Kakuol and asarinin protecting liver injury via HSP90AA1/CDK2/mTOR signaling pathway.

IF 2.5 3区 医学 Q3 CHEMISTRY, MEDICINAL
Ling Jiang, Cai-Bo Tian, Rui-Han Ye, Nian Shi, Xing-Chao He, Yun-Li Zhao, Xiao-Dong Luo
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引用次数: 0

Abstract

Drug-induced liver injury caused acute hepatic failure and hepatitis frequently. In this investigation, kakuol and asarinin reduced the levels of serum alanine transaminase (ALT), aspartate transaminase (AST) and malondialdehyde (MDA) dramatically, and ameliorated the pathological damage of liver tissues in APAP-induced mice. Furthermore, both compounds increased the viabilities of APAP-induced L-O2 cells and extracellular glutathione (GSH) levels accompanied significantly by reducing the level of intracellular ROS in vitro. In addition, HSP90AA1/CDK2/mTOR signaling pathway and five target proteins (CDK2, HSP90AA1, HRAS, MMP1, mTOR) were proposed from network pharmacology and molecular docking prediction, and then the up-regulation of protein expression of CDK2, mTOR and down-regulation of HSP90AA1, HRAS, MMP1 by kakuol and asarinin in western blotting supported their mechanism.

Kakuol和asarinin通过HSP90AA1/CDK2/mTOR信号通路保护肝损伤。
药物引起的肝损伤经常导致急性肝功能衰竭和肝炎。在这项研究中,卡枯酚和皂苷能显著降低 APAP 诱导的小鼠血清丙氨酸转氨酶(ALT)、天门冬氨酸转氨酶(AST)和丙二醛(MDA)的水平,改善肝组织的病理损伤。此外,这两种化合物通过降低细胞内 ROS 水平,显著提高了 APAP 诱导的 L-O2 细胞的活力和细胞外谷胱甘肽(GSH)水平。此外,通过网络药理学和分子对接预测,提出了HSP90AA1/CDK2/mTOR信号通路和五个靶蛋白(CDK2、HSP90AA1、HRAS、MMP1、mTOR),然后通过Western blotting检测卡枯酚和asarinin对CDK2、mTOR蛋白表达的上调和对HSP90AA1、HRAS、MMP1蛋白表达的下调支持了它们的作用机制。
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来源期刊
Fitoterapia
Fitoterapia 医学-药学
CiteScore
5.80
自引率
2.90%
发文量
198
审稿时长
1.5 months
期刊介绍: Fitoterapia is a Journal dedicated to medicinal plants and to bioactive natural products of plant origin. It publishes original contributions in seven major areas: 1. Characterization of active ingredients of medicinal plants 2. Development of standardization method for bioactive plant extracts and natural products 3. Identification of bioactivity in plant extracts 4. Identification of targets and mechanism of activity of plant extracts 5. Production and genomic characterization of medicinal plants biomass 6. Chemistry and biochemistry of bioactive natural products of plant origin 7. Critical reviews of the historical, clinical and legal status of medicinal plants, and accounts on topical issues.
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