詳細

萬瀬　貴昭 （マンセ　ヨシアキ）

  • 薬学総合研究所　講師
Last Updated :2024/04/19

コミュニケーション情報 byコメンテータガイド

  • コメント

    ・生薬をはじめとする植物の化学成分に関する事項 ・化粧品に用いられる植物成分に関する事項 ・化粧品（特に育毛剤）に利用される成分と作用に関する事項

研究者情報

学位

  • 博士（薬学）（近畿大学）

ホームページURL

科研費研究者番号

  • 40933990

J-Global ID

研究キーワード

  • 和漢薬   

現在の研究分野（キーワード）

    ・生薬をはじめとする植物の化学成分に関する事項
    ・化粧品に用いられる植物成分に関する事項
    ・化粧品（特に育毛剤）に利用される成分と作用に関する事項

研究分野

  • ライフサイエンス / 環境、天然医薬資源学 / 天然物化学,

学歴

  • 2006年04月 - 2008年03月   近畿大学 大学院   薬学研究科   薬学専攻
  • 2002年04月 - 2006年03月   近畿大学   薬学部   薬学科

研究活動情報

論文

  • Akifumi Nagatomo; Mamiko Kohno; Hirosato Kawakami; Yoshiaki Manse; Toshio Morikawa
    Journal of Natural Medicines 78 1 180 - 190 2024年01月 
    An acylated flavonol glycoside, trans-tiliroside (1), is found in certain parts of different herbs, including the seeds of Rosa canina (Rosaceae). Previous studies on compound 1 have focused on triglyceride (TG) metabolism, including its anti-obesity and intracellular TG reduction effects. In the present study, the effects of compound 1 on cholesterol (CHO) metabolism were investigated using human hepatocellular carcinoma-derived HepG2 cells and mice. Compound 1 decreased CHO secretion in HepG2 cells, which was enhanced by mevalonate in a concentration-dependent manner and decreased the secretion of apoprotein B (apoB)-100, a marker of very low-density lipoprotein (VLDL). Compound 1 also inhibited the activity of microsomal triglyceride transfer proteins, which mediate VLDL formation from cholesterol and triglycerides in the liver. In vivo, compound 1 inhibited the accumulation of Triton WR-1339-induced TG in the blood of fasted mice and maintained low levels of apoB-100. These results suggest that compound 1 inhibits the secretion of CHO as VLDL from the liver and has the potential for use for the prevention of dyslipidemia. Graphical abstract: [Figure not available: see fulltext.]
  • Berberineの放射線障害緩和作用におけるREDOXの関与について(第2報)
    上林 將人; 松田 久司; 中西 郁夫; 荘司 好美; 萬瀬 貴昭; 森川 敏生
    日本生薬学会年会講演要旨集 69回 174 - 174 (一社)日本生薬学会 2023年09月
  • アシル化フラボノール配糖体trans-tilirosideの肝臓からのVLDL分泌に及ぼす影響
    長友 暁史; 河野 麻実子; 川上 宏智; 萬瀬 貴昭; 森川 敏生
    日本生薬学会年会講演要旨集 69回 203 - 203 (一社)日本生薬学会 2023年09月
  • Hisashi Matsuda; Akifumi Nagatomo; Misaki Hatakeyama; Yoshiaki Manse; Masayuki Yoshikawa; Toshio Morikawa
    Traditional and Kampo Medicine 10 2 132 - 141 2023年08月 
    Aim: Bombycis Feces (BF) and Bombyx Batryticatus (BB) are traditional medicines derived from silkworm. We investigated the suppressive effects of BF and BB extracts on elevated blood glucose levels in disaccharide-loaded rats. Methods: Effects of BF and BB extracts on serum glucose levels in sugar-loaded rats and streptozotocin (STZ)-induced diabetic mice were recorded, and several glucosidase inhibitory activities were determined in vitro by comparing with those of the natural medicines obtained from the mulberry plant (e.g., Mori Folium, Mori Cortex, and Mori Fructus). Results: BF and BB methanol extracts were found to suppress the elevated blood glucose level in sucrose-loaded mice, whereas they did not exhibit any activity in the glucose-loaded model and in the STZ-induced model. Through the bioassay-guided separation of the BF methanol extract using sucrase and maltase inhibitory activities, several pseudo-sugars, including 1-deoxynojirimycin (1), fagomine (2), and cis-5-hydroxy-L-pipecolic acid (3) were isolated as the active constituents. Oral administration (10 mg/kg) of constituent 1 simultaneous to sucrose loading in rats was found to significantly suppress elevation of the serum glucose level. Conclusion: BF and BB extracts were found to inhibit the elevated blood glucose level in disaccharides-loaded rats due to their α-glucosidase inhibitory activities. The suppressive effects of BF and BB extracts as well as of the active constituent 1 on the increase in blood glucose were estimated to dwindle at a limited time after administration. Therefore, it is suggested that BF and BB extracts might exert their effective antidiabetic effects when taken with meals.
  • Yusuke Sakamoto; Naoki Inoue; Yusuke Nakanishi; Kiyofumi Ninomiya; Masayuki Yoshikawa; Osamu Muraoka; Yoshiaki Manse; Toshio Morikawa
    Biological and Pharmaceutical Bulletin 46 6 848 - 855 2023年06月 
    A methanol extract of rhizomes of Picrorhiza kurroa Royle ex Benth. (Plantaginaceae) showed hepatoprotective effects against D-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced liver injury in mice. We had previously isolated 46 compounds, including several types of iridoid glycosides, phenylethanoid glycosides, and aromatics, etc., from the extract. Among them, picroside II, androsin, and 4-hydroxy-3-methoxyacetophenone exhibited active hepatoprotective effects at doses of 50-100mg/kg, per os (p.o.) To characterize the mechanisms of action of these isolates and to clarify the structural requirements of phenylethanoid glycosides for their hepatoprotective effects, their effects were assessed in in vitro studies on (i) D-GalN-induced cytotoxicity in mouse primary hepatocytes, (ii) LPS-induced nitric oxide (NO) production in mouse peritoneal macrophages, and (iii) tumor necrosis factor-α (TNF-α)-induced cytotoxicity in L929 cells. These isolates decreased the cytotoxicity caused by D-GalN without inhibiting LPS-induced macrophage activation and also reduced the sensitivity of hepatocytes to TNF-α. In addition, the structural requirements of phenylethanoids for the protective effects of D-GalN-induced cytotoxicity in mouse primary hepatocytes were evaluated.
  • 延命草由来ent-kaurane型ジテルペノイドの抗炎症作用およびその作用機序解析
    萬瀬 貴昭; 山田 さくら; 隅田 昂太; 坂本 裕介; 森川 敏生
    日本栄養・食糧学会大会講演要旨集 77回 278 - 278 (公社)日本栄養・食糧学会 2023年03月
  • セリ科植物ヒュウガトウキ(Angelica furcijuga)由来ケラクトン型クマリン類の生体機能性の解明
    長友 暁史; 森川 敏生; 坂本 裕介; 武田 匠平; 萬瀬 貴昭; 中嶋 聡一; 中村 誠宏; 二宮 清文; 吉川 雅之; 松田 久司
    日本栄養・食糧学会大会講演要旨集 77回 288 - 288 (公社)日本栄養・食糧学会 2023年03月
  • 肥満症に用いられる3種の漢方薬の女性ホルモン様作用と脂肪蓄積抑制効果
    山口 朋子; 羅 鳳琳; 橋本 統星; 赤木 淳二; 萬瀬 貴昭; 二宮 清文; 森川 敏生
    診療と新薬 60 3 179 - 187 (株)医事出版社 2023年03月 
    卵巣摘出によりエストロゲン分泌を低下させたマウスに,漢方エキス(防已黄耆湯エキス:BOT,防風通聖散エキス:BTS,大柴胡湯エキス:DST)を添加した高脂肪食を与えたところ,対照群(高脂肪食)と比べて体重増加が有意に抑えられ,血清中の総コレステロールや,AST,ALTなどの肝数値についても改善した。また,飼育6週間後の内臓脂肪量および皮下脂肪量を測定したところ対照群よりも有意に低く,これらの漢方エキスにエストロゲン低下に伴う脂肪蓄積の抑制効果が認められた。次に,エストロゲン依存的に増殖するMCF-7細胞を用いてBOT,BTSおよびDSTのエストロゲン様作用を検討したところ,BOTは10μg/mL以上の濃度において,BTSおよびDSTは100μg/mLの濃度においてMCF-7細胞の増殖が誘導され,これらの漢方エキスにエストロゲン様の活性が認められた。それぞれの漢方薬の構成生薬について検討した結果,カンゾウ,ダイオウ,キジツ,オウギ,オウゴン,マオウ,およびハッカから調製したエキスに活性が認められた。これらの結果から,肥満症に用いられる上記3種の漢方薬はいずれもエストロゲン様作用を有し,継続的な服用により,エストロゲン低下に伴う脂肪蓄積に対して抗肥満効果を発揮することを見出した。(著者抄録)
  • Fenglin Luo; Yoshiaki Manse; Saowanee Chaipech; Yutana Pongpiriyadacha; Osamu Muraoka; Toshio Morikawa
    Pharmaceuticals 16 2 2023年02月 
    A methanol extract of the flowers of Mammea siamensis (Miq.) T. Anders. (Calophyllaceae) showed anti-proliferative activity against human prostate carcinoma LNCaP cells (IC50 = 2.0 µg/mL). Two new coumarin-related polysubstituted benzofurans, mammeasins P (1) and Q (2), and a known polysubstituted coumarin mammea B/AC cyclo F (39) were isolated from the extract along with 44 previously reported polysubstituted coumarin constituents (3–38 and 40–47). The structures of two new compounds (1 and 2) were determined based on their spectroscopic properties derived from the physicochemical evidence including NMR and MS analyses and taking the plausible generative pathway into account. Among the coumarin constituents, mammeasins A (3, IC50 = 1.2 µM) and B (4, 0.63 µM), sugangin B (18, 1.5 µM), kayeassamins E (24, 3.0 µM) and G (26, 3.5 µM), and mammeas E/BA (40, 0.88 µM), E/BB (41, 0.52 µM), and E/BC (42, 0.12 µM) showed relatively potent anti-proliferative activity.
  • Fenglin Luo; Yoshiaki Manse; Satoshi Ishikawa; Sakura Nishi; Anshin Chen; Tao Wang; Toshio Morikawa
    Journal of Natural Medicines 77 2 387 - 396 2023年01月 
    Methanol extract from the capitula of Coreopsis tinctoria Nutt. (Asteraceae), which is also known as a flowering tea or blooming tea “Snow Chrysanthemum,” was found to inhibit the enzymatic activity of aromatase. A total of 24 known isolates (1–24) were identified from the extract, including three chalcones (1–3), an aurone (4), five flavanones (5–9), four flavanols (10–13), a flavonol (14), and two biflavanones (15, 16). Among them, okanin (1, Ki = 1.6 μM), (2S)-naringenin (5, 0.90 μM), isookanin (6, 0.81 μM), (2S)-7,3',5'-trihydroxyflavaone (7, 0.13 μM), and (2S)-5,7,3',5'-tetrahydroxyflavanone (8, 0.32 μM) exhibited relatively potent competitive inhibition. Specifically, the isolates 7 and 8, having a common 3',5'-resorcinol moiety at the B ring in their flavanone skeleton, exhibited potent inhibitory activities compared to those of a clinically applied aminoglutethimide (0.84 μM) and naturally occurring flavone, chrysin (0.23 μM), which is a common non-steroidal aromatase inhibitor. Importantly, the active flavonoid constituents (1 and 5–8) did not inhibit the activity of 5α-reductase enzyme, which normally reacts with the same substrate “testosterone,” thus, these compounds were suggested to be specific to aromatase.
  • Shogo Takeda; Akari Yoneda; Kenchi Miyasaka; Yoshiaki Manse; Toshio Morikawa; Hiroshi Shimoda
    International Journal of Molecular Sciences 24 1 2022年12月 
    Ceramide (Cer) plays an important role in skin barrier functions in the stratum corneum (SC). The ingestion of food-derived glucosylceramides (GlcCer) attenuates transepidermal water loss (TEWL). However, the moisturizing effects of single molecules of GlcCer and Cer remain unclear. Therefore, we herein purified 13 GlcCer and 6 Cer, including elasticamide, which has the same structure as human Cer[AP], from rice and compared their epidermal moisturizing effects in a reconstructed human epidermal keratinization model. The results obtained showed that 10 µM of 5 GlcCer[d18:2] with a 4E,8Z sphingadienine and C18 to C26 fatty acids and 10 µg/mL of 3 Cer with C23 or C24 fatty acids significantly reduced TEWL. The moisturizing effects of these GlcCer were dependent on the length of fatty acids. Furthermore, 10 µg/mL of elasticamide increased the SC Cer contents by promoting the expression of GlcCer synthase. Electron microscopic observations revealed that 1 µM of GlcCer[d18:2(4E,8Z)/26:0] increased the number of keratohyalin granules and desmosomes. Immunostaining and Western blotting indicated that 1 µM of GlcCer[d18:2(4E,8Z)/26:0] up-regulated the expression of filaggrin and corneodesmosin, which contribute to epidermal hydration. This comparative study on epidermal moisturization by GlcCer and Cer isolated from rice revealed differences in their hydration mechanisms.
  • Akifumi Nagatomo; Kiyofumi Ninomiya; Shinsuke Marumoto; Chie Sakai; Shuta Watanabe; Wakana Ishikawa; Yoshiaki Manse; Takashi Kikuchi; Takeshi Yamada; Reiko Tanaka; Osamu Muraoka; Toshio Morikawa
    International journal of molecular sciences 23 21 2022年10月 
    The seed oil of Carapa guianensis Aublet (Andiroba) has been used in folk medicine for its insect-repelling, anti-inflammatory, and anti-malarial activities. This study aimed to examine the triglyceride (TG) reducing effects of C. guianensis-derived limonoids or other commercially available limonoids in human hepatoblastoma HepG2 cells and evaluate the expression of lipid metabolism or autophagy-related proteins by treatment with 7-deacetoxy-7-oxogedunin (DAOG; 1), a principal limonoid of C. guianensis. The gedunin-type limonoids, such as DAOG (% of control at 20 μM: 70.9 ± 0.9%), gedunin (2, 74.0 ± 1.1%), epoxyazadiradione (4, 73.4 ± 2.0%), 17β-hydroxyazadiradione (5, 79.9 ± 0.6%), 7-deacetoxy-7α-hydroxygedunin (6, 61.0 ± 1.2%), andirolide H (7, 87.4 ± 2.2%), and 6α-hydroxygedunin (8, 84.5 ± 1.1%), were observed to reduce the TG content at lower concentrations than berberine chloride (BBR, a positive control, 84.1 ± 0.3% at 30 μM) in HepG2 cells pretreated with high glucose and oleic acid. Andirobin-, obacunol-, nimbin-, and salannin-type limonoids showed no effect on the intracellular TG content in HepG2 cells. The TG-reducing effect of DAOG was attenuated by the concomitant use of compound C (dorsomorphin), an AMPK inhibitor. Further investigation on the detailed mechanism of action of DAOG at non-cytotoxic concentrations revealed that the expressions of autophagy-related proteins, LC3 and p62, were upregulated by treatment with DAOG. These findings suggested that gedunin-type limonoids from Andiroba could ameliorate fatty liver, and that the action of DAOG in particular is mediated by autophagy.
  • Katsuki Takashima; Miyu Teramachi; Shinsuke Marumoto; Fumihiro Ishikawa; Yoshiaki Manse; Toshio Morikawa; Genzoh Tanabe
    Bioorganic & medicinal chemistry letters 78 129034 - 129034 2022年10月 
    Although 4,5-didehydroguadiscine (12a), an alkaloid with potent melanogenesis-inhibitory activity isolated from Hornschuchia obliqua (Annonaceae), consists of an aporphine nucleus with an aromatized B-ring, to date, it has not been utilized as a template for structure-activity relationship (SAR) studies of pharmacological activities because of its exceptional structure. Accordingly, herein, five analogs (12b-12f) of 12a and five benzylisoquinoline analogs (13b-13f) lacking the C11a-C11b bond of 12b-12f were prepared. The inhibitory effects of 12b-12f and 13b-13f on melanogenesis in theophylline-stimulated B16 melanoma 4A5 cells were examined and compared with those of 12a. Melanogenesis-inhibitory activities of 12b-12f were the same as that of 12a, whereas the melanogenesis-inhibitory activities of 13b-13f were significantly inferior to those of 12a and 12b-12f. These results suggest that the C11a-C11b bond plays an essential role in the melanogenesis-inhibitory activities of 12a-12e.
  • Fenglin Luo; Yoshiaki Manse; Saowanee Chaipech; Yutana Pongpiriyadacha; Osamu Muraoka; Toshio Morikawa
    International journal of molecular sciences 23 19 2022年09月 
    With the aim of searching for phytochemicals with aromatase inhibitory activity, five new prenylcoumarins, mammeasins K (1), L (2), M (3), N (4), and O (5), were isolated from the methanolic extract of Mammea siamensis (Miq.) T. Anders. flowers (fam. Calophyllaceae), originating in Thailand. The stereostructures of 1-5 were elucidated based on their spectroscopic properties. Among the new compounds, 1 (IC50 = 7.6 µM) and 5 (9.1 µM) possessed relatively strong inhibitory activity against aromatase, which is a target of drugs already used in clinical practice for the treatment and prevention of estrogen-dependent breast cancer. The analysis through Lineweaver-Burk plots showed that they competitively inhibit aromatase (1, Ki = 3.4 µM and 5, 2.3 µM). Additionally, the most potent coumarin constituent, mammea B/AB cyclo D (31, Ki = 0.84 µM), had a competitive inhibitory activity equivalent to that of aminoglutethimide (0.84 µM), an aromatase inhibitor used in therapeutics.
  • Kenchi Miyasaka; Yoshiaki Manse; Akari Yoneda; Shogo Takeda; Norihito Shimizu; Wakana Yamada; Toshio Morikawa; Hiroshi Shimoda
    Journal of food biochemistry 46 10 e14353  2022年08月 
    Glucosylceramides (GlcCer), which are present in many edible plants, suppress melanin production in mouse melanocytes. Rice GlcCer consist of multiple molecules that comprise different types of sphingoid bases as well as diverse lengths and stereotypes of free fatty acids. Adjacent to the GlcCer fraction, there are free ceramides (Cer) as minor constituents. However, the anti-melanogenic activities of individual GlcCer and Cer remain unknown. Therefore, we herein isolated 13 GlcCer and elasticamide, a Cer [AP] from the gummy by-products of rice bran oil, and examined their anti-melanogenic activities. In theophylline-induced melanogenesis in B16 melanoma cells, GlcCer [d18:2(4E,8Z)/18:0], GlcCer [d18:2(4E,8Z)/20:0], and elasticamide significantly suppressed melanin production with IC50 values of 6.6, 5.2, and 3.9 μM, respectively. Elasticamide, but not GlcCer [d18:2 (4E,8Z)/20:0], suppressed melanogenesis in human 3D-cultured melanocytes and the expression of tyrosinase-related protein 1 in normal human melanocytes. Based on these results, we conducted a clinical trial on the effects of rice ceramide extract (Oryza ceramide®), containing 1.2 mg/day of GlcCer and 56 μg/day of elasticamide, on UV-B-induced skin pigmentation. The ingestion of Oryza ceramide® for 8 weeks significantly suppressed the accumulation of melanin 7 days after UV irradiation (1288 and 1546 mJ/cm2 ·S). Rice-derived GlcCer and elasticamide, which exhibited anti-melanogenic activities, were suggested to contribute to the suppressive effects of Oryza ceramide® on UV-induced skin pigmentation. Although the mechanisms underlying the anti-melanogenic activities of GlcCer remain unclear, elasticamide was identified as a promising Cer that exhibits anti-melanogenic activity. PRACTICAL APPLICATIONS: The anti-melanogenic activities of rice-derived GlcCer and elasticamide currently remain unclear. We herein demonstrated the inhibitory effects of individual GlcCer and elasticamide on melanogenesis in melanoma cells, melanocytes, and human skin.
  • タイ天然薬物Mammea siamensis花部由来の新規クマリン成分および前立腺がん細胞増殖抑制活性
    羅 鳳琳; 萬瀬 貴昭; 杉田 秀美; 佐伯 竣介; Saowanee Chaipech; Yutana Pongpiriyadacha; 村岡 修; 森川 敏生
    日本生薬学会年会講演要旨集 68回 130 - 130 (一社)日本生薬学会 2022年08月
  • 米由来各種グルコシルセラミドの表皮保湿作用
    米田 朱里; 竹田 翔伍; シュレスタ・サリタ; 萬瀬 貴昭; 下田 博司; 森川 敏生
    日本生薬学会年会講演要旨集 68回 173 - 173 (一社)日本生薬学会 2022年08月
  • タイ天然薬物Bunnak(Mesua ferrea L.)花部由来ビスフラボノイド成分の抗アレルギー活性
    楡 光世; 萬瀬 貴昭; 宮地 大樹; 橋本 佳典; 坂本 裕介; Saowanee Chaipech; Yutana Pongpiriyadacha; 森川 敏生
    日本生薬学会年会講演要旨集 68回 213 - 213 (一社)日本生薬学会 2022年08月
  • 地膚子(Kochia scoparia、果実)の血中中性脂肪上昇抑制作用成分
    高田 隆矢; 長友 暁史; 森本 真由; 萬瀬 貴昭; 森川 敏生
    日本生薬学会年会講演要旨集 68回 214 - 214 (一社)日本生薬学会 2022年08月
  • ブラジル生薬Andiroba(Carapa guianensis)由来リモノイド成分の細胞内中性脂肪低減作用における構造活性相関
    渡邉 秀太; 長友 暁史; 石川 和奏; 萬瀬 貴昭; 森川 敏生
    日本生薬学会年会講演要旨集 68回 310 - 310 (一社)日本生薬学会 2022年08月
  • 蚕砂および白僵蚕の抗糖尿病作用成分
    長友 暁史; 森川 敏生; 萬瀬 貴昭; 吉川 雅之; 松田 久司
    和漢医薬学会学術大会要旨集 39回 70 - 70 (一社)和漢医薬学会 2022年08月
  • Berberineの放射線障害緩和作用および血管収縮抑制作用におけるREDOXの関与について
    上林 將人; 松田 久司; 中西 郁夫; 荘司 好美; 萬瀬 貴昭; 森川 敏生
    和漢医薬学会学術大会要旨集 39回 74 - 74 (一社)和漢医薬学会 2022年08月
  • Yoshiaki Manse; Yusuke Sakamoto; Taiki Miyachi; Mitsuyo Nire; Yoshinori Hashimoto; Saowanee Chaipech; Yutana Pongpiriyadacha; Toshio Morikawa
    Separations 9 5 127 - 127 2022年05月
  • 香辛料素材Alpinia galanga果実由来ネオリグナン成分のケモカイン受容体CCR3アンタゴニスト活性
    森川 敏生; 萬瀬 貴昭; 坂本 裕介; 楡 光世; 綿原 光司; 原 雄大; 松尾 一彦; 中山 隆志
    日本栄養・食糧学会大会講演要旨集 76回 199 - 199 (公社)日本栄養・食糧学会 2022年05月
  • 延命草由来ジテルペノイド成分のiNOS発現抑制を介した抗炎症作用
    山田 さくら; 萬瀬 貴昭; 隅田 昂太; 坂本 裕介; 森川 敏生
    日本栄養・食糧学会大会講演要旨集 76回 199 - 199 (公社)日本栄養・食糧学会 2022年05月
  • トマト種子サポニンlycoperoside Hの角層セラミド増加による表皮保湿作用およびステロイド様抗炎症作用
    竹田 翔伍; 宮坂 賢知; シュレスタ・サリタ; 萬瀬 貴昭; 森川 敏生; 下田 博司
    日本栄養・食糧学会大会講演要旨集 76回 236 - 236 (公社)日本栄養・食糧学会 2022年05月
  • Akifumi Nagatomo; Naoki Inoue; Takuya Konno; Yin Xu; Chinatsu Sakamoto; Mayuko Sone; Aya Shibasaka; Osamu Muraoka; Kiyofumi Ninomiya; Masayuki Yoshikawa; Yoshiaki Manse; Toshio Morikawa
    Journal of natural medicines 76 3 654 - 669 2022年03月 
    The methanol extract from the leaves of Ilex paraguariensis A. St.-Hil. (Aquifoliaceae), popularly known as mate, maté, or yerba maté, inhibits the intracellular triglyceride accumulation in HepG2 cells and suppresses the plasma triglyceride elevation in olive oil-treated mice. Three new triterpene saponins, termed mateosides I (1), II (2), and III (3), were isolated from the extract along with 29 known compounds. The structures of 1-3 were elucidated based on chemical and spectroscopic evidence. Among the isolates, principal saponin constituents, 2 and matesaponins 1 (7) and 2 (9), potently inhibited the triglyceride accumulation in HepG2 cells simultaneously treated with oleic acid and high glucose. In vivo assay of the methanol extract of I. paraguariensis revealed that 7 and 9 showed anti-hyperlipidemic activities in olive oil-treated mice. These results suggested that the saponin constituents of I. paraguariensis could be valuable bioactive marker for the anti-obesogenic activity.
  • メース(Myristica fragrans、仮種皮)含有成分の抗炎症作用とその構造活性相関
    坂本 裕介; 萬瀬 貴昭; 隅田 昂太; 山田 さくら; 八幡 郁子; 尾関 快天; 森川 敏生
    日本薬学会年会要旨集 142年会 27T - pm03S (公社)日本薬学会 2022年03月
  • 延命草由来ジテルペノイド成分のマクロファージにおける一酸化窒素産生に与える影響
    萬瀬 貴昭; 隅田 昂太; 山田 さくら; 坂本 裕介; 森川 敏生
    日本薬学会年会要旨集 142年会 27T - pm07 (公社)日本薬学会 2022年03月
  • 米由来各種グルコシルセラミドおよび遊離型セラミドelasticamideのメラニン産生抑制作用
    宮坂 賢知; 米田 朱里; 竹田 翔伍; シュレスタ・サリタ; 萬瀬 貴昭; 森川 敏生; 下田 博司
    日本薬学会年会要旨集 142年会 26PO6 - 07 (公社)日本薬学会 2022年03月
  • 延命草含有ジテルペノイド成分のアロマターゼ阻害活性
    羅 鳳琳; 萬瀬 貴昭; 西本 裕; 森川 敏生
    日本薬学会年会要旨集 142年会 27PO8 - 09S (公社)日本薬学会 2022年03月
  • メース(Myristica fragrans、仮種皮)含有成分の抗炎症作用とその構造活性相関
    坂本 裕介; 萬瀬 貴昭; 隅田 昂太; 山田 さくら; 八幡 郁子; 尾関 快天; 森川 敏生
    日本薬学会年会要旨集 142年会 27T - pm03S (公社)日本薬学会 2022年03月
  • 延命草由来ジテルペノイド成分のマクロファージにおける一酸化窒素産生に与える影響
    萬瀬 貴昭; 隅田 昂太; 山田 さくら; 坂本 裕介; 森川 敏生
    日本薬学会年会要旨集 142年会 27T - pm07 (公社)日本薬学会 2022年03月
  • 米由来各種グルコシルセラミドおよび遊離型セラミドelasticamideのメラニン産生抑制作用
    宮坂 賢知; 米田 朱里; 竹田 翔伍; シュレスタ・サリタ; 萬瀬 貴昭; 森川 敏生; 下田 博司
    日本薬学会年会要旨集 142年会 26PO6 - 07 (公社)日本薬学会 2022年03月
  • 延命草含有ジテルペノイド成分のアロマターゼ阻害活性
    羅 鳳琳; 萬瀬 貴昭; 西本 裕; 森川 敏生
    日本薬学会年会要旨集 142年会 27PO8 - 09S (公社)日本薬学会 2022年03月
  • Shogo Takeda; Kenchi Miyasaka; Sarita Shrestha; Yoshiaki Manse; Toshio Morikawa; Hiroshi Shimoda
    Molecules (Basel, Switzerland) 26 19 2021年09月 
    Tomatoes are widely consumed, however, studies on tomato seeds are limited. In this study, we isolated 11 compounds including saponins and flavonol glycosides from tomato seeds and evaluated their effects on epidermal hydration. Among the isolated compounds, tomato seed saponins (10 µM) significantly increased the mRNA expression of proteins related to epidermal hydration, including filaggrin, involucrin, and enzymes for ceramide synthesis, by 1.32- to 1.91-fold compared with the control in HaCaT cells. Tomato seed saponins (10 µM) also decreased transepidermal water loss by 7 to 13 g/m2·h in the reconstructed human epidermal keratinization (RHEK) models. Quantitative analysis of the ceramide content in the stratum corneum (SC) revealed that lycoperoside H (1-10 µM) is a promising candidate to stimulate ceramide synthesis via the upregulation of ceramide synthase-3, glucosylceramide synthase, and β-glucocerebrosidase, which led to an increase in the total SC ceramides (approximately 1.5-fold) in concert with ceramide (NP) (approximately 2-fold) in the RHEK models. Evaluation of the anti-inflammatory and anti-allergic effects of lycoperoside H demonstrated that lycoperoside H is suggested to act as a partial agonist of the glucocorticoid receptor and exhibits anti-inflammatory effects (10 mg/kg in animal test). These findings indicate that lycoperoside H can improve epidermal dehydration and suppress inflammation by increasing SC ceramide and steroidal anti-inflammatory activity.
  • 延命草由来enmeinのヒト毛乳頭細胞における細胞増殖促進活性とその作用機序
    森川 敏生; 萬瀬 貴昭; 羅 鳳琳; 宮地 大樹; 加藤 和寛; 岡田 枝里子[西田]; 岡崎 茜; 柳田 満廣; 中村 翔
    日本薬学会年会要旨集 141年会 28P02 - 045 (公社)日本薬学会 2021年03月
  • Yoshiaki Manse; Fenglin Luo; Kazuhiro Kato; Akane Okazaki; Eriko Okada-Nishida; Mitsuhiro Yanagida; Sho Nakamura; Toshio Morikawa
    Journal of natural medicines 75 2 326 - 338 2021年03月 
    A methanol extract from Isodonis Herba demonstrated significant proliferative effect on human hair follicle dermal papilla cells (HFDPC, % of control: 150.0 ± 2.0% at 20 µg/mL, p < 0.01). From the extract, 14 ent-kaurane-type diterpenoids (1-14), two abietane-type diterpenoids (15 and 16) and four triterpenoids (17-20) were isolated. Among the isolates, enmein (1, 160.9 ± 3.0% at 20 µM, p < 0.01), isodocarpin (2, 169.3 ± 4.9% at 5 µM, p < 0.01), nodosin (4, 160.5 ± 12.4% at 20 µM, p < 0.01), and oridonin (8, 165.4 ± 10.6% at 10 µM, p < 0.01) showed the proliferative effects. The principal component enmein (1) activated the expression of vascular endothelial growth factor (VEGF) mRNA, upregulated the production of VEGF and increased levels of phospho-Akt, phospho-GSK-3β, and β-catenin accumulation in HFDPC, which could be the mechanism of these activate proliferation activity.
  • Takara, T.; Yamamoto, K.; Suzuki, N.; Yamashita, S.; Lio, S.-I.; Noguchi, H.; Kakinuma, T.; Baba, A.; Takeda, S.; Yamada, W.; Shrestha, S.; Manse, Y.; Morikawa, T.; Shimoda, H.
    Functional Foods in Health and Disease 11 8 2021年
  • Toshio Morikawa; Yoshiaki Manse; Fenglin Luo; Haruko Fukui; Yamato Inoue; Tsuyoshi Kaieda; Kiyofumi Ninomiya; Osamu Muraoka; Masayuki Yoshikawa
    Chemical & pharmaceutical bulletin 69 5 464 - 471 2021年 
    A methanol extract from the underground part of Calanthe discolor Lindl. (Orchidaceae) demonstrated significant proliferative activity on human hair follicle dermal papilla cells (HFDPC, % of control: 120.8 ± 0.2%) at 100 µg/mL against HFDPC. Through bioassay-guided separation of the extract, a new indole glycoside named 6'-O-β-D-apiofuranosylindican (1) was isolated along with six known compounds (2-7) including three indole glycosides. The stereostructure of 1 was elucidated based on its spectroscopic properties and chemical characteristics. Among the isolates, 1 (110.0 ± 1.0%), glucoindican (3, 123.9 ± 6.8%), and calanthoside (4, 158.6 ± 7.1%) showed significant proliferative activity at 100 µM. Furthermore, the active indole glycosides (1, 3, and 4) upregulated the expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor-7 (FGF-7) mRNA and protein in HFDPC, which could be the mechanism of their proliferative activity.
  • Toshio Morikawa; Naoki Inoue; Yusuke Nakanishi; Yoshiaki Manse; Hideyuki Matsuura; Kenji Okino; Shinya Hamasaki; Masayuki Yoshikawa; Osamu Muraoka; Kiyofumi Ninomiya
    Fitoterapia 143 104584 - 104584 2020年06月 
    Three new acylated phenylethanoid glycosides, kurroaosides A (14), B (15), and C (16), and a new acylated cucurbitane-type triterpene glycoside, kurroaoside D (17), were isolated from a methanol extract of the rhizomes of Picrorhiza kurroa Royle ex Benth. (Plantaginaceae) along with 29 known isolates including 10 acylated phenylethanoid glycosides (18-27), three cucurbitane-type triterpene glycosides (32-34), and a nortriterpene glycoside (35). The structures of these new compounds (14-17), including their stereochemistry, were determined based on chemical and physicochemical evidence derived from NMR and MS analysis. Among the isolates, acylated iridoid glycosides, picrosides I (8), II (9), III (10), and IV (11) and 6-feruloylcatalpol (12), phenylethanoid glycosides (14-16), triterpene glycosides, cucurbitacin B 2-O-β-D-glucopyranoside (32) and 25-acetoxy-2-β-D-glucopyranosyloxy-3,16,20-trihydroxy-9-methyl-19-norlanosta-5-en-22-one (35), and an acetophenone glycoside, picein (36), significantly promoted collagen synthesis at 10-30 μM, with no cytotoxicity being observed at the effective concentrations. Furthermore, acylated phenylethanoid glycosides, calceolarioside A (19, IC50 = 69.2 μM), plantamajoside (20, 51.8 μM), isoplantamajoside (21, 76.8 μM), and scroside E (23, 65.5 μM), exhibited collagenase inhibitory activity equivalent to that of positive agents caffeic acid (75.6 μM) and epigallocatechin 3-O-gallate (75.4 μM).
  • Toshio Morikawa; Yusuke Nakanishi; Naoki Inoue; Yoshiaki Manse; Hideyuki Matsuura; Shinya Hamasaki; Masayuki Yoshikawa; Osamu Muraoka; Kiyofumi Ninomiya
    Phytochemistry 169 112185 - 112185 2020年01月 
    Seven new acylated iridoid glycosides, picrorhizaosides A-G (1-7), were isolated from the methanol extract of the rhizomes of Picrorhiza kurroa Royle ex Benth. (Plantaginaceae), in addition to six known iridoid glycosides (8-13). The structures of these new iridoids, including their stereochemistry, were determined based on chemical and physicochemical evidence derived from NMR and MS analysis. Of the isolates, picrorhizaosides D (4, IC50 = 43.4 μM) and E (5, 35.8 μM); picrosides I (8, 60.7 μM), II (9, 22.3 μM), and IV (11, 59.2 μM); and minecoside (13, 57.2 μM), exhibited a similar or stronger hyaluronidase inhibitory activity than those of the antiallergic medicines disodium cromoglycate (64.8 μM), ketotifen fumarate (76.5 μM), and tranilast (227 μM).
  • Toshio Morikawa; Fenglin Luo; Yoshiaki Manse; Hidemi Sugita; Shunsuke Saeki; Saowanee Chaipech; Yutana Pongpiriyadacha; Osamu Muraoka; Kiyofumi Ninomiya
    Frontiers in chemistry 8 199 - 199 2020年 
    Geranylated coumarin constituents, kayeassamin I (1) and mammeasins E (2) and F (3) were newly isolated from the methanol extract of the flowers of Mammea siamensis (Calophyllaceae) originating in Thailand, along with five known isolates, such as mammea E/BC (23), deacetylmammea E/AA cyclo D (31), deacetylmammea E/BB cyclo D (32), mammea A/AA cyclo F (34), and mammea A/AC cyclo F (35). These compounds (1-3) were obtained as an inseparable mixture (ca. 1:1 ratio) of the 3″R and 3″S forms, respectively. Among the isolated coumarins from the extract, mammeasins E (2, 22.6 μM), A (4, 19.0 μM), and B (5, 24.0 μM), kayeassamins E (9, 33.8 μM), F (10, 15.9 μM), and G (11, 17.7 μM), surangin C (13, 5.9 μM), and mammeas A/AA (17, 19.5 μM), E/BB (22, 16.8 μM), and A/AA cyclo F (34, 23.6 μM), were found to inhibit testosterone 5α-reductase.
  • Toshio Morikawa; Shuhei Okugawa; Yoshiaki Manse; Osamu Muraoka; Masayuki Yoshikawa; Kiyofumi Ninomiya
    Natural Product Communications 14 6 1934578X1985783 - 1934578X1985783 2019年06月 
    Using a recently developed analytical protocol, distributions of 5 aporphine alkaloids, nuciferine (1), nornuciferine (2), N-methylasimilobine (3), asimilobine (4), and pronuciferine (5), and 5 benzylisoquinoline alkaloids, armepavine (6), norarmepavine (7), N-methylcoclaurine (8), coclaurine (9), and norjuziphine (10), in lotus flowers (the flower buds of Nelumbo nucifera) were analyzed. The flowers were collected at different blooming states (beginning of blooming, one-third in bloom, half in bloom, three-quarters in bloom, and in full bloom) from Saga prefecture, Japan (NN-S1–5). The samples from the beginning of blooming state (NN-S1, 16.35 mg/g in dried material) were found to possess the richest total alkaloid content (1-10). The samples of half in bloom (NN-S3, 52.69 mg per flower of dried material) had the highest total alkaloid content per flower. Among the alkaloid constituents, nornuciferine (2, IC50 = 22.5 µM), asimilobine (4, 11.7 μM), norarmepavine (7, 26.4 μM), coclaurine (9, 11.4 μM), and norjuziphine (10, 24.3 μM) exhibited hyaluronidase inhibitory activity, which was more potent than that of the antiallergic medicine disodium cromoglycate (DSCG, 64.8 μM).
  • Genzoh Tanabe; Yoshiaki Manse; Teppei Ogawa; Naoki Sonoda; Shinsuke Marumoto; Fumihiro Ishikawa; Kiyofumi Ninomiya; Saowanee Chaipech; Yutana Pongpiriyadacha; Osamu Muraoka; Toshio Morikawa
    The Journal of organic chemistry 83 15 8250 - 8264 2018年08月 
    A hitherto unreported member of γ-alkylidenebutenolides in Melodorum fruticosum (Annonaceae), (4 E)-6-benzoyloxy-7-hydroxy-2,4-heptadiene-4-olide, named as isofruticosinol (4) was isolated from the methanol extract of flowers, along with the known related butenolides, namely, the (4 Z)-isomer (3) of 4, melodrinol (1), and its (4 E)-isomer (2). To unambiguously determine the absolute configuration at the C-6 position in these butenolides, the first total syntheses of both enantiomers of 2-4 were achieved over 6-7 steps from commercially available D- or L-ribose (D- and L-5). Using the same protocol, both enantiomers of 1 were also synthesized. Based on chiral HPLC analysis of all synthetic compounds ( S- and R-1-4), all naturally occurring butenolides were assigned as partial racemic mixtures with respect to the chiral center at C-6 (enantiomeric ratio, 6 S/6 R = ∼83/17). Furthermore, the melanogenesis inhibitory activities of S- and R-1-4 were evaluated, with all shown to be potent inhibitors with IC50 values in the range 0.29-2.9 μM, regardless of differences in the stereochemistry at C-6. In particular, S-4 (IC50 = 0.29 μM) and R-4 (0.39 μM) showed potent inhibitory activities compared with that of reference standard arbutin (174 μM).
  • Toshio Morikawa; Yoshiaki Manse; Mika Koda; Saowanee Chaipech; Yutana Pongpiriyadacha; Osamu Muraoka; Kiyofumi Ninomiya
    Journal of natural medicines 72 2 542 - 550 2018年03月 
    Two new aromatic glycosides, elengiosides A (1) and B (2), were isolated from the methanolic extract of the flowers of Mimusops elengi (Sapotaceae) together with 26 known compounds. Their stereostructures were elucidated based on their spectroscopic properties and chemical evidence. Among the isolates, a phenylethanoid glycoside, undatuside C (14), was found to exhibit hyaluronidase inhibitory activity.
  • Yoshiaki Manse; Kiyofumi Ninomiya; Ryosuke Nishi; Yoshinori Hashimoto; Saowanee Chaipech; Osamu Muraoka; Toshio Morikawa
    Molecules (Basel, Switzerland) 22 12 2017年12月 
    In our continuing study of biologically active natural products from the fruit of Alpinia galanga (Zingiberaceae), we newly isolated three new labdane-type diterpenes, termed galangalditerpenes A-C (1-3), along with four known sesquiterpenes (4-7) and two diterpenes (8 and 9). The stereostructures of 1-3 were elucidated on the basis of their spectroscopic properties. The melanogenesis inhibitory activities in theophylline-stimulated murine B16 melanoma 4A5 cells of these isolates, including the new diterpenes (1-3, IC50 = 4.4, 8.6, and 4.6 μM, respectively), were found to be more than 6-87-fold higher than that of arbutin (174 μM), a commercially available positive control.
  • Yoshiaki Manse; Kiyofumi Ninomiya; Akane Okazaki; Eriko Okada-Nishida; Takahiro Imagawa; Mami Imamura-Mizushima; Yuki Yamano; Kinji Kaname; Sho Nakamura; Toshio Morikawa
    Natural Product Communications 12 8 1934578X1701200 - 1934578X1701200 2017年08月 
    A methanol extract from the aerial part of Isodon trichocarpus (Labiatae) demonstrated inhibitory effects on melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells (IC50 = 1.6 μg/mL). From the extract, nine diterpenoids (1–9) and four triterpenoids (10–13) were isolated. Among the isolates, enmein (1, IC50 = 0.22 μM), isodocarpin (2, 0.19 μM), nodosin (4, 0.46 μM), and oridonin (6, 0.90 μM) showed an inhibitory effect without notable cytotoxicity at the effective concentrations. These diterpenoids (1, 2, 4, and 6) inhibited the expression of tyrosinase, tyrosine-related protein (TRP)-1, and TRP-2 mRNA, which could be the mechanism of melanogenesis inhibitory activity.
  • Ryosuke Satoh; Kanako Hagihara; Kazuki Matsuura; Yoshiaki Manse; Ayako Kita; Tatsuki Kunoh; Takashi Masuko; Mariko Moriyama; Hiroyuki Moriyama; Genzoh Tanabe; Osamu Muraoka; Reiko Sugiura
    Genes to cells : devoted to molecular & cellular mechanisms 22 7 608 - 618 2017年07月 
    The extracellular signal-regulated kinase (ERK) signaling pathway is essential for cell proliferation and is frequently deregulated in human tumors such as melanoma. Melanoma remains incurable despite the use of conventional chemotherapy; consequently, development of new therapeutic agents for melanoma is highly desirable. Here, we carried out a chemical genetic screen using a fission yeast phenotypic assay and showed that ACA-28, a synthetic derivative of 1'-acetoxychavicol acetate (ACA), which is a natural ginger compound, effectively inhibited the growth of melanoma cancer cells wherein ERK MAPK signaling is hyperactivated due to mutations in the upstream activating regulators. ACA-28 more potently inhibited the growth of melanoma cells than did the parental compound ACA. Importantly, the growth of normal human epidermal melanocytes (NHEM) was less affected by ACA-28 at the same 50% inhibitory concentration. In addition, ACA-28 specifically induced apoptosis in NIH/3T3 cells which were oncogenically transformed with human epidermal growth factor receptor-2 (HER2/ErbB2), but not in the parental cells. Notably, the ACA-28-induced apoptosis in melanoma and HER2-transformed cells was abrogated when ERK activation was blocked with a specific MEK inhibitor U0126. Consistently, ACA-28 more strongly stimulated ERK phosphorylation in melanoma cells, as compared in NHEM. ACA-28 might serve as a promising seed compound for melanoma treatment.
  • Yoshiaki Manse; Kiyofumi Ninomiya; Ryosuke Nishi; Iyori Kamei; Yushi Katsuyama; Takahito Imagawa; Saowanee Chaipech; Osamu Muraoka; Toshio Morikawa
    Bioorganic & medicinal chemistry 24 23 6215 - 6224 2016年12月 
    An aqueous acetone extract from the fruit of Alpinia galanga (Zingiberaceae) demonstrated inhibitory effects on melanogenesis in theophylline-stimulated murine B16 melanoma 4A5 cells (IC50=7.3μg/mL). Through bioassay-guided separation of the extract, a new 7-O-9'-linked neolignan, named galanganol D diacetate (1), was isolated along with 16 known compounds including 14 phenylpropanoids (2-15). The structure of 1, including its absolute stereochemistry in the C-7 position, was elucidated by means of extensive NMR analysis and total synthesis. Among the isolates, 1 (IC50=2.5μM), 1'S-1'-acetoxychavicol acetate (2, 5.0μM), and 1'S-1'-acetoxyeugenol acetate (3, 5.6μM) exhibited a relatively potent inhibitory effect without notable cytotoxicity at effective concentrations. The following structural requirements were suggested to enhance the inhibitory activity of phenylpropanoids on melanogenesis: (i) compounds with 4-acetoxy group exhibit higher activity than those with 4-hydroxy group; (ii) 3-methoxy group dose not affect the activity; (iii) acetylation of the 1'-hydroxy moiety enhances the activity; and (iv) phenylpropanoid dimers with the 7-O-9'-linked neolignan skeleton exhibited higher activity than those with the corresponding monomer. Their respective enantiomers [1' (IC50=1.9μM) and 2' (4.5μM)] and racemic mixtures [(±)-1 (2.2μM) and (±)-2 (4.4μM)] were found to exhibit melanogenesis inhibitory activities equivalent to those of the naturally occurring optical active compounds (1 and 2). Furthermore, the active compounds 1-3 inhibited tyrosinase, tyrosine-related protein (TRP)-1, and TRP-2 mRNA expressions, which could be the mechanism of melanogenesis inhibitory activity.
  • Tomohisa Yasuhara; Yoshiaki Manse; Takayuki Morimoto; Wang Qilong; Hisashi Matsuda; Masayuki Yoshikawa; Osamu Muraoka
    Bioorganic & medicinal chemistry letters 19 11 2944 - 6 2009年06月 
    Through SAR studies on 1'S-1'-acetoxychavicol acetate (1) against Type I antiallergic activity by indexing release of beta-hexosaminidase, a marker of antigen-IgE-mediated degranulation in RBL-2H3 cells, more stable and potent analogue, 4-(methoxycarbonyloxyphenylmethyl)phenyl acetate (16), has been developed. The compound 16 also strongly inhibited the antigen-IgE-mediated TNF-alpha and IL-4 production.
  • Hirofumi Takada; Masayuki Nishimura; Yuta Asayama; Yoshiaki Mannse; Shunji Ishiwata; Ayako Kita; Akira Doi; Aiko Nishida; Naoyuki Kai; Sayako Moriuchi; Hideki Tohda; Yuko Giga-Hama; Takayoshi Kuno; Reiko Sugiura
    Molecular Biology of the Cell 18 12 4794 - 4802 2007年12月 
    In fission yeast, knockout of the calcineurin gene resulted in hypersensitivity to Cl−, and the overexpression of pmp1+encoding a dual-specificity phosphatase for Pmk1 mitogen-activated protein kinase (MAPK) or the knockout of the components of the Pmk1 pathway complemented the Cl−hypersensitivity of calcineurin deletion. Here, we showed that the overexpression of ptc1+and ptc3+, both encoding type 2C protein phosphatase (PP2C), previously known to inactivate the Wis1–Spc1–Atf1 stress-activated MAPK signaling pathway, suppressed the Cl−hypersensitivity of calcineurin deletion. We also demonstrated that the mRNA levels of these two PP2Cs and pyp2+, another negative regulator of Spc1, are dependent on Pmk1. Notably, the deletion of Atf1, but not that of Spc1, displayed hypersensitivity to the cell wall-damaging agents and also suppressed the Cl−hypersensitivity of calcineurin deletion, both of which are characteristic phenotypes shared by the mutation of the components of the Pmk1 MAPK pathway. Moreover, micafungin treatment induced Pmk1 hyperactivation that resulted in Atf1 hyperphosphorylation. Together, our results suggest that PP2C is involved in a negative feedback loop of the Pmk1 signaling, and results also demonstrate that Atf1 is a key component of the cell integrity signaling downstream of Pmk1 MAPK.

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