肝纤维化相关信号通路及中药活性成分靶向调节作用机制
DOI: 10.3969/j.issn.1001-5256.2022.11.033
Research progress on signal pathways in hepatic fibrosis and targeted regulation mechanisms of active ingredients from traditional Chinese medicine
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摘要: 肝纤维化是许多慢性肝病的共同病理阶段,肝星状细胞的激活被认为是肝纤维化过程的关键环节。肝纤维化的发病受多种细胞因子及信号通路的调控,主要涉及NF-κB信号通路、TGFβ/Smad信号通路、Wnt/β-catenin信号通路、Hedgehog信号通路等。随着现代药理学及生物科技的发展,中药活性成分抗肝纤维化的作用机制被进一步阐明,本文对肝纤维化相关信号通路及中药活性成分抗肝纤维化的研究成果作一总结,以期为医治肝纤维化提供潜在候选药物,开拓肝纤维化治疗的新领域。Abstract: Hepatic fibrosis is a common pathological stage of many chronic liver diseases. Activation of hepatic stellate cells is considered as a key event in the progression of hepatic fibrosis. The pathogenesis of liver fibrosis is modulated by various cytokines involved in several signal pathways, including NF-κB, TGF-β/Smad, Wnt/β-catenin, Hedgehog etc. With the rapid development of modern pharmacology and biotechnology, the underlying molecular mechanism of anti-liver fibrosis of active components from traditional Chinese medicine has been further elucidated. This article summarizes scientific outcomes of signal pathways involved in liver fibrosis and how active components of Chinese herbal medicines exhibit anti-liver fibrosis effects, aiming to provide a potential drug candidate as a treatment for liver fibrosis and to open up a new research field of therapeutics for liver fibrosis.
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Key words:
- Liver Cirrhosis /
- Hepatic Stellate Cells /
- Signal Transduction /
- Drugs, Chinese Herbal
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表 1 中药活性成分靶向信号通路抗肝纤维化的机制总结
Table 1. Mechanism of anti-hepatic fibrosis by targeted signal pathway of active ingredients of Chinese medicine
类别 名称 来源 信号通路 抗肝纤维化作用 文献 酚类 Cur 姜黄、莪术、郁金等 TGFβ/Smad HSC增殖↓、促纤维化分子↓ [22-23] RSV 虎杖、藜芦、决明等 NF-κB、Hh HSC凋亡↑、上皮细胞间质转化↓ [25-26] SalA、B 丹参 Wnt/β-catenin、NF-κB、TGFβ/Smad α-SMA↓、TIMP-1↓、胶原合成↓ [27-28] 萜类 ART 青蒿素 Wnt/β-catenin、NF-κB、MAPK HSC凋亡↑、胶原合成↓ [32-33] UA 枇杷、女贞、夏枯草等 TGFβ/Smad、PI3K/Akt、MAPK MMP-1↑、TIMP-1↓、PPARγ↑、HSC增殖↓ [34-35] 生物碱类 TMPZ 川芎、郁金等 TGFβ/Smad、JAK/STAT IL-6↓、IL-1β↓、IL-10↑、HSC凋亡↑ [36-38] OMT 苦参 Wnt/β-catenin HSC活化↓ [40-41] 皂苷类 DIO 黄山药、菝葜等 PI3K/Akt、MAPK α-SMA↓、胶原合成↓ [42-43] PNS 三七 TGFβ/Smad Bcl-2↑、Bax↓、肝细胞凋亡↓ [44-45] 黄酮类 QUE 紫花地丁、仙鹤草、车前子、三七等 Wnt/β-catenin、NF-κB、MAPK 胶原沉积↓、羟脯氨酸↓ [46-47] TFL 荔枝核 TGFβ/Smad、NF-κB PPARγ↑、HSC活化↓ [48-49] 多糖类 DP 石斛 NF-κB HSC活化↓、胶原沉积↓、肠屏障通透性↓ [50-51] LBP 枸杞 NF-κB IGF-2↓、HSC活化↓ [52-53] DCP 狗肝菜 MAPK、NF-κB 胶原沉积↓ [54-55] 注:↑代表上升;↓代表下降。 -
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