绿原酸通过调节PI3K/AKT/mTOR自噬途径改善ccl4诱导的肝纤维化

IF 2.6 4区 医学 Q3 CHEMISTRY, MEDICINAL
Amr Negm, Amira A El-Neanaey, Abada El Sayed Khadr, Maher Abd El Naby Kamel, Abd El-Hamid Abdo Ismail, Ibrahim El Tantawy El Sayed, Wael Sobhy Darwish, Mabrouk Attia Abd Eldaim, Raghda Sobhy Okaz, Mohamed Hamdy Bahr, Nihal Almuraikhi, Nermine Beshara, Tamer M Shawky, Ezat A Mersal
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引用次数: 0

摘要

背景:肝纤维化通过降低生活质量和增加肝细胞癌的机会,对全球健康构成严重风险,而自噬的复杂作用取决于其功能,可以减轻或加重纤维化。目的:研究绿原酸对ccl4诱导肝纤维化的治疗作用,探讨绿原酸可能的分子靶点自噬途径。方法:给大鼠注射四氯化碳(1ml/kg)诱导肝纤维化10周。在本研究中,肝纤维化大鼠每天给予绿原酸(20、40和60 mg/kg)治疗,持续30天。评估肝功能、肾功能、脂质过氧化、抗氧化酶、抗炎NF-κB水平及自噬途径参数(PI3K、AKT、mTOR、LC3、Beclin-1)。结果:CCl4提高了血清AST和ALT活性,以及肝脏丙二醛、PI3K、AKT和mTOR的表达。降低LC3、Beclin-1表达及肝谷胱甘肽水平。结果表明,绿原酸处理能改善肝功能。降低血清AST和ALT活性,提高肝脏GSH浓度,降低脂质过氧化,下调肝组织中PI3K、AKT和mTOR蛋白表达。绿原酸增加了LC3和Beclin-1在肝脏中的表达。同时显著降低NF-kB的表达。结论:绿原酸可能通过影响细胞自噬过程和调节抗氧化和炎症标志物水平来减轻CCl4所致大鼠肝损伤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Chlorogenic Acid Ameliorates CCl4-induced Liver Fibrosis by Modulating the PI3K/AKT/mTOR Autophagy Pathway.

Background: Liver fibrosis represents a serious risk to global health by impairing quality of life and elevating the chances of hepatocellular carcinoma, while the intricate role of autophagy can either alleviate or worsen fibrosis depending on its functioning.

Objective: Herein, we aimed to investigate the therapeutic effect of chlorogenic acid in CCl4-induced hepatic fibrosis and explore the autophagy pathway as the possible molecular target of chlorogenic acid.

Methods: Rats were injected with carbon tetrachloride (1ml/kg) to induce liver fibrosis for 10 weeks. In the current study, the liver fibrosis rats were treated daily with chlorogenic acid (20, 40, and 60 mg/kg) for 30 days. Liver function tests, renal function tests, lipid peroxidation, antioxidant enzyme, anti-inflammatory NF-κB level, and autophagy pathway parameters (PI3K, AKT, mTOR, LC3, and Beclin-1) were assessed.

Results: CCl4 elevated serum AST and ALT activity, and hepatic malondialdehyde, PI3K, AKT, and mTOR expressions. It decreased LC3, Beclin-1 expression, and hepatic glutathione level. The results indicated that chlorogenic acid treatment ameliorated the hepatic functions. It declined serum AST and ALT activities, improved hepatic GSH concentration, decreased lipid peroxidation, and downregulated PI3K, AKT, and mTOR protein expressions in hepatic tissue. Moreover, chlorogenic acid increased the hepatic expression of LC3 and Beclin-1. It also significantly decreased NF-kB expression.

Conclusion: Chlorogenic acid showed promise in reducing liver damage in rats caused by CCl4 by influencing the autophagy process and adjusting levels of antioxidant and inflammatory markers.

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来源期刊
Anti-cancer agents in medicinal chemistry
Anti-cancer agents in medicinal chemistry ONCOLOGY-CHEMISTRY, MEDICINAL
CiteScore
5.10
自引率
3.60%
发文量
323
审稿时长
4-8 weeks
期刊介绍: Formerly: Current Medicinal Chemistry - Anti-Cancer Agents. Anti-Cancer Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of anti-cancer agents. Each issue contains a series of timely in-depth reviews and guest edited issues written by leaders in the field covering a range of current topics in cancer medicinal chemistry. The journal only considers high quality research papers for publication. Anti-Cancer Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in cancer drug discovery.
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