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虎杖活性成分治疗非酒精性脂肪性肝病的相关信号通路及相互作用
DOI: 10.3969/j.issn.1001-5256.2022.04.033
利益冲突声明：所有作者均声明不存在利益冲突。
作者贡献声明：李淑娣负责课题设计，资料分析; 陈欣菊、刘江凯、王振、段飞负责修改论文; 袁卓雅、梁磊负责归纳总结文献资料; 李素领负责拟定写作思路，指导撰写文章并最后定稿。
Signaling pathways involved in the active components of Polygonum cuspidatum in treatment of nonalcoholic fatty liver disease and their interaction
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摘要: 非酒精性脂肪性肝病(NAFLD)的发病机制尚不清楚，且目前尚无任何治疗NAFLD的有效药物获批。虎杖是药用历史悠久的天然中药，研究证实其在治疗NAFLD中可发挥重要作用。本文通过梳理近年来虎杖活性成分应用于NAFLD的相关研究成果，可见虎杖活性成分通过调控核因子E2相关因子2、腺苷酸活化蛋白激酶、NF-κB、沉默信息调节因子1和过氧化物酶体增殖物激活受体α等多条相关信号通路，发挥改善胰岛素抵抗、抗氧化应激、调节脂质代谢、改善内质网应激、减轻炎症浸润等作用，达到防治NAFLD的作用，以期为NAFLD治疗药物研发及机制探索提供依据和思路。Abstract: The pathogenesis of nonalcoholic fatty liver disease (NAFLD) remains unclear, and currently no effective drugs have been approved for the treatment of NAFLD. Polygonum cuspidatum is a natural traditional Chinese medicine with a long history of application, and studies have shown that it plays an important role in the treatment of NAFLD. This article summarizes related research findings in the active components of Polygonum cuspidatum applied in the treatment of NAFLD, and it is found that the active components of Polygonum cuspidatum can improve insulin resistance, exert an anti-oxidative stress effect, regulate lipid metabolism, improve endoplasmic reticulum stress, and alleviate inflammatory infiltration by regulating the signaling pathways including Nrf2, AMPK, NF-κB, SIRT1, and PPARα, thereby exerting a preventive and therapeutic effect on NAFLD, so as to provide a basis and ideas for developing drugs for NAFLD and exploring related mechanisms.
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图 1 虎杖活性成分治疗NAFLD的细胞信号通路机制
Figure 1. Mechanism of cell signaling pathway in treatment of NAFLD by active ingredients of Polygonum cuspidatum
表 1 虎杖活性成分调节Nrf2通路作用于NAFLD的效应路径
Table 1. Active ingredients of Polygonum cuspidatum regulates the effect pathway of Nrf2 pathway on NAFLD
路径 效应指标 抗氧化应激 SOD、GSH、CAT↑; MDA↓ 调节脂质代谢 HO-1、CPT1↑ 减轻炎症反应 TNFα、IL-1β、IL-6↓ 注：↑上调; ↓下调。 
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表 2 虎杖活性成分调节AMPK通路作用于NAFLD的效应路径
Table 2. Active ingredients of Polygonum cuspidatum regulates the pathway of AMPK pathway on NAFLD
路径 效应指标 调节脂质代谢 PPARα、SREBP-1c、ChREBP↑; FASN、SCD1↓ 改善胰岛素抵抗 脂联素↑ 减轻炎症反应 SREBP-1c↓ 注：↑上调; ↓下调。FASN，脂肪酸合酶; SCD1，硬脂酰辅酶A去饱合酶1。
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表 3 虎杖活性成分调节NF-κB通路作用于NAFLD的效应路径
Table 3. Active ingredients of Polygonum cuspidatum regulates the pathway of NF-κB pathway on NAFLD
路径 效应指标 减轻炎症反应 TNFα、IL-1β、IL-6↓ 改善胰岛素抵抗 ERK、IL-6、TNFα、LPS↓ 注：↓下调。
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表 4 虎杖活性成分调节SIRT1通路作用于NAFLD的效应路径
Table 4. Active ingredients of Polygonum cuspidatum regulates the pathway of SIRT1 pathway on NAFLD
路径 效应指标 调节脂质代谢 ATF6、LC3↓; GLUT4↑ 改善内质网应激 ERK、IL-6、TNFα、LPS↓ 注：↑上调; ↓下调。
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表 5 虎杖活性成分调节PPARα通路作用于NAFLD的效应路径
Table 5. Active ingredients of Polygonum cuspidatum regulates the pathway of PPARα pathway on NAFLD
路径 效应指标 调节脂质代谢 FASN、SCD1↓; PPARα、CPT1↑ 改善氧化应激 PKA、AMPK↑ 注：↑上调; ↓下调。
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