JP5608082B2 - プテロスチルベン投与を介して酸化的ストレスを改善し、かつ作業記憶を向上させる方法 - Google Patents
プテロスチルベン投与を介して酸化的ストレスを改善し、かつ作業記憶を向上させる方法 Download PDFInfo
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- JP5608082B2 JP5608082B2 JP2010524125A JP2010524125A JP5608082B2 JP 5608082 B2 JP5608082 B2 JP 5608082B2 JP 2010524125 A JP2010524125 A JP 2010524125A JP 2010524125 A JP2010524125 A JP 2010524125A JP 5608082 B2 JP5608082 B2 JP 5608082B2
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Description
本明細書および特許請求の範囲において用いられるように、単数形の表現は、その文脈が明らかに他の意を指示しないのであれば、複数の参照を含む。例えば、用語「1つの細胞(a cell)」は複数の細胞を含み、それらの混合物を含む。
42匹の19ヶ月齢の雄性Fischer344ラットをNIA colony(Harlan Sprague Dawley、インディアナポリス、インディアナ州)から得た。ラットを、ステンレス製の網の吊り下げたケージにおいて個々に飼育し、自由に食事および水を提供し、12時間の明暗サイクルを維持した。ラットに1週間を与えて新たな環境に適合させ、その後、ラットの体重を合わせ、次いで、コントロール、低用量のプテロスチルベン(0.004%、体重1キログラム当り2.5mgに等しい)、または高用量のプテロスチルベン(0.016%、体重1キログラム当り10mgに等しい)の3つの食事のうちの1つをランダムに、合計12〜13週間(n=14/群)、与えた。全ての動物を、疾患の臨床的兆候について毎日観察した。
アフリカミドリザルの腎臓由来の細胞株である、COS−7細胞を、10%のウシ胎仔血清(FBS)を補い、100U/mlのペニシリンおよび100μg/mlの硫酸ストレプトマイシンを含有するダルベッコ変法イーグル培地(D−MEM)中で増殖させた。トランスフェクトする24時間前に、細胞をトリプシンで回収し、計測し、5×106細胞/プレートにて100mm2の組織培養プレートに播いた。細胞を、DEAEデキストラン法によりラットムスカリン性受容体サブタイプ1 DNAで一時的にトランスフェクトした。トランスフェクション後、細胞を、DNAの分解を最小化するために80μMのクロロキンを含有する増殖培地中で2.5時間、インキュベートした。次いで、トランスフェクトした細胞を、48時間、増殖培地中に維持し、トリプシンで回収し、カルシウムイメージングのために35mmプレート中のカバーガラスに播き、一晩、インキュベートした。
ブルーベリー(BB)抽出物(2mg/ml)、スチルベン[レスベラトロル(50μg/ml)、ピノスチルベン(50μg/ml)、デスオキシラポンチゲニン(25μg/ml)、プテロスチルベン(10μg/ml)、プテロスチルベングルコシド(10μg/ml)、レスベラトロルトリメチルエーテル(10μg/ml)、ピセタノール(10μg/ml)]およびドーパミン(1mM)処理を、Joseph J.ら、2004.J.Alz.Dis.6:403−411(本明細書に参照により援用される)に以前に記載されるように実施した。BB抽出物およびスチルベンを増殖培地に溶解し、その後、細胞を、処理した増殖培地を用いて37℃で45分間インキュベートし、続いて、4時間、ドーパミン投与した。これらのインキュベーションの後、細胞を、試験前に抽出物を含まない増殖培地で3回洗浄した。
モリス水迷路(MWM)は、被験体の空間学習および記憶を試験するための方法である。Richard Morrisによって開発されたMWMは、被検体が、遠位の手がかりに基づいて、円形の水のプール(直径134cm×高さ50cm、23℃に維持)の水面下(2cm)に置かれた隠されたプラットフォーム(直径10cm)を見つけて、以前の試行からその位置を記憶することを必要とする年齢および食事感受性の学習パラダイムである。正確な進路決定により、水からプラットフォーム上への避難が得られる。このために、被検体は、効果的に見つけるために、ポスター、実験者、コンピューター、ケージラック、などの遠位の手がかりを使用する。MWMの作業記憶バージョン(Brandeisら,1989.Int J Neurosci.48:29−69;Morris R.,1984.J Neurosci Methods.11:47−60.)を、午前および午後の時間、各時間2回の試行で(2回の試行の間、10分の試行間隔をあけて)、第9週目の処置の間、4日連続で毎日実施した。ラットは、各群から1匹の被検体を連続して試験するように制限してランダムに試験した。各試行の開始時に、被検体を、4つのランダムにした開始位置のうちの1つで水中に穏やかに浸した。各被検体に、プラットフォーム上に避難させるのに120秒を与えた;被検体がこの時間内に避難できない場合、プラットフォームに導いた。被検体がプラットフォームに到達すると、そこに15秒間維持した(試行1;参照記憶または獲得試行)。試行の間(10分)、被検体をそのホームケージに戻した。試行2(作業記憶または回復試行)は、試行1と同じプラットフォームの位置および開始位置を使用した。行動を録画し、潜伏(秒)(プラットフォームを見つけるまでの時間)、路程(cm)、および水泳速度(cm/秒;潜伏/路程)の測定を可能にする画像追跡ソフトウェア(HVS Image,UK)で分析した。使用した迷路およびパラダイムの詳細な説明は、Shukitt−Haleら、1998.Experimental Gerontology,33:615−624(本明細書に参照として援用される)に開示されている。
海馬大脳組織を、モリス水迷路試験の2〜3週間後に安楽死させた被検体から抽出した。その組織試料を−80℃で保存し、抽出前に氷中で解凍した。組織を、500μLのリン酸バッファー(pH7.4)で均質化し、次いで遠心分離(7000g、4℃、15分)した。その上清を回収し、均質化を繰り返した。合わせた上清を、酢酸エチルで抽出した(500μL×2)。その酢酸エチル抽出物を、窒素のストリーム下で乾燥させた。
Josephら,1988.Brain Res.,454:140−8;Josephら,1988.Brain Res.,454:149−55;Joseph J.ら,1990.Brain Res.,537:40−48;Josephら,1996.Free Radic.Biol.Med.,20:821−30(本明細書に参照として援用される)に開示されているように、表面灌流した線条体片からのK+誘発ドーパミン放出(K+−ERDA)のムスカリンの増加は、受容体感受性および線条体機能の指標であり、老化および酸化的ストレスに感受性がある。さらに、Josephら,1998.J.Neurosci.18:8047−8055;Josephら,1999.J.Neurosci.,19:8114−8121;Youdimら,2000.Nutr Neurosci.,3:383−97;Shukitt−Haleら,2005.Age.,27:49−57;Shukitt−Haleら,2006.Nutrition,22:295−302(本明細書に参照として援用される)に開示されているように、ドーパミン放出のムスカリンの増加は、食事補給に感受性がある。コントロール群および補給した群から得た線条体組織の保護能力を、線条体K+−ERDAのオキソトレモリン増加の差を調べることによりアッセイした。ドーパミン放出を、高用量、低用量およびコントロール食事を与えた被検体の脳から新たに解剖して、クロスカット(300μm、McIlwain組織チョッパー)した線条体片で、行動試験の2〜3週後に実施した。その片を、95%O2/5%CO2とともに30分間泡立て、21mMのNaHCO3、3.4mMのグルコース、1.3mMのNaH2PO4、1mMのEGTA、0.93mMのMgCl2、127mMのNaClおよび2.5mMのKCl(低KCl)(pH7.4)を含む改変Krebs−Ringer基礎放出培地(BRM)を含有する小さなガラスバイアルに入れた。組織の半分を、酸化的ストレスの条件下で食事の効果を評価するために50μMのH2O2で処理した。その片を灌流チャンバに入れ、37℃に維持し、30分間、BRMで灌流した。この平衡期間の後、培地を、(mMで)KCl30(高KCl)、CaCl2.2H2O1.26(EGTAの代わり)、NaCl57、および0または500μMのオキソトレモリンを含むものに移し、次いでK+−ERDAの増加を評価した。ドーパミン放出を、電気化学的検出に接続したHPLCにより定量し、Lowry法によって測定されるようにpmoles/mgタンパク質として表した。
Claims (8)
- 被検体の体重の1キログラムあたり、前記10mgの治療有効量のプテロスチルベンが投与される、請求項1に記載の組成物。
- 前記治療有効量のプテロスチルベンは、スノキ属ベリー類由来である、請求項1に記載の組成物。
- 前記スノキ属ベリー類はブルーベリーである、請求項3に記載の組成物。
- 前記被検体に酸化的ストレッサーを受けさせた場合に、ドーパミン放出が減少しない、請求項1に記載の組成物。
- プテロスチルベンは、ムスカリン性受容体サブタイプのカルシウムを緩衝する能力を増加させる、請求項1に記載の組成物。
- 前記ムスカリン性受容体サブタイプはM1である、請求項6に記載の組成物。
- 医薬担体をさらに含む、請求項1に記載の組成物。
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US9737495B2 (en) * | 2009-06-22 | 2017-08-22 | Indus Biotech Private Limited | Process for obtaining purified pterostilbene and methods of use thereof |
US20100119499A1 (en) * | 2009-09-17 | 2010-05-13 | Kneller Bruce W | Stilbene-based compositions and methods of use therefor |
US20110280850A1 (en) * | 2010-05-12 | 2011-11-17 | Starr Elizabeth I | Compositions Containing DNA Repair Enzyme And Anogeissus Extract |
US20120237494A1 (en) * | 2010-09-30 | 2012-09-20 | Daly Susan M | Compositions Containing Zinc PCA And Anogeissus Extract |
EP2537513A3 (en) * | 2011-03-11 | 2015-04-29 | ELC Management LLC | Use of anogeissus extract for fibrillin production in skin |
US9439875B2 (en) * | 2011-05-11 | 2016-09-13 | The United States Of America, As Represented By The Secretary Of Agriculture | Anxiolytic effect of pterostilbene |
US20130072509A1 (en) * | 2011-09-15 | 2013-03-21 | ChromaDex Inc. | Pterostilbene and statin combination for treatment of metabolic disease, cardiovascular disease, and inflammation |
WO2013051459A1 (ja) * | 2011-10-02 | 2013-04-11 | キユーピー 株式会社 | RNA干渉によるmRNA発現の抑制を促進する促進剤およびその用途 |
JP5901547B2 (ja) | 2012-03-28 | 2016-04-13 | 富士フイルム株式会社 | 組成物、これを含む皮膚外用剤、又は機能性食品 |
MX2021009652A (es) | 2013-10-30 | 2022-07-26 | Chromadex Inc | Composiciones de ribosido de nicotinamida para uso topico en el tratamiento de afecciones de la piel. |
WO2017011318A1 (en) | 2015-07-10 | 2017-01-19 | University Of Miami | Methods for treating mucopolysaccharidosis |
AU2017316614B2 (en) | 2016-08-22 | 2023-06-15 | Elysium Health, Inc. | Nicotinamide riboside and pterostilbene compositions and methods for treatment of neurodegenerative disorders |
WO2018089830A1 (en) | 2016-11-11 | 2018-05-17 | The Queen's University Of Belfast | Efficient and scalable syntheses of nicotinoyl ribosides and reduced nicotinoyl ribosides, modified derivatives thereof, phosphorylated analogs thereof, adenylyl dinucleotide conjugates thereof, and novel crystalline forms thereof |
US11071747B2 (en) | 2016-11-29 | 2021-07-27 | University Of Iowa Research Foundation | Use of NAD precursors for breast enhancement |
MX2019006278A (es) | 2016-11-29 | 2019-08-21 | Univ Iowa Res Found | Uso de precursores de nad para mejorar la salud materna y/o salud de la descendencia. |
SG11202010115RA (en) * | 2018-05-15 | 2020-11-27 | Alkahest Inc | Treatment of aging-associated disease with modulators of leukotriene a4 hydrolase |
JP7345312B2 (ja) * | 2019-08-09 | 2023-09-15 | キユーピー株式会社 | 発酵乳 |
CN112618520A (zh) * | 2021-01-14 | 2021-04-09 | 姚大纯 | 紫檀芪或白藜芦醇在制备用于治疗或改善孤独症谱系障碍的药物中的应用 |
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US20060057231A1 (en) * | 2004-08-19 | 2006-03-16 | Rimando Agnes M | Pterostilbene as a new agonist for the peroxisome proliferator-activated receptor alpha isoform |
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JP7558402B2 (ja) | 2020-09-25 | 2024-09-30 | シージェイ チェルジェダン コーポレイション | スチルベン系化合物を含む抗コクシジウム症組成物およびその用途 |
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CN103083288B (zh) | 2016-04-13 |
US20090069444A1 (en) | 2009-03-12 |
CN101820869B (zh) | 2012-12-12 |
WO2009032870A2 (en) | 2009-03-12 |
US9028887B2 (en) | 2015-05-12 |
KR20100075468A (ko) | 2010-07-02 |
CA2698661A1 (en) | 2009-03-12 |
US20120035272A1 (en) | 2012-02-09 |
HK1148932A1 (en) | 2011-09-23 |
HK1185257A1 (zh) | 2014-02-14 |
US20140256827A1 (en) | 2014-09-11 |
AU2008296293A1 (en) | 2009-03-12 |
CA2698661C (en) | 2016-03-29 |
US8809400B2 (en) | 2014-08-19 |
ES2526648T3 (es) | 2015-01-14 |
JP2010538077A (ja) | 2010-12-09 |
CN103083288A (zh) | 2013-05-08 |
CN101820869A (zh) | 2010-09-01 |
BRPI0816317A2 (pt) | 2017-07-25 |
EP2200597A2 (en) | 2010-06-30 |
WO2009032870A3 (en) | 2009-05-22 |
EP2200597A4 (en) | 2010-09-08 |
EP2200597B1 (en) | 2014-11-12 |
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