百板康範, 町田浩一, 菊地正雄
東北薬科大学研究誌 ( 50 ) 81 - 84 2003 [Refereed]
Research paper (journal)