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阿兰托拉克衍生物通过与阿兰托拉克不同的机制抑制瘤亡因子α诱导的核因子kB通路

Quy Van Vu¹, Kosuke Baba¹, Saki Sasaki¹

¹Department of Applied Biology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto, 606-8585, Japan.

European journal of pharmacology

|February 23, 2024

概括

阿兰托拉克衍生物通过与阿兰托拉克不同的新型机制抑制炎症分子ICAM-1的表达. 这些化合物为新的抗炎疗法提供了潜力.

科学领域:

自然产品化学自然产品化学
分子药理学分子药理学
免疫学免疫学免疫学

背景情况:

阿兰托拉克是一种酸乳,具有抗炎性质.
细胞间粘附分子-1 (ICAM-1) 在炎症反应中起着关键作用.
抑制ICAM-1是炎症性疾病的治疗点.

研究的目的:

为了确定具有ICAM-1抑制活性的alantolactone衍生物.
阐明这些衍生品的作用机制.
为了比较它们的抗炎作用与alantolactone.

主要方法:

使用RIKEN自然产品存储库库对alantolactone衍生物的选.
在受刺激的人静脉内皮细胞和A549肺腺癌细胞中抑制ICAM-1表达的测试.
核因子-κB (NF-κB) 信号通路的分析,包括蛋白质酸化,降解和DNA结合.

主要成果:

六种alantolactone衍生物抑制了A549细胞中的ICAM-1表达,其IC50值为13-21μM.
阿兰托拉克抑制了ICAM-1表达,IC50为5μM,并调节了NF-κB通路组件 (IκBα,RelA).
阿兰托拉克衍生物抑制了RelA与ICAM-1促进体的结合,但没有影响IκBα降解或RelA核转位,这表明有不同的机制.

结论:

阿兰托拉克衍生物代表了一类新的ICAM-1抑制剂.
与alantolactone相比,它们通过不同的机制产生抗炎作用,准IkBα降解下游的NF-κB通路.
这些发现表明,在炎症条件下,alantolactone衍生物的潜在治疗应用.

关键词:

亚兰托拉克顿是一种.细胞间粘附分子-1-1 核因子 κBB 核因子瘤死亡因子-α α-甲基烯 γ-乳酸盐

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