尿素D:鞣花单宁在对抗氧化应激中的一种有前途的代谢物

IF 4.7 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Žiko Milanović
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引用次数: 0

摘要

本研究的目的是研究尿素D (UroD, 3,4,8,9-四羟基- 6h -苯并[c]铬-6- 1),一种从鞣花单宁中获得的代谢物,在减轻氧化应激中的功能。本研究的基础是估计UroD在生理条件下作为抗氧化剂的机制,强调标准的抗氧化机制,如正式的氢原子转移(f-HAT)、自由基加合物形成(RAF)/自由基偶联形成(RCF)和单电子转移后的质子转移(SET-PT)。本研究利用先进的量子力学技术,特别是密度泛函数理论(DFT)和基于量子力学的总自由基清除活性测试(QM-ORSA)方法,来评估UroD在活性自由基HOO•、ch300•和ccl300•存在下的热力学和动力学参数。估计的总速率常数(koverall)表明反应性为ccl300•(koverall = 2.06 × 1010 M−1s−1)>;HOO•(koverall = 2.59 × 109 M−1s−1)>;ch300•(koverall = 1.89 × 109 M−1s−1)。对产物相对比例(%)的检测表明,UroD主要通过所有检测机制表现出抗自由基作用,主要涉及单洋葱和碘离子酸碱种。除了直接对抗ROS的能力外,UroD还可以修复氧化性DNA损伤,特别是针对通常与2-脱氧鸟苷(2dg)相关的氧化副产物,这些副产物易受氧化应激影响。UroD通过SET机制再生g中心自由基阳离子(2dg•+),通过f-HAT再生糖段c中心自由基(2dg•),并通过顺序氢原子转移脱水(SHATD)修复i-OH-2dG损伤。此外,在抗氧化过程中形成的自由基产物可以在O2•−存在下再生成阴离子,阴离子随后被质子化成中性物质,可以重新参与抗氧化活性。这些发现强调了UroD清除自由基的效率,并提示其在保持细胞完整性和防止氧化应激相关疾病方面的潜在作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Urolithin D: A promising metabolite of ellagitannin in combatting oxidative stress

Urolithin D: A promising metabolite of ellagitannin in combatting oxidative stress
The objective of this research is to examine the function of urolithin D (UroD, 3,4,8,9-tetrahydroxy-6H-benzo[c]chromen-6-one), a metabolite obtained from ellagitannins, in the mitigation of oxidative stress. The research is based on estimating the mechanisms through which UroD acts as an antioxidant under physiological conditions, emphasizing standard antioxidant mechanisms such as formal Hydrogen Aatom Transfer (f-HAT), Radical Adduct Formation (RAF)/Radical Coupling Formation (RCF), and Single Electron Transfer followed by Proton Transfer (SET-PT). This study utilised advanced quantum mechanical techniques, specifically density functional theory (DFT) and the Quantum Mechanics-based test for Overall free Radical Scavenging activity (QM-ORSA) methodology, to assess the thermodynamic and kinetic parameters of UroD in the presence of reactive radical species HOO, CH3OO and CCl3OO. The estimated overall rate constants (koverall) indicate a reactivity order of CCl3OO (koverall = 2.06 × 1010 M−1s−1) > HOO (koverall = 2.59 × 109 M−1s−1) > CH3OO (koverall = 1.89 × 109 M−1s−1). The examination of the relative proportions of products (%) indicates that UroD exhibits antiradical action primarily through all examined mechanisms, with the predominant involvement of mononion and dianion acid-base species. In addition to its capacity to directly counteract ROS, UroD can restore oxidative DNA damage, specifically targeting oxidative byproducts commonly associated with 2-deoxyguanosine (2 dG), which are susceptible to oxidative stress. The UroD regenerates G-centered radical cations (2 dG•+) through the SET mechanism, C-centered radicals (2 dG) in the sugar moiety through f-HAT, and repairs i-OH-2dG lesions through sequential hydrogen atom transfer dehydration (SHATD). Additionally, the radical products formed during antioxidant action can be regenerated in the presence of O2•− into anionic species, which are subsequently protonated into neutral species that can re-engage in antioxidant activity. These findings underscore the efficiency of UroD in scavenging free radicals and suggest its potential role in preserving cellular integrity and protecting against oxidative stress-related diseases.
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来源期刊
CiteScore
7.70
自引率
3.90%
发文量
410
审稿时长
36 days
期刊介绍: Chemico-Biological Interactions publishes research reports and review articles that examine the molecular, cellular, and/or biochemical basis of toxicologically relevant outcomes. Special emphasis is placed on toxicological mechanisms associated with interactions between chemicals and biological systems. Outcomes may include all traditional endpoints caused by synthetic or naturally occurring chemicals, both in vivo and in vitro. Endpoints of interest include, but are not limited to carcinogenesis, mutagenesis, respiratory toxicology, neurotoxicology, reproductive and developmental toxicology, and immunotoxicology.
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