Qi Shuwen, Zhang Chunzi, Yan Junlin, Ma Xiaoyan, Zhong Yewei, Hou Wenhui, Zhang Juan, Pang Tuxia, Ma Xiaoli
College of Pharmacy, Xinjiang Medical University, Urumqi 830011, China.
Key Laboratory of Active Components of Xinjiang Natural Medicine and Drug Release Technology, Urumqi 830000, China.
Metabolites. 2025 Jan 10;15(1):41. doi: 10.3390/metabo15010041.
Alcoholic liver disease (ALD) is a significant global health concern, primarily resulting from chronic alcohol consumption, with oxidative stress as a key driver. The ethyl acetate extract of (CGE) exhibits antioxidant and hepatoprotective properties, but its detailed mechanism of action against ALD remains unclear. This study investigates the effects and mechanisms of CGE in alleviating alcohol-induced oxidative stress and liver injury.
Ultra-Performance Liquid Chromatography coupled with Quadrupole-Orbitrap Mass Spectrometry (UPLC-Q-Orbitrap-MS) was used to identify CGE components. A C57BL/6J mouse model of ALD was established via daily oral ethanol (56%) for six weeks, with CGE treatment at low (100 mg/kg) and high doses (200 mg/kg). Silibinin (100 mg/kg) served as a positive control. Liver function markers, oxidative stress indicators, and inflammatory markers were assessed. Transcriptomic and network pharmacology analyses identified key genes and pathways, validated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blotting.
UPLC-Q-Orbitrap-MS identified 81 CGE compounds, mainly including terpenoids, flavonoids, and phenylpropanoids. CGE significantly ameliorated liver injury by reducing alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) levels and enhancing antioxidative markers such as total antioxidant capacity (T-AOC) and total superoxide dismutase (T-SOD) while lowering hepatic malondialdehyde (MDA) levels. Inflammation was mitigated through reduced levels of Tumor Necrosis Factor Alpha (TNF-α), Interleukin-1 Beta (IL-1β), and C-X-C Motif Chemokine Ligand 10 (CXCL-10). Transcriptomic and network pharmacology analysis revealed seven key antioxidant-related genes, including , , , , , , and , validated by RT-qPCR. CGE activated the P21/Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2)/Heme Oxygenase-1 (HO-1) signaling axis, increasing P21, Nrf2, and HO-1 protein levels while suppressing Kelch-like ECH-associated Protein 1 (Keap1) expression.
CGE mitigates oxidative stress and liver injury by activating the P21/Nrf2/HO-1 pathway and regulating antioxidant genes. Its hepatoprotective effects and multi-target mechanisms highlight CGE's potential as a promising therapeutic candidate for ALD treatment.
酒精性肝病（ALD）是一个重大的全球健康问题，主要由长期饮酒引起，氧化应激是关键驱动因素。[植物名称]的乙酸乙酯提取物（CGE）具有抗氧化和肝脏保护特性，但其针对ALD的详细作用机制尚不清楚。本研究调查了CGE在减轻酒精诱导的氧化应激和肝损伤方面的作用及机制。
采用超高效液相色谱-四极杆-轨道阱质谱联用技术（UPLC-Q-Orbitrap-MS）鉴定CGE成分。通过每日口服乙醇（56%）建立C57BL/6J小鼠ALD模型，为期六周，CGE以低剂量（100 mg/kg）和高剂量（200 mg/kg）进行治疗。水飞蓟宾（100 mg/kg）作为阳性对照。评估肝功能指标、氧化应激指标和炎症指标。转录组学和网络药理学分析确定关键基因和通路，并通过逆转录定量聚合酶链反应（RT-qPCR）和蛋白质免疫印迹法进行验证。
UPLC-Q-Orbitrap-MS鉴定出81种CGE化合物，主要包括萜类、黄酮类和苯丙素类。CGE通过降低丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）和碱性磷酸酶（ALP）水平，增强总抗氧化能力（T-AOC）和总超氧化物歧化酶（T-SOD）等抗氧化指标，同时降低肝脏丙二醛（MDA）水平，显著改善肝损伤。通过降低肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）和C-X-C基序趋化因子配体10（CXCL-10）水平减轻炎症。转录组学和网络药理学分析揭示了七个关键的抗氧化相关基因，包括[基因名称1]、[基因名称2]、[基因名称3]、[基因名称4]、[基因名称5]、[基因名称6]和[基因名称7]，经RT-qPCR验证。CGE激活P21/核因子红细胞2相关因子2（Nrf2）/血红素加氧酶-1（HO-1）信号轴，增加P21、Nrf2和HO-1蛋白水平，同时抑制kelch样ECH相关蛋白1（Keap1）表达。
CGE通过激活P21/Nrf2/HO-1通路并调节抗氧化基因减轻氧化应激和肝损伤。其肝脏保护作用和多靶点机制突出了CGE作为ALD治疗有前景的候选药物的潜力。
