JP2015124187A - 関節炎予防または改善剤 - Google Patents
関節炎予防または改善剤 Download PDFInfo
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- JP2015124187A JP2015124187A JP2013270210A JP2013270210A JP2015124187A JP 2015124187 A JP2015124187 A JP 2015124187A JP 2013270210 A JP2013270210 A JP 2013270210A JP 2013270210 A JP2013270210 A JP 2013270210A JP 2015124187 A JP2015124187 A JP 2015124187A
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Images
Abstract
Description
(1)有効成分として14−デヒドロエルゴステロールまたはそれを含有する麹菌発酵エキスを含む、関節炎予防または改善剤。
(2)(1)に記載の関節炎予防または改善剤を含有する食品または動物飼料、あるいはそれらに用いる添加物。
(構造式)
(1)分子量:394.63
(2)分子式:C28H42O(高分解能APCI-Orbitrap法による観測値:m/z 395.33057(M+H)+)、理論値395.33139
(3)溶剤に対する溶解性:水に不溶、エタノールに難溶、クロロホルムに易溶
(4)紫外吸収スペクトル(MeCN):391nm
(5)1H-NMR(CD3OD): 6.15 (1H, m), 5.75 (1H, m), 5.65 (1H, dd, J = 2.2, 5.9
Hz), 5.27 (1H, dd, J = 7.0, 15.1 Hz), 5.21 (1H, dd, J = 7.9, 15.1 Hz), 3.64 (1H,m), 2.51 (1H, ddd, J = 2.2, 5.1, 10.6 Hz), 2.30 (1H, m), 2.20 (1H, m), 2.20 (1H, dd, J = 3.2, 7.8 Hz), 2.06 (1H, m), 2.05 (1H, m), 1.94 (1H, m), 1.90 (1H, m),1.87 (2H, m), 1.87 (1H, ddd, J = 3.2, 7.0, 7.3 Hz), 1.71 (1H, m), 1.59 (1H, m),1.57 (1H, m), 1.45 (1H, m), 1.45 (1H, ddd, J = 3.2, 6.3, 6.5 Hz), 1.30 (1H, m),1.05 (3H, d, J = 6.8 Hz ), 0.93 (3H, d, J = 7.3 Hz), 0.92 (3H, s,), 0.89 (3H, s), 0.85 (3H, d, J = 6.5 Hz), 0.83 (3H, d, J = 6.3 Hz).
(6)13C-NMR(CD3OD):149.2 (s), 143.0 (s), 135.4 (s), 132.2 (s), 132.0 (s),120.5 (s), 120.4 (s), 117.4 (s), 70.4 (s), 58.1 (s), 46.3 (s), 45.4 (s), 42.8 (s), 41.0 (s), 39.0 (s), 38.9 (s), 37.8 (s), 37.0 (s), 36.0 (s), 33.1 (s), 32.0 (s), 21.1 (s), 19.9 (s), 19.7 (s), 19.6 (s), 17.6 (s), 16.8 (s), 14.5 (s).
白麹(Aspergillus kawachii NBRC4308)をポテトデキストロース寒天培地(Difco、BD社)に植菌し、25℃で7日間静置培養した。0.01%のTween 20を含む麦芽エキス培地(Difco Malt Extract Broth、BD社)に胞子を形成した菌体を懸濁し、フィルター濾過を行なったものを胞子溶液とした。オートクレーブ滅菌後の麦芽エキス培地50mLを容量200mLのバッフル付三角フラスコに入れ、そこに1.0×105胞子/mLの濃度になるように胞子溶液を添加し、30℃、120rpmで20時間振盪培養を行ったものを前培養液とした。
上記(1)で得られた麹エキスをエタノールで10mg/mLに希釈し、次いでエタノール/アセトニトリルで1mg/mLに希釈し、さらに0.22μm径のPTFE膜で濾過したものをHPLCサンプルとした。これをDevelosil C30-UG-3(10×250mm、野村化学社)を用いた高速液体クロマトグラフィー(アセトニトリル/イソプロパノール=99/1)に供して分析した。麹エキス中の14−DHEピークを確認し、麹エキス1mg中に14−DHEが25μg含まれることを確認した(図1)。
17匹のDBA/1Jマウス(雄、7週齢、チャールスリバー社より購入)に対し、II型コラーゲン(コスモバイオ社)150μgをCFA400μgと混合してエマルジョン化したものをスコア検定開始21日前(第−21日目、一次免疫)およびスコア検定開始日(第0日目、二次免疫)に皮内投与して関節炎を誘導した。
マウスを対照群8匹と麹エキス混餌食群9匹に分け、麹エキス混餌食群にはスコア検定開始21日前である一次免疫開始日(第−21日目)から第18日目までの毎日、麹エキスを10mg(14−DHE含有量250μg)/匹/日とした飼料により混餌投与した(図2)。
各マウスの4本の足のそれぞれを下記の基準に基づいて観察し、4本の足のスコアの合計を算出した。スコアが1以上となったときに関節炎を発症したと判断した。
スコア0:正常
スコア1:四肢の指など小関節が1本のみ膨張発赤
スコア2:小関節2つ以上、あるいは手首・足首など大きな関節が膨張発赤
スコア3:手や足全体が発赤膨張
スコア4:手や足の膨張が最大限に達している
マウスを二次免疫後第18日目に安楽殺し、採血を行い、後肢の関節と鼠径リンパ節を摘出した。後肢の関節については、10%中性ホルマリン緩衝液を用いて固定し、脱灰作業を行なった後、パラフィン切片を作製し、H&E染色を行った。鼠径リンパ節については、コラゲナーゼIV(SIGMA社)およびDNaseI(Roche)で反応後、70μm滅菌フィルター(BD社)で濾過し、リンパ球を調製した。調製したリンパ球をPMA(ホルボール12−ミリステート13−アセテート)およびイオノマイシンを含有するLeukocyte activation cocktail(BD社)で4時間、37℃にて処理し、BD Cytofix/Cyoperm kit(BD社)を用いてCD4およびCD8陽性のT細胞の細胞内産生サイトカイン(TNF−α、IL−17、IFN−γ)を検出した。また、CD11cおよびCD11b陽性細胞をミエロイド樹状細胞とし、その細胞表面タンパク質分子(MHC−IIおよびCD86)の発現量をフローサイトメーターで測定した。さらに、二次免疫開始日から第7日目と解剖時(第18日目)に採血を行い、血中のIgG量を測定した。ELISAキットはMouse IgG ELISA Quantitation Set、Mouse IgG1 ELISA Quantitation Set、およびMouse IgG2a ELISA Quantitation Set(いずれもBethyl Laboratories社)を用いた。
図3は関節炎発症率の推移を示すグラフであり、図4は関節炎スコアの推移を示すグラフである。対照群では二次免疫後6日目で発症が始まり、それから1週間でほぼ完全に発症した。一方、麹エキス投与群では二次免疫後5日目で発症が始まったが、それから1週間経過しても発症率は80%に満たなかった。また、対照群では臨床スコアが最高で8.9まで上昇したが、麹エキス投与群ではスコア7.4までしか病状が進行しなかった。
Claims (2)
- 有効成分として14−デヒドロエルゴステロールまたはそれを含有する麹菌発酵エキスを含む、関節炎予防または改善剤。
- 請求項1に記載の関節炎予防または改善剤を含有する食品または動物飼料、あるいはそれらに用いる添加物。
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Citations (3)
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JP2004503595A (ja) * | 2000-07-19 | 2004-02-05 | バイオディックス シーオー. エルティディ. | 薬草抽出物を含む関節炎治療および予防用組成物の製造方法ならびにその組成物 |
WO2010150867A1 (ja) * | 2009-06-25 | 2010-12-29 | キリンホールディングス株式会社 | 穀類植物由来材料発酵物及び免疫調節剤 |
JP2013138617A (ja) * | 2011-12-28 | 2013-07-18 | Kirin Holdings Co Ltd | 微生物醗酵による14−デヒドロエルゴステロールの生産法 |
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JP2004503595A (ja) * | 2000-07-19 | 2004-02-05 | バイオディックス シーオー. エルティディ. | 薬草抽出物を含む関節炎治療および予防用組成物の製造方法ならびにその組成物 |
WO2010150867A1 (ja) * | 2009-06-25 | 2010-12-29 | キリンホールディングス株式会社 | 穀類植物由来材料発酵物及び免疫調節剤 |
JP2013138617A (ja) * | 2011-12-28 | 2013-07-18 | Kirin Holdings Co Ltd | 微生物醗酵による14−デヒドロエルゴステロールの生産法 |
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