Lu Jun, Wang Chen
School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 311402, China; College of Pharmacy, Guilin Medical University, Guilin, 541104, China.
School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou, 311402, China.
J Ethnopharmacol. 2025 Feb 10;338(Pt 3):119118. doi: 10.1016/j.jep.2024.119118. Epub 2024 Nov 17.
ETHNOPHARMACOLOGICAL RELEVANCE: Angelica sinensis (Oliv.) Diels is a well-known traditional medicinal plant. In China, it is a common blood tonic drug that has been inherited for thousands of years. There is a consensus that Angelica sinensis (Oliv.) Diels has a protective effect against various liver diseases. However, the effects and mechanisms of Angelica sinensis (Oliv.) Diels and its active components on alcoholic liver disease (ALD) have not been clearly defined yet. AIM OF THE STUDY: The aim of this study is to evaluate the effect and explore the mechanism of ferulic acid (FA) from Angelica sinensis (Oliv.) Diels ameliorates lipid metabolism in ALD. METHODS: C57BL/6 mice were fed ethanol-containing liquid feeds to establish ALD model in vivo. The lipid metabolism-related indexes were detected by kits, H&E staining and oil red O staining were used to analyze liver histopathological changes and fat deposition, to evaluate the protective effect of water extraction and ethanol precipitation of Angelica sinensis radix (WEEPAS) on ethanol-induced liver injury. The active components and potential targets of Angelica sinensis (Oliv.) Diels for ALD were screened by network pharmacology and molecular docking. Ethanol was co-incubated with HepG2 cells to construct the ALD model in vitro, then the same approaches were used to explore the effect of FA for ALD in vivo and in vitro. The levels of proteins and mRNA related to AMPK/ACC and PI3K/AKT pathways were detected by Western Blotting and RT-qPCR. RESULTS: WEEPAS could protect mice from ethanol-induced liver tissues injury by ameliorating fat deposition and inhibiting oxidative stress response. Network pharmacology and molecular docking results suggested that FA might be the main bioactive component in Angelica sinensis (Oliv.) Diels for ALD, and its mechanism might be related to the regulation of AMPK and PI3K/AKT signaling pathways. In vitro and in vivo experiments further demonstrated that FA regulated lipid metabolism via AMPK/ACC and PI3K/AKT pathways, thereby ameliorating ethanol-induced liver tissues injury and lipid metabolism disorders in HepG2 cells and mice, which were consistent with the network pharmacology results. CONCLUSION: In summary, the results indicated that FA from Angelica sinensis (Oliv.) Diels was able to ameliorate ethanol-induced ALD. The mechanism may be related to the regulation of lipid metabolism via AMPK/ACC and PI3K/AKT pathways.
民族药理学相关性：当归是一种著名的传统药用植物。在中国，它是一种传承了数千年的常见补血药物。人们普遍认为当归对各种肝脏疾病具有保护作用。然而，当归及其活性成分对酒精性肝病（ALD）的作用和机制尚未明确。 研究目的：本研究旨在评估当归中的阿魏酸（FA）改善ALD脂质代谢的作用并探索其机制。 方法：给C57BL/6小鼠喂食含乙醇的液体饲料以在体内建立ALD模型。通过试剂盒检测脂质代谢相关指标，采用苏木精-伊红（H&E）染色和油红O染色分析肝脏组织病理学变化和脂肪沉积，以评估当归水提醇沉物（WEEPAS）对乙醇诱导的肝损伤的保护作用。通过网络药理学和分子对接筛选当归治疗ALD的活性成分和潜在靶点。将乙醇与HepG2细胞共孵育以在体外构建ALD模型，然后采用相同方法探索FA在体内和体外对ALD的作用。通过蛋白质免疫印迹法（Western Blotting）和实时定量聚合酶链反应（RT-qPCR）检测与腺苷酸活化蛋白激酶/乙酰辅酶A羧化酶（AMPK/ACC）和磷脂酰肌醇-3激酶/蛋白激酶B（PI3K/AKT）通路相关的蛋白质和mRNA水平。 结果：WEEPAS可通过改善脂肪沉积和抑制氧化应激反应保护小鼠免受乙醇诱导的肝组织损伤。网络药理学和分子对接结果表明，FA可能是当归治疗ALD的主要生物活性成分，其机制可能与调节AMPK和PI3K/AKT信号通路有关。体内和体外实验进一步证明，FA通过AMPK/ACC和PI3K/AKT通路调节脂质代谢，从而改善乙醇诱导的HepG2细胞和小鼠肝组织损伤及脂质代谢紊乱，这与网络药理学结果一致。 结论：综上所述，结果表明当归中的FA能够改善乙醇诱导的ALD。其机制可能与通过AMPK/ACC和PI3K/AKT通路调节脂质代谢有关。
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