JP6967261B2 - メタボリックシンドロームの予防又は改善用食品組成物及び医薬組成物 - Google Patents
メタボリックシンドロームの予防又は改善用食品組成物及び医薬組成物 Download PDFInfo
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Description
(1)ウエスト周囲径が、男性の場合で85cm以上、女性の場合で90cm以上(内臓脂肪面積100cm2以上に相当する。)
(2)血中トリグリセリドが150mg/dL以上、且つ/又は、血中HDLコレステロールが40mg/dL以下
(3)収縮期血圧が130mmHg以上、且つ/又は、拡張期血圧が85mmHg以上
(4)空腹時血糖値が110mg/dL以上
[1]67LRアゴニストと、ネギ属植物抽出物中に見出される含硫化合物とを有効成分として含有する、メタボリックシンドロームの予防又は改善用食品組成物。
[2]前記ネギ属植物抽出物中に見出される含硫化合物が、アリイン、アリシン、ジアリルジスルフィド、ジアリルトリスルフィド又はジアリルテトラスルフィドを含む、[1]に記載のメタボリックシンドロームの予防又は改善用食品組成物。
[3]前記67LRアゴニストが、EGCG、ウーロン茶重合ポリフェノール、プロシアニジンC1又はこれらの誘導体を含む、[1]又は[2]に記載のメタボリックシンドロームの予防又は改善用食品組成物。
[4][1]〜[3]のいずれかに記載の食品組成物をヒト又は動物に摂取させる工程を備える、メタボリックシンドロームの予防又は改善方法(但し、ヒトに対する医療行為を除く。)。
[5]67LRアゴニストと、ネギ属植物抽出物中に見出される含硫化合物とを有効成分として含有する、メタボリックシンドロームの予防又は治療用医薬組成物。
[6]前記ネギ属植物抽出物中に見出される含硫化合物が、アリイン、アリシン、ジアリルジスルフィド、ジアリルトリスルフィド又はジアリルテトラスルフィドを含む、[5]に記載のメタボリックシンドロームの予防又は治療用医薬組成物。
[7]前記67LRアゴニストが、EGCG、ウーロン茶重合ポリフェノール、プロシアニジンC1、これらの誘導体又は67LRアゴニスト抗体を含む、[5]又は[6]に記載のメタボリックシンドロームの予防又は治療用医薬組成物。
1実施形態において、本発明は、67LRアゴニストと、ネギ属植物抽出物中に見出される含硫化合物とを有効成分として含有する、メタボリックシンドロームの予防又は改善用食品組成物を提供する。
本実施形態の食品組成物において、67LRアゴニストとしては、67kDaラミニンレセプター(67LR)にシグナルを伝達することができる物質であれば特に制限なく用いることができる。67LRアゴニストは食品への添加が認められるものであることが好ましい。
本実施形態の食品組成物において、ネギ属植物としては、ニンニク、ネギ、ニラ、タマネギ、ラッキョウ等が挙げられる。
1実施形態において、本発明は、上述した食品組成物をヒト又は動物に摂取させる工程を備える、メタボリックシンドロームの予防又は改善方法(但し、ヒトに対する医療行為を除く。)を提供する。本実施形態のメタボリックシンドロームの予防又は改善方法において、医療行為とは、医師(医師の指示を受けた者を含む。)がヒトに対して治療を実施する行為を意味する。
1実施形態において、本発明は、67LRアゴニストと、ネギ属植物抽出物中に見出される含硫化合物とを有効成分として含有する、メタボリックシンドロームの予防又は治療用医薬組成物を提供する。
1実施形態において、本発明は、67LRアゴニスト及びネギ属植物抽出物中に見出される含硫化合物の有効量を、治療を必要とする患者に投与することを含む、メタボリックシンドロームの予防又は治療方法を提供する。ここで、67LRアゴニスト、ネギ属植物抽出物中に見出される含硫化合物としては、医薬組成物について上述したものと同様である。
(緑茶抽出物及びジアリルジスルフィドの併用摂取による抗肥満作用)
マウスに高脂肪高ショ糖食、緑茶抽出物、ジアリルジスルフィド(以下、「DADS」という場合がある。)を組み合わせて摂取させ、肥満に対する影響を検討した。
(緑茶抽出物及びDADSの併用摂取による体脂肪蓄積抑制作用)
実験例1で屠殺した各群のマウスから、白色脂肪組織、腎臓周辺脂肪組織及び睾丸周辺脂肪組織を摘出し、それぞれ質量を測定した。図2(a)は、白色脂肪組織の質量を測定した結果を示すグラフである。図2(b)は、腎臓周辺脂肪組織の質量を測定した結果を示すグラフである。図2(c)は、睾丸周辺脂肪組織の質量を測定した結果を示すグラフである。
(緑茶抽出物及びDADSの併用摂取による中性脂肪低下作用)
実験例1で屠殺した各群のマウスから採血した血液を37℃で2時間静置して凝固させた後、4℃、2,000×gで15分間遠心して血清を採取した。続いて、得られた血清中の中性脂肪を、市販のトリグリセリド測定キット(和光純薬工業社製)を用いて測定した。また、実験例1で各群のマウスから採取した肝臓組織中の中性脂肪を、市販のトリグリセリド測定キット(和光純薬工業社製)を用いて測定した。
(緑茶抽出物及びDADSの併用摂取による血清コレステロール低下作用)
実験例3で調製した各群のマウスの血清中の総コレステロールを、市販のコレステロール測定キット(和光純薬工業社製)を用いて測定した。
(緑茶抽出物及びDADSの併用摂取による脂質代謝関連遺伝子の発現に対する効果)
実験例1で屠殺した各群のマウスから採取した肝臓組織からcDNAを調製し、リアルタイムPCRにより、下記表3に示す各脂質代謝関連タンパク質をコードする遺伝子のmRNAの発現量を測定した。表3には、各遺伝子のPCRに用いたプライマーの塩基配列の配列番号も示す。
(緑茶抽出物及びDADSの併用摂取による、白色脂肪組織における脂質代謝関連遺伝子の発現に対する効果)
実験例1で屠殺した各群のマウスから採取した白色脂肪組織からcDNAを調製し、リアルタイムPCRにより、下記表4に示す各脂質代謝関連タンパク質をコードする遺伝子のmRNAの発現量を測定した。表4には、各遺伝子のPCRに用いたプライマーの塩基配列の配列番号も示す。
(緑茶抽出物及びDADSの併用摂取による、腎臓周辺脂肪組織織における脂質代謝関連遺伝子の発現に対する効果)
実験例1で屠殺した各群のマウスから採取した腎臓周辺脂肪組織からcDNAを調製し、リアルタイムPCRにより、下記表5に示す各脂質代謝関連タンパク質をコードする遺伝子のmRNAの発現量を測定した。表5には、各遺伝子のPCRに用いたプライマーの塩基配列の配列番号も示す。
(緑茶抽出物及びDADSの併用摂取による、褐色脂肪組織における脂質代謝関連遺伝子の発現に対する効果)
実験例1で屠殺した各群のマウスから採取した褐色脂肪組織からcDNAを調製し、リアルタイムPCRにより、下記表6に示す各脂質代謝関連タンパク質をコードする遺伝子のmRNAの発現量を測定した。表6には、各遺伝子のPCRに用いたプライマーの塩基配列の配列番号も示す。
(緑茶抽出物及びDADSの併用摂取による、骨格筋における脂質代謝関連遺伝子の発現に対する効果)
実験例1で屠殺した各群のマウスから採取した骨格筋からcDNAを調製し、リアルタイムPCRにより、下記表7に示す各脂質代謝関連タンパク質をコードする遺伝子のmRNAの発現量を測定した。表7には、各遺伝子のPCRに用いたプライマーの塩基配列の配列番号も示す。
(緑茶抽出物及びDADSの併用摂取による血糖値上昇抑制効果)
実験例3で調製した各群のマウスの血清中のグルコース濃度(血糖値)を、市販のグルコース測定キット(和光純薬工業社製)を用いて測定した。
(緑茶抽出物及びDADSの併用摂取による血清遊離脂肪酸低下作用)
実験例3で調製した各群のマウスの血清中の遊離脂肪酸濃度を、市販の遊離脂肪酸測定キット(和光純薬工業社製)を用いて測定した。
(緑茶抽出物及びDADSの併用摂取によるインスリン抵抗性改善効果)
実験例3で調製した各群のマウスの血清中のインスリン濃度をELISA法により測定した。また、測定したインスリン濃度と、実験例10で測定した血糖値に基づいて、インスリン抵抗性の指標であるHOMA−IR値を算出した。HOMA−IR値は、下記式(F1)にしたがって算出した。
HOMA−IR値=(空腹時の血中インスリン濃度(μU/mL)×空腹時血糖値(mg/dL))/405 …(F1)
(緑茶抽出物及びDADSの併用摂取による、白色脂肪組織における炎症関連遺伝子の発現抑制効果)
脂肪組織における慢性的な炎症が肥満の一因であるといわれている。そこで、実験例1で屠殺した各群のマウスから採取した白色脂肪組織からcDNAを調製し、リアルタイムPCRにより、炎症関連タンパク質であるmonocyte chemotactic protein 1(MCP1)をコードする遺伝子のmRNAの発現量を測定した。プライマーとしては、センスプライマー(配列番号37)及びアンチセンスプライマー(配列番号38)を使用した。MCP1は、各種炎症性疾患において単球及びT細胞の組織浸潤に関与するタンパク質である。
(緑茶抽出物及びDADSの併用摂取による、肝傷害の評価)
実験例3で調製した各群のマウスの血清中のAspartate Aminotransferase(AST)活性及びAlanine aminotransferase(ALT)活性を市販のキット(和光純薬工業社製)を用いて測定した。AST活性及びALT活性は肝傷害の指標である。
(EGCG及びDADSの併用処理による、脂肪細胞における脂質代謝関連遺伝子の発現に対する効果)
まず、前駆脂肪細胞株を成熟脂肪細胞に分化させた。具体的には、マウス前駆脂肪細胞株である3T3−L1細胞を、2mLディッシュに1×105個/mLとなるように播種し、37℃、水蒸気飽和した5%CO2条件下で培養した。培地には10%ウシ胎児血清(FCS)を添加したダルベッコ改変イーグル培地(DMEM)を用いた。続いて、細胞がコンフルエントの状態になってから48時間後に、培地を、デキサメタゾン(1μM)、インスリン(10μg/mL)、3−イソブチル−1−メチルキサンチン(IBMX、0.5μM)を添加した10%FCS−DMEMに置換した。更に48時間培養後に、培地を、インスリン(10mg/mL)を添加した10%FCS−DMEMに置換した。その後、48時間毎に培地を10%FCS−DMEMに2回置換し、細胞を成熟脂肪細胞へと分化させた。
Claims (7)
- 67kDaラミニンレセプター(67LR)アゴニストと、ネギ属植物抽出物中に見出される含硫化合物とを有効成分として含有し、
前記67LRアゴニストが、緑茶抽出物、ウーロン茶抽出物又は紅茶抽出物であり、
前記含硫化合物が、アリイン、アリシン、ジアリルジスルフィド、ジアリルトリスルフィド又はジアリルテトラスルフィドである、メタボリックシンドロームの予防又は改善用食品組成物。 - 67LRアゴニストと、ネギ属植物抽出物中に見出される含硫化合物とを有効成分として含有し、
前記67LRアゴニストが、エピガロカテキンガレート(EGCG)、ウーロン茶重合ポリフェノール又はこれらの誘導体であり、
前記含硫化合物が、アリイン、アリシン、ジアリルジスルフィド、ジアリルトリスルフィド又はジアリルテトラスルフィドである、メタボリックシンドロームの予防又は改善用食品組成物。 - 67LRアゴニストと、ネギ属植物抽出物中に見出される含硫化合物とを有効成分として含有し、
前記67LRアゴニストがEGCGであり、
前記含硫化合物がジアリルジスルフィドである、メタボリックシンドロームの予防又は改善用食品組成物。 - 請求項1〜3のいずれか一項に記載の食品組成物を非ヒト動物に摂取させる工程を備える、メタボリックシンドロームの予防又は改善方法。
- 67LRアゴニストと、ネギ属植物抽出物中に見出される含硫化合物とを有効成分として含有し、
前記67LRアゴニストが、緑茶抽出物、ウーロン茶抽出物又は紅茶抽出物であり、
前記含硫化合物が、アリイン、アリシン、ジアリルジスルフィド、ジアリルトリスルフィド又はジアリルテトラスルフィドである、メタボリックシンドロームの予防又は治療用医薬組成物。 - 67LRアゴニストと、ネギ属植物抽出物中に見出される含硫化合物とを有効成分として含有し、
前記67LRアゴニストが、EGCG、ウーロン茶重合ポリフェノール又はこれらの誘導体であり、
前記含硫化合物が、アリイン、アリシン、ジアリルジスルフィド、ジアリルトリスルフィド又はジアリルテトラスルフィドである、メタボリックシンドロームの予防又は治療用医薬組成物。 - 67LRアゴニストと、ネギ属植物抽出物中に見出される含硫化合物とを有効成分として含有し、
前記67LRアゴニストがEGCGであり、
前記含硫化合物がジアリルジスルフィドである、メタボリックシンドロームの予防又は治療用医薬組成物。
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JP7061303B2 (ja) * | 2016-08-10 | 2022-04-28 | 国立大学法人九州大学 | 67kDaラミニンレセプター活性化剤及びその使用 |
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