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麸炒苍术醇提物通过代谢调节缓解胆管结扎诱导小鼠肝纤维化作用

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中草药 | 药理与临床 2026,57(5): 1742-1758

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中草药 |药理与临床 2026 , 57 (5) : 1742 -1758

麸炒苍术醇提物通过代谢调节缓解胆管结扎诱导小鼠肝纤维化作用

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王琦^1,2,3, 王燕^1,2,3, 王光忠^1,2,3, 刘艳菊^1,2,3, 涂济源^1,2,3, 周仲实^1,2,3

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通讯作者:

周仲实

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王琦: 王琦,女,硕士研究生,研究方向为中药炮制工艺、质量控制及原理研究。E-mail:2609160413@qq.com

Ethanol extract of bran-fried Atractylodis Rhizoma alleviates bile duct ligation-induced liver fibrosis in mice through metabolic regulation

WANG Qi, WANG Yan, WANG Guangzhong, LIU Yanju, TU Jiyuan, ZHOU Zhongshi

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doi: 10.7501/j.issn.0253-2670.2026.05.014

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目的研究麸炒苍术醇提物（ethanol extract of bran-fried Atractylodis Rhizoma，EBAR）对胆管结扎诱导的小鼠肝纤维化模型的治疗作用，并从调节肝脏代谢物的角度探讨其治疗肝纤维化的机制。方法 C57BL/6小鼠采用胆管结扎法构建肝纤维化模型，给予EBAR干预14 d。检测血清中肝功能及炎症因子水平；采用免疫组化、qRT-PCR、Western blotting检测肝组织α-平滑肌肌动蛋白（α-smooth muscle actin，α-SMA）、Ⅰ型胶原（collagen type I，COL1A1）和COL4A2表达。采用转化生长因子-β（transforming growth factor-β，TGF-β）诱导JS1细胞建立肝星状细胞活化模型，给予EBAR干预后，采用免疫荧光、qRT-PCR、Western blotting检测α-SMA、COL1A1、COL4A2和基质金属蛋白酶组织抑制因子1（tissue inhibitor of metalloproteinases 1，TIMP1）表达。采用网络药理学、分子对接、分子动力学模拟和代谢组学研究EBAR抗肝纤维化的潜在机制，并采用Western blotting验证关键机制。结果肝纤维化小鼠模型中，EBAR显著降低小鼠的肝脏指数及血清中肝功能指标和炎症因子水平（P＜0.05、0.01），显著抑制肝组织α-SMA、COL1A1和COL4A2表达（P＜0.05、0.01），明显减轻肝脏纤维组织增生和胶原沉积，改善肝脏组织的病理损伤。网络药理学分析显示，苍术主要通过调控腺苷酸活化蛋白激酶（adenosine 5’-monophosphate-activated protein kinase，AMPK）等信号通路发挥抗肝纤维化的作用。代谢组学分析显示，EBAR影响肝纤维化小鼠模型肝脏组织中多种代谢物的生成，尤其是柠檬酸循环和脂肪酸代谢等相关途径代谢物。进一步的机制研究表明，EBAR通过促进AMPK的磷酸化（P＜0.05、0.01），激活AMPK/沉默信息调节因子1（silent information regulator 1，SIRT1）/过氧化物酶体增殖物激活受体γ共激活因子-1α（peroxisome proliferator-activated receptor gamma coactivator-1α，PGC-1α）信号通路，从而发挥抗肝纤维化作用。结论 EBAR通过激活AMPK/SIRT1/PGC-1α信号通路，调节肝脏能量代谢，发挥抗纤维化作用。

关键词

麸炒苍术 / 肝纤维化 / 代谢组学 / 网络药理学 / 分子动力学 / 柠檬酸循环 / 脂肪酸代谢 / 苍术素 / 白术内酯Ⅰ / 白术内酯Ⅱ / 白术内酯Ⅲ / AMPK/SIRT1/PGC-1α信号通路

Abstract

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Objective To investigate the therapeutic effect of ethanol extract of bran-fried Cangzhu (Atractylodis Rhizoma) (EBAR) on bile duct ligation-induced liver fibrosis in mice and explore the mechanism of its treatment for liver fibrosis from the perspective of regulating hepatic metabolites. Methods C57BL/6 mice were subjected to bile duct ligation to establish a liver fibrosis model and treated with EBAR for 14 d. Levels of liver function markers and inflammatory cytokines in serum were measured. The expressions of α-smooth muscle actin (α-SMA), collagen type I (COL1A1) and COL4A2 in liver tissues were detected by immunohistochemistry, qRT-PCR and Western blotting. JS1 cells were induced with transforming growth factor-β (TGF-β) to establish a hepatic stellate cell activation model. After EBAR intervention, the expressions of α-SMA, COL1A1, COL4A2 and tissue inhibitor of metalloproteinases 1 (TIMP1) were examined by immunofluorescence, qRT-PCR and Western blotting. Network pharmacology, molecular docking, molecular dynamics simulation and metabolomics were employed to investigate the potential mechanisms of EBAR against liver fibrosis, and key mechanisms were validated by Western blotting. Results In the liver fibrosis mouse model, EBAR significantly reduced liver index, serum liver function indicators and inflammatory cytokine levels (P < 0.05, 0.01), significantly inhibited the expressions of α-SMA, COL1A1 and COL4A2 in liver tissues (P < 0.05, 0.01), significantly alleviated hepatic fibrous tissue hyperplasia and collagen deposition and improved pathological damage in liver tissue. Network pharmacology analysis revealed that Atractylodis Rhizoma exerts anti-hepatic fibrotic effects primarily by regulating signaling pathways such as adenosine 5’-monophosphate-activated protein kinase (AMPK). Metabolomic analysis showed that EBAR affected the generation of various metabolites in liver tissues of liver fibrosis mouse model, particularly metabolites related to the citric acid cycle and fatty acid metabolism. Further mechanistic studies demonstrated that EBAR exerted anti-hepatic fibrotic effects by promoting AMPK phosphorylation (P < 0.05, 0.01) and activating AMPK/silent information regulator 1 (SIRT1)/peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α) signaling pathway. Conclusion EBAR exerts anti-fibrotic effects by activating AMPK/SIRT1/PGC-1α signaling pathway and regulating hepatic energy metabolism.

Key words

bran-fried Atractylodis Rhizoma / liver fibrosis / metabolomics / network pharmacology / molecular dynamics / citric acid cycle / fatty acid metabolism / atractylodin / atractylenolide I / atractylenolide II / atractylenolide III / AMPK/SIRT1/PGC-1α signaling pathway

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王琦, 王燕, 王光忠, 刘艳菊, 涂济源, 周仲实. 麸炒苍术醇提物通过代谢调节缓解胆管结扎诱导小鼠肝纤维化作用. 中草药, 2026 , 57 (5) : 1742 -1758 . DOI: 10.7501/j.issn.0253-2670.2026.05.014

WANG Qi, WANG Yan, WANG Guangzhong, LIU Yanju, TU Jiyuan, ZHOU Zhongshi. Ethanol extract of bran-fried Atractylodis Rhizoma alleviates bile duct ligation-induced liver fibrosis in mice through metabolic regulation[J]. Chinese Traditional and Herbal Drugs, 2026 , 57 (5) : 1742 -1758 . DOI: 10.7501/j.issn.0253-2670.2026.05.014

基金

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湖北省自然科学基金创新发展联合基金项目 (2025AFD477)

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2026年第57卷第5期

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doi: 10.7501/j.issn.0253-2670.2026.05.014

接收时间：2025-08-21
首发时间：2026-09-09

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收稿日期：2025-08-21

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2种不同金属材料的力学参数

科 Family	属数 Number of genus	种数 Number of species	占总种数比例 Percentage of total species (%)	属 Genus	种数 Number of species	占总种数比例 Percentage of total species (%)
鹅膏菌科Amanitaceae	2	11	5.26	鹅膏菌属 Amanita	10	4.78
小菇科 Mycenaceae	2	12	5.74	丝盖伞属 Inocybe	5	2.39
多孔菌科 Polyporaceae	8	14	6.70	蜡蘑属 Laccaria	5	2.39
红菇科 Russulaceae	3	23	11.00	小皮伞属 Marasmius	6	2.87
				小菇属 Mycena	11	5.26
				光柄菇属 Pluteus	5	2.39
				红菇属 Russula	17	8.13
				栓菌属 Trametes	5	2.39

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