中药有效成分及其复方防治非酒精性脂肪性肝病的现状与展望

潘雨晴; 毛傲洁; 于楚楚; 胡义扬

doi:10.12449/JCH241002

中药有效成分及其复方防治非酒精性脂肪性肝病的现状与展望

DOI: 10.12449/JCH241002

上海中医药大学附属曙光医院，上海中医药大学肝病研究所，上海中医药大学教育部肝肾疾病重点实验室，上海市中医临床重点实验室，上海 201203

基金项目:

国家自然科学基金面上项目 (82174186)

利益冲突声明：本文不存在任何利益冲突。

作者贡献声明：潘雨晴负责查阅文献，撰写论文；毛傲洁、于楚楚负责查阅文献；胡义扬负责拟定文章思路，修改并最终定稿。

详细信息

通信作者:
胡义扬， yyhuliver@163.com （ORCID： 0000-0001-9127-7002）

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出版历程
- 收稿日期: 2024-07-03
- 录用日期: 2024-07-30
- 出版日期: 2024-10-25

Active components of traditional Chinese medicine and their compound prescriptions in prevention and treatment of nonalcoholic fatty liver disease： Current status and prospects

Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine；Institute of Liver Diseases，Shanghai University of Traditional Chinese；Key Laboratory of Liver and Kidney Diseases of the Ministry of Education，Shanghai University of Traditional Chinese Medicine；Shanghai Key Laboratory of Traditional Chinese Clinical Medicine，Shanghai 201203，China

Research funding:

General Project of National Natural Science Foundation of China (82174186)

More Information

Corresponding author: HU Yiyang， yyhuliver@163.com （ORCID： 0000-0001-9127-7002）

摘要

摘要: 非酒精性脂肪性肝病（NAFLD）是目前全球患病率最高的慢性肝病，发病机制复杂，临床治疗手段局限。近20多年来，从中药中发现治疗NAFLD的有效成分以及能发挥多靶点综合作用的成分复方是研究热点之一。本文根据其化学成分，以黄酮类、酚类、萜类、生物碱类、皂苷类分类阐述具有治疗NAFLD前景的中药有效成分，以及具有配伍增效作用的有效成分复方，以期进一步为NAFLD药物治疗策略提供新思路。
- 非酒精性脂肪性肝病 /
- 中药 /
- 复方配伍
Abstract: Nonalcoholic fatty liver disease （NAFLD） is currently a chronic liver disease with the highest prevalence rate in the world， with complex pathogeneses and limited clinical treatment methods. Over the past 20 years， the discovery of active components for NAFLD treatment from traditional Chinese medicine and compound prescriptions of the components that can exert a multi-target effect has been one of the research hotspots. Based on the chemical components of traditional Chinese medicine， this article elaborates on the active components with a promising future in the treatment of NAFLD， including flavonoids， phenols， terpenoids， alkaloids， and saponins， as well as the compound prescriptions of active components with a synergistic effect， in order to provide new ideas for the strategies of pharmacotherapy for NAFLD.
- Non-alcoholic Fatty Liver Disease /
- Traditional Chinese Drugs /
- Concerted Application of Prescription

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表 1 治疗NAFLD的中药有效成分

Table 1. Effective components of traditional Chinese medicine for the treatment of NAFLD

分类	有效成分	NAFLD模型构建	剂量	作用机制
黄酮类	槲皮素^［12］	db/db小鼠；高糖和FFA诱导 HepG2细胞	体内：50/100/150 mg/kg；体外：10/20/40 μmol/L	mTOR/YY1↓ CYP7A1↑
	水飞蓟宾^［13］	HFD小鼠	100/300 mg/kg	产SCFA菌↑： Blautia，Bacteroides，Akkermansia
	木犀草素^［14］	HFD大鼠	HFD饮食含0.5%木犀草素	ZO-1↑ LPS↓TLR4/NF-κB↓
	葛根素^［16］	NASH小鼠、斑马鱼模型； FFA诱导HepG2细胞； LPS+INF-γ诱导RAW 264.7细胞	小鼠：100 mg/kg；斑马鱼：100/200/400 μg/mL；细胞：20/40/80 μmol/L	AMPK↑—mTOR↓—pULK-1—PAI-1↓—STAT3/HIF1α↓ PI3K/AKT↑
	二氢杨梅素^［18］	HFD大鼠； PA诱导HepG2细胞	体内：50/100/200 mg/kg；体外：10 μmol/L	AMPK/PGC-1α↑ PPARα↑
	山柰酚^［20］	db/db小鼠；油酸诱导HepG2细胞	体内：50 mg/kg；体外：10^-6/-7/-8 mol/L	Sirt1/AMPK/PGC-1α↑ ACC/FAS/SREBP1↓
酚类	白藜芦醇^［21］	HFD大鼠	50/100 mg/kg	产SCFA菌↑：Ruminococcaceae、Lachnospiraceae 产LPS菌↓：Desulfovibrio
	姜黄素^［22］	HFD大鼠； FFA诱导LSEC细胞、L02细胞	体内：25/50/100 g/kg；体外：1/2/4/8/10 mol/L	NF-κB↓ PI3K/Akt/HIF-1α↓
	绿原酸^［23］	HFD小鼠； AML12细胞；THLE-2细胞	体内：50 mg/kg；体外：12.5/25/50/100 μmol/L	AXL/ERK/LKB1↓ AMPK/ULK-1↑
	EGCG^［24］	HFD大鼠； LPS诱导Caco-2细胞	体内：100/200 mg/kg；体外：25/50/75/100 μmol/L	LPS/TLR4/NF-κB↓ Nrf2—ZO-1/Occludin↑
	和厚朴酚^［25］	胆碱缺乏的高脂肪饮食小鼠； FFA诱导AML12细胞	体内：2.5/10 mg/kg；体外：5/10 μmol/L	SIRT3/AMPK↑ 维持线粒体功能
萜类	栀子苷^［26］	tyloxapol诱导NAFLD模型小鼠； FFA诱导HepG2细胞	体内：50/75/100 g/kg；体外：65/130/260 μmol/L	Nrf2/HO-1/AMPK↑ mTOR↓
	白术内酯Ⅲ^［27］	HFD小鼠； FFA诱导HepG2细胞	体内：10 mg/kg灌胃+ 1 mg/mL尾静脉注射；体外：25 μg/mL	AdipoR1/AMPK/SIRT1↑
	白桦脂酸^［28］	HFD小鼠； MCD小鼠； HepG2细胞；Hepa1-6细胞	体内：150 mg/kg；体外：10 μmol/L	YY1/FAS↓
	丹参酮ⅡA^［29］	FFA诱导HepG2细胞、Huh7细胞	5/10 μmol/L	LXRα/SREBP1↓
生物碱	小檗碱^［34］	HFD小鼠；油酸诱导原代肝细胞	体内：1.4 g/kg；体外：4 μmol/L	SCD1/FABP1/CD36/CPT1A↓
	氧化小檗碱^［35］	HFD大鼠	100 mg/kg	IRS-1/PI3K/AKT↑
	甜菜碱^［36］	CDA-HFD小鼠	0.2%/0.5%/1%	Atg7/LC3Ⅱ/Ⅰ↑ AMPK↑ ACC↑ Bip/ATF6↓
	氧化苦参碱^［37］	HFD饮食联合链脲佐菌素注射； PA诱导 HepG2细胞	体内：45/90 mg/kg；体外：0.1/0.2 mg/mL	NLRP3/IL-1β↓
皂苷	人参皂苷Rb1^［39］	HFD小鼠	10 mg/kg	PPAR-γ↑
	人参皂苷Re^［40］	HFD小鼠	20/40 mg/kg	PI3K/AKT↓ TLR4/NF-κB↓
	人参皂苷RO^［41］	HFD小鼠	45/90 mg/kg	GLP-1↑ TGR5↑
	黄芪皂苷Ⅳ^［42］	HFD大鼠	20/40/80 mg/kg	TLR4↓、MyD88 ↓、NF-κB↓
	绞股蓝皂苷LXXV^［43］	MCD小鼠； PA诱导HepG2细胞； TGF-β诱导LX2细胞； LPS+ATP诱导THP-1细胞	体内：15/30 mg/kg；体外：0.001～10 μg/mL	α-SMA、TGF-β1、TNF-α、MCP-1、IL-1β、NF-κB、GRP78↓

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表 2 治疗NAFLD的中药有效成分复方

Table 2. Effective component compound of traditional Chinese medicine for the treatment of NAFLD

中药有效成分复方	比例及剂量	作用机制
栀子苷+绿原酸^［46-48］	67.16∶1； 90 mg/kg+1.34 mg/kg	SCD-1↓ LPS/TLR-4、TNF-α、 IL-1β↓ MAPK↓
花生皮提取物+栀子苷+异槲皮素^［49］	16∶10∶1； 80 mg/kg+50 mg/kg+5 mg/kg	TLR4/NF-κB↓ AMPK/ACC/CPT1↑ AMPK/UKL-1/LC3B↑
葛根素+小檗碱^［51］	10∶1～40∶1	PPARγ
葛根素+小檗碱+黄芩苷^［52］	10∶1∶1～10∶1∶2	PPARγ
小檗碱+姜黄素^［53-54］	50 mg/kg+50 mg/kg	PPARγ↑ caveolin-1↑ SREBP-1c↓ SCD-1↓ NF-κB↓TNF-α↓
小檗碱+生育三烯酚+绿原酸^［56］	小鼠：87.84 mg/kg+5.27 mg/kg+5.28 mg/kg；人：500 mg+30 mg+30 mg	miR-122↑ miR-34a↓
丹酚酸B+苦杏仁苷+五味子酯甲^{［10，57］}	16 mg/kg+0.5 mg/kg+2 mg/kg	CK7、CK19、EpCAM、OV6↓ Notch↓
水飞蓟宾+丹酚酸B+葛根素^［58］	总质量100.3 g，干预饲料含：0.101 g+0.046 g+0.042 g	益生菌↑：Akkermansia、Blautia；次生胆汁酸合成相关的属↓：Clostridium、Bacteroides
原人参二醇+丹参酮ⅡA+大黄素^［60］	10∶10∶1	血清ALT、TC、HDL-c、LDL-c ↓
阿魏酸+香豆酸^［61］	1∶1.3	HDAC1↓ PPARγ/FABP/CD36↓
木犀草素+番茄红素^［62］	体内：20 mg/kg+20 mg/kg；体外：20 μmol/L+10 μmol/L	Sirt1/AMPK/β氧化↑ NF-κB/IL-6、IL-1β、TNF-α↓
毛冬青皂苷A1+海南冬青苷D^［63］	41.6∶54.4，60/120/240 mg/kg	ZO-1、Occludin↑ Akkermansia↑ Desulfovibrio↓
EGCG+咖啡因^［64］	40 mg/kg+20 mg/kg	TNF-α、IL-6、MCP-1↓
姜黄素+白藜芦醇^［65］	8∶2，150 mg/kg	PI3K/AKT/mTOR/STAT3/ HIF-1α/VEGF↓

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