展开保护:Terminalia arjuna针对UPR通路,以抵消肝毒性中ER压力的肝毒性
Wania Nasir1, Shamshad Ul Hassan1, Bilal Aslam1
1Institute of Physiology and Pharmacology, Faculty of Veterinary Science, University of Agriculture Faisalabad, Pakistan.
Pakistan journal of pharmaceutical sciences
|February 28, 2026
概括
特米纳利亚阿尔朱纳树皮提取物 (TAE) 显示出显著的肝脏保护作用,可以与N-乙半氨酸 (NAC) 相比,在大鼠中对乙胺诱导的肝损伤产生显著的肝脏保护作用. TAE有效地减轻氧化应激,调节关键细胞通路,为急性肝损伤管理提供了潜力.
科学领域:
- 药理学 药理学是指药理学的学科.
- 肝病学 肝病学是一种肝病学.
- 毒理学 毒理学 毒理学
背景情况:
- 乙氨基 (APAP) 过量服用会导致药物诱导的肝损伤 (DILI) 通过内分泌网膜 (ER) 应激,氧化损伤,亡和炎症.
- 了解APAP诱导的肝毒性分子机制对于开发有效的治疗方法至关重要.
研究的目的:
- 在大鼠模型中评估Terminalia arjuna树皮提取物 (TAE) 对APAP诱导的肝毒性的肝护功效.
- 通过分析关键信号和炎症标志物,比较TAE与N-乙半氨酸 (NAC) 的影响,这是一个标准治疗方法.
主要方法:
- 维斯特鼠被分为四组:对照组,APAP诱导的毒性,APAP + NAC和APAP + TAE.
- 使用乙氨基 (350毫克/公斤) 诱导肝损伤. 治疗 (NAC 150毫克/公斤,TAE 80毫克/公斤) 进行了14天.
- 分析了生物化学标记物 (肝酶,氧化应激),基因表达 (Keap1, Nrf2, ER应激标记物) 和组织病理学.
主要成果:
- 乙氨基诱导显著的肝毒性,由肝酶升高,氧化应激增加,基因表达改变和组织学损伤证明.
- 无论是NAC和TAE治疗都减轻了APAP诱导的肝损伤,TAE在氧化应激标志物中表现出优异的改善.
- TAE和NAC治疗调节了Keap1-Nrf2通路,减少了肝脏缩,保持了肝脏结构.
结论:
- 特米纳利亚阿尔朱纳树皮提取物显示出强大的肝保护性质,可以预防乙氨基引起的肝损伤.
- TAE的疗效与NAC相当,通过调节氧化应激,亡和ER应激通路而起作用.
- 需要进一步的研究来探索TAE在治疗急性肝损伤方面的临床潜力.
相关概念视频
01:37The Unfolded Protein Response
6.6K
The ER is the hub of protein synthesis in a cell. It has robust systems to quality control protein folding and also for degradation of terminally misfolded proteins. Under normal conditions, a small proportion of misfolded proteins that cannot be salvaged need to be transported to the cytoplasm by the ER-associated degradation or ERAD pathways. However, if the ERAD cannot handle the misfolded proteins, the cell activates the unfolded protein response or UPR to adjust the protein folding...
6.6K
01:31Regulation of the Unfolded Protein Response
3.1K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
3.1K
01:18Treatment for Pulmonary Arterial Hypertension: Endothelin Receptor Antagonists
511
Endothelins (ETs) are potent vasoactive peptides critical in the human body's various physiological and pathological processes. One of the most promising therapeutic strategies for treating pulmonary arterial hypertension (PAH) involves counteracting the effects of these endothelins using a class of drugs known as endothelin receptor antagonists.
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
ETs are synthesized through a complex sequence of enzymatic steps, primarily involving an enzyme referred to as endothelin-converting enzyme...
511
01:17Role of ER in the Secretory Pathway
7.6K
Eukaryotic cells have a special pathway that enables communication between various intracellular membrane-bound compartments and also with the extracellular environment. This pathway is termed as the secretory pathway.
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
Components of the secretory pathway
About a third of proteins synthesized in the cell are sorted via the secretory route. They shuffle between different compartments in membrane-bound vesicles until they reach their final destination. The main intracellular compartments involved...
7.6K
01:11Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
56
Genetic polymorphisms in drug targets have emerged as critical determinants of interindividual variability in drug response and toxicity. Pharmacogenomic investigations increasingly focus on identifying these variations to personalize and optimize therapeutic interventions. A drug target may be a receptor, enzyme, or signaling protein involved in pharmacologic responses or disease-related pathways. While early pharmacogenetic studies focused primarily on drug metabolism, current research...
56
01:27Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
42
Phase II biotransformation reactions are essential for detoxifying and eliminating xenobiotics, including many pharmaceutical compounds. These reactions typically involve conjugation, the covalent attachment of polar endogenous groups such as glucuronic acid, sulfate, methyl, or acetyl moieties to functional groups introduced during Phase I metabolism. The resulting conjugates are more water-soluble, enabling efficient renal or biliary excretion.The major classes of Phase II enzymes include...
42