柚皮素对自身免疫性肝炎的防治作用及分子机制

林昌稳; 任秋怡; 郑梦洁; 颜欢; 李佳; 冯嘉欣; 林海英; 舒发明; 周晓玲; 毛德文; 龙富立

doi:10.12449/JCH260627

柚皮素对自身免疫性肝炎的防治作用及分子机制

DOI: 10.12449/JCH260627

1.
广西中医药大学第一临床医学院，南宁 530023
2.
大连医科大学附属第一医院神经内科，辽宁大连 116011
3.
广西中医药大学第一附属医院肝病科，南宁 530023

基金项目:

国家自然科学基金 (82260907);

国家自然科学基金 (82274434);

广西科技计划项目 (2024GXNSFDA010020);

广西科技计划项目 (Guikefa ［2024］ No.10);

广西名中医传承工作室建设项目 (GZY2024012);

广西壮族自治区中医药重点研究室建设项目 (Guizhongyiyaokejiaofa ［2023］ No.9)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：毛德文、龙富立负责拟定写作思路，指导撰写文章并最后定稿；林昌稳负责设计论文框架，撰写论文；任秋怡、郑梦洁、李佳负责文献检索及汇总；颜欢、冯嘉欣、林海英负责绘制机制图；周晓玲、舒发明负责指导论文的修改。

详细信息

通信作者:
龙富立， longfuli005@163.com （ORCID： 0000-0003-1196-2697）

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- 文章访问数: 9
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- 被引次数: 0
出版历程
- 收稿日期: 2025-10-31
- 录用日期: 2025-12-12
- 出版日期: 2026-06-25

Role of naringenin in the prevention and treatment of autoimmune hepatitis and its molecular mechanism

1.
The First Clinical Medical College of Guangxi University of Chinese Medicine，Nanning 530023，China
2.
Department of Neurology，The First Affiliated Hospital of Dalian Medical University，Dalian，Liaoning 116011，China
3.
Department of Hepatology，The First Affiliated Hospital of Guangxi University of Chinese Medicine，Nanning 530023，China

Research funding:

National Natural Science Foundation of China (82260907);

National Natural Science Foundation of China (82274434);

Guangxi Science and Technology Plan Projects (2024GXNSFDA010020);

Guangxi Science and Technology Plan Projects (Guikefa ［2024］ No.10);

Construction Project of Guangxi Famous TCM Physicians Inheritance Studios (GZY2024012);

Construction Project of Key TCM Laboratories in Guangxi Zhuang Autonomous Region (Guizhongyiyaokejiaofa ［2023］ No.9)

More Information

Corresponding author: LONG Fuli， longfuli005@163.com （ORCID： 0000-0003-1196-2697）

摘要

摘要: 自身免疫性肝炎（AIH）是一种由T淋巴细胞介导的慢性炎症性肝病，若未及时干预可进展为肝硬化甚至肝衰竭。天然黄酮类化合物柚皮素（NAR）具有重塑免疫稳态、靶向抑制炎症通路、抗氧化、调节肝细胞代谢与凋亡、改善线粒体功能及调节肠道菌群等多重机制，在AIH防治中展现出潜在价值。但柚皮素自身存在生物利用度低、肝靶向递送效率不足等问题，使其临床转化与应用受到制约。本文系统综述NAR防治AIH的作用机制，深入探讨其在AIH防治中可能涉及的信号通路，并分析当前其转化应用存在的挑战及未来的研究方向，以期为NAR在AIH防治领域的进一步研究和临床应用提供理论参考。
- 柚皮素 /
- 肝炎，自身免疫性 /
- 免疫调节 /
- 信号转导
Abstract: Autoimmune hepatitis （AIH） is a chronic inflammatory liver disease mediated by T lymphocytes， and it can progress to liver cirrhosis or even liver failure without timely intervention. As a natural flavonoid compound， naringenin （NAR） shows a potential value in the prevention and treatment of AIH through multiple mechanisms such as remodeling immune homeostasis， targeted inhibition of inflammatory pathways， antioxidation， regulating hepatocyte metabolism and apoptosis， improving mitochondrial function， and regulating intestinal flora. However， the clinical translation and application of NAR is limited by issues such as low bioavailability and insufficient efficiency of liver-targeted delivery. This article systematically reviews the mechanism of action of NAR in the prevention and treatment of AIH， explores the potential signaling pathways involved in this process， and analyzes existing challenges in its translation and application and future research directions， so as to provide a reference for further research on NAR and its application in the prevention and treatment of AIH.
- Naringenin /
- Hepatitis， Autoimmune /
- Immunomodulation /
- Signal Transduction

HTML全文

注： JAK1/JAK2，Janus激酶1/2；STAT1/STAT3，信号转导与转录激活因子1和3；PI3K/PKB，磷脂酰肌醇-3-激酶-蛋白激酶B；MAPK，促分裂原活化的蛋白激酶；ERK，胞外信号调节激酶；JNK，c-Jun氨基末端激酶；IκBα，κB抑制蛋白α；NF-κB，核因子-κB；RORγt，RORγt转录因子；Foxp3，叉头框蛋白P3；Th，辅助性T细胞；IFN-γ，干扰素γ；IL，白细胞介素；TNF-α，肿瘤坏死因子α；Treg，调节性T细胞；TLR4，Toll样受体4；MyD88，髓系分化初级反应蛋白质88；TRAF6，肿瘤坏死因子受体相关因子6；TAK1，转化生长因子β活化激酶1；cGAS-STING，环鸟苷酸-腺苷酸合酶/干扰素基因刺激因子通路；IKK，IκB激酶；AP-1，激活蛋白-1；Nrf2，核转录因子红系2相关因子2；MDA，丙二醛；Bax，Bcl-2相关X蛋白；caspase，胱天蛋白酶；HO-1，血红素加氧酶-1；NQO1，醌氧化还原酶1；GSH，谷胱甘肽；SOD，超氧化物歧化酶；TGF-β，转化生长因子β；HSC，肝星状细胞；α-SMA，平滑肌肌动蛋白α；collagen Ⅰ，Ⅰ型胶原；Bifidobacterium，双歧杆菌；Lactobacillus，乳杆菌；Enterobacteriaceae，肠杆菌；AMPK，腺苷一磷酸活化的蛋白质激酶；SIRT1，沉默信息调节因子1；Occludin、Claudin-1、ZO-1，均为紧密连接蛋白；LPS，脂多糖；MPO，髓过氧化物酶；Keap1，Kelch样ECH关联蛋白1；ARE，抗氧化响应元件；GCLC，谷氨酸-半胱氨酸连接酶催化亚基；GCLM，谷氨酸-半胱氨酸连接酶调节亚基；PGC-1α，过氧化物酶体增殖物激活受体γ共激活因子1α；TFAM，线粒体转录因子A；ATP，三磷酸腺苷；ROS，活性氧；•OH，羟自由基；O₂⁻•，超氧阴离子自由基；Cyt c，细胞色素c；ULK1，UNC-51样激酶1；LC3-Ⅱ，微管相关蛋白1轻链3-Ⅱ；CHOP，C/EBP同源蛋白；MPTP，线粒体膜通透性转换孔。

图 1 柚皮素防治AIH的作用机制

Figure 1. Mechanism of Naringenin in preventing and treating AIH

下载: 全尺寸图片幻灯片

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