亚特米西亚阿尔吉精油通过CYP2E1和γ-glutamyl循环重编程改善了乙氨基引起的肝毒性
Weiqi Cui1, Qianwen Cao2, Luyao Liu2
1Henan Key Laboratory of Rehabilitation Medicine, Henan Joint International Research Laboratory of Chronic Liver Injury, Henan Workshop of Chronic Liver Injury for Outstanding Overseas Scientists, Zhengzhou Key Laboratory of Metabolic-dysfunction-associated Fatty Liver Disease, Department of Pharmacy, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China; Key Laboratory of Advanced Drug Preparation Technologies, Ministry of Education of China, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan 450001, China.
阿尔盖精油 (AAEO) 通过增强抗氧化能力和调节新陈代谢途径,保护免受乙氨基 (APAP) 诱导的肝损伤. 治疗AAEO可以减少肝损伤,促进保护性化合物的合成,减轻APAP的毒性.
科学领域:
- 药理学 药理学是指药理学的学科.
- 毒理学 毒理学 毒理学
- 自然产品 化学 化学
背景情况:
- 乙氨基 (APAP) 过量服用是药物诱导的肝损伤的主要原因.
- 作为中国传统医学的组成部分,阿尔盖精油 (AAEO) 显示出潜在的肝脏保护作用.
- 在减轻APAP诱导的肝毒性方面,AAEO的作用仍然在很大程度上未被描述.
研究的目的:
- 在小鼠中研究AAEO对APAP诱导的肝损伤的肝保护作用.
- 阐明AAEO保护作用背后的代谢变化和机制.
- 为了确定AAEO的关键活性成分,负责其治疗效益.
主要方法:
- 在C57BL/6 J小鼠中建立APAP诱导的肝损伤模型.
- 评估肝功能酶和组织病理学变化.
- 对小分子代谢物和AAEO化学成分的UPLC-MS/MS和GC-MS/MS分析.
- 评估氧化应激,炎症和CYP2E1活动.
- 在体外研究中使用AML12细胞与siRNA介导的CYP2E1敲击.
主要成果:
- AAEO显著降低了肝功能酶升高和由APAP引起的组织病理损伤.
- 通过降低不和脂肪酸生物合成的调节和促进SOD和CAT活性,AAEO增强了抗氧化能力.
- AAEO促进了谷氨 (GSH) 合成,形成了APAP-GSH结合物,并减少了APAP的积累.
- 确定了二-β-离子子和 (-) - 子作为AAEO的潜在活性成分.
- AAEO调节了CYP2E1水平,可能减少有毒代谢物产量.
结论:
- 在小鼠中,AAEO对APAP诱导的肝毒性产生显著的肝保护作用.
- 保护机制涉及调节CYP2E1活动和γ-glutamyl循环路径.
- AAEO增强了抗氧化剂防御,并促进了APAP的排毒.
更多相关视频
相关概念视频
Phase I Reactions: Oxidation of Aliphatic and Aromatic Carbon-Containing Systems
Oxidation reactions are fundamental in aromatic carbon-containing systems. An example is the hydroxylation of phenobarbital, a process that transforms it into...
Hepatic Drug Excretion: Enterohepatic Cycling
Post-release drugs and metabolites can be reabsorbed into the body from the intestine. For conjugated metabolites like glucuronides, reabsorption requires enzymatic hydrolysis by intestinal microflora. This...
Phase II Reactions: Acetylation Reactions
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
Phase II Reactions: Glutathione Conjugation and Mercapturic Acid Formation
Several distinctive characteristics distinguish glutathione conjugation from other phase II...
Enhanced Elimination of Poison
Antidotes serve a crucial role in counteracting the effects of poison by inhibiting enzymes responsible for producing harmful drug metabolites. In some cases, these toxic metabolites can be neutralized by endogenous cosubstrates, which are maintained at specific concentrations to prevent interaction with cellular macromolecules and subsequent cell death.
Renal excretion is the...
Phase II Reactions: Sulfation and Conjugation with α-Amino Acids


