JP2017023134A - ジンセノサイドf1を含むアミロイドプラーク除去用組成物 - Google Patents
ジンセノサイドf1を含むアミロイドプラーク除去用組成物 Download PDFInfo
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- JP2017023134A JP2017023134A JP2016125023A JP2016125023A JP2017023134A JP 2017023134 A JP2017023134 A JP 2017023134A JP 2016125023 A JP2016125023 A JP 2016125023A JP 2016125023 A JP2016125023 A JP 2016125023A JP 2017023134 A JP2017023134 A JP 2017023134A
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- ginsenoside
- amyloid
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- amyloid plaques
- alzheimer
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- A61K31/7034—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin
- A61K31/704—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages attached to a carbocyclic compound, e.g. phloridzin attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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Abstract
【解決手段】ジンセノサイドF1またはその食品学的に許容可能な塩を含むアミロイドプラーク除去用食品組成物。
【選択図】図3
Description
ジンセノサイドF1の記憶力回復効果を確認するために、C57B6、JXSJL、及びJ雑種マウスにアルツハイマー病関連遺伝子を導入(knock-in)したアルツハイマー病モデルマウスを準備した。
ジンセノサイドF1を実験対象となるマウスに投与するために、ジンセノサイドF1が含まれた飼料混合物を製造した。
実施例3−1:細胞の培養
マウスの脳組織の細胞の一つであるNeuro−2a(N2a)細胞を準備した。5%の二酸化炭素、90%の湿気、及び37℃の温度条件下で10%の不活性化されたウシ胎児血清(FBS)が含まれた90%のDMEM培地に前記細胞を培養させた。
アミロイドβは、10mのM濃度になるように滅菌されたPBSバッファに溶かした。その後、37℃で48時間静置してアミロイドβの凝集を誘発した。
ジンセノサイドF1は、100mMの濃度になるようにDMSOに溶かした。その後、前記ジンセノサイドF1を希釈して使用した。
前記実施例2で準備したジンセノサイドF1が含まれた混合物を摂取したマウスの脳にジンセノサイドF1が効果的に伝達されるか否かを確認した。
前記実施例1で準備したアルツハイマー病モデルマウスに、前記実施例2で製造されたジンセノサイドF1が混合された混合物を投与した後、ジンセノサイドF1が記憶力回復に効果があるかを確認するために、動物実験を実施した。
ジンセノサイドF1がアルツハイマー病モデルマウスの記憶回復に及ぼす効果を検証するために、幅60mm、高さ125mmであるY−mazeチャンバーの中央に実験動物を位置させた後、8分間自由に探索できるようにするY−mazeテストを実施した。
ジンセノサイドF1がアルツハイマー病モデルマウスの記憶回復に及ぼす効果を検証するために、アルツハイマー病モデルマウスの空間恐怖記憶テストを実施した。
実施例2で準備した飼料混合物を摂取した実施例1のアルツハイマー病モデルマウスの脳領域である海馬のアミロイドプラークの数を観察した。
b)前記脳切片サンプルをブロッキング剤(0.1%BSA、0.2%Triton X-100、2%goat-serum in PBS)で1時間常温放置した。
c)その後、ウサギ抗アミロイドβ(rabbit anti-amyloid beta)抗体を、脳切片サンプルに1:1000の割合で処理した後、4℃で48時間培養した。
d)HRPが結合されたヤギ抗ウサギ(HRP conjugated goat anti-rabbit)抗体を、前記段階c)で培養した脳切片サンプルに1:2000の割合で処理した後、常温で2時間培養した。
e)前記段階d)で培養した脳切片サンプルをABC溶液で、常温で1時間培養した。
f)前記段階e)で培養した脳切片サンプルをDAB溶液で、常温で8分間培養した後、0.3%の過酸化水素水30μlを添加して、常温で1分30秒間培養した。
g)前記a)〜f)段階を経て染色された脳切片サンプルをスライドガラスに載せた後、キシレンが添加されたcytosealで封入し、脳の領域である海馬のアミロイドプラークの数を測定した。
前記実施例3−1で培養された細胞に、凝集したアミロイドβ及びジンセノサイドF1を処理した後、LDH assay kitを用いて細胞毒性を測定した。
b)前記実施例3−2で凝集したアミロイドβを、前記a)段階の培地に10uMとなるように入れた後、30分間培養した。
c)前記b)段階の培地に、前記実施例3−3で準備されたジンセノサイドF1を100uMとなるように入れた後、48時間培養した。
d)前記b)段階、及びc)段階の培養上層液を48ウェルプレートに移し、冷蔵保管した。
凝集したアミロイドβに対するジンセノサイドF1の凝集抑制効果を確認するために、凝集したアミロイドβとチオフラビンT(Thioflavin T)の結合によって現われる蛍光スペクトルの変化を測定した。
b)使用前に、300uMの濃度で溶かしたチオフラビンT溶液を50倍希釈した。
c)培養が終了した試料100μlに希釈したチオフラビンT溶液を100μl入れ、暗室状態で常温にて30分間放置した。
d)マルチモードマイクロプレートリーダー(multi mode microplate reader)を用いて、励起450nm及び放出490nmで蛍光値を測定した。
ジンセノサイドF1によって、凝集したアミロイドβの分解に作用するタンパク質であるインスリン分解酵素(Insulin-degrading enzyme、IDE)とネプリライシン(Neprilysin、NPE)の発現が誘導されるか否かを確認するために、リアルタイムPCRとウエスタンブロット(Western blot)を用いてmRNA発現とタンパク質の発現に対する変化を測定した。
b)前記a)段階の培地にRNA抽出試薬(RNA extraction reagent)メーカー(TaKaRa)から提供された試薬を600ulずつ、それぞれの細胞培養培地に入れて溶解させた。
c)前記b)段階で溶解された液を1.5mlの遠心分離用チューブに移し、クロロホルム溶液を300ulずつ入れて混ぜた後、遠心分離してRNAが存在する上層液を回収した。
d)前記c)段階で回収した液と同量のイソプロパノールを入れて遠心分離してRNAペレットを得た。
e)前記d)段階で得られたRNAペレットを75%のエタノールを用いて洗浄し、乾燥させて高純度のRNAペレットを得た。
f)前記e)段階で得られたRNAペレットをジエチルピロカーボネート(diethylpyrocarbonate、DEPC)で処理した蒸留水で溶かした後、ナノドロップ装置(Nano-drop machine)を用いてRNA量を定量した。
g)前記f)段階で得られたRNAを、逆転写酵素キットのメーカー(Solgent)から提供された試薬を用いて、50℃で2時間反応させてcDNAを合成した。
h)前記g)の段階で作製したcDNAに、プライマーのメーカー(ジェノテック)に依頼して製作したインスリン分解酵素、ネプリライシン及びβアクチンのプライマーをSYBR Premix Ex Taqキットのメーカー(TaKaRa)から提供された試薬とそれぞれ混合した後、リアルタイムPCR装置を用いてインスリン分解酵素とネプリライシンのmRNA転写レベルを測定した(real-time PCR)。
b)前記a)段階の培地に1xPBS(pH7.4)1mlを入れ、セルスクレーパー(cell scraper)を用いて細胞を回収し、1.5mlの遠心分離用チューブに挿入して遠心分離して細胞ペレットを得た。
c)前記b)段階で得られたペレットにタンパク質分解酵素阻害剤を添加した細胞溶解バッファーを100ulずつ入れて混合して細胞を溶解させた後、遠心分離して上清液を得た。
d)タンパク質定量キットメーカー(iNtRON)から提供された試薬を使用し、前記c)段階で得られた上清液のタンパク質を定量した。
e)SDS−PAGE還元用染色液と前記d)で定量したタンパク質を、それぞれ混合して5分間沸騰させた後、12%のSDS−PAGEゲルに点滴し、70ボルトで1時間30分間、電気泳動した。
f)前記e)段階で電気泳動したSDS−PAGEゲルをメンブレントランスファー装置を用いてPVDFメンブレンに移した。
g)前記f)段階でトランスファーされたPVDFメンブレンに5%のスキムミルクを用いて1時間ブロッキングした。
h)1xTBST溶液を使用し、前記g)段階のメンブレンを洗浄し、マウス由来のインスリン分解酵素、ネプリライシン及びβアクチン1次抗体をそれぞれ入れて2時間反応させた。
i)1xTBST溶液を使用し、前記h)段階のメンブレンを洗浄し、HRPが結合された抗ウサギ免疫グロブリン二次抗体またはHRPが結合された抗マウス免疫グロブリン二次抗体をそれぞれ入れて2時間反応させた。
j)ウェスタンブロット検出キットのメーカー(iNtRON)から提供された基質溶液と増幅溶液を1:1の割合で混ぜて反応混合物を製造した。1xTBST溶液を使用し、前記i)段階のメンブレンを洗浄し、前記反応混合物2mlをメンブレンと反応させた。その後、蛍光及び化学イメージ分析装置を用いてタンパク質を検出した(Western blot)。
Claims (9)
- ジンセノサイドF1またはその食品学的に許容可能な塩を含むアミロイドプラーク除去用食品組成物。
- 前記組成物は、ジンセノサイドF1を組成物の総重量の0.01〜99.9重量%の割合で含む、請求項1に記載の食品組成物。
- 前記組成物は、食品学的に許容可能な担体をさらに含む、請求項1に記載の食品組成物。
- ジンセノサイドF1またはその食品学的に許容可能な塩を含む、アミロイドプラーク除去用飼料組成物。
- 前記組成物は、ジンセノサイドF1を組成物の総重量の0.01〜99.9重量%の割合で含む、請求項4に記載の飼料組成物。
- 前記組成物は、食品学的に許容可能な担体をさらに含む、請求項4に記載の飼料組成物。
- ジンセノサイドF1をヒト以外の個体に投与する段階を含む、アミロイドプラーク除去方法。
- 前記方法は、アミロイドプラークを、ジンセノサイドF1を投与しない個体に比べて2倍以上減少させるものである、請求項7に記載の除去方法。
- 前記組成物は、インスリン分解酵素(Insulin-degrading enzyme、IDE)、及びネプリライシン(Neprilysin、NPE)の発現を誘導することを特徴とする、請求項1に記載の組成物。
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CN106389449A (zh) | 2017-02-15 |
EP3130341A1 (en) | 2017-02-15 |
KR20170013793A (ko) | 2017-02-07 |
JP6300285B2 (ja) | 2018-03-28 |
US20170027969A1 (en) | 2017-02-02 |
US10307436B2 (en) | 2019-06-04 |
EP3130341B1 (en) | 2018-11-21 |
KR101777920B1 (ko) | 2017-09-14 |
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