JP2014087278A - トルラ酵母由来グルコシルセラミドの線維芽細胞増殖促進剤としての利用 - Google Patents
トルラ酵母由来グルコシルセラミドの線維芽細胞増殖促進剤としての利用 Download PDFInfo
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- JP2014087278A JP2014087278A JP2012238743A JP2012238743A JP2014087278A JP 2014087278 A JP2014087278 A JP 2014087278A JP 2012238743 A JP2012238743 A JP 2012238743A JP 2012238743 A JP2012238743 A JP 2012238743A JP 2014087278 A JP2014087278 A JP 2014087278A
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- Prior art keywords
- glucosylceramide
- yeast
- cell proliferation
- fibroblast cell
- extract
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Abstract
【解決手段】酵母由来、特にトルラ酵母由来のグルコシルセラミドについて線維芽細胞増殖促進効果を確認したところ、植物原料のコメ、トウモロコシ、こんにゃく由来のグルコシルセラミドに比較して、優れた線維芽細胞増殖促進効果があることを見出した。
【選択図】図2
Description
(1)、酵母エキス抽出後のトルラ酵母菌体から抽出されたグルコシルセラミドを含有する線維芽細胞増殖促進剤、
(2)、(1)の線維芽細胞増殖促進剤を含有する飲食品、
(3)、(1)の線維芽細胞増殖促進剤を含有する化粧品、
(4)、(1)の線維芽細胞増殖促進剤を含有する皮膚外用剤及び医薬品。
前処理としてグルコシルセラミド組成物20mgを2mlの0.4N KOH EtOHに溶解し、37℃で2時間インキュベートした。インキュベート後は0.4N HCl EtOHを2ml加えて中和し、遠心分離後の上清4ulをTLCに供した。TLCはシリカゲルプレート(メルク社製Silicagel60、層厚0.25m)を使用し、クロロホルム:エタノール:水=65:16:2(容量比)で展開した。展開後はシリカゲルプレートを乾燥させ、アニスアルデヒド硫酸試液を噴霧して加熱することで発色させた。
前処理としてグルコシルセラミド組成物20mgを2mlの0.4N KOH EtOHに溶解し、37℃で2時間インキュベートした。インキュベート後は0.4N HCl EtOHを2ml加えて中和し、塩類をフィルター除去してからHPLCに供した。カラムにはGLサイエンス社製Inertsil 100Aを用い、グルコシルセラミドの検出は蒸発光散乱検出器(島津製ELSD−LTII)で行った。溶出溶媒にはクロロホルムとメタノール:水=95:5(容量比)のグラジエントを用いた。カラム温度は35℃、流速は1ml/min、ドリフトチューブ温度は40℃で窒素ガス圧力は350kPaであった。
キャンディダ・ウチリスCS7529株(FERMP−3340)を予めYPD培地(酵母エキス1%、ポリペプトン2%、グルコース2%)を含む三角フラスコで種母培養し、これを30L容発酵槽に18L培地に1〜2%植菌した。培地組成は、グルコース4%、燐酸一アンモニウム0.3%、硫酸アンモニウム0.161%、塩化カリウム0.137%、硫酸マグネシウム0.08%、硫酸銅1.6ppm、硫酸鉄14ppm、硫酸マンガン16ppm、硫酸亜鉛14ppmを用いた。培養条件は、pH4.0、培養温度30℃、通気量1vvm、撹拌600rpmで行い、アンモニアを添加しpHのコントロールを行った。16時間菌体培養した後、培養液を回収し、遠心分離により集菌し、180gの湿潤酵母菌体を得た。
菌体培養後の湿潤酵母菌体を蒸留水に懸濁して遠心分離を繰り返すことで洗浄した。洗浄後は湿潤菌体を蒸留水に再度懸濁するか、凍結乾燥または熱風乾燥させた乾燥菌体を蒸留水に懸濁し、以下の条件に調整することでエキス抽出を行った。
自己消化: 1N HClでpH5.0に調整後、55℃で4時間攪拌
酵素抽出:1N NaOHでpH7に調整後、細胞壁溶解酵素(ツニカーゼ)或いはプロテアーゼで55℃、4時間攪拌抽出(再現性確認中)
酸抽出:1N硫酸でpH2以下に調整後、65℃で2分間攪拌抽出
アルカリ抽出:2N NaOHでpH13に調整後、70℃で20分間攪拌抽出
比較例1〜3の評価(コメ、トウモロコシ、こんにゃく)
植物性グルコシルセラミドであるコメ(比較例1)、トウモロコシ(比較例2)、及びこんにゃく由来グルコシルセラミド(比較例3)について、ヒト皮膚線維芽細胞の賦活作用を測定した。
次に、上記製法により得られた本発明の線維芽細胞増殖促進剤である酵母由来グルコシルセラミドについて、線維芽細胞増殖促進作用を測定した。
コメ由来グルコシルセラミドには一般的に市販で入手可能なコメ由来のグルコシルセラミドを使用した。線維芽細胞増殖促進効果の評価においてコメ由来グルコシルセラミド濃度5μg/mlとなるように添加したところ、ヒト正常線維芽細胞で110%の増殖促進作用を示した。
トウモロコシ由来グルコシルセラミドには一般的に市販で入手可能なトウモロコシ由来のグルコシルセラミドを使用した。線維芽細胞増殖促進効果の評価においてトウモロコシ由来のグルコシルセラミドをセラミド濃度5μg/mlとなるように添加したところ、ヒト正常線維芽細胞において、116%の線維芽細胞の増殖を促進した。
こんにゃく由来グルコシルセラミドには一般的に市販で入手可能なこんにゃく由来のグルコシルセラミドを使用した。線維芽細胞増殖促進効果の評価においてこんにゃく由来のグルコシルセラミドをセラミド濃度5μg/mlとなるように添加したところ、ヒト正常線維芽細胞において、69%の線維芽細胞の増殖率を示した。
菌体培養後に洗浄し、熱風乾燥させたトルラ酵母の乾燥菌体5kgを蒸留水50Lに懸濁し、2N NaOHでpH13.0に調整した後、70℃で30分間エキス抽出した。抽出後は遠心分離で酵母残渣を回収し、酵母残渣の蒸留水への懸濁と遠心分離を3回繰り返すことで洗浄した。洗浄後は酵母残渣を真空乾燥することで3.3kgのエキス抽出酵母残渣が得られた。得られた酵母残渣全量を2倍量の90%エタノールに懸濁し、60℃で10時間攪拌してグルコシルセラミドを抽出した。遠心分離により抽出液を回収し、酵母残渣をエタノールで3回洗浄した洗浄液と合わせて濃縮した結果、抽出物300gが得られた。これをグルコシルセラミド含有組成物とし、HPLC−ELSDで分析した結果、グルコシルセラミドが2.1%含有されていた。またTLCによる分析の結果、夾雑物のステロール配糖体は確認されなかった。線維芽細胞促進効果の確認には、上記抽出物15gをさらにシリカカラムで精製することで、グルコシルセラミド含量を34%含有する組成物11gが得られた。得られた酵母由来グルコシルセラミド粗精製物を使用して線維芽細胞増殖促進効果の評価を行った。
Claims (4)
- 酵母エキス抽出後のトルラ酵母菌体から抽出されたグルコシルセラミドを含有する線維芽細胞増殖促進剤。
- 請求項1の線維芽細胞増殖促進剤を含有する飲食品。
- 請求項1の線維芽細胞増殖促進剤を含有する化粧品。
- 請求項1の線維芽細胞増殖促進剤を含有する皮膚外用剤及び医薬品。
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JP2017178842A (ja) * | 2016-03-30 | 2017-10-05 | 小林製薬株式会社 | 真皮線維芽細胞賦活剤、及びその用途 |
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JP6261031B2 (ja) * | 2012-10-30 | 2018-01-17 | 興人ライフサイエンス株式会社 | トルラ酵母由来グルコシルセラミドの大腸癌抑制剤としての利用 |
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