绿原酸通过调节PI3K/AKT/mTOR自噬途径改善四氯化碳诱导的肝纤维化。

Chlorogenic Acid Ameliorates CCl-induced Liver Fibrosis by Modulating the PI3K/AKT/mTOR Autophagy Pathway.

作者信息

Negm Amr, El-Neanaey Amira Afifi, Khadr Abada El Sayed, Kamel Maher Abd El Naby, Abdo Ismail Abd El-Hamid, El Sayed Ibrahim El Tantawy, Darwish Wael Sobhy, Abd Eldaim Mabrouk Attia, Okaz Raghda Sobhy, Bahr Mohamed Hamdy, Almuraikhi Nihal, Beshara Nermine, Shawky Tamer Mohamed, Mersal Ezat A

机构信息

Department of Chemistry, College of Science, King Faisal University, Al-Ahsa, 31982, Saudi Arabia.

Chemistry Department, Faculty of Science, Mansoura University, Mansoura, 35516, Egypt.

出版信息

Anticancer Agents Med Chem. 2025;25(13):913-920. doi: 10.2174/0118715206357043250116063202.

DOI:10.2174/0118715206357043250116063202

PMID:39844564

Abstract

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 CCl-induced hepatic fibrosis and explored 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

CCl 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 CCl by influencing the autophagy process and adjusting levels of antioxidant and inflammatory markers.

摘要

背景

肝纤维化通过损害生活质量和增加肝细胞癌的发生几率，对全球健康构成严重风险，而自噬的复杂作用根据其功能状态可减轻或加重纤维化。

目的

本研究旨在探讨绿原酸对四氯化碳诱导的肝纤维化的治疗作用，并探索自噬途径作为绿原酸可能的分子靶点。

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，对肝纤维化大鼠每日给予绿原酸（20、40和60mg/kg）治疗30天。评估肝功能、肾功能、脂质过氧化、抗氧化酶、抗炎性核因子κB水平以及自噬途径参数（PI3K、AKT、mTOR、LC3和Beclin-1）。

结果

四氯化碳升高了血清天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）活性，以及肝脏丙二醛、PI3K、AKT和mTOR的表达。它降低了LC3、Beclin-1的表达以及肝脏谷胱甘肽水平。结果表明，绿原酸治疗改善了肝功能。它降低了血清AST和ALT活性，提高了肝脏谷胱甘肽浓度，减少了脂质过氧化，并下调了肝组织中PI3K、AKT和mTOR蛋白的表达。此外，绿原酸增加了肝脏中LC3和Beclin-1的表达。它还显著降低了核因子κB的表达。