中药调控Toll样受体4/核因子-κB通路改善非酒精性脂肪性肝炎的研究进展

田格格; 夏恩蕊; 张素妍; 张顺贞; 徐福荣

doi:10.3969/j.issn.1001-5256.2021.12.047

中药调控Toll样受体4/核因子-κB通路改善非酒精性脂肪性肝炎的研究进展

DOI: 10.3969/j.issn.1001-5256.2021.12.047

云南中医药大学中药学院，昆明 650000

基金项目:

国家自然科学基金 (81760818);

云南省高校中医证候微观辨证重点实验室 (20190720);

云南省科技厅中医联合专项 (2018FF001(-042))

详细信息

通信作者:
张顺贞，694415176@qq.com

徐福荣，xfrong99@163.com

中图分类号: R575.5
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出版历程
- 收稿日期: 2021-05-22
- 录用日期: 2021-07-21
- 出版日期: 2021-12-20

Research advances in traditional Chinese medicine in improving nonalcoholic steatohepatitis by regulating the Toll-like receptor 4/nuclear factor-kappa B signaling pathway

School of Traditional Chinese Medicine, Yunnan University of Traditional Chinese Medicine, Kunming 650000, China

Research funding:

National Natural Science Foundation of China (81760818);

Key Laboratory of Microcosmic Syndrome Differentiation of TCM Syndrome in Yunnan Province (20190720);

Joint Special Project of Traditional Chinese Medicine of Yunnan Provincial Science and Technology Department (2018FF001(-042))

摘要

摘要: 非酒精性脂肪性肝炎(NASH)是非酒精性脂肪性肝病的严重类型，可发展为威胁生命的肝硬化和肝癌。Toll样受体4(TLR4)是先天免疫中的一类模式识别受体，被激活可引发级联反应，活化介导炎症反应的核因子-κB(NF-κB)。TLR4/NF-κB通路是经典的炎症通路。临床上用中药治疗NASH取得了良好的疗效，TLR4/NF-κB通路是中药治疗NASH的途径之一，通过检索相关文献，总结了可调控TLR4/NF-κB通路改善NASH的中药活性成分和复方，旨在为今后的研究和用药提供思路。
- 非酒精性脂肪性肝炎 /
- Toll样受体4 /
- NF-κB /
- 中草药
Abstract: Nonalcoholic steatohepatitis (NASH) is a serious type of nonalcoholic fatty liver disease (NAFLD) and can develop into life-threatening liver cirrhosis and liver cancer. Toll-like receptor 4 (TLR4) is a type of pattern recognition receptor in innate immunity, and after being activated, it can trigger a cascade reaction and activate nuclear factor-κB (NF-κB) which mediates inflammatory response. The TLR4/NF-κB signaling pathway is a classic inflammatory pathway. In clinical practice, traditional Chinese medicine has achieved a good effect in the treatment of NASH, and the TLR4/NF-κB signaling pathway is one of the approaches for traditional Chinese medicine to treat NASH. By searching the relevant literature, this article summarizes the active components and compounds of traditional Chinese medicine that can regulate the TLR4/NF-κB signaling pathway to alleviate NASH, so as to provide ideas for future research and medication.
- Nonalcoholic Steatohepatitis /
- Toll-Like Receptor 4 /
- NF-kappa B /
- Drugs, Chinese Herbal

HTML全文

图 1 TLR4/NF-κB通路

注：TRAF-6，肿瘤坏死因子相关因子。当肝脏中各类免疫细胞与非免疫细胞表面的TLR4被激活，MyD88适配子磷酸化，活化TRAF-6使得TAK1、IKKs被激活^[13]。IκB在IKKs的作用下从静息状态下的NF-κB聚合体中分离，与IκB分离后的NF-κB进入细胞核，介导IL-6、IL-1β、TNFα等炎症因子的基因转录和释放^[14]。

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表 1 中药活性成分调控TLR4/NF-κB通路改善NASH

类别	药物	造模方式	通路相关分子表达情况	相关炎症因子表达情况	文献
黄酮类	杨梅素	低蛋氨酸和胆碱缺乏及L-氨基酸限定的高脂饮食/LPS干预	下调TLR4、MyD88、p-NF-κB/NF-κB、p-IκBα/IκBα	下调TNFα、IL-6、IL-1β；上调IL-10	[15]
	槲皮素	蛋氨酸-胆碱缺乏饮食	下调TLR4、NF-κB P65	下调TNF-α、IL-6	[16]
	黄芩苷	蛋氨酸-胆碱缺乏饮食	下调TLR4、MyD88、p-NF-κB p65	下调TNF-α、IL-6、IL-1β	[17]
	胡桃苷	高果糖饮食	下调TLR4、MyD88、IRAK4、IRAK1、TRAF6、TAK1、P-IKKα、P-IκBα、p-NF-κB	下调TNFα、IL-1β、IL-18、IL-6	[18]
	银杏黄酮	高脂饮食	下调TLR4、p-NF-κB p65	下调IL-6、TNFα	[19]
	豹皮樟总黄酮	脂肪乳剂	下调TLR4、NF-κB	下调TNFα	[20]
萜类	白果内酯	高脂饮食	下调TLR4、TAK1、p-NF-κB p65/NF-κB p65	下调TNFα、IL-6、IL-1β	[21]
	青蒿琥酯	高脂饮食	下调TLR4、MyD88、NF-κB	下调TNFα	[22-23]
	黄芪甲苷	高脂饮食	下调TLR4、MyD88、NF-κB p65	下调IL-6、TNFα、IL-8	[24]
	绞股蓝总苷	高脂饮食/游离脂肪酸干预	下调TLR4、MyD88、p-NF-κB/NF-κB、p-IκBα/IκBα	下调IL-1β、TNFα	[25]
醌类	紫草素	蛋氨酸-胆碱缺乏饮食	下调P-P65	下调TNFα、IL-6、IL-1β	[26]
	决明子蒽醌苷	高脂饮食	下调TLR4、NF-κB	下调IL-1β、IL-6、TNFα、IL-1α	[27]
	大黄酸	高脂高果糖饮食	下调TLR4、MyD88、NF-κB		[28]
生物碱类	小檗碱	高脂饮食	下调TLR4、MyD88、NF-κB p65	下调IL-6、TNFα、IL-1β	[29]
	槐果碱	油酸干预	下调TLR4、P-IKKα/β、IKKα、IKKβ	下调IL-6、TNFα	[31]
多酚类	姜黄素	高脂饮食	TLR4、MyD88、NF-κB p65	IL-6、TNFα、IL-1β	[32]
	二苯乙烯苷	高脂饮食	TLR4、P-IKKα/β、IKKα、IKKβ	IL-6、TNFα	[33]
多糖类	枸杞多糖	高脂饮食	下调P-P65	下调TNFα、IL-6、IL-1β	[34]
	狗肝菜多糖	高脂饮食	下调TLR4、p-NF-κB p65	下调IL-6、TNFα、IL-1β	[19]
其他类	滨蒿内酯	蛋氨酸-胆碱缺乏饮食	TLR4、MyD88、IκBα、p-NF-κB p65	IL-1β、TNFα、IL-6、IL-10	[35]
	砂仁挥发油	高脂饮食	TLR4、NF-κB、Ikk、IκB	TNFα、IL-6、IL-1α、IL-10	[36]
	丹参提取物	高脂饮食	TLR4、TIRAP、IRAK1、IRAK4、TRAF6、P-IκB、IκB、NF-κB P65、P-NF-κB P65	TNFα、IL-1β、IL-6	[37]

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表 2 中药复方调控TLR4/NF-κB通路改善NASH

中药复方	功效	造模方式	通路相关分子表达情况	相关炎症因子表达情况	文献
祛痰活血方	疏肝健脾、活血化瘀	蛋氨酸-胆碱缺乏饮食	下调TLR4、MyD88、NF-κB		[42]
附子理中汤	温阳健脾	脂肪乳灌胃	下调CD4、TLR4、NF-κB p65	下调IL-2、IL-6、TNFα	[43]
加味泽泻汤	健脾利湿	高脂饮食	下调TLR4、MyD88、NF-κB p65、p-p65		[44]
健脾清化饮	健脾益气、清热化湿	高脂饮食	下调TLR4、MyD88、NF-κB	下调TNFα	[45]
复方渣金颗粒	健脾化湿、活血化瘀、疏肝解郁	高脂高果糖饮食	下调TLR4、MyD88	下调TNFα	[46-47]
大柴胡汤	疏肝利胆健脾	高脂高果糖饮食	下调TLR4、NF-κB	下调TNFα	[48]

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