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卡库尔和阿萨里宁通过HSP90AA1/CDK2/mTOR信号通路保护肝损伤
Ling Jiang1, Cai-Bo Tian1, Rui-Han Ye1
1Yunnan Characteristic Plant Extraction Laboratory, Key Laboratory of Medicinal Chemistry for Natural Resource, Ministry of Education, Yunnan Key Laboratory of Research and Development for Natural Products, School of Pharmacy, School of Chemical Science and Technology, Yunnan University, Kunming 650091, PR China.
Fitoterapia
|November 17, 2024
概括
卡库尔和阿萨里宁通过减少肝损伤标志物和氧化应激来保护免受药物诱导的肝损伤. 这些化合物还调节HSP90AA1 / CDK2 / mTOR通路中的关键蛋白质,提供潜在的治疗机制.
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.
- 生物化学 生物化学
背景情况:
- 药物诱导性肝损伤 (DILI) 是一个重要的临床问题,通常导致急性肝衰竭和肝炎.
- 乙氨基 (APAP) 过量服用是DILI的常见原因,需要开发有效的治疗干预措施.
研究的目的:
- 在体外和体内研究卡库尔和阿萨里宁对APAP诱导的肝损伤的保护作用.
- 阐明潜在的分子机制,包括HSP90AA1 / CDK2 / mTOR信号通路的参与.
主要方法:
- 使用APAP诱导的小鼠进行体内研究,以评估肝损伤标志物 (ALT,AST,MDA) 和组织病理学.
- 使用L-O2细胞进行体外研究,以评估细胞活力,活性氧物种 (ROS) 和谷氨 (GSH) 水平.
- 网络药理学和分子对接被用来预测潜在的治疗点.
- 西方涂抹被用来验证在拟议的信号通路中关键蛋白质的调制.
主要成果:
- 卡库尔和阿萨里宁显著降低了血清ALT,AST和MDA水平,并改善了APAP治疗小鼠的肝脏组织损伤.
- 这两种化合物都提高了L-O2细胞活力,增加了细胞外GSH,同时在体外减少了细胞内ROS.
- 网络药理学和分子对接确定了HSP90AA1 / CDK2 / mTOR途径和五个标蛋白.
- 西部斑点分析证实,卡库尔和阿萨里宁调节了CDK2,mTOR,HSP90AA1,HRAS和MMP1.1的表达.
结论:
- 卡库尔和阿萨里宁对APAP诱导的肝损伤表现出显著的肝保护作用.
- 治疗机制包括减少氧化应激和调节HSP90AA1/CDK2/mTOR信号通路.
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