村田 和也(ムラタ カズヤ)

薬学部 創薬科学科准教授

Last Updated :2024/09/14

■教員コメント

コメント

天然にある植物や生薬から、医薬品、香粧品、さらには健康食品、サプリメントに応用可能なものを探しています。見出した素材から有効成分を精製して、その化学構造を決定するのが専門です。

報道関連出演・掲載一覧

<報道関連出演・掲載一覧> ●2016/10/14  NHK総合「ぐるっと関西 おひるまえ」  近畿大学薬用植物園を紹介

■研究者基本情報

学位

  • 博士(農学)(東北大学)

研究キーワード

  • 化学構造解析   生理活性物質   機器分析   

現在の研究分野(キーワード)

天然にある植物や生薬から、医薬品、香粧品、さらには健康食品、サプリメントに応用可能なものを探しています。見出した素材から有効成分を精製して、その化学構造を決定するのが専門です。

研究分野

  • ライフサイエンス / 環境、天然医薬資源学 / 薬用資源学

■経歴

経歴

  • 2016年04月 - 現在  近畿大学 薬学部Faculty of Pharmacy准教授
  • 2008年09月 - 2016年03月  近畿大学薬学部講師
  • 2014年04月 - 2015年03月  Scripps Institution of Oceanography訪問研究員
  • 2003年04月 - 2008年08月  協和発酵工業株式会社(現 協和キリン株式会社)
  • 2000年04月 - 2003年03月  日本学術振興会研究員(サントリー生物有機科学研究所)大阪市立大学大学院理学研究科

学歴

  • 1997年04月 - 2000年03月   東北大学大学院   農学研究科博士後期課程
  • 1995年04月 - 1997年03月   東北大学大学院   農学研究科博士前期課程
  • 1990年04月 - 1994年03月   東北大学   農学部   食糧化学科

委員歴

  • 2022年06月 - 現在   Natural Product Communications Advisory Editorial Board
  • 2019年09月 - 現在   生薬分析シンポジウム事務局
  • - 現在   日本生薬学会関西支部委員
  • 2022年01月 - 2022年12月   Natural Product Communications誌Guest Editor
  • 2021年01月 - 2022年12月   Separations誌Guest Editor
  • 2018年09月 - 2019年09月   Natural Product Communications誌Guest Editor

■研究活動情報

論文

  • Kazuya; Satomi Suzuki; Akane Miyamoto; Miki Horimoto; Suzuna Nanko; Daisuke Mori; Hiroshi Kanamaru; Yuichi Endo
    Separations 9 5 107 - 107 2022年04月 
    The demand for skin-whitening agents is high across the world, including Asian countries. An extensive screening using a tyrosinase inhibition assay was performed in order to discover novel plant materials. In our research program investigating a safe and effective agent, 50% ethanolic extracts prepared from discarded parts of Prunus persica were screened for in vitro tyrosinase inhibitory activity. Among the extracts tested, twig extract showed the most potent inhibitory activity: 38% inhibition at 500 µg/mL. The investigation of active compounds in twig extract found four flavanones that acted as moderate inhibitors, including (−)-prunin, persiconin, (+)-dihydrokaempferol, and (−)-naringenin. These compounds were only observed in the twig extract following preliminary quantification by HPLC, with the following concentrations: (−)-prunin, 1.8 mg/g sample; persiconin, 0.8 mg/g sample; (+)-dihydrokaempferol, 0.8 mg/g sample; (−)-naringenin, 1.7 mg/g sample. These results suggest that twig extracts can be more useful for skin-whitening compared with other parts of the plant. In addition, a new constituent of twig extract was identified, namely isoquercitrin, which suggests that twig extract can be a potent source of flavones and flavanones. Further studies on the identification of novel compounds from twig extract are now underway in our laboratory.
  • 出口 貴浩; 得永 裕美子; 銭谷 武司; 榎本 雅夫; 村田 和也; 遠藤 雄一
    薬理と治療 49 11 1877 - 1887 ライフサイエンス出版(株) 2021年11月 
    日ごろから鼻や目の不快感があり、症状緩和の目的で医薬品を常用していない成人男女80名を対象として、未熟ウンシュウミカン果実の乾燥粉末(CUP)を含有する食品(1日あたりhesperidin 215mg、narirutin 48mgを含有)を8週間連続摂取するランダム化二重盲検プラセボ対照並行群間比較試験を行い、被験食品の鼻や目の不快感に対する効果を検証した。摂取前、4週目、8週目のquality of life調査票、visual analogue scale調査票、医師所見、検査所見および鼻や目の不快感日誌を評価した。その結果、被験食品の8週間摂取によって鼻汁(鼻かみ回数)に起因する鼻の不快感が有意に軽減し、鼻汁中好酸球数の変化量は有意に大きかった。CUP含有食品は免疫応答を維持したまま鼻の不快感につながる炎症反応を抑制する可能性が示唆された。
  • Kimihisa Itoh; Tetsuya Matsukawa; Takahiro Deguchi; Momona Yamagami; Norimichi Tomohiro; Kazuya Murata; Shin’ichiro Kajiyama; Yuichi Endo; Hideaki Matsuda; Shigeru Shigeoka
    Journal of Plant Studies 10 2 1 - 7 2021年04月 [査読有り]
     
    This study examines the effect of quantity sold (sales volume) on profitability of market participating smallholder farmers in northern Ghana. Market participation has been shown to be important for increasing incomes and improving production efficiency for farm households but still remains low in SSA. While agribusiness and development experts generally advocate for more intensive market participation, it is not clear if selling more results in more profits for smallholder farmers in remote markets that are prone to exorbitant transaction costs. The data used in this study is from the APS survey conducted in 2013 and 2014 in Northern Ghana which had a sample size of 527. The study is based on the theory of profit maximization, in which separability is inferred from observed market participation. OLS regression is used for empirical estimation after rejecting the hypothesis of endogeneity in the model. Mean gross margin/ kg across four groups of farmers ranked by quantity sold is also statistically examined. The results confirm the existence of economies of scale and also show that different crops have different effects on profitability. The results also show that although unambiguously positive, the relationship between quantity sold and profitability may not be linear.
  • Kimihisa Itoh; Tetsuya Matsukawa; Takahiro Deguchi; Momona Yamagami; Norimichi Tomohiro; Kazuya Murata; Shin’ichiro Kajiyama; Yuichi Endo; Hideaki Matsuda; Shigeru Shigeoka
    Journal of Plant Studies 10 2 1 - 1 2021年04月 
    During the course of Citrus unshiu fruit cultivation, large amounts of plant material including pruned leaves, thinned-out flowers and unripe fruit are obtained; these materials are generally considered unusable and discarded as plant wastes. We have previously attempted to establish an effective use of such plant wastes as beneficial natural resources and found that a methanolic extract of pruned Citrus leaves (CUL-ext) exhibited inhibitory activity against porcine pancreatic lipase. In this study, we sought to identify further the effective uses of C. unshiu plant wastes by determining the lipase inhibitory activity of methanolic extracts of thinning out flowers (CUF-ext) and unripe fruit (CUUF-ext). We accordingly found that the inhibitory activity of CUF-ext was superior to that of CUUF-ext and comparable to that previously observed using CUL-ext. Fractionation of CUF-ext and CUUF-ext, followed by chromatographic analyses, revealed that the pancreatic lipase inhibitory activities of these extracts could be attributed, at least in part, to the flavonoids hesperidin, nobiletin, narirutin and rutin. On the basis of present findings, we propose that, in addition to pruned Citrus leaves, the thinned-out flowers and unripe fruit of C. unshiu are natural resources which are suitable for preparing constituents with lipase inhibitory activity.
  • Murata Kazuya
    NATURAL PRODUCT COMMUNICATIONS 14 12 2019年12月 [査読有り]
  • Deguchi Takahiro; Hata Yusuke; Tamai Atsushi; Yamamoto Moe; Fujita Takanori; Yoshioka Yuri; Iwaki Masahiro; Murata Kazuya
    NATURAL PRODUCT COMMUNICATIONS 14 12 2019年12月 [査読有り]
     
    The heartwood of Pterocarpus marsupium is called as "Asana" in Ayurveda. Its aquatic infusion was used for treating "prameha," which indicates a polyuria disease in modern medicine. In our research program to investigate a novel agent to improve hyperuricemia, we focused on the extract of Asana as a xanthine oxidase (XOD) inhibitor. Asana extract (50% ethanolic extract, PM-ext) showed 11%, 35%, and 38% inhibition at 50, 200, and 500 mu g/mL, respectively. Subsequently, PM-ext was partitioned with ethyl acetate (AcOEt), butanol, and water. Among them, AcOEt-soluble fraction indicated the most potent XOD inhibitory activity and was consecutively fractionated using various liquid chromatography to obtain liquiritigenin (1), isoliquiritigenin (2), and marsupsin (3) as active principles. Compound 1 showed 16% inhibition at 200 mu M while 2 showed 20%, 32%, and 46% inhibition at 50, 100, and 200 mu M, respectively. Compound 3 showed 15% inhibition at 500 mu M. This is the first report on the XOD inhibitory activity of 3. From these results, PM-ext is a promising candidate material for improvement of hyperuricemia. Here, Asana was recognized as an effective material against noncommunicable disease and is expected to be developed as a functional ingredient.
  • Kazuya Murata; Takeshi Yasumoto
    Toxins 11 10 2019年10月 [査読有り]
     
    Ciguatera is the term for poisoning resulting from eating fish from tropical or subtropical regions. The causative toxins collectively named ciguatoxins (CTXs) widely differ in structures depending on their geographic origins, which range from the Pacific Ocean and the Indian Ocean to the Caribbean Sea. Neurotoxic shellfish poisoning (NSP) is caused by the ingestion of bivalve shellfish contaminated with brevetoxins (BTXs). Structurally, both CTXs and BTXs consist of fused ether rings aligned in a ladder shape. Pharmacologically, they bind at the same site (site-5) of voltage-gated sodium channels. However, the great structural diversity and the rare availability of reference toxins hinder LC-MS and ELISA methods, which operate on structure-based recognition. In this study, we prepared a chemiluminescent ligand, acridinium BTXB2 (ABTX), and tested its suitability for use in competitive binding assays to detect CTXs and BTXs. The affinity of ABTX to the rat brain synaptosome estimated by Ki (1.66 pM) was approximately two-fold higher than that of PbTx-3 (BTX3). In addition, the equilibrium dissociation constant (KD) was 0.84 nM, the maximum number of binding was 6.76 pmol toxin/mg protein, and the detection limit was 1.4 amol. The assays performed on samples spiked with CTX3C or BTXB4 (N-palmitoylBTXB2) at 0.2-1.0 ng CTX/g fish flesh, and 200-800 ng BTXB4/g shellfish showed a linear relationship between the theoretical and observed toxin amounts.
  • Deguchi Takahiro; Miyamoto Akane; Miyamoto Kana; Kawata-Tominaga Takuya; Yoshioka Yuri; Iwaki Masahiro; Murata Kazuya
    NATURAL PRODUCT COMMUNICATIONS 14 10 2019年10月 [査読有り]
     
    Asana used in Ayurveda medicine originates from the heartwood of Fabaceae Pterocarpus marsupium. In our previous report, we demonstrated that a 50% ethanolic extract (PM-ext) of Asana was a promising candidate as a skin-whitening agent based on its anti-tyrosinase and antioxidative activities. Moreover, the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity of PM-ext was demonstrated and one of the active constituents was identified as oxyresveratrol. However, the potency of oxyresveratrol was low and the other active constituent has not yet been investigated. Activity-guided purification led us to isolate (+)-dihydrorobinetin (DHR). DHR had a potent DPPH radical-scavenging activity (half-maximal inhibitory concentration [IC50] = 1.3 mu M) and also showed suppressive activity of advanced glycation end products (AGEs) production (IC50 = 132 mu M), as well as superoxide dismutase (SOD)-like activity (half-maximal effective concentration=27 mu M). In a PM-ext, this is the first report to identify DHR and to demonstrate the suppressive activity of AGEs production and SOD-like activity of DHR. From these results, PM-ext containing DHR is a promising candidate as a multifunctional material with multiple anti-oxidant activities.
  • Deguchi Takahiro; Tamai Atsushi; Asahara Keito; Miyamoto Kana; Miyamoto Akane; Nomura Mio; Kawata-Tominaga Takuya; Yoshioka Yuri; Murata Kazuya
    NATURAL PRODUCT COMMUNICATIONS 14 10 2019年10月 [査読有り]
     
    Asana (the heartwood of Pterocarpus marsupium) has been utilized as an agent for diabetes mellitus in Ayurveda traditional medicine. In our research program to explore novel functions of asana extract, we focused on its skin-whitening effect because asana has been used as a remedy for chronic skin diseases. In addition, the authors have already reported an improvement in blood fluidity that brightens dull facial skin. Based on these effects, asana is a promising candidate agent that possesses both blood fluidity and anti-tyrosinase activities. We focused on the anti-tyrosinase activity and anti-oxidative activities of asana and the results are summarized in this report. We found that a 50% ethanolic extract obtained from asana (PM-ext) showed 23%, 53%, and 71% inhibition against mushroom tyrosinase at 12.5, 50, and 200 mu g/mL. Oxyresveratrol and isoliquiritigenin were identified as the active compounds by activity-guided purification. Oxyresveratrol has higher potency than isoliquiritigenin and the IC50 of oxyresveratrol was estimated to be 2.1 mu M. On the other hand, isoliquiritigenin showed 21%, 28%, and 38% inhibition at 10, 50, and 100 mu M, respectively. The inhibitory activity of oxyresveratrol was compared with 3 stilbenes, pterostilbene, resveratrol, and piceatannol. Although oxyresveratrol showed 72.8%, 81.0%, and 85.4% inhibition at 2, 5, and 10 mu M, respectively, pterostilbene, resveratrol, and piceatannol showed no effects at the same concentration; these compounds also demonstrated anti-melanogenesis activity on B16 murine melanoma cells. As a result, oxyresveratrol showed the most potent activity, without cytotoxicity, with 38%, 74%, and 84% inhibition at 2, 10, and 20 mu M, respectively, while pterostilbene showed 26%, 71%, and 79% inhibition at the same concentration with cytotoxicity at 10 and 20 mu M. Resveratrol showed 20%, 41%, and 57% inhibition without cytotoxicity at 2, 10, and 20 mu M, respectively. Auto-oxidation is one of the major factors in melanin biosynthesis and anti-oxidative activity is suitable for an anti-melanogenesis agent. We investigated the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity by PM-ext. As a result, PM-ext showed 16%, 33%, and 73% DPPH radical-scavenging activity at 10, 20, and 50 mu g/mL, respectively. Oxyresveratrol showed 19%, 31%, and 59% scavenging activity at 10, 20, and 50 mu M, respectively, similar to piceatannol. In addition, PM-ext showed 29%, 48%, and 80% suppressive activity on AGEs production at 3.1, 12.5, and 50 mu g/mL, respectively. Oxyresveratrol showed 32%, 47%, and 55% activity at 10, 50, and 100 mu M, respectively, and this was the most potent among the stilbenes tested. These results suggest that PM-ext could be a promising candidate as skin-whitening agent.
  • Kawamoto Hirokazu; Takeshita Fumiaki; Murata Kazuya
    NATURAL PRODUCT COMMUNICATIONS 14 10 2019年10月 [査読有り]
  • Murata Kazuya
    NATURAL PRODUCT COMMUNICATIONS 14 9 2019年09月 [査読有り]
  • Kimihisa Itoh; Tetsuya Matsukawa; Kazuya Murata; Ryota Nishitani; Momona Yamagami; Norimichi Tomohiro; Shin'ichiro Kajiyama; Masahiko Fumuro; Morio Iijima; Shigeru Shigeoka; Yuichi Endo; Hideaki Matsuda
    Natural Product Communications 14 9 1934578X1987343 - 1934578X1987343 2019年09月 [査読有り]
     
    In the cultivation of Citrus fruit, pruning in late winter after harvest is important to obtain excellent flower buds in the next spring and a rich harvest of superior fruit in the following winter; a large number of pruned leaves are usually discarded. The purpose of this study was to determine the utility value of pruned leaves of Citrus unshiu. A methanol extract of pruned C. unshiu leaves showed a porcine pancreatic lipase inhibitory activity. Fractionation of C. unshiu leaf extract (CUL-ext) followed by bibliographic and chromatographic analyses revealed that a part of the pancreatic lipase inhibitory activity of CUL-ext was attributable to nobiletin (1), rutin (2), and hesperidin (3). Thus, pruned C. unshiu leaves may be a reasonable natural resource for the preparation of ingredients with lipase inhibitory activity.
  • Kawamoto Hirokazu; Takeshita Fumiaki; Murata Kazuya
    NATURAL PRODUCT COMMUNICATIONS 14 8 2019年08月 [査読有り]
  • Katherine D Bauman; Jie Li; Kazuya Murata; Simone M Mantovani; Samira Dahesh; Victor Nizet; Hanna Luhavaya; Bradley S Moore
    Cell chemical biology 26 5 724 - 736 2019年05月 [査読有り]
     
    The disconnect between the genomic prediction of secondary metabolite biosynthetic potential and the observed laboratory production profile of microorganisms is well documented. While heterologous expression of biosynthetic gene clusters (BGCs) is often seen as a potential solution to bridge this gap, it is not immune to many challenges including impaired regulation, the inability to recruit essential building blocks, and transcriptional and/or translational silence of the biosynthetic genes. Here we report the discovery, cloning, refactoring, and heterologous expression of a cryptic hybrid phenazine-type BGC (spz) from the marine actinomycete Streptomyces sp. CNB-091. Overexpression of the engineered spz pathway resulted in increased production and chemical diversity of phenazine natural products belonging to the streptophenazine family, including bioactive members containing an unprecedented N-formylglycine attachment. An atypical discrete adenylation enzyme in the spz cluster is required to introduce the formylglycine moiety and represents a phylogenetically distinct class of adenylation proteins.
  • Honda-Yokota Mami; Murata Kazuya; Anraku Takuya; Iwaki Masahiro
    NATURAL PRODUCT COMMUNICATIONS 13 10 1259 - 1262 2018年10月 [査読有り]
  • Fumiko Sekiguchi; Tomoyo Fujita; Takahiro Deguchi; Sakura Yamaoka; Ken Tomochika; Maho Tsubota; Sumire Ono; Yamato Horaguchi; Maki Ichii; Mio Ichikawa; Yumiko Ueno; Nene Koike; Tadatoshi Tanino; Huy Du Nguyen; Takuya Okada; Hiroyuki Nishikawa; Shigeru Yoshida; Tsuyako Ohkubo; Naoki Toyooka; Kazuya Murata; Hideaki Matsuda; Atsufumi Kawabata
    Neuropharmacology 138 232 - 244 2018年08月 [査読有り]
     
    Since Cav3.2 T-type Ca2+ channels (T-channels) expressed in the primary afferents and CNS contribute to intractable pain, we explored T-channel-blocking components in distinct herbal extracts using a whole-cell patch-clamp technique in HEK293 cells stably expressing Cav3.2 or Cav3.1, and purified and identified sophoraflavanone G (SG) as an active compound from SOPHORAE RADIX (SR). Interestingly, hop-derived SG analogues, (2S)-6-prenylnaringenin (6-PNG) and (2S)-8-PNG, but not naringenin, also blocked T-channels; IC50 (μM) of SG, (2S)-6-PNG and (2S)-8-PNG was 0.68-0.75 for Cav3.2 and 0.99-1.41 for Cav3.1. (2S)-6-PNG and (2S)-8-PNG, but not SG, exhibited reversible inhibition. The racemic (2R/S)-6-PNG as well as (2S)-6-PNG potently blocked Cav3.2, but exhibited minor effect on high-voltage-activated Ca2+ channels and voltage-gated Na+ channels in differentiated NG108-15 cells. In mice, the mechanical allodynia following intraplantar (i.pl.) administration of an H2S donor was abolished by oral or i.p. SR extract and by i.pl. SG, (2S)-6-PNG or (2S)-8-PNG, but not naringenin. Intraperitoneal (2R/S)-6-PNG strongly suppressed visceral pain and spinal ERK phosphorylation following intracolonic administration of an H2S donor in mice. (2R/S)-6-PNG, administered i.pl. or i.p., suppressed the neuropathic allodynia induced by partial sciatic nerve ligation or oxaliplatin, an anti-cancer agent, in mice. (2R/S)-6-PNG had little or no effect on open-field behavior, motor performance or cardiovascular function in mice, and on the contractility of isolated rat aorta. (2R/S)-6-PNG, but not SG, was detectable in the brain after their i.p. administration in mice. Our data suggest that 6-PNG, a hop component, blocks T-channels, and alleviates neuropathic and visceral pain with little side effects.
  • Keiji Nishiwaki; Kanae Ohigashi; Takahiro Deguchi; Kazuya Murata; Shinya Nakamura; Hideaki Matsuda; Isao Nakanishi
    Chemical & pharmaceutical bulletin 66 7 741 - 747 2018年07月 [査読有り]
     
    Hydroxychavicol (HC), which is obtained from the leaves of Piper betle LINN. (Piperaceae), inhibits xanthine oxidase (XO) with an IC50 value of 16.7 µM, making it more potent than the clinically used allopurinol (IC50=30.7 µM). Herein, a structure-activity relationship analysis of the polar part analogs of HC was conducted and an inhibitor was discovered with a potency 13 times that of HC. Kinetic studies have revealed that HC and its active analog inhibit XO in an uncompetitive manner. The binding structure prediction of these inhibitor molecules to the XO complex with xanthine suggested that both compounds (HC and its analog) could simultaneously form hydrogen bonds with xanthine and XO.
  • Anraku Takuya; Deguchi Takahiro; Yokota-Honda Mami; Kawata Takuya; Fujita Takanori; Yoshioka Yuri; Matsumura Shinichi; Matsuda Hideaki; Murata Kazuya
    NATURAL PRODUCT COMMUNICATIONS 13 7 837 - 840 2018年07月 [査読有り]
     
    In our research program to investigate novel agents for anti -malodor activity from natural plant resources, we focused on Pterocarpus marsupium, which has been used as a "toothbrush tree" in Asian countries for many years. A 50% ethanol extract (PM-ext) was prepared and tested for anti-methioninase and anticollagenase activity along with suppressive activity against matrix metalloprotease (MMP)-1 from interleukin-lfl stimulated human gingival fibroblast. PM-ext showed moderate anti-methioninase and anti-collagenase activity as 35 and 33% at 500 mu g/mL, while PM-ext showed suppression of MMP-1 release at 10 mu g/mL. The active principles of MMP-1 release suppression were revealed as pterostilbene, (+)-liquiritigenin, isoliquiritigenin and alpha-epi-coatline A. Among them, pterostilbene showed suppression at 0.5 mu M, which was the most potent of the four compounds.
  • Murata Kazuya; Tanaka Kanae; Akiyama Reina; Noro Ibuki; Nishio Arisa; Nakagawa Sayaka; Matsumura Shinichi; Matsuda Hideaki
    NATURAL PRODUCT COMMUNICATIONS 13 7 803 - 806 2018年07月 [査読有り]
  • Kamei H; Noguchi K; Matsuda H; Murata K
    Biological & pharmaceutical bulletin 41 8 1307 - 1310 2018年 [査読有り]
     
    In our research program to find novel agents for alopecia from natural plant resources, we screened Euphorbiaceae plant extracts using an anti-5α-reductase assay. Among the samples tested, the extract of Phyllanthus urinaria showed the most potent activity with 24.3 and 64.6% inhibition at 50 and 200 µg/mL against the enzyme, respectively. The extract also suppressed the androgen activity of dihydrotestosterone in LNCaP cell line. These results show that the extract of P. urinaria may be a multi-potent agent for androgen-derived alopecia. We tested for activity on a hair regrowth model using mice. The extract of P. urinaria showed hair regrowth activity at 5 mg/mouse/d administration. Furthermore, the active principle for anti-5α-reductase activity was determined as stigmasterol glucoside from activity-guided fractionation and the IC50 was 27.2 µM. These results suggest that extract of P. urinaria may be a promising candidate anti-alopecia agent.
  • Kimihisa Itoh; Kazuya Murata; Nao Sakaguchi; Kohei Akai; Tomoka Yamaji; Kohsuke Shimizu; Kaoru Isaki; Tetsuya Matsukawa; Shin'ichiro Kajiyama; Masahiko Fumuro; Morio Iijima; Hideaki Matsuda
    Journal of Plant Studies 6 2 102 - 107 2017年07月 [査読有り]
     
    The purpose of this study was to examine an inhibitory effect of mango leaf extracts on advanced glycation end products (AGEs) formation and to identify these active ingredients, and also to investigate a relationship between leaves maturation and the inhibitory activity. A methanolic extract of old dark green mango leaf extract (OML-ext) exhibited an inhibitory activity of AGEs formation in nonenzymatic glycation of albumin. The inhibitory activity of OML-ext was attributable to 3-C-β-D-glucosyl-2,4,4’,6-tetrahydroxybenzophenone (1), mangiferin (2) and chlorophyll. Inhibitory effect of young dark reddish brown mango leaf extract (YDL-ext) on AGEs formation was similar to that of OML-ext. The inhibitory activity of YDL-ext was attributable to 1 and 2, in addition, a part of the the activity of YDL-ext due to anthocyanins whose content is highest in young dark reddish brown mango leaves. Considering the amounts of leaves obtained from pruning, old dark green leaves may be a reasonable natural resource for the preparation of ingredients with inhibitory activity of AGEs formation.
  • Kazuya Murata; Takahiro Deguchi; Masayuki Yasuda; Ryutaro Endo; Takanori Fujita; Shinichi Matsumura; Yuri Yoshioka; Hideaki Matsuda
    NATURAL PRODUCT COMMUNICATIONS 12 7 1089 - 1093 2017年07月 [査読有り]
     
    The decoction from a tumbler made of heartwood of the Indian kino tree (Asana, Pterocarpus marsupium, PM) was a remedy for diabetes mellitus in Ayurveda. Diabetes mellitus is a one of the lifestyle-related diseases that finally leads to the induction of fatal diseases such as arterial sclerosis and cerebral infarction. In this study, effects on blood fluidity was investigated using extract obtained from the heartwood of PM. Oral administration of the extract reduced passage time of the blood obtained from disseminated intravascular coagulation model rats. In addition, the extract inhibited the reduction of platelets, which suggests that this attributed to the inhibition of platelet aggregation. The extract also demonstrated suppressive effects on both collagen- and arachidonic acid induced platelet aggregation. Moreover, the extract showed inhibition against cyclooxygenase. The active principle was determined to be pterostilbene by collagen-induced platelet aggregation inhibitory activity-guided purification. Pterostilbene is a derivative of resveratrol, which is known to be in red wine and to possess beneficial effects for prevention of life-style related diseases. Pterostilbene exhibited 56 and 57% inhibition on both collagen- and arachidonic acid induced platelet aggregation at 20 mu M, respectively. These results demonstrate that the extract of PM heartwood may be a promising candidate as a multifunctional agent for treating lifestyle-related diseases.
  • Kazuya Murata; Yusuke Ishida; Arisa Nishio; Sayaka Nakagawa; Hirokazu Kawamoto; Hideaki Matsuda
    NATURAL PRODUCT COMMUNICATIONS 12 7 1053 - 1056 2017年07月 [査読有り]
     
    In our research program for investigating anti-dementia agents from natural plant resources, we screened extracts from 15 spice samples. Among the plant extracts tested, ethyl acetate extract prepared from rhizome of Zmgiber zerumbet showed potent activity. Activity-guided purification led to determination of afzelin and its acetylated compound as the active principles. Afzelin showed moderate inhibitory activity against acetylcholinesterase and may also be expected to possess anti-butyrylcholinesterase activity. This is the first report to reveal the anti-cholinesterase activities of ethyl acetate extract of Z. zerumbet and afzelin. Furthermore, Z zerumbet may be a potential therapeutic agent for the improvement of dementia, especially Alzheimer's disease.
  • Sekiguchi Fumiko; Noda Sayuri; Ono Sumire; Murata Kazuya; Matsuda Hideaki; Huy Du Nguyen; Toyooka Naoki; Harada Narinobu; Ito Yukari; Kawabata Atsufumi
    JOURNAL OF PHARMACOLOGICAL SCIENCES 133 3 S176  2017年03月 [査読有り]
  • Itoh, K; Murata, K; Futamura-Masuda, M; Deguchi, T; Ono, Y; Eshita, M; Fumuro, M; Iijima, M; Matsuda, H
    Journal of plant studies 6 1 23 - 30 2017年 [査読有り]
     
    The purpose of this study was to search edible ripe Citrus fruits which are applicable for functional food materials as juice, tea and/or jam with sweet taste and rich aroma. A fifty percent ethanolic extract (CMR-ext) obtained from the edible ripe fruit of Citrus madurensis exhibited an inhibitory activity of antigen-induced degranulation in anti-dinitrophenyl (DNP) IgE antibody sensitized rat basophilic leukemia (RBL) -2H3 cells. The inhibitory effect of the CMR-ext on degranulation in RBL-2H3 cells was attributable to 3’,5’-di-C-β-glucopyranosylphloretin (1) which is a constituent of C. madurensis. The effect of 1 on Akt and mitogen-activated protein kinases (MAPK) phosphorylation was examined in RBL-2H3 cells. Western blot analysis revealed that 1 (50 μM) inhibited the degranulation by suppression of Akt and p38 phosphorylation.
  • Hiroko Kawakami; Shin G Goto; Kazuya Murata; Hideaki Matsuda; Yasushi Shigeri; Tomohiro Imura; Hidetoshi Inagaki; Tetsuro Shinada
    The journal of venomous animals and toxins including tropical diseases 23 1 29 - 29 2017年 [査読有り]
     
    BACKGROUND: Mass spectrometry-guided venom peptide profiling is a powerful tool to explore novel substances from venomous animals in a highly sensitive manner. In this study, this peptide profiling approach is successfully applied to explore the venom peptides of a Japanese solitary carpenter bee, Xylocopa appendiculata (Hymenoptera: Apoidea: Apidae: Anthophila: Xylocopinae: Xylocopini). Although interesting biological effects of the crude venom of carpenter bees have been reported, the structure and biological function of the venom peptides have not been elucidated yet. METHODS: The venom peptide profiling of the crude venom of X. appendiculata was performed by matrix-assisted laser desorption/ionization-time of flight mass spectroscopy. The venom was purified by a reverse-phase HPLC. The purified peptides were subjected to the Edman degradation, MS/MS analysis, and/or molecular cloning methods for peptide sequencing. Biological and functional characterization was performed by circular dichroism analysis, liposome leakage assay, and antimicrobial, histamine releasing and hemolytic activity tests. RESULTS: Three novel peptides with m/z 16508, 1939.3, and 1900.3 were isolated from the venom of X. appendiculata. The peptide with m/z 16508 was characterized as a secretory phospholipase A2 (PLA2) homolog in which the characteristic cysteine residues as well as the active site residues found in bee PLA2s are highly conserved. Two novel peptides with m/z 1939.3 and m/z 1900.3 were named as Xac-1 and Xac-2, respectively. These peptides are found to be amphiphilic and displayed antimicrobial and hemolytic activities. The potency was almost the same as that of mastoparan isolated from the wasp venom. CONCLUSION: We found three novel biologically active peptides in the venom of X. appendiculata and analyzed their molecular functions, and compared their sequential homology to discuss their molecular diversity. Highly sensitive mass analysis plays an important role in this study.
  • Kazuya Murata; Daiki Iida; Yoshihiro Ueno; Keiichi Samukawa; Toshihiko Ishizaka; Takeshi Kotake; Hideaki Matsuda
    Journal of natural medicines 71 1 114 - 122 2017年01月 [査読有り]
     
    In our research program to identify cholinesterase and β-secretase inhibitors, we investigated Ginseng (root of Panax ginseng), a crude drug described as a multifunctional drug in the ancient Chinese herbal book Shennong Ben Cao Jing. Results from hexane and methanol extracts showed moderate inhibitory activities. This suggests that ginseng roots may be effective for the prevention of and therapy for dementia. We then focused on hexane extracts of raw ginseng root and dried ginseng root since the determination of hexane extract constituents has not been studied extensively. Activity-guided fractionation and purification led to the isolation of 4 polyacetylene compounds; homopanaxynol, homopanaxydol, (9Z)-heptadeca-1, 9-diene-4,6-diyn-3-one, and (8E)-octadeca-1,8-diene-4,6-diyn-3,10-diol. The chemical structures of these compounds, including stereochemistry, were determined. This is the first study to identify the structure of homopanaxynol and homopanaxydol. Moreover, the modes of action of some compounds were characterized as competitive inhibitors. This study showed, for the first time, that polyacetylene compounds possess acetylcholinesterase inhibitory activities.
  • Shinichi Matsumura; Kazuya Murata; Nobuhiro Zaima; Yuri Yoshioka; Masanori Morimoto; Hirona Kugo; Ayami Yamamoto; Tatsuya Moriyama; Hideaki Matsuda
    Natural product communications 11 12 1785 - 1788 2016年12月 [査読有り]
     
    The need for a preventive agent against dementia led us to screen natural plant resources. Among the herbs and spices tested, turmeric, from rhizomes of Curcuma longa, showed high potency against β-secretase. The active principles were determined as α-turmerone, β-turmerone and ar-turmerone, with IC(50) values of 39, 62 and 92 μM respectively. In this study, the efficiency of collecting the essential oil using steam distillation of the volatile substance was disclosed The active principles were explored, and four sesquiterpenoids and five monoterpenoids were revealed as active principles against β-secretase; On the other hand, α-turmerone, β-turmerone and ar-turmerone were also investigated in a pharmacokinetic absorption experiment. After oral administration, these compounds were detected in an intact form in the brain and serum. These results suggest that consumption of-turieric constituents may prevent dementia.
  • Shinichi Matsumura; Kazuya Murata; Nobuhiro Zaima; Yuri Yoshioka; Masanori Morimoto; Hideaki Matsuda; Masahiro Iwaki
    Natural product communications 11 11 1671 - 1674 2016年11月 [査読有り]
     
    The need for a preventive agent against dementia led us to screen natural plant resources. Among the herbs and spices tested, sesame seed prepared from Sesamum indicum seeds showed potent β-secretase inhibitory activity. The active principles were determined to be sesamin and sesamolin, typical lignans in S. indicum. The IC(50) values of sesamin and sesamolin were 257 and 140 μM, respectively. These compounds were investigated in a preliminary absorption experiment. After oral administration, these compounds were detected in an intact form in the brain and serum. These results suggest that consumption of sesame seeds may prevent dementia by sesamin and sesamolin, the constituents in sesame seeds.
  • A Pancreatic Lipase Inhibitory Activity by Mango (Mangifera indica) Leaf Methanolic Extract
    Kimihisa Itoh; Kazuya Murata; Yuta Nakagaki; Ayaka Shimizu; Yusuke Takata; Kohsuke Shimizu; Tetsuya Matsukawa; Shin'ichiro Kajiyama; Masahiko Fumuro; Morio Iijima; Hideaki Matsuda
    Journal of Plant Studies 5 2 72 - 78 2016年09月 [査読有り]
  • Megumi Futamura-Masuda; Mami Yokota-Honda; Takuya Anraku; Kanae Nakanishi; Kazuya Murata; Tetsuro Shinada; Hideaki Matsuda
    BIOLOGICAL & PHARMACEUTICAL BULLETIN 39 5 823 - 831 2016年05月 [査読有り]
     
    Asiasarum root (roots and rhizome of Asiasarum sieboldii or A. heterotropoides var. mandshuricum) has been frequently used in traditional Chinese medicinal formulas for the management of oral malodor syndrome caused by periodontal disease. However, there are no scientific reports concerning these effects and the mechanism of action: The objective of this study was to examine the inhibitory effects of Asiasarum root and its constituents on oral malodor syndrome and periodontal disease. A 50% ethanolic extract of Asiasarum root (AR-ext) showed L-methionine gamma-lyase (METase) inhibitory activity at a concentration of 200 mu g/mL, and inhibited interleukin (IL)-1 beta-stimulated matrix metalloproteinase (MMP)-1 secretion from human gingival fibroblasts (HGFs) at a concentration of 10 and 50 mu g/mL without cytotoxic effects. Activity-guided fractionation of the AR-ext suggested that METase inhibitory activity was attributable to a mixture of linoleic and oleic acid, because these unsaturated fatty acids showed weak METase inhibitory activities. Similar fractionation using MMP-1 secretion inhibitory activity led to the isolation of two unsaturated fatty acid amides, (2E,4E,8Z,10E)-N-(2-methylpropyl)dodeca-2,4,8,10-tetraenamide (1) and (2E,4E,8Z,10Z)-N-(2-methylpropyl)dodeca-2,4,8,10-tetraenamide (2), as active constituents with inhibitory activity on MMP-1 secretion from HGFs. To elucidate the inhibition mechanism on MMP-1 secretion, the effect of 2 on mitogen-activated protein kinase (MAPK) phosphorylation was examined. Western blotting analysis revealed that 2 (10 mu M) reduced the phosphorylation of p38 and c-Jun-N-terminal kinase. These results suggested that 2 suppresses intracellular MMP-1 expression and MMP-1 secretion from IL-1 beta-stimulated HGFs by down-regulation of MAPK phosphorylation.
  • Shinichi Matsumura; Kazuya Murata; Yuri Yoshioka; Hideaki Matsuda
    NATURAL PRODUCT COMMUNICATIONS 11 4 507 - 510 2016年04月 [査読有り]
     
    The growing number of Alzheimer's disease (AD) patients prompted us to seek effective natural resources for the prevention of AD. We focused on the inhibition of beta-secretase, which is known to catalyze the production of senile plaque. Sixteen spices used in Asian countries were selected for the screening. Among the extracts tested, hexane extracts obtained from turmeric, cardamom, long pepper, cinnamon, Sichuan pepper, betel, white turmeric and aromatic ginger showed potent inhibitory activities. Their active principles were identified as sesquiterpenoids, monoterpenoids, fatty acid derivatives and phenylpropanoids using GC-MS analyses. The chemical structures and IC50 values of the compounds are disclosed. The results suggest that long-term consumption of aromatic compounds from spices could be effective in the prevention of AD.
  • Matsumura S; Murata K; Yoshioka Y; Matsuda H
    Natural product communications 11 4 507 - 10 2016年04月 [査読有り]
     
    The growing number of Alzheimer's disease (AD) patients prompted us to seek effective natural resources for the prevention of AD. We focused on the inhibition of β-secretase, which is known to catalyze the production of senile plaque. Sixteen spices used in Asian countries were selected for the screening. Among the extracts tested, hexane extracts obtained from turmeric, cardamom, long pepper, cinnamon, Sichuan pepper, betel, white turmeric and aromatic ginger showed potent inhibitory activities. Their active principles were identified as sesquiterpenoids, monoterpenoids, fatty acid derivatives and phenylpropanoids using GC-MS analyses. The chemical structures and IC50 values of the compounds are disclosed. The results suggest that long-term consumption'of aromatic compounds from spices could be effective in the prevention of AD.
  • Ono Sumire; Yamaoka Sakura; Sekiguchi Fumiko; Ichii Maki; Fujita Tomoyo; Deguchi Takahiro; Tsubota Maho; Nishikawa Hiroyuki; Yoshida Shigeru; Murata Kazuya; Matsuda Hideaki; Toyooka Naoki; Ohkubo Tsuyako; Kawabata Atsufumi
    JOURNAL OF PHARMACOLOGICAL SCIENCES 130 3 S146 - S146 2016年03月 [査読有り]
  • Futamura-Masuda M; Yokota-Honda M; Anraku T; Nakanishi K; Murata K; Shinada T; Matsuda H
    Biological & pharmaceutical bulletin 39 5 823 - 31 2016年 [査読有り]
     
    Asiasarum root (roots and rhizome of Asiasarum sieboldii or A. heterotropoides var. mandshuricum) has been frequently used in traditional Chinese medicinal formulas for the management of oral malodor syndrome caused by periodontal disease. However, there are no scientific reports concerning these effects and the mechanism of action. The objective of this study was to examine the inhibitory effects of Asiasarum root and its constituents on oral malodor syndrome and periodontal disease. A 50% ethanolic extract of Asiasarum root (AR-ext) showed L-methionine γ-lyase (METase) inhibitory activity at a concentration of 200 µg/mL, and inhibited interleukin (IL)-1β-stimulated matrix metalloproteinase (MMP)-1 secretion from human gingival fibroblasts (HGFs) at a concentration of 10 and 50 µg/mL without cytotoxic effects. Activity-guided fractionation of the AR-ext suggested that METase inhibitory activity was attributable to a mixture of linoleic and oleic acid, because these unsaturated fatty acids showed weak METase inhibitory activities. Similar fractionation using MMP-1 secretion inhibitory activity led to the isolation of two unsaturated fatty acid amides, (2E,4E,8Z,10E)-N-(2-methylpropyl)dodeca-2,4,8,10-tetraenamide (1) and (2E,4E,8Z,10Z)-N-(2-methylpropyl)dodeca-2,4,8,10-tetraenamide (2), as active constituents with inhibitory activity on MMP-1 secretion from HGFs. To elucidate the inhibition mechanism on MMP-1 secretion, the effect of 2 on mitogen-activated protein kinase (MAPK) phosphorylation was examined. Western blotting analysis revealed that 2 (10 µM) reduced the phosphorylation of p38 and c-Jun-N-terminal kinase. These results suggested that 2 suppresses intracellular MMP-1 expression and MMP-1 secretion from IL-1β-stimulated HGFs by down-regulation of MAPK phosphorylation.
  • Murata K; Matsumura S; Yoshioka Y; Ueno Y; Matsuda H
    Journal of natural medicines 69 1 123 - 9 2015年01月 [査読有り]
     
    The therapeutic agents for dementia are limited due to the complex system underlying the mechanisms. Taking a preventive point of view, we focused on the inhibition of β-secretase and acetylcholinesterase (AChE). In addition, plant resources including herbs and spices have been widely consumed, and further, may be consumed for a long period over a lifetime. Considering this background, we screened β-secretase and AChE inhibitors from curry spices. Amongst them, curry leaf, black pepper, and turmeric extracts were effective to inhibit β-secretase. Furthermore, black pepper and turmeric extracts were also effective to inhibit AChE. Having these results in hand, we focused on the investigation of β-secretase inhibitors since the inhibitor of this enzyme has not previously been well investigated. As a result, α- and β-caryophyllene, β-caryophyllene oxide (from curry leaf), piperine (from black pepper), curcumin, demethoxycurcumin, and bisdemethoxycurcumin (from turmeric) were successfully identified as low molecular inhibitors. This is the first report to determine α- and β-caryophyllene, β-caryophyllene oxide, and piperine as β-secretase inhibitors. These compounds may pass through the blood brain barrier since their molecular weights are relatively low.
  • Kazuya Murata; Yumi Abe; Megumi Futamura-Masuda; Akemi Uwaya; Fumiyuki Isami; Shixin Deng; Hideaki Matsuda
    Journal of natural medicines 68 3 498 - 504 2014年07月 [査読有り]
     
    The aim of this study was to investigate the effect of Morinda citrifolia fruit on blood fluidity. M. citrifolia fruit extract (MCF-ext) was investigated for its influence on blood aggregation and fibrinolysis. MCF-ext inhibited polybrene-induced erythrocyte aggregation and thrombin activity. The fibrinolytic activity of MCF-ext, in the euglobulin lysis time test and fibrin plate assay, is reported here for the first time. One of the active compounds was an iridoid glycoside, asperulosidic acid. The results indicated that MCF-ext is a potentially useful health food which is capable of improving blood flow and preventing lifestyle-related diseases.
  • Kazuya Murata; Yumi Abe; Kaito Shinohara; Megumi Futamura-Masuda; Akemi Uwaya; Fumiyuki Isami; Hideaki Matsuda
    Pharmacognosy research 6 3 260 - 5 2014年07月 [査読有り]
     
    BACKGROUND: Morinda citrifolia (Rubiaceae), commonly known as noni is distributed throughout tropical and sub-tropical regions of the world. Anti-allergic effects of noni have not been reported despite the clinical usage as an anti-allergic agent. MATERIALS AND METHODS: To investigate the anti-allergic effects of the 50% ethanolic extract of M. citrifolia fruits and leaves (MCF-ext and MCL-ext), dinitrofluorobenzene (DNFB)-induced triphasic cutaneous reaction and picryl chloride-induced contact dermatitis (PC-CD) tests were performed. RESULTS: In DNFB-induced triphasic cutaneous reaction, oral administration of MCF-ext and MCL-ext exhibited dose-dependent inhibition of cutaneous reaction at 1 h (immediate phase response) after the DNFB challenge. MCF-ext also inhibited ear swelling at 24 h (late phase response) and 8 days (very late phase response) after the DNFB challenge. The effect of MCL-ext on the immediate phase response was attributed to the anti-degranulation from RBL-2H3 cells, while MCF-ext had no significant effect on degranulation. The active components of anti-degranulation activity in MCL-ext were determined to be ursolic acid, rutin and kaempferol-3-O-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside. In the PC-CD test, both MCF-ext and MCL-ext showed an anti-swelling effect but the potency of MCF-ext was stronger than MCL-ext. CONCLUSION: These data suggest that noni fruits and leaves can be a daily consumable material for the prevention of allergic symptoms.
  • Atsushi Kawase; Ayano Yamada; Yuko Gamou; Chika Tahara; Fumiaki Takeshita; Kazuya Murata; Hideaki Matsuda; Keiichi Samukawa; Masahiro Iwaki
    Journal of natural medicines 68 2 395 - 401 2014年04月 [査読有り]
     
    An extract from red ginseng (steamed and dried roots of Panax ginseng C.A. Meyer; RGE) has been shown to promote cholesterol metabolism in the liver. We have reported that RGE induced the hepatic expression of cytochrome P450 (CYP)7A1, involved in cholesterol metabolism. Other cholesterol metabolism-related proteins, such as CYP8B1, CYP27A1, multidrug resistance-associated protein (MRP)2, MRP3, and Na(+) taurocholate cotransporting polypeptide (NTCP), are involved in cholesterol metabolism. The purpose of this study was to clarify whether RGE affected mRNA expression of cholesterol metabolism-related CYPs and transporters in the liver of hypercholesterolemic rats and rat primary hepatocytes. In-vivo studies showed little differences in CYP8B1, CYP27A1, MRP2, MRP3, and NTCP mRNA expression levels between hypercholesterolemic rats with or without RGE treatments. However, the disruption of the membrane localization of MRP2 was suppressed by RGE treatments in hypercholesterolemic rats. In-vitro studies using rat primary hepatocytes showed upregulation of CYP8B1 and MRP2 mRNA by the addition of RGE (100 and 500 μg/mL). We further examined which ginsenosides contributed to the upregulation of CYP8B1 and MRP2 mRNA levels. Ginsenoside Re enhanced the mRNA level of CYP8B1, whereas ginsenosides Rb2 and Rg2 enhanced MRP2 mRNA levels. These results suggest that the in-vitro exposure of hepatocytes to RGE or some ginsenosides could lead to upregulation of CYP8B1 and MRP2, resulting in the alteration of biosynthesis and disposition of bile acids.
  • Kazuya Murata; Yumi Abe; Megumi Futamura-Masudaa; Akemi Uwaya; Fumiyuki Isami; Hideaki Matsuda
    Natural product communications 9 4 445 - 50 2014年04月 [査読有り]
     
    Morinda citrifolia, commonly known as noni, is a traditional natural medicine in French Polynesia and Hawaii. Functional foods derived from M. citrifolia fruit have been marketed to help prevent diseases and promote good health. The objective of this study was to assess the effects of M. citrifolia fruit on cell-mediated immunity. In the picryl chloride-induced contact dermatitis test, M. citrifolia fruit extract (Noni-ext) inhibited the suppression of cell-mediated immunity by immunosuppressive substances isolated from freeze-dried ascites of Ehrlich carcinoma-bearing mice (EC-sup). In addition, Noni-ext inhibited reduction of IL-2 production in EC-sup-treated mice and activated natural killer cells in normal mice. These results suggest that Noni-ext has multiple effects on the recovery of cell-mediated immunity. Furthermore, we investigated the active principles of Noni-ext and identified an iridoid glycoside, deacetylasperulosidic acid. Oral administration of deacetylasperulosidic acid inhibited the reduction of ear swelling, and also cancelled the suppression of IL-2 production along with the activation of natural killer cells in the same manner as that of Noni-ext.
  • Kazuya Murata; Keisuke Takahashi; Haruka Nakamura; Kimihisa Itoh; Hideaki Matsuda
    Natural product communications 9 2 185 - 8 2014年02月 [査読有り]
     
    In our research program for discovering novel skin-whitening materials, screening of extracts from flowers of some Prunus species was performed using an anti-tyrosinase assay. Among the tested plants, the flowers of P. persica showed the most potent inhibitory activity. In addition, P. persica also showed suppression of melanogenesis in B16 rat melanoma cells. The active principles of tyrosinase inhibition and suppression of melanogenesis were revealed to be an afzelin (3-O-alpha-L-rhamnosylkaempferol) and a flavanone, naringenin. The mechanism of the anti-melanogenesis effect of these two compounds was disclosed, for the first time, as the suppression of the expression of tyrosinase protein, which was controlled by the inhibition of phosphorylation of p38 MAPK. These findings show that these compounds could be candidates for the novel molecular target for a skin-whitening agent.
  • Kazuya Murata; Yumi Abe; Kaito Shinohara; Megumi Futamura-Masuda; Akemi Uwaya; Fumiyuki Isami; Hideaki Matsuda
    Pharmacognosy Research 6 3 260 - 265 2014年 [査読有り]
     
    Background: Morinda citrifolia (Rubiaceae), commonly known as noni is distributed throughout tropical and sub-tropical regions of the world. Anti-allergic effects of noni have not been reported despite the clinical usage as an anti-allergic agent. Materials and Methods: To investigate the anti-allergic effects of the 50% ethanolic extract of M. citrifolia fruits and leaves (MCF-ext and MCL-ext), dinitrofluorobenzene (DNFB)-induced triphasic cutaneous reaction and picryl chloride-induced contact dermatitis (PC-CD) tests were performed. Results: In DNFB-induced triphasic cutaneous reaction, oral administration of MCF-ext and MCL-ext exhibited dose-dependent inhibition of cutaneous reaction at 1 h (immediate phase response) after the DNFB challenge. MCF-ext also inhibited ear swelling at 24 h (late phase response) and 8 days (very late phase response) after the DNFB challenge. The effect of MCL-ext on the immediate phase response was attributed to the anti-degranulation from RBL-2H3 cells, while MCF-ext had no significant effect on degranulation. The active components of anti-degranulation activity in MCL-ext were determined to be ursolic acid, rutin and kaempferol-3-O-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside. In the PC-CD test, both MCF-ext and MCL-ext showed an anti-swelling effect but the potency of MCF-ext was stronger than MCL-ext. Conclusion: These data suggest that noni fruits and leaves can be a daily consumable material for the prevention of allergic symptoms.
  • Kentaro Maeda; Yu-ichi Kiniwa; Yasufumi Ohfune; Shinichi Ishiguro; Koichi Suzuki; Kazuya Murata; Hideaki Matsuda; Tetsuro Shinada
    RSC ADVANCES 4 92 50639 - 50643 2014年 [査読有り]
     
    A new method has been developed for the synthesis of 3-(1-aminoalkyl)- 4-hydroxycyclobut-3-ene-1,2-dione [alpha-amino squaric acid (alpha-Asq)]-containing peptides using solid phase peptide synthesis according to an Fmoc protecting group strategy. FmocHN-Gly-[alpha-Asq]-Oi-Pr was successfully used as a coupling unit in this method, which allowed for the construction of alpha-Asq-containing hexapeptide libraries including Sq-Gly and Sq-Phe units using the Wang-resin. Peptides containing the alpha-Asq moiety exhibited inhibitory activity towards a digestive enzyme.
  • Fumiko Sekiguchi; Tomoyo Fujita; Takahiro Deguchi; Maki Ichii; Hiroyuki Nishikawa; Shigeru Yoshida; Kazuya Murata; Hideaki Matsuda; Tsuyako Ohkubo; Atsufumi Kawabata
    JOURNAL OF PHARMACOLOGICAL SCIENCES 124 185P - 185P 2014年 [査読有り]
  • 苦参由来T型Ca2+チャネル阻害物質の検索 ヒトCav3.2発現HEK293細胞における電気生理学的検討とマウスにおける硫化水素誘起痛覚過敏に対する抑制効果の評価
    藤田 友代; 関口 富美子; 出口 貴浩; 吉田 繁; 村田 和也; 松田 秀秋; 大久保 つや子; 川畑 篤史
    日本薬理学雑誌 142 5 10P - 10P (公社)日本薬理学会 2013年11月
  • Kazuya Murata; Takahiro Deguchi; Takanori Fujita; Hideaki Matsuda
    Journal of natural medicines 67 4 719 - 24 2013年10月 [査読有り]
     
    Improvement in blood fluidity leads to the prevention of various lifestyle-related diseases. A raw material for improving blood fluidity has been long desired in the research area of functional and supplemental foods. We successfully showed an improvement in blood fluidity by the Zingiberaceae plant, Kaempferia parviflora. The rhizome of the plant reduced the blood passage time through a micro slit using a disseminated intravascular coagulation model. The mechanism was attributed to the activation of fibrinolysis, as demonstrated by elongation of the euglobulin lysis time and an in-vitro fibrinolysis assay. The active principles were determined to be methoxyflavones. The results show that the rhizome of K. parviflora is a promising candidate preventive agent for treating lifestyle-related diseases.
  • Kazuya Murata; Hirotaka Hayashi; Shinichi Matsumura; Hideaki Matsuda
    Pharmacognosy research 5 4 309 - 14 2013年10月 [査読有り]
     
    BACKGROUND: Kaempferia parviflora rhizome is used as a folk medicine in Thailand for the treatment of various symptoms. In the present study, the inhibitory activities of extract from K. parviflora rhizome against 5α-reductase (5αR) were subjected. Furthermore, the effects of the extract from K. parviflorar hizome in benign prostate hyperplasia (BPH) were studied using the model mice. MATERIALS AND METHODS: Preparations of extracts from the rhizomes of K. parviflora, Curcuma zedoaria and Zingiber officinale, and methoxyflavones isolated from K. parviflora was used for 5αR inhibition assay. The effects of K. parviflora extract on growth suppression for the prostates and seminal vesicles were performed based on the Hershberger's method. The K. parviflora extract was administered to castrated mice for 14 days. RESULTS: K. parviflora extract showed more potent inhibitory activity on 5αR than C. zedoaria and Z. officinale extracts. The active principles were identified as 3,5,7,3',4'-pentamethoxyflavone and 5,7,3',4'-tetramethoxyflavone by activity guided fractionation. Furthermore, K. parviflora extract suppressed the weights of prostates and seminal vesicles in BPH model rats by daily administration for 14 days. CONCLUSION: These results indicate that K. parviflora extract can be a promising agent for the treatment of BPH.
  • Kazuya Murata; Seiya Takano; Megumi Masuda; Munekazu Iinuma; Hideaki Matsuda
    Journal of natural medicines 67 3 643 - 6 2013年07月 [査読有り]
     
    The anti-degranulating activity of flavonoids present in Citrus fruits was comprehensively evaluated. Among these, hesperetin and naringenin, respectively aglycones of hesperidin and narirutin, showed significant activity. The targets of hesperetin and naringenin were found: hesperetin inhibited phosphorylation of Syk and Akt, while naringenin suppressed the expression of Lyn and inhibited the phosphorylation of Akt. These results suggest that hesperetin and naringenin inhibit degranulation by suppression of pathway signals and reduce the symptoms of allergy by inhibiting phosphorylation of Akt, which leads to the suppression of cytokines. In addition, hesperetin showed inhibitory activity against the degranulation induced by calcium ionophores, indicating that hesperetin exerts its inhibitory activity by stabilizing the membrane structure.
  • Kawase A; Yamada A; Gamou Y; Tahara C; Takeshita F; Murata K; Matsuda H; Samukawa K; Iwaki M
    Journal of natural medicines 67 3 545 - 53 2013年07月 [査読有り]
     
    An extract from red ginseng [steamed and dried roots of Panax ginseng C.A. Meyer (RGE)] has been shown to have various actions on physiological functions. The mechanisms by which RGE promotes cholesterol metabolism in the liver are unclear, but RGE decreases the plasma levels of cholesterol. We investigated whether RGE affected the mRNA expression of cholesterol metabolism-related proteins such as cytochrome P450 (CYP)7A1 and bile salt export pump (BSEP) in the liver in hypercholesterolemic rats and rat primary hepatocytes. In-vivo studies showed the upregulation of CYP7A1 mRNA in hypercholesterolemic rats treated with RGE. Treatment with RGE exhibited decreased ratios of low-density lipoprotein-cholesterol to high-density lipoprotein-cholesterol compared with hypercholesterolemia without RGE. In-vitro studies also showed the upregulation of CYP7A1 mRNA and protein levels by the addition of RGE to rat primary hepatocytes. The mRNA levels of BSEP exhibited few changes. The sustained levels of the liver X receptor (LXR) in vivo and the increased levels of LXR in vitro on RGE treatment could be involved in the upregulation of CYP7A1. To clarify the effects of 11 ginsenosides including RGE on the mRNA levels of CYP7A1 and BSEP, we performed in-vitro experiments using rat primary hepatocytes. The ginsenosides Ro, Rg3, Re, Rg1, and Rg2 exhibited increased mRNA levels of CYP7A1. These results suggest that several ginsenosides including RGE promoted cholesterol metabolism due to upregulation of CYP7A1.
  • Kazuya Murata; Kazuma Noguchi; Masato Kondo; Mariko Onishi; Naoko Watanabe; Katsumasa Okamura; Hideaki Matsuda
    Phytotherapy research : PTR 27 2 212 - 7 2013年02月 [査読有り]
     
    Topical administration of Rosmarinus officinalis leaf extract (RO-ext, 2 mg/day/mouse) improved hair regrowth in C57BL/6NCrSlc mice that experienced hair regrowth interruption induced by testosterone treatment. In addition, RO-ext promoted hair growth in C3H/He mice that had their dorsal areas shaved. To investigate the antiandrogenic activity mechanism of RO-ext, we focused on inhibition of testosterone 5α-reductase, which is well recognized as one of the most effective strategies for the treatment of androgenic alopecia. RO-ext showed inhibitory activity of 82.4% and 94.6% at 200 and 500 µg/mL, respectively. As an active constituent of 5α-reductase inhibition, 12-methoxycarnosic acid was identified with activity-guided fractionation. In addition, the extract of R. officinalis and 12-methoxycarnosic acid inhibited androgen-dependent proliferation of LNCaP cells as 64.5% and 66.7% at 5 µg/mL and 5 μM, respectively. These results suggest that they inhibit the binding of dihydrotestosterone to androgen receptors. Consequently, RO-ext is a promising crude drug for hair growth.
  • Kazuya Murata; Kikuyo Nakao; Kenzo Moriyama; Takanori Fujita; Hideaki Matsuda
    Journal of Traditional Medicines 30 3 140 - 144 2013年 [査読有り]
     
    A screening of extracts from seven Lamiaceae plants for their effects on xanthine oxidase, a key enzyme in the biosynthesis of uric acid, was performed. Among the plants tested, peppermint (dried leaves of Mentha piperita) showed the potent inhibitory activity. Inhibitory activity guided purification of the active constituent led us to obtain pratensein and apigenin. This is the first report on the inhibitory activity of pratensein on xanthine oxidase. © 2013, Medical and Pharmaceutical Society for WAKAN-YAKU. All rights reserved.
  • Kazuya Murata; Hirotaka Hayashi; Shinichi Matsumura; Hideaki Matsuda
    Pharmacognosy Research 5 4 309 - 314 2013年 [査読有り]
     
    Background: Kaempferia parviflora rhizome is used as a folk medicine in Thailand for the treatment of various symptoms. In the present study, the inhibitory activities of extract from K. parviflora rhizome against 5a-reductase (5aR) were subjected. Furthermore, the effects of the extract from K. parviflorar hizome in benign prostate hyperplasia (BPH) were studied using the model mice. Materials and Methods: Preparations of extracts from the rhizomes of K. parviflora, Curcuma zedoaria and Zingiber officinale, and methoxyflavones isolated from K. parviflora was used for 5aR inhibition assay. The effects of K. parviflora extract on growth suppression for the prostates and seminal vesicles were performed based on the Hershberger′s method. The K. parviflora extract was administered to castrated mice for 14 days. Results: K. parviflora extract showed more potent inhibitory activity on 5aR than C. zedoaria and Z. officinale extracts. The active principles were identified as 3,5,7,3′,4′-pentamethoxyflavone and 5,7,3′,4′- tetramethoxyflavone by activity guided fractionation. Furthermore, K. parviflora extract suppressed the weights of prostates and seminal vesicles in BPH model rats by daily administration for 14 days. Conclusion: These results indicate that K. parviflora extract can be a promising agent for the treatment of BPH.
  • Kazuya Murata; Kensuke Namba; Hideaki Matsuda; Yasuyuki Tsukioka; Kenzo Moriyama; Kikuyo Nakao; Keiichi Samukawa
    Journal of Traditional Medicines 29 4 169 - 178 2012年 [査読有り]
     
    The effect of 70% methanolic extract of Red Ginseng (Panax ginseng C. A. MEYER, RG-ext) was investigated on blood fluidity in rats. Evaluation of blood fluidity was carried out by measuring whole blood passage time using a micro channel array flow analyzer (MC-FAN), polybrene-induced erythrocyte aggregation (PEA), and the euglobulin lysis time (ELT). RG-ext inhibited the elongation of the passage time caused by cold stress (5°C), whereas White Ginseng extract (WG-ext) showed no effect. In addition, RG-ext showed inhibition of PEA. The aggregation inhibitory activity of RG-ext was stronger than that of WG-ext. These data indicated that effects of RG-ext on blood fluidity are superior to those of WG-ext. Successive oral administration of RG-ext (50 and 200 mg/kg, p.o.) to adjuvant-induced arthritis model rats inhibited the elongations of both the whole blood passage time and ELT caused by arthritis, although RG-ext showed no effect on right hind paw swelling. In order to identify active constituents, the effects of several Ginseng saponins [ginsenoside-Ro, -Rb1, -Rg1 and 20(S)-ginsenoside-Rg3[20(S)-Rg3]] in Red Ginseng on the elongation of whole blood passage time in low temperature-treated rat blood and PEA were examined. Among these, 20(S)-Rg3, a saponin characteristic of Red Ginseng, showed the most potent inhibitory activity on elongation of whole blood passage time and showed concentration-dependent inhibition of PEA. Therefore, part of the effect of Red Ginseng on improving blood fluidity may be attributable to 20(S)-Rg3. © 2012, Medical and Pharmaceutical Society for WAKAN-YAKU. All rights reserved.
  • Megumi Masuda; Kazuya Murata; Shunsuke Naruto; Akemi Uwaya; Fumiyuki Isami; Hideaki Matsuda
    Biological & pharmaceutical bulletin 35 2 210 - 5 2012年 [査読有り]
     
    The objective of this study was to examine whether a 50% ethanolic extract (MCS-ext) of the seeds of Morinda citrifolia (noni) and its constituents have matrix metalloproteinase-1 (MMP-1) inhibitory activity in UVA-irradiated normal human dermal fibroblasts (NHDFs). The MCS-ext (10 μg/mL) inhibited MMP-1 secretion from UVA-irradiated NHDFs, without cytotoxic effects, at 48 h after UV exposure. The ethyl acetate-soluble fraction of MCS-ext was the most potent inhibitor of MMP-1 secretion. Among the constituents of the fraction, a lignan, 3,3'-bisdemethylpinoresinol (1), inhibited the MMP-1 secretion at a concentration of 0.3 μM without cytotoxic effects. Furthermore, 1 (0.3 μM) reduced the level of intracellular MMP-1 expression. Other constituents, namely americanin A (2), quercetin (3) and ursolic acid (4), were inactive. To elucidate inhibition mechanisms of MMP-1 expression and secretion, the effect of 1 on mitogen-activated protein kinases (MAPKs) phosphorylation was examined. Western blot analysis revealed that 1 (0.3 μM) reduced the phosphorylations of p38 and c-Jun-N-terminal kinase (JNK). These results suggested that 1 suppresses intracellular MMP-1 expression, and consequent secretion from UVA-irradiated NHDFs, by down-regulation of MAPKs phosphorylation.
  • Murata K; Takeshita F; Samukawa K; Tani T; Matsuda H
    Phytotherapy research : PTR 26 1 48 - 53 2012年01月 [査読有り]
     
    This research program on the novel functions of Panax ginseng C. A. Meyer focused on the effects of ginseng rhizome on hair re-growth in androgenetic alopecia. Extracts of red ginseng rhizome showed greater dose-dependent inhibitory effects against testosterone 5α-reductase (5αR) when compared with extracts of the main root. Ginsenoside Ro, the predominant ginsenoside in the rhizome, and ginsenoside Rg(3), a unique ginsenoside in red ginseng, showed inhibitory activity against 5αR with IC(50) values of 259.4 and 86.1 µm, respectively. The rhizome of P. japonicus, which contains larger amounts of ginsenoside Ro, also inhibited 5αR. Topical administration of extracts of red ginseng rhizomes (2 mg/mouse) and ginsenoside Ro (0.2 mg/mouse) to shaved skin inhibited hair re-growth suppression after shaving in the testosterone-treated C57BL/6 mice. These results suggest that red ginseng rhizomes containing both oleanane- and dammarane-type ginsenosides are a promising raw material for cosmetic use. This is the first report that ginsenoside Ro enhances in vivo hair re-growth based on their inhibitory activity against 5αR in the androgenetic alopecia model.
  • Murata K; Noguchi K; Kondo M; Onishi M; Watanabe N; Okamura K; Matsuda H
    Journal of natural medicines 66 1 158 - 65 2012年01月 [査読有り]
     
    Crude drugs expected to have an estrogenic effect were screened for their inhibitory activity on testosterone 5α-reductase. Testosterone 5α-reductase is an enzyme catalyzing the conversion of testosterone to dihydrotestosterone, which possesses high affinity for the androgen receptor. Among the crude drugs tested, we focused on Puerariae Flos (the flowers of Pueraria thomsonii) due to its potent inhibitory activity and suitability for commercial use. The 50% ethanolic extract of Puerariae Flos (PF-ext) showed inhibitory activity of 60.2% at 500 μg/ml against testosterone 5α-reductase. Interestingly, it was more potent than that of Puerariae Radix (roots of Pueraria lobata). PF-ext also showed in vivo anti-androgenic activity using a hair growth assay in testosterone-sensitive male C57Black/6NCrSlc strain mice. We demonstrated saponins, including soyasaponin I and kaikasaponin III, to be active components in PF-ext. In addition, hair growth promotion activity in C3H/He mice at 2 mg/mouse/day of the topical administration of PF-ext was demonstrated. Thus, Puerariae Flos is a promising crude drug for treating androgenic alopecia.
  • Megumi Masuda; Kimihisa Itoh; Kazuya Murata; Shunsuke Naruto; Akemi Uwaya; Fumiyuki Isami; Hideaki Matsuda
    Biological & pharmaceutical bulletin 35 1 78 - 83 2012年 [査読有り]
     
    The objective of this study was to examine the effects of Morinda citrifolia (noni) extract and its constituents on α-melanocyte stimulating hormone (α-MSH)-stimulated melanogenesis in cultured murine B16 melanoma cells (B16 cells). A 50% ethanolic extract of noni seeds (MCS-ext) showed significant inhibition of melanogenesis with no effect on cell proliferation. MCS-ext was more active than noni leaf and fruit flesh extracts. Activity guided fractionation of MCS-ext led to the isolation of two lignans, 3,3'-bisdemethylpinoresinol (1) and americanin A (2), as active constituents. To elucidate the mechanism of melanogenesis inhibition by the lignans, α-MSH-stimulated B16 cells were treated with 1 (5 μM) and 2 (200 μM). Time-dependent increases of intracellular melanin content and tyrosinase activity, during 24 to 72 h, were inhibited significantly by treatment with the lignans. The activity of 1 was greater than that of 2. Western blot analysis suggested that the lignans inhibited melanogenesis by down regulation of the levels of phosphorylation of p38 mitogen-activated protein kinase, resulting in suppression of tyrosinase expression.
  • Megumi Masuda; Kazuya Murata; Kimihisa Itoh; Shunsuke Naruto; Akemi Uwaya; Fumiyuki Isami; Hideaki Matsuda
    Journal of Traditional Medicines 28 2 47 - 54 2011年 [査読有り]
     
    Functional foods derived from noni (Morinda citrifolia) have been marketed to help prevent lifestyle-related diseases. Many lifestyle-related diseases, such as hypertension and hyperlipemia, are associated with poor blood fluidity. The objective of this study was to examine the effect of 50% ethanolic extracts from noni, and their constituents, on blood fluidity, in a lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) rat model with a micro channel array flow analyzer (MC-FAN). Oral administrations of the noni leaf extract (MCL-ext) and the noni seed extract (MCS-ext) to DIC rats resulted in a reduction of the passage time of whole blood, as compared to the vehicle control. The MCL-ext and its constituents, namely ursolic acid (1), rutin (2), and kaempferol-3-O-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside (3) inhibited collagen-induced platelet aggregation. MCL-ext, as well as MCS-ext and its constituents, namely 1, americanin A (4), and 3, 3′-bisdemethylpinoresinol (5), inhibited polybrene-induced erythrocyte aggregation. Inhibition of erythrocyte aggregation by MCL-ext and MCS-ext was mainly attributable to 1. The euglobulin lysis time (ELT) assay indicated that oral administration of MCL-ext or MCS-ext induces fibrinolysis activity in rats. This is the first report of the effects of noni extracts on blood fluidity. MCL-ext exhibited more in vitro anti-platelet activity, and improvement of blood fluidity and fibrinolysis activity in vivo than MCS-ext. © 2011, Medical and Pharmaceutical Society for WAKAN-YAKU. All rights reserved.
  • Kikuyo Nakao; Kazuya Murata; Kimihisa Itoh; Yuko Hanamoto; Megumi Masuda; Kenzo Moriyama; Takahiro Shintani; Hideaki Matsuda
    Journal of Traditional Medicines 28 1 10 - 15 2011年 [査読有り]
     
    In our search for novel materials possessing anti-hyperuricemic effects, we examined immature Citrus unshiu fruit. Extracts of immature C. unshiu fruit showed moderate anti-hyperuricemic effects in a hyperuricemic model the extract reduced increased serum urate level by 36% at 500 mg/kg, p.o. The extract did not show significant xanthine oxidase inhibitory activity, but the metabolite of the main flavanone glycoside in the fruit, hesperetin, showed potent anti-hyperuricemic effects hesperetin reduced increased serum urate level by 44% at 200 mg/kg, p.o. Furthermore, hesperetin showed dose-dependent xanthine oxidase inhibitory activity of 52% at 200 μM. Thus, the anti-hyperuricemic effects of immature C. unshiu may be attributed to hesperetin, a metabolite of hesperidin via xanthine oxidase inhibition. © 2011, Medical and Pharmaceutical Society for WAKAN-YAKU. All rights reserved.
  • 中尾 紀久世; 森山 健三; 村田 和也; 松田 秀秋; 谿 忠人
    薬史学雑誌 46 2 91 - 101 日本薬史学会 2011年 
    Rates of gouty arthritis with hyperuricemia have increased recently as it has become a lifestyle-related disease. We reviewed historical treatments for pain due to gouty arthritis in traditional Chinese medical books, with special interest in pathological causes, including dietary and drinking habits, as well as the frequency of crude drugs used in historical prescriptions. From the present historical survey, we showed that six traditional terms may be equivalent to modern gouty arthritis and that the "Manbyokaishun," a formulary edited in the 16th century in China, included medical information for gouty arthritis. Furthermore, the 46 prescriptions, including Sokeikakketsuto, mentioned in the "Manbyokaishun," were selected as likely treatments for gouty arthritis. The most common crude drugs in the 46 prescriptions were aconite root, angelica root, cinnamon bark, peony root and saposhnikovia root. The inhibitory activity of these crude drugs extracts against xanthine oxidase was investigated. Angelica root and saposhnikovia root showed more potent inhibitory activity (20% at 250 microg/mL) than aconite root (16%), notopterygium rhizome (15%) and cinnamon bark (12%).
  • Kikuyo Nakao; Kazuya Murata; Takahiro Deguchi; Kimihisa Itoh; Takanori Fujita; Masayuki Higashino; Yuri Yoshioka; Shin-Ichi Matsumura; Rika Tanaka; Tetsuro Shinada; Yasufumi Ohfune; Hideaki Matsuda
    Biological & pharmaceutical bulletin 34 7 1143 - 6 2011年 [査読有り]
     
    Kaempferia parviflora (KP), a Zingiberaceae plant, is used as a folk medicine in Thailand for the treatment of various symptoms, including general pains, colic gastrointestinal disorders, and male impotence. In this study, the inhibitory activities of KP against xanthine oxidase (XOD) were investigated. The extract of KP rhizomes showed more potent inhibitory activity (38% at 500 µg/ml) than those of the other Zingiberaceae plants tested. Ten methoxyflavones were isolated from the KP extract as the major chemical components and their chemical structures were elucidated by X-ray crystallography. The structurally confirmed methoxyflavones were subjected to the XOD inhibitory test. Among them, 3,5,7,4',5'-pentamethoxyflavone and 3',4',5,7-tetramethoxyflavone showed inhibitory activities (IC(50) of 0.9 and >4 mM, respectively) and their modes of inhibition are clarified as competitive/non-competitive mixed type. To the best of our knowledge, this is the first report to present the inhibitory activities of KP, 3,5,7,4',5'-pentamethoxyflavone and 3',4',5,7-tetramethoxyflavone against XOD.
  • 増田 めぐみ; 村田 和也; 松田 秀秋; 本田 麻美; 本田 俊一; 谿 忠人
    薬史学雑誌 46 1 5 - 12 日本薬史学会 2011年 
    Bad breath is a topic of general interest. In this study, the treatment for bad breath in traditional Chinese medicine was reviewed with a special focus on pathologic diagnosis and crude drug prescriptions. It was shown that bad breath developed based on both systemic and local diseases. Some systemic conditions, including nasal, paranasal, pulmonary and digestive diseases, are considered to cause bad breath. The morbid state of a patient with bad breath has been recognized as being based on "heat syndrome" and "Qi-stagnation syndrome." Bad breath based on "heat syndrome" is manifested as thirst and ulceration of the oral cavity, and has been treated with crude drugs such as Coptis rhizome, Scutellaria root and gypsum. One case study reported that bad breath resulting from a dry mouth was treated with byakkokaninjinto, a Kampo formulation containing gypsum. "Qi" is considered to be the vital energy of all life forms including for the functioning of organs and mental and emotional activity. "Qi-stagnation syndrom," referring to the dysfunction of organs, is manifested as psychosomatic symptoms such as irritability, a flushed face and restlessness. Bad breath based on "Qi-stagnation syndrome" has been treated with crude drugs such as Cnidium rhizome, clove and cinnamon bark. Modern dental and medical treatment both accept the participation of psychogenic agents in the development of bad breath. Bad breath also develops based on periodontal and oral diseases. This type of bad breath has been treated with mouth-wash (collutorium) containing Asiasarum root, Angelica dahurica root and Cnidium rhizome. This historical evidence regarding crude drug prescriptions contributes to the development of mouth care products for preventing and treating bad breath.
  • 松田 秀秋; 村田 和也; 竹下 文章; 高田 敬士; 寒川 慶一; 谿 忠人
    薬史学雑誌 45 1 40 - 48 日本薬史学会 2010年06月
  • Kazunori Inaba; Kazuya Murata; Shunsuke Naruto; Hideaki Matsuda
    Journal of natural medicines 64 2 219 - 22 2010年04月 [査読有り]
     
    Successive oral administration (50 mg/kg) of a 50% ethanolic extract (HP-ext) of devil's claw, the secondary root of Harpagophytum procumbens, showed a significant anti-inflammatory effect in the rat adjuvant-induced chronic arthritis model. HP-ext dose-dependently suppressed the lipopolysaccharide (LPS)-induced production of inflammatory cytokines [interleukin-1beta (IL-1beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)] in mouse macrophage cells (RAW 264.7). Harpagoside, a major iridoid glycoside present in devil's claw, was found to be one of the active agents in HP-ext and inhibited the production of IL-1beta, IL-6, and TNF-alpha by RAW 264.7.
  • Kimihisa Itoh; Megumi Masuda; Shunsuke Naruto; Kazuya Murata; Hideaki Matsuda
    Biological & pharmaceutical bulletin 33 4 659 - 64 2010年 [査読有り]
     
    The enhancement of blood fluidity may lead to improvements in skin problems resulting from unsmooth circulation or blood stagnation. Since a 50% ethanolic extract (CH-ext) obtained from unripe Citrus hassaku fruits may be a useful ingredient in skin-whitening cosmetics, the present study was designed to examine the effect of CH-ext on blood fluidity. CH-ext concentration-dependently inhibited in vitro collagen-induced rabbit platelet aggregation and in vitro polybrene-induced rat erythrocyte aggregation. The CH-ext showed in vitro fibrinolysis activity in fibrin plate assay. Activity-guided fractionation of the CH-ext using antiplatelet activity, inhibitory activity of erythrocyte aggregation, and fibrinolysis activity revealed that these activities of CH-ext were attributable to naringenin-7-glycoside (prunin). Successive oral administration of CH-ext to rats inhibited the lipopolysaccharide (LPS)-induced decrease of blood platelets and fibrinogen, and LPS-induced increase of fibrin degradation products (FDP) in LPS-induced disseminated intravascular coagulation (DIC) model rats. Effects of CH-ext on blood fluidity were analyzed by a micro channel array flow analyzer (MC-FAN). Preventive oral administration of CH-ext to rats showed dose-dependent reduction of the passage time of whole blood flow of the DIC model rats in comparison with that of the vehicle control rats. These results imply that CH-ext may have effects which improve effects on blood fluidity.
  • Hideaki Matsuda; Kazuya Murata; Fumiaki Takeshita; Keiishi Takada; Keiichi Samukawa; Tadato Tani
    Yakushigaku zasshi 45 1 40 - 8 2010年 [査読有り]
     
    Ginseng is prepared from Panax ginseng C.A. Meyer root. The root of wild P. ginseng has long tortuous rhizome called traditionally "Rozu" in Japanese. In the present historical studies on ginseng, it has been proven that ginseng has sometimes been used after removing "Rozu" due to its emetic effects. However, ginseng with "Rozu" is prescribed in almost all the present Kampo formulations used clinically in China and Japan. Possible reasons for this are (1) some formulations including "Rozu" have been used for vomiting resulting from the retention of fluid in the intestine and stomach, "tan-in" in Japanese, and (2) the present cultivated ginseng has shorter "Rozu" than wild ginseng. Furthermore, it is proved that "Rozu", rich in ginsenoside Ro with oleanane-type aglycone, is distinguished from ginseng roots rich in ginsenosides Rb1 and Rg1 with dammarane-type aglycone. This is the first report to declare the distribution of ginsenosides in underground parts of wild P. ginseng. Ginsenoside Ro is a minor ginsenoside in ginseng whereas it is the major ginsenoside in P. japonicus rhizome (chikusetsu-ninjin in Japanese). Ginsenoside Ro is characterized by antiinflammatory effects which differ from ginsenosides Rb1 and Rg1 responsible for adaptogenic effects of ginseng. These results suggest that "Rozu" containing both oleanane- and dammarane-type ginsenosides might be a promising raw material distinct from ginseng root or P. japonicus rhizome.
  • Atsushi Kawase; Fumiaki Takeshita; Ayano Yamada; Kazuya Murata; Hideaki Matsuda; Keiichi Samukawa; Masahiro Iwaki
    JOURNAL OF HEALTH SCIENCE 55 5 809 - 813 2009年10月 [査読有り]
     
    A 70% methanol extract from red ginseng (steamed and dried roots of Panax ginseng C. A. Meyer, a kind of Ginseng Radix) has been shown to have various actions on physiological functions. We investigated whether the ginseng extract (Ext.) affected the mRNA expression of cytochrome P450 (CYP) CYP1A1, 2B1, 2C11, 2D1, 3A1, and 3A2 in rat primary hepatocytes. After treatment with ginseng extract, the levels of CYP3A1 and 1A1 mRNA were significantly increased compared with those of the control. The increased protein levels of CYP3A1 were also observed after treatment with Ext. The mRNA levels of other examined CYPs exhibited little change. The mRNA levels of the pregnane X receptor, but not the constitutive androstane receptor, both transcription factors for CYPs, also significantly increased after treatment with ginseng extract. These results raise the possibility that ginseng Ext. promotes xenobiotic metabolism via an increase in CYP3A1. and 1A1 expression.
  • Xing-hua Gao; Xian-xiang Xu; Rong Pan; Ying Li; Yu-bin Luo; Yu-feng Xia; Kazuya Murata; Hideaki Matsuda; Yue Dai
    Journal of natural medicines 63 4 421 - 9 2009年10月 [査読有り]
     
    Sepsis remains the leading cause of death in intensive care units. Uncontrolled systemic inflammation and an impaired protein C pathway are two important contributors to sepsis pathophysiology. Based on the beneficial effects of the saponin fraction from Astragalus membranaceus roots (SAM) against inflammation, liver dysfunction, and endothelium injury, we investigated the potential protective roles and underlying mechanisms of SAM on polymicrobial sepsis induced by cecal ligation and puncture (CLP) in mice. SAM, orally administered 1 h before and after CLP, significantly elevated the survival rate of mice. At 96 h after CLP operation, all mice in the model group died, whereas 33.3% of mice in the SAM (400 mg/kg)-treated group survived. SAM attenuated both inflammatory factors and their abilities to induce tissue dysfunction, which was mainly evidenced by decreased infiltration of polymorphonuclear leukocytes, tissue edema, and lung wet-to-dry weight ratio, lowered levels of myeloperoxidase (MPO), nitric oxide (NO), lactate dehydrogenase (LDH), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) in serum, as well as downregulated expressions of iNOS and IL-1beta mRNA in livers. Furthermore, we addressed the effects of SAM on the protein C (PC) pathway, closely linked with sepsis. In CLP-induced septic mice, SAM elevated the impaired expression of PC mRNA in livers. In vitro, SAM reversed the decreased expressions of thrombomodulin (TM) and endothelial PC receptor (EPCR) mRNA induced by lipopolysaccharide (LPS) in endothelial cells. These findings suggest that SAM is able to restore the impaired protein C pathway. Taken together, the current study demonstrates that SAM has protective effects on polymicrobial sepsis in mice. The mechanisms of action involve anti-inflammation and upregulation of the PC pathway.
  • Kimihisa Itoh; Megumi Masuda; Shunsuke Naruto; Kazuya Murata; Hideaki Matsuda
    Journal of natural medicines 63 4 443 - 50 2009年10月 [査読有り]
     
    Oral administration of a 50% ethanolic extract (CH-ext) obtained from unripe Citrus hassaku fruits collected in July exhibited a potent dose-dependent inhibition of IgE (immunoglobulin E)-mediated triphasic cutaneous reaction at 1 h [immediate phase response (IPR)], 24 h [late phase response (LPR)] and 8 days [very late phase response (vLPR)] after dinitrofluorobenzene challenge in mice. Naringin, a major flavanone glycoside component of CH-ext, showed a potent dose-dependent inhibition against IPR, LPR and vLPR. Neohesperidin, another major glycoside component of CH-ext, showed an inhibition against vLPR. The effect of CH-ext on type IV allergic reaction was examined by determining inhibitory activity against ear swelling in mice by using the picryl chloride-induced contact dermatitis (PC-CD) model. Oral administration (p.o.) of CH-ext and subcutaneous administration (s.c.) of prednisolone inhibited ear swelling during the induction phase of PC-CD. The inhibitory activities of combinations of CH-ext (p.o.) and prednisolone (s.c.) against PC-CD in mice were more potent than those of CH-ext alone and prednisolone alone, without enhancing the adverse effects. Other combinations of prednisolone (s.c.) and flavanone glycoside (p.o.) components of CH-ext, i.e. naringin and neohesperidin, exerted similar synergistic effects.
  • Kazuya Murata; Tetsuro Shinada; Yasufumi Ohfune; Miki Hisada; Akikazu Yasuda; Hideo Naoki; Terumi Nakajima
    Amino acids 37 2 389 - 94 2009年07月 [査読有り]
     
    Two novel biologically active peptides, Eumenine mastoparan-OD and Orancis-Protonectin, were isolated from a solitary wasp, Orancistrocerus drewseni drewseni (Eumeninae, Vespidae). MALDI-TOF MS analysis of a small amount of the crude venom gave two intensive molecular-related ion peaks at m/z 1269.9 and 1552.9 that were expected to be novel based on a peptide database search. Purification of the crude venom by HPLC gave two peptide fractions, P-1 and P-2. The amino acid sequence of P-1 (GRILSFIKAGLAEHL-NH2) and P-2 (ILGIITSLLKSL-NH2) were determined by ESI-MS/MS, automated Edman degradation, and amino acid analysis. According to the high sequence homology with those of mastoparan and protonectin, P-1 and P-2 were labeled Eumenine mastoparan-OD and Orancis-Protonectin, respectively. Orancis-Protonectin is the first example of a protonectin analog isolated from the venom of a solitary wasp. The hemolytic activities of these new peptides were more potent than that of mastoparan.
  • Megumi Masuda; Kazuya Murata; Akiko Fukuhama; Shunsuke Naruto; Tadashi Fujita; Akemi Uwaya; Fumiyuki Isami; Hideaki Matsuda
    Journal of natural medicines 63 3 267 - 73 2009年07月 [査読有り]
     
    A 50% ethanolic extract (MCS-ext) from seeds of Morinda citrifolia ("noni" seeds) showed more potent in vitro inhibition of elastase and tyrosinase, and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity than extracts of M. citrifolia leaves or flesh. Activity-guided fractionation of MCS-ext using in vitro assays led to the isolation of ursolic acid as an active constituent of elastase inhibitory activity. 3,3'-Bisdemethylpinoresinol, americanin A, and quercetin were isolated as active constituents having both tyrosinase inhibitory and radical scavenging activities. Americanin A and quercetin also showed superoxide dismutase (SOD)-like activity. These active compounds were isolated from noni seeds for the first time.
  • Kazuya Murata; Kikuyo Nakao; Noriko Hirata; Kensuke Namba; Takao Nomi; Yoshihisa Kitamura; Kenzo Moriyama; Takahiro Shintani; Munekazu Iinuma; Hideaki Matsuda
    Journal of natural medicines 63 3 355 - 9 2009年07月 [査読有り]
     
    The screening of Piperaceous plants for xanthine oxidase inhibitory activity revealed that the extract of the leaves of Piper betle possesses potent activity. Activity-guided purification led us to obtain hydroxychavicol as an active principle. Hydroxychavicol is a more potent xanthine oxidase inhibitor than allopurinol, which is clinically used for the treatment of hyperuricemia.
  • Kimihisa Itoh; Noriko Hirata; Megumi Masuda; Shunsuke Naruto; Kazuya Murata; Keitaro Wakabayashi; Hideaki Matsuda
    Biological & pharmaceutical bulletin 32 3 410 - 5 2009年03月 [査読有り]
     
    The 50% ethanolic extract (CH-ext) obtained from the unripe fruit of Citrus hassaku exhibited significant tyrosinase inhibitory activity. The CH-ext showed antioxidant activity, such as superoxide dismutase (SOD)-like activity and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity. Activity-guided fractionation of the CH-ext indicated that flavanone glycoside-rich fractions showed potent tyrosinase inhibitory activity. Further examination revealed that the tyrosinase inhibitory activity and antioxidant activity of the CH-ext were attributable to naringin and neohesperidin, respectively. The CH-ext showed inhibition of melanogenesis without any effects on cell proliferation in cultured murine B16 melanoma cells after glucosamine exposure. The topical application of the CH-ext to the dorsal skin of brownish guinea pigs showed in vivo preventive effects against UVB-induced pigmentation.
  • Inhibitory Effect of Constituents of Morinda citrifolia Seed on Elastase and Tyrosinase
    増田 めぐみ; 村田 和也; 福浜 明子; 成戸 俊介; 藤田 忠; 松田 秀秋; 上家 明美; 勇
    J. Nat. Med. 63 355 - 359 2009年
  • 福田 浩三; 村田 和也; 松田 秀秋; 谷口 雅彦; 芝野; 真喜雄; 馬場 きみ江; Shiratori M; 谿 忠人
    J. Trad. Med. 26 169 - 178 2009年
  • 福田 浩三; 村田 和也; 松田 秀秋
    薬史学雑誌 44 1 10 - 17 日本薬史学会 2009年
  • Kozo Fukuda; Kazuya Murata; Kimihisa Itoh; Hideaki Matsuda; Masahiko Taniguchi; Makio Shibano; Kimiye Baba; Makoto Shiratori; Tadato Tani
    Journal of Traditional Medicines 26 42496 210 - 218 2009年 
    The dried roots of Angelica acutiloba (Yamato-toki in Japanese) are an important crude drug component of traditional Chinese prescriptions used to improve menopausal symptoms. The improvement in blood circulation by Yamato-toki was revealed by the oral administration of (Z)-ligustilide, a major ingredient of Yamato-toki, which showed significant shortening of euglobulin lysis time. This is the first report to reveal fibrinolytic activity of (Z)-ligustilide. Furthermore, ferulic acid and adenosine were two active ingredients with antiplatelet, antierythrocyte aggregation, and fibrinolytic activities. A. acutiloba roots are processed into Yamato-toki by Yumomi treatment, which is a traditional processing procedure involving blanching in hot water. Methanol extracts of A. acutiloba roots with or without Yumomi treatment showed similar dose-dependent and significant antierythrocyte aggregation activities. There was no discernable difference in the (Z)-ligustilide, ferulic acid, and adenosine contents between A. acutiloba roots with or without Yumomi treatment. Sugar analysis results indicated that Yumomi processing increases the monosaccharide content, which enhances sweetness. The results showed that (Z)-ligustilide was a fibrinolytic activator. However, there was no enhancement of biological activity following Yumomi treatment. Thus, Yumomi is utilized mainly to improve appearance and quality, as evaluated by sensory tests, and to enhance sweetness and brownish color rather than raising the contents of ingredients. © 2009, Medical and Pharmaceutical Society for WAKAN-YAKU. All rights reserved.
  • Kozo Fukuda; Kazuya Murata; Hideaki Matsuda; Tadato Tani
    Yakushigaku zasshi 44 1 10 - 7 2009年 [査読有り]
     
    Japanese Angelica root, Toki in Japanese, is prepared from the roots of cultivated Angelica acutiloba or A. acutiloba var. sugiyamae. Since Toki has been frequently used as a crude drug in traditional Chinese formulations, the stable supply and quality of Toki are essential issues in Japanese clinical practice. To clarify the historical and present conditions of Toki, a historical survey on herbal books and a field investigation on the cultivation condition of A. acutiloba in the Fuki area (Wakayama Prefecture) were carried out. From the present historical survey, it was proven that Yamato-Toki produced in the Yamato area, an old local area including the current Nara and Wakayama prefectures in Japan, had been considered to be superior merchandise. It was also proven that a special processing method to prevent flower stalk growth ("Mekuri" in Japanese) is an original method different from Chinese methods. From the present field investigation, it was also proven that the traditional transplant operation of the second year has been handed down since the 1930s and that washing roots in hot water ("Yumomi" in Japanese) is an original method of preparing Yamato-Toki. Toki is one of the precious crude drugs cultivated and prepared in Japan. The present study may help to pass on traditional cultivation culture and contribute to an expansion in the volume of Yamato-Toki produced in Japan.
  • Kazuya Murata; Tetsuro Shinada; Yasufumi Ohfune; Miki Hisada; Akikazu Yasuda; Hideo Naoki; Terumi Nakajima
    Biological & pharmaceutical bulletin 29 12 2493 - 7 2006年12月 [査読有り]
     
    Four novel peptides, polistes-mastoparan-R1, 2, 3, and polistes-protonectin, were isolated from the venom of a paper wasp, Polistes rothneyi iwatai. MALDI-TOF MS analysis of a small amount of the crude venom gave six molecular-related ion peaks. Among them, m/z 1565 was expected to be a novel peptide. Purification of the crude venom by HPLC gave two known kinins, Thr6-bradykinin and Ala-Arg-Thr6-bradykinin, and four novel peptides named polistes-mastoparan-R1, 2, and 3, and polistes-protonectin. Polistes-mastoparan-R1, 2, and 3 (Pm-R) were tetradecapeptides that possess high sequence homology with that of mastoparan. The sequence of polistes-protonectin was similar to that of protonectin isolated from a Brazilian paper wasp. Histamine-releasing activities of Pm-R1, 2, and 3 were more potent than that of mastoparan. Polistes-protonectin exhibited the most potent hemolytic activity in comparison with the four novel peptides and mastoparan.
  • Miki Hisada; Honoo Satake; Katsuyoshi Masuda; Masato Aoyama; Kazuya Murata; Testuro Shinada; Takashi Iwashita; Yasufumi Ohfune; Terumi Nakajima
    Biochemical and biophysical research communications 330 4 1048 - 54 2005年05月 [査読有り]
     
    The solitary spider wasp, Anoplius samariensis, is known to exhibit a unique long-term, non-lethal paralysis in spiders that it uses as a food source for its larvae. However, neither detailed venom components nor paralytic compounds have ever been characterized. In this study, we examined the components in the low molecular weight fraction of the venom and the paralytic activity of the high molecular weight fraction. The major low molecular weight components of the venom were identified as gamma-aminobutyric acid and glutamic acid by micro-liquid chromatography/electrospray ionization mass spectrometry and nuclear magnetic resonance spectrometry analysis. The sodium dodecyl sulfate-polyacrylamide gel electrophoresis and mass analysis revealed that the A. samariensis venom contained the various proteins with weights of 4-100 kDa. A biological assay using Joro spiders (Nephila clavata) clearly showed that the high molecular weight fraction of the venom prepared by ultrafiltration exerted as potent non-lethal long-term paralysis as the whole venom, whereas the low molecular weight fraction was devoid of any paralytic activity. These results indicated that several venomous proteins in the high molecular weight fraction are responsible for the paralytic activity. Furthermore, we determined the primary structure of one component designated As-fr-19, which was a novel multiple-cysteine peptide with high sequence similarity to several sea anemone and snake toxins including dendrotoxins, rather than any insect toxic peptides identified so far. Taken together, our data showed the unprecedented molecular and toxicological profiles of wasp venoms.
  • Kazuya Murata; Masayuki Satake; Hideo Naoki; Heinrich F. Kaspar; Takeshi Yasumoto
    Tetrahedron 54 5-6 735 - 742 1998年01月 [査読有り]
     
    A new brevetoxin analog, brevetoxin B2 (BTXB2), was isolated from greenshell mussels, Perna canaliculus, collected at the time of the neurotoxic shellfish poisoning incident in New Zealand. The structure was elucidated based on NMR, CAD PAB MS/MS, and chemical degradation experiments.
  • Akio Morohashi; Masayuki Satake; Kazuya Murata; Hideo Naoki; Heinrich F. Kaspar; Takeshi Yasumoto
    Tetrahedron Letters 36 49 8995 - 8998 1995年12月 [査読有り]
     
    A new brevetoxin analog, brevetoxm B3 (BTXB3 1). was isolated from the greenshell mussel, Perna canaliculus from New Zealand. In BTXB3 the brevetoxin B skeleton is modified by cleavage of ring D. esterification of the resulting alcohol, and oxidation of the aldehydic terminus. © 1995 Elsevier Science Ltd.

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  • 薬用資源学特論近畿大学
  • 創薬科学系先進特論薬用資源学近畿大学
  • 科学英語近畿大学
  • 生命の科学近畿大学
  • 基礎化学英語近畿大学
  • 漢方薬学近畿大学
  • 天然物薬化学近畿大学
  • 薬用資源学近畿大学

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  • 日本農芸化学会   アメリカ化学会   日本生薬学会   日本薬学会   日本化学会   

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