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厚朴酚是超氧自由基和过氧自由基的高效清除剂。

Honokiol is a potent scavenger of superoxide and peroxyl radicals.

作者信息

Dikalov Sergey, Losik Tanya, Arbiser Jack L

机构信息

Division of Cardiology, Emory University School of Medicine, 1639 Pierce Drive, Suite 319 WMB, Atlanta, GA 30322, United States.

出版信息

Biochem Pharmacol. 2008 Sep 1;76(5):589-96. doi: 10.1016/j.bcp.2008.06.012. Epub 2008 Jul 2.

Abstract

Honokiol, a compound extracted from Magnolia officinalis, has antitumor and antiangiogenic properties in several tumor models in vivo. Among the downstream pathways inhibited by honokiol is nuclear factor kappa beta (NFkappabeta). A prime physiologic stimulus of NFkappabeta is reactive oxygen species. The chemical structure of honokiol suggests that it may be an effective scavenger of reactive oxygen species. In this work, we have studied the reactions of honokiol with superoxide and peroxyl radicals in cell-free and cellular systems using electron spin resonance (ESR) and high-performance liquid chromatography (HPLC) techniques. Honokiol efficiently scavenged superoxide radicals in xanthine oxidase and cytochrome P-450 cell-free systems with the rate constant 3.2x10(5)M(-1)s(-1), which is similar to reactivity of ascorbic acid but 20-times higher than reactivity of vitamin E analog trolox. Honokiol potently scavenged intracellular superoxide within melanoma cells. In addition, honokiol scavenged peroxyl radicals generated by 2,2'-azo-bis(2-amidinopropane hydrochloride) (AAPH). The rate constant of the reaction of honokiol with peroxyl radicals (1.4x10(6)M(-1)s(-1)) was calculated from the competition with spin trap 5-(ethoxycarbonyl)-5-methyl-1-pyrroline N-oxide (EMPO), and was found close to reactivity of trolox (2.5x10(6)M(-1)s(-1)). Therefore, honokiol is an effective scavenger of both superoxide and peroxyl radicals, which may be important for physiological activity of honokiol.

摘要

厚朴酚是从厚朴中提取的一种化合物,在多种体内肿瘤模型中具有抗肿瘤和抗血管生成特性。厚朴酚抑制的下游信号通路之一是核因子κB(NFκB)。NFκB的主要生理刺激物是活性氧。厚朴酚的化学结构表明它可能是一种有效的活性氧清除剂。在这项研究中,我们使用电子自旋共振(ESR)和高效液相色谱(HPLC)技术,研究了厚朴酚在无细胞和细胞系统中与超氧阴离子和过氧自由基的反应。厚朴酚在黄嘌呤氧化酶和细胞色素P-450无细胞系统中能有效清除超氧阴离子自由基,速率常数为3.2×10⁵M⁻¹s⁻¹,这与抗坏血酸的反应活性相似,但比维生素E类似物托可索仑的反应活性高20倍。厚朴酚能有效清除黑色素瘤细胞内的超氧阴离子。此外,厚朴酚还能清除2,2'-偶氮二(2-脒基丙烷盐酸盐)(AAPH)产生的过氧自由基。通过与自旋捕获剂5-(乙氧羰基)-5-甲基-1-吡咯啉N-氧化物(EMPO)竞争计算得出厚朴酚与过氧自由基反应的速率常数为1.4×10⁶M⁻¹s⁻¹,发现其与托可索仑的反应活性接近(2.5×10⁶M⁻¹s⁻¹)。因此,厚朴酚是超氧阴离子和过氧自由基的有效清除剂,这可能对厚朴酚的生理活性具有重要意义。

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