目的 探讨线纹香茶菜醇提物（ILEE）对CCl₄诱导的小鼠肝纤维化的作用及其机制。方法 建立超高效液相色谱四级杆飞行时间串联质谱（UPLC-Q-TOF/MS）结合UNIFI平台的分析方法，表征ILEE的化学成分。将昆明小鼠随机分为对照组、模型组、秋水仙碱（阳性药，0.20 mg·kg^-1）和ILEE高、中、低剂量（16.28、8.14、4.07 g·kg^-1）组，每组12只。除了对照组外，所有小鼠均ip 10% CCl4橄榄油溶液，剂量为4 mL·kg^-1，3 d 1次，连续6周，建立肝纤维化模型。从模型建立的第1天起，同时ig给药，对照组和模型组小鼠ig 0.1%羧甲基纤维素钠溶液（20 mL·kg^-1），其余各组小鼠ig对应的药物，每天1次，连续6周。试剂盒法检测血清丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、Ⅲ型前胶原（PC-Ⅲ）、Ⅳ型胶原（COL-Ⅳ）、层黏蛋白（LN）和透明质酸（HA）水平；观察肝组织病理形态学变化。采用UPLC-MS/MS技术检测对照组、模型组和ILEE高剂量组小鼠肝脏代谢物的变化，并进行差异代谢物筛选。采用网络药理学对化学成分和差异代谢物进行整合分析。结果 共鉴定了24个化学成分；与模型组相比，ILEE高、中剂量显著降低了血清中ALT、AST、PC-Ⅲ、COL-Ⅳ、LN和HA水平（P＜0.05、0.01、0.001）；病理切片显示，ILEE各剂量均减轻了肝细胞肿大、炎症细胞浸润和纤维化程度。代谢组学分析表明，ILEE高剂量对肝纤维化小鼠肝脏中13种差异代谢物具有显著回调作用。整合分析显示异泽兰黄素、迷迭香酸、丹酚酸B、laxiflorin B等9个成分可能作用于胸苷酸合成酶（TYMS）、酪氨酸酶（TYR）、醛酮还原酶家族1成员A1（AKR1A1）等17个靶点，影响酪氨酸代谢、糖酵解/糖异生和叶酸的一碳代谢通路，调节肝纤维化小鼠肝脏中维生素B₉、甲状腺素、邻羟基苯乙酸和2-磷酸-D-甘油酸的水平。结论 ILEE对CCl₄所致小鼠肝纤维化具有良好的防治作用，其机制可能与酪氨酸代谢、糖酵解/糖异生和叶酸的一碳代谢通路等途径有关。

Objective To investigate the anti-liver fibrosis effects and the underlying mechanisms of the ethanol extract of Isodon lophanthoides (ILEE) on CCl₄-induced liver fibrosis in mice.Methods An analytical method based on ultra-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) combined with the UNIFI platform was established to characterize the chemical constituents of ILEE. KM mice were randomly divided into a control group, a model group, a colchicine (positive drug, 0.20 mg·kg^-1) group, and high-, medium-, and low-dose ILEE groups (16.28, 8.14, and 4.07 g·kg^-1), with 12 mice in each group. Except for the control group, all mice were intraperitoneally injected with 10% CCl₄ olive oil solution at a dose of 4 mL·kg^-1 once every 3 days for six consecutive weeks to establish a liver fibrosis model. From the first day of model establishment, intragastric administration was simultaneously given. Mice in the control and model groups were intragastrically administered 0.1% sodium carboxymethyl cellulose solution (20 mL·kg^-1), while mice in the other groups were intragastrically administered the corresponding drugs once a day for 6 consecutive weeks. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels, type III procollagen (PC-III), type IV collagen (COL-IV), laminin (LN), and hyaluronic acid (HA) were measured. Liver tissue pathological changes were also observed. UPLC-MS/MS technology was employed to assess changes in liver metabolites across the control, model, and high-dose groups, enabling differential metabolite screening. Network pharmacology was employed to perform an integrated analysis of the chemical components and differential metabolites.Results A total of 24 chemical components were identified. Compared with the model group, the high-and medium-dose ILEE significantly reduced the serum levels of ALT, AST, PCIII, COL-IV, LN, and HA (P<0.05, 0.01, 0.001). Pathological sections revealed that ILEE at high, medium, and low doses reduced hepatocyte enlargement, inflammatory cell infiltration, and fibrosis. Metabolomic analysis demonstrated that high doses of ILEE significantly reversed 13 differential metabolites in the livers of mice with liver fibrosis. Integrated analysis indicated that nine components including eupatilin, rosmarinic acid, salvianolic acid B, and laxiflorin B, may act on 17 targets such as TYMS, TYR, and AKR1A1, affecting tyrosine metabolism, glycolysis/gluconeogenesis, and one carbon pool by folate, regulating the levels of vitamin B9, thyroxine, 2-hydroxyphenylacetic acid, and 2-phospho-D-glyceric acid in the livers of mice with liver fibrosis.Conclusion ILEE exhibits significant preventive and therapeutic effects on CCl₄-induced liver fibrosis in mice, with its mechanism may be associated with tyrosine metabolism, glycolysis/gluconeogenesis, and the one carbon pool by folate.

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广西科技基地与人才专项（桂科AD21238032）；广西青年科学基金资助项目（2023GXNSFBA026276）；国家重大新药创制科技重大专项资助项目（2019ZX09201004）；广西中医药大学博士科研启动项目（2020BS015）；广西中医药大学青年科学基金资助项目（2021QN006，2024QN47）；广西中医药大学第三批“岐黄工程”高层次人才团队培育项目（202406）