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オキナワモズク由来フコイダンの免疫調節機能及び体内動態に関する臨床基礎研究

友利, 誠 TOMORI, Makoto トモリ, マコト 九州大学

2022.03.23

概要

フコイダンは、昆布、ワカメ、モズクなどの褐藻類に含まれる硫酸化多糖類の総称であり、その海藻の種類によって化学構造が異なる。フコイダンの原料となる海藻は古くから食用として利用され、その食経験から安全性は高い。本研究ではフコイダンの原料海藻として沖縄県の基幹水産物であるオキナワモズク(Cladosiphon okamuranus Tokida)に着目した。オキナワモズクは栽培によって流通する食用海藻であり、生育分布は鹿児島県奄美大島を北限(北緯29度)に沖縄県八重山諸島を南限(北緯24度)とする。フコイダンの先行研究では抗炎症、抗血液凝固、抗血栓、抗血管新生、抗ウイルス、抗腫瘍、抗酸化作用など様々な生理活性が報告されている。同様にオキナワモズク由来フコイダン(モズクフコイダン)における先行研究では、抗腫瘍、抗ウイルス、Helicobacter pylori(H. pylori)接着阻害作用、機能性胃腸症改善、整腸作用、免疫調節機能が報告されている。

 本研究の第Ⅰ章ではマウスを用いた動物試験によってモズクフコイダンの免疫調節作用を網羅的に検証し、第Ⅱ章では健常成人を対象にモズクフコイダン摂取がNK細胞の活性に与える影響を検討した。さらに第Ⅲ章ではモズクフコイダンの吸収に関与する因子としてH. pylori感染の有無とモズクの食習慣との関連を検証した。

 第Ⅰ章では8週齢BALB/c雌マウスを用いてモズクフコイダンの免疫調節作用を検証した。マウスを対照群とモズクフコイダン投与4群(102.5、205.0、410.0、1025.0mg/kg)の合計5群(10匹/群)にて実施した。試験は6週間行い、試験期間中はモズクフコイダンを連続経口投与した。試験終了後は脾臓、血液及び腹腔マクロファージを速やかに回収し、各試験に供した。その結果、モズクフコイダン群は対照群と比較して濃度依存的に脾臓由来免疫細胞の増殖及び腹腔マクロファージの貪食作用を有意に亢進した。また血中サイトカインは、コンカナバリンA(ConA)条件下ではインターロイキン(IL)-2が有意に亢進したが、IL-5は有意に減少した。一方、リポ多糖(LPS)条件下ではインターフェロン(IFN)-γ及びIL-2が濃度依存的に有意に亢進したが、IL-4及びIL-5は全てのモズクフコイダン群で有意に減少した。血中抗体濃度は、IgM、IgG及びIgAは濃度依存的に有意に亢進したが、IgEは全てのモズクフコイダン群で有意に減少した。

 第Ⅱ章では健常成人(20〜65歳)を対象にモズクフコイダン摂取におけるNK細胞の活性と安全性に与える影響についてヒト試験で評価した。試験はプラセボ対照ランダム化二重盲検並行群間試験法で実施し、40名の健康な被験者をモズクフコイダン群(男性10名、女性10名:平均年齢47.0±7.6歳)とプラセボ群(男性10名、女性10名:平均年齢45.5±7.8歳)に偏りがないように割り当てた。試験デザインは、摂取期間:12週間、休薬期間:4週間の合計16週間で行い、モズクフコイダン群の被験者は3g/日を摂取した。その結果、モズクフコイダン群では摂取8週後、摂取前と比較して有意にNK細胞活性が亢進した。特に男性被験者において、摂取8週後のモズクフコイダン群とプラセボ群の比較ではモズクフコイダン群が有意に高いNK細胞活性を認めた。また安全性評価では、被験者の血液及び生化学検査について問題となるような変化は認められなかった。またモズクフコイダン摂取を原因とする有害事象も認められなかった。

 第Ⅲ章ではモズクフコイダンの吸収H. pylori感染及びモズクの食習慣との相関についてヒトを対象に検証した。健康な日本人を対象にインターネットで募集し、同意の得られた259名を被験者としてリクルートした。被験者にはモズクフコイダン3g(1500mg/本×2本)を摂取してもらい、摂取前及び摂取後3、6、9時間後の尿をサンプルとして回収した。回収した尿サンプル中のモズクフコイダン濃度と抗H. pylori抗体価を測定した。さらに、モズク食事習慣と尿中モズクフコイダン濃度、抗H. pylori抗体価との相関を検証した。その結果、尿中モズクフコイダン濃度は摂取前と比較して摂取後有意に上昇した。また、H. pylori陽性者のΔMaxフコイダン濃度(尿中最大濃度-摂取前尿中濃度)を年齢別に比較したところ、40歳以上の被験者で有意に低い値を示した。モズク食習慣との相関関係は以下の通りであった。

1) H. pylori陰性者では,モズクをよく食べる人は,ほとんど食べない人に比べて,尿中モズクフコイダンの基礎値が有意に高い。
2) H. pylori陽性者では,月1回以上モズクを食べる40歳以上の被験者のΔMaxフコイダン濃度は,40歳未満の被験者のΔMaxフコイダン濃度よりも有意に低い。
3) モズクをよく食べる40歳以上のH. pylori陽性者のΔMaxフコイダン値は、40歳未満のH. pylori陰性者のΔMaxフコイダン値よりも有意に低い。
4) H. pylori陽性者において、月1回以上モズクを食べる被験者の尿中フコイダン基礎値とΔMaxフコイダン値との間に正の相関(r=0.315)を認めた。

 本研究の成果は、日常的な感染症(かぜ症候群等)におけるセルフメディケーションをサポートするための健康維持やQOL(Quality of Life)の向上に貢献し、また、H. pylori感染とモズクの食習慣がモズクフコイダンの吸収に関係していることが示唆され、モズクフコイダンの吸収及び代謝の一端を明らかにした。今回の知見は、消化器系や免疫系の分野での栄養補助食品や医薬品の開発に貢献すると考えられる。

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