JP2005239585A - 冬虫夏草より見出された新規抗酸化活性物質とその利用 - Google Patents
冬虫夏草より見出された新規抗酸化活性物質とその利用 Download PDFInfo
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- JP2005239585A JP2005239585A JP2004048805A JP2004048805A JP2005239585A JP 2005239585 A JP2005239585 A JP 2005239585A JP 2004048805 A JP2004048805 A JP 2004048805A JP 2004048805 A JP2004048805 A JP 2004048805A JP 2005239585 A JP2005239585 A JP 2005239585A
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Abstract
Description
A) 下記の式(1)により表される化合物(即ち、3,4-diguanidinobutanoyl-DOPA:3,4−ジグアニジノブタノイル-DOPA)、又はその薬理上許容される塩。
C) 上記式(1)により表される化合物、又はその薬理上許容される塩を含有する機能性食品。
D) 上記式(1)により表される化合物、又はその薬理上許容される塩を有効成分とする医薬。
E) 下記の式(2)により表される化合物(3,4-diguanidinobutanoyltyrosine:3,4−ジグアニジノブタノイルチロシン)、又はその薬理上許容される塩。
G) 上記式(1)により表される化合物を、2,3-diaminopropanoic acid(2,3−ジアミノプロパン酸)より化学合成する方法。
本発明者は、ハナサナギタケ(Isaria japonica)の抽出物から強い抗酸化活性を有する画分を得た。さらに、得られた画分に含まれる化合物について、その構造を1H−核磁気共鳴(NMR)スペクトル法、13C−核磁気共鳴スペクトル法、および質量分析法(MALDI-TOF-MSとHR-FAB-MS)により決定したところ、上記式(1)の構造を有する新規化合物3,4−ジグアニジノブタノイル-DOPAであると同定し、ハナサナギタケから得られた新規物質として「ハナサナギン」と命名した。
図1および図2に、本実施例の精製方法(一部)が示される。
まず、ハナサナギタケを蚕蛹からピンセットでつまみ取り、湿重で193g(シヤーレ50枚分、蚕蛹750個体)得た。このハナサナギタケ(湿重193g)を液体窒素中で凍結粉砕後、60%エタノールを用い、室温で6回抽出を行いエタノール粗抽出物41.3gを得た。さらに、60%エタノール抽出残渣について、102℃、60分の条件下で、熱水抽出を2回行い、熱水粗抽出物14.6gを得た。
上記方法により得られた新規抗酸化活性物質とその前駆体の各構造を決定する目的で、一次元NMR,MALDI−TOF−MS,HR−FAB−MSを測定した。それらのうち、1H,13C−NMRデータ(重水中)が図4および図5に示される。
上記のように、ハナサナギンおよびその前駆体の2つの化合物は、分子内に官能基として二つのグアニジノ基を有していると推測された。
これにより、誘導化を行う前に推定していた平面構造を確定した。
構造決定した前駆体(Natural)をチロシナーゼ(酵素)で処理し、ハナサナギン(Enzymatic)へと誘導する反応を行った(下記Scheme.2)。図8には、ハナサナギン(Natural)、チロシナーゼ添加前の前駆体(Natural)、チロシナーゼ添加後、ハナサナギン(Enzymatic)の各HPLC分析クロマトグラムの結果が示される。また、この反応により得られたハナサナギン(Enzymatic)についてNMR,MALDI−TOF−MSを測定し、生合成的前駆体であると決定した。1H−NMRデータ(重水中)が図9に示される。
〔DPPHラジカル消去能〕
上記ハナサナギンとアスコルビン酸(ポジティブコントロール)についてDPPH(1,1-diphenyl-2-picrylhydrazyl)ラジカル消去能をESRにより測定した。
試験管内の水:エタノール(100:80)の混合水溶液180μLに試料の50%エタノール水溶液200μLを加え、さらに300μM DPPHエタノール溶液を20μL加えてよく攪拌し、一部をセルに採取し、90秒後にESR測定した。コントロールは試料の代わりに50%エタノール水溶液を用いた。
温度 室温
マイクロ波出力 4mW
磁場 336.0mT
変調 100kHz,0.63×1mT
増幅率 7.9×100
応答時間 0.03秒
掃引時間 2分
測定溶媒 50%エタノール
試験結果が図10のグラフに示される。アスコルビン酸とハナサナギンは、それぞれ3.1μM、8.1μMで50%のラジカル消去能を示した(同グラフ中、破線)。ハナサナギンはアスコルビン酸より約2.6倍弱い結果であったが、DPPHラジカル消去能は認められた。尚、同グラフ中、横軸に示した濃度は試験管内における最終濃度である。また、縦軸のラジカル消去率は次式で求めた。
消去率=[1−{試料の(B/A)/コントロールの(B/A)}]×100
A:MnO(内部標準)のシグナルの高さ
B:DPPH
次に、ハナサナギンとアスコルビン酸(ポジティブコントロール)についてスーパ−オキシドアニオン消去能をESRにより測定した。
試験管に5.5mMジエチレンアミン五酢酸リン酸緩衝液70μL、2mMヒポキサンチンリン酸緩衝液100μLを入れ、試料のリン酸緩衝液100μL、0.92M DMPO(5,5-Dimethyl-1-Pyrroline-N-oxide)リン酸緩衝液30μLを順次加え、最後に0.4Unit/mLキサンチンオキシダーゼリン酸緩衝液100μLを加えてよく攪拌し、一部をセルに採取し、40秒後にESR測定した。コントロールは試料の代わりにリン酸緩衝液を用いた。
温度 室温
マイクロ波出力 8mW
磁場 336.0mT
変調 100kHz,0.79×1mT
増幅率 10×100
応答時間 0.03秒
掃引時間 2分
測定溶媒 100mMリン酸緩衝液(pH=7.8)
試験結果が図11のグラフに示される。アスコルビン酸とハナサナギンは、それぞれ40μM、21μMでY=5の値を示し(同グラフ中、破線)、ハナサナギンはアスコルビン酸より約1.9倍強い結果となった。尚、同グラフ中、横軸に示した濃度は試験管内における最終濃度である。また、縦軸のY値は、直線変換型検量線方式により次式で求めた。
Y={コントロールの(B/A)/試料の(B/A)}−1
A:MnO(内部標準)のシグナルの高さ
B:DMPO−OOHのシグナルの高さ
Claims (7)
- 請求項1記載の式(1)により表される化合物、又はその薬理上許容される塩を有効成分とする抗酸化剤。
- 請求項1記載の式(1)により表される化合物、又はその薬理上許容される塩を含有する機能性食品。
- 請求項1記載の式(1)により表される化合物、又はその薬理上許容される塩を有効成分とする医薬。
- 請求項5記載の式(2)により表される化合物をチロシナーゼで処理することにより、請求項1記載の式(1)により表される化合物を製造する方法。
- 請求項1記載の式(1)により表される化合物を、2,3-diaminopropanoic acidより化学合成する方法。
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JP2008154488A (ja) * | 2006-12-22 | 2008-07-10 | Masami Moriyama | 自然免疫機能性飲食物 |
JP2012056867A (ja) * | 2010-09-07 | 2012-03-22 | Iwate Univ | ハナサナギタケ(P.tenuipes)粉末の熱水抽出物を含有する脳機能改善剤 |
KR101483915B1 (ko) | 2014-10-08 | 2015-01-16 | 성균관대학교산학협력단 | 4-이소프로필-2,6-비스(1-페닐에틸)아닐린을 유효성분으로 포함하는 염증성 질환 예방 또는 치료용 약학적 조성물 |
CN113736669A (zh) * | 2021-09-24 | 2021-12-03 | 滁州学院 | 一种虫草真菌新种及其分离鉴定方法 |
WO2023227145A1 (zh) * | 2022-05-27 | 2023-11-30 | 开贝科技(苏州)有限公司 | 一种铂纳米粒的制备方法及其制备的铂纳米粒和铂纳米粒的应用 |
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JP2002233332A (ja) * | 2001-02-05 | 2002-08-20 | Nobutoshi Tanaka | 高い抗酸化活性を有するイチョウ葉エキス含有組成物 |
JP2002272267A (ja) * | 2001-03-21 | 2002-09-24 | Toshikatsu Imamura | 冬虫夏草の人工培養方法並びにハナサナギタケの抽出組成物及びそれを用いた機能性食品 |
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JP2002233332A (ja) * | 2001-02-05 | 2002-08-20 | Nobutoshi Tanaka | 高い抗酸化活性を有するイチョウ葉エキス含有組成物 |
JP2002272267A (ja) * | 2001-03-21 | 2002-09-24 | Toshikatsu Imamura | 冬虫夏草の人工培養方法並びにハナサナギタケの抽出組成物及びそれを用いた機能性食品 |
JP2003128515A (ja) * | 2001-10-17 | 2003-05-08 | Toshikatsu Imamura | 化粧料 |
Cited By (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2008154488A (ja) * | 2006-12-22 | 2008-07-10 | Masami Moriyama | 自然免疫機能性飲食物 |
JP2012056867A (ja) * | 2010-09-07 | 2012-03-22 | Iwate Univ | ハナサナギタケ(P.tenuipes)粉末の熱水抽出物を含有する脳機能改善剤 |
KR101483915B1 (ko) | 2014-10-08 | 2015-01-16 | 성균관대학교산학협력단 | 4-이소프로필-2,6-비스(1-페닐에틸)아닐린을 유효성분으로 포함하는 염증성 질환 예방 또는 치료용 약학적 조성물 |
CN113736669A (zh) * | 2021-09-24 | 2021-12-03 | 滁州学院 | 一种虫草真菌新种及其分离鉴定方法 |
WO2023227145A1 (zh) * | 2022-05-27 | 2023-11-30 | 开贝科技(苏州)有限公司 | 一种铂纳米粒的制备方法及其制备的铂纳米粒和铂纳米粒的应用 |
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