フラボノールは,オキシダティブ・ストレスを誘発した細胞のアポプトシス死を抑制することによって,内蔵された細菌による細胞の反応を妨害する
Ruoyi Lv1, Ziwen Cai2, Zhigang Sun3
1Beijing Key Laboratory of Traditional Chinese Veterinary Medicine, Beijing University of Agriculture, No.7 Beinong Road, Changping, Beijing 102206, China; Beijing Traditional Chinese Veterinary Engineering Center, Beijing University of Agriculture, No.7 Beinong Road, Changping, Beijing 102206, China.
International journal of antimicrobial agents
|August 22, 2025
まとめ
ミリセチン,ケンフェロール,クエルセチンのようなフラボノールは 宿主指向の治療法として 持続的な細菌感染に対して有望です これらの化合物は細胞内細菌の植民を減らし,アポトーシスを抑制することによって宿主細胞の損傷を軽減します.
科学分野:
- 微生物学
- 細胞生物学
- 薬理学について
背景:
- 内蔵されたバクテリアは 宿主細胞の反応を 乗っ取ることで 持続的な感染を引き起こします
- 従来の抗生物質は 細胞内細菌に対して しばしば無効です
- 宿主指向の治療法が 有望な代替手段として登場していますが 分子標的は不明です
研究 の 目的:
- 三つのフラボノール (ミリセチン,カエンフェロール,クエルセチン) の宿主指向の抗菌作用を調査する.
- 細胞内細菌感染症のフラボノール媒介抑制の基礎にある分子機構と標的を特定する.
- 内蔵された細菌による持続的な感染症に対する治療薬としてのフラボノールの可能性を評価する.
主な方法:
- 肺の上皮細胞を内蔵された Staphylococcus aureus と Streptococcus pneumoniae に対してフラボノールで治療する.
- 細胞内細菌のコロニー化と抗生物質感受性の定量分析 (MBCIN vs MBcex)
- 分子標的を特定するためにネットワーク薬理学とトランスクリプトミクスの適用.
- 反応性酸素種 (ROS) 生成とミトコンドリア膜ポテンシャル (ΔΨm) の評価
- PI3K/Bcl-2とカスパース-9/カスパース-3カスケードを含むアポプトシス細胞死経路の調査,in vitroとin vivo.
主要な成果:
- フラボノール治療は細胞内細菌の植民を著しく減少させた (約 細胞内最小細菌殺菌濃度 (MBCIN) を細胞外細菌殺菌濃度 (MBCex) に比べて低下させた.
- ネットワーク薬理学とトランスクリプトミクスは,アポプトティック細胞死亡の抑制を重要なメカニズムとして特定した.
- フラボノールはROSの産生を減らし,ミトコンドリア膜ポテンシャル (ΔΨm) を回復させ,それによって細菌内化誘発のアポトーシスを弱めた.
- 最も高いフェノルヒドロキシル含有量を持つミリセチンは,最も顕著な効果を示した.
- フラボノールはPI3K/Bcl-2とカスパース-9/カスパース-3のシグナル伝達経路を調節し,アポトーシスを軽減した.
結論:
- ミリセチン,カエンフェロール,クエルセチンは,内蔵された細菌に対する有意な宿主指向の抗菌性を持っています.
- フラボノールは,ROS,ミトコンドリア機能,特定のシグナルキャスケードを調節することにより,宿主上皮細胞を細菌誘発のアポトーシスから保護する.
- これらの発見は,細胞内病原体によって媒介される持続的な感染症との闘いにおけるフラボノールの治療的可能性を強調しています.
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