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天然黄酮黄芩素的自由基反应及其膜保护特性的可能机制。

Free radical reactions of a naturally occurring flavone baicalein and possible mechanisms towards its membrane protective properties.

作者信息

Adhikari S, Tilak Jai C, Devasagayam T P A

机构信息

Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Mumbai 400 085, India.

出版信息

Indian J Biochem Biophys. 2011 Aug;48(4):275-82.

PMID:22053697
Abstract

Baicalein (5, 6, 7-trihydroxy-2-phenyl-4H-1-benzopyran-4-one), a naturally occurring flavone present in some of the medicinal plants is known for its potential therapeutic effects, such as cardioprotective, anticancer and anti-inflammatory properties. However, detailed role and mechanisms behind its protective properties against different generators for oxidative stress have not been examined. In the present study, we investigated the possible protective ability of baicalein against the membrane damage caused by reactive oxygen species (ROS) and reactive nitrogen species (RNS) and the mechanisms involved using pulse radiolysis technique. Baicalein offered efficient protection even at a concentration of 10 microM towards membrane damage caused by lipid peroxidation induced by the gamma-radiation, peroxyl radicals, ascorbate-Fe2+ and peroxynitrite in rat liver mitochondria and heart homogenate. To elucidate its reaction mechanisms with biologically relevant radicals, transient absorption spectroscopy employing pulse radiolysis technique was used. Baicalein showed fairly high rate constants (3.7 x 10(9), 1.3 x 10(9) and 8.0 x 10(8) dm3 mol(-1) s(-1) for hydroxyl, azidyl and alkylchloroperoxyl radicals, respectively), suggesting that baicalein can act as an effective scavenger of these radicals. In each case, the phenoxyl radical of baicalein was generated. Thus, it was evident that the phenolic moiety of baicalein was responsible for the free radical scavenging process. Baicalein also reacts with linoleic acid peroxyl radical (LOO*), indicating its ability to act as a chain breaking antioxidant. Peroxynitrite-mediated radicals were shown to be reactive towards baicalein and the bimolecular rate constants were 2.5 x 10(7) and 3 x 10(8) dm3 mol(-1) s(-1) for NO2 and CO3(-) radicals, respectively. In conclusion, our results revealed the potential of baicalein in protecting mitochondrial membrane against oxidative damage induced by the four different agents. We propose that the protective effect is mediated via scavenging of primary and secondary radicals generated during oxidative stress.

摘要

黄芩素(5,6,7 - 三羟基 - 2 - 苯基 - 4H - 1 - 苯并吡喃 - 4 - 酮)是一种存在于某些药用植物中的天然黄酮,以其潜在的治疗作用而闻名,如心脏保护、抗癌和抗炎特性。然而,其针对不同氧化应激源的保护特性背后的详细作用和机制尚未得到研究。在本研究中,我们使用脉冲辐解技术研究了黄芩素对活性氧(ROS)和活性氮(RNS)引起的膜损伤的可能保护能力及其相关机制。即使在浓度为10微摩尔时,黄芩素对大鼠肝线粒体和心脏匀浆中由γ辐射、过氧自由基、抗坏血酸 - Fe2 + 和过氧亚硝酸盐诱导的脂质过氧化引起的膜损伤也提供了有效的保护。为了阐明其与生物相关自由基的反应机制,采用了脉冲辐解技术的瞬态吸收光谱法。黄芩素显示出相当高的速率常数(分别对羟基、叠氮基和烷基氯过氧自由基为3.7×10^9、1.3×10^9和8.0×10^8 dm3 mol^(-1) s^(-1)),表明黄芩素可以作为这些自由基的有效清除剂。在每种情况下,都生成了黄芩素的苯氧自由基。因此,很明显黄芩素的酚部分负责自由基清除过程。黄芩素还与亚油酸过氧自由基(LOO*)反应,表明其作为链断裂抗氧化剂的能力。过氧亚硝酸盐介导的自由基对黄芩素具有反应性,对于NO2和CO3(-)自由基,双分子速率常数分别为2.5×10^7和3×10^8 dm3 mol^(-1) s^(-1)。总之,我们的结果揭示了黄芩素在保护线粒体膜免受四种不同试剂诱导的氧化损伤方面的潜力。我们提出这种保护作用是通过清除氧化应激期间产生的初级和次级自由基来介导的。

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