抗代谢相关脂肪性肝病的天然活性物质研究进展

doi:10.11843/j.issn.0366-6964.2025.01.005

摘要/Abstract

摘要：

代谢相关脂肪性肝病是一种与代谢紊乱相关的慢性肝疾病，通常由体内脂肪、碳水化合物和蛋白质等代谢紊乱引起，其发病机制与炎症反应、氧化应激、胰岛素抵抗和肠道菌群稳态失调等有关。该病严重影响人和动物的肝健康，导致肝损伤、肝衰竭甚至肝癌的发生，增加糖尿病、心血管疾病等并发症乃至死亡的发生风险。源自蔬菜、水果、谷物及植物药材中的具有调节糖和脂类物质代谢、抗氧化应激、缓解炎症反应、改善肠道微生物菌群的天然活性物质可以调节肝代谢功能，减轻炎症反应，修复肝损伤，在代谢相关脂肪性肝病的预防和治疗中有着独特的优势。本文总结了能够调节糖脂代谢、抗氧化应激、缓解炎症反应、改善肠道菌群和胆汁酸代谢紊乱的天然活性物质，并阐述了这些活性物质在人和动物代谢相关脂肪性肝病中的潜在防治作用及其可能的机制，以期为临床医学或畜牧业生产实践中开发防治代谢相关脂肪性肝病的新药物提供理论参考。

Abstract:

Metabolic associated fatty liver disease is a chronic liver disease associated with metabolic disorders, usually caused by disturbances in the body's metabolism of fats, carbohydrates and proteins, and its pathogenesis is related to inflammatory response, oxidative stress, insulin resistance, and intestinal microbiota dysbiosis. This disease seriously affects the liver health of humans and animals, leading to liver injury, hepatic failure and even the occurrence of liver cancer, increasing the risk of complications such as diabetes, cardiovascular disease and even death. Natural active substances derived from vegetables, fruits, grains and plant medicinal herbs that regulate sugar and lipid metabolism, resist antioxidant stress, relieve inflammatory response, and improve intestinal microbiota balance can regulate liver metabolic function, reduce inflammatory response, and repair liver injury, and have unique benefits in the prevention and treatment of metabolic associated fatty liver disease. This article summarizes natural active substances that can regulate glucose and lipid metabolism, resist oxidative stress, relieve inflammatory response, improve intestinal flora and bile acid metabolism disorders, and discusses potential preventive and therapeutic effects and possible mechanisms of these agents in human and animal metabolic associated fatty liver disease, with the aim of providing a theoretical reference for the development of new drugs for the prevention and treatment of metabolic associated fatty liver disease in clinical medicine or animal husbandry practice.

Key words: natural active substances, metabolic associated fatty liver disease, prevention and treatment, research progress, humans and animals

中图分类号:

S859

吕永乐, 郑雯, 王签慧, 朱家琦, 黄晓琦, 曹中赞, 栾新红. 抗代谢相关脂肪性肝病的天然活性物质研究进展[J]. 畜牧兽医学报, 2025, 56(1): 45-62.

LÜ Yongle, ZHENG Wen, WANG Qianhui, ZHU Jiaqi, HUANG Xiaoqi, CAO Zhongzan, LUAN Xinhong. Research Progress of Natural Active Substances against Metabolic Associated Fatty Liver Disease[J]. Acta Veterinaria et Zootechnica Sinica, 2025, 56(1): 45-62.

图/表 5

表 1

调节脂质代谢的天然活性物质"

天然活性物质 Natural active substances	来源 Source	试验模型 Model	剂量/给药途径/给药时间 Dose/Route/Duration	效果/作用机制 Effect/Mechanisms	文献 Reference
黄酮类Flavone
槲皮素 Quercetin	水果和蔬菜	雄性C57BLKS/J小鼠/2型糖尿病模型	每日100 mg·kg^-1/胃内注射/8周	通过ACC1/AMPK/PP2A轴减轻肝脂质积累，降低血糖	[19]
染料木黄酮 Genistein	大豆	雄性C57BL/6N小鼠/HFD模型	每日1、2、4 g·kg^-1/口服/12周	改善小鼠血脂异常，降低肝和肾脂肪变性	[20]
越橘花青素 Bilberry Anthocyanins	越橘	雄性Sprague-Dawley大鼠/HFD模型	每日2%饲料添加量/口服/12周	减轻小鼠血脂异常，改善肠道菌群结构	[21]
山楂叶黄酮 Hawthorn leaf flavonoids	山楂	雄性Sprague-Dawley大鼠/HFD模型	每日50、100 mg·kg^-1/口服/12周	增强脂联素/AMPK途径，改善脂质代谢紊乱	[22]
萜类Terpene
梓醇 Catapol	熟地黄根茎	C57BL/6J小鼠/HFD模型	每日100、200、400 mg·kg^-1/口服/18周	降低肝重和脂质积累，加快脂肪酸代谢	[23]
五加酸 Pentacaric acid	刺五加根皮	C57BL/6小鼠/HFD模型	每日40 mg·kg^-1/口服/12周	改善小鼠血脂异常和肝脂质积累，降低肝纤维化	[24]
熊果酸Ursolic acid	琵琶等植物	雄性Sprague-Dawley大鼠/HFD模型	0.125%、0.25%、0.5%饮食持续6周	改善脂质代谢紊乱，降低血糖	[25]
多酚类Polyphenols
四角菱多酚 Tetrahydrocalcite polyphenol	四角菱果皮	雄性ICR小鼠/HFD模型	每日15、30 mg·kg^-1/口服/8周	改善血脂异常和肝脂质积累，降低胰岛素抵抗	[26]
巴西莓多酚 Acai berry polyphenols	巴西莓	F344大鼠/HFD模型	每日2 g/口服/6周	减轻肝脂肪变性和肝损伤，改善抗氧化状态	[27]
阿魏酸 Ferulic acid	谷物	雄性C57BL/6J小鼠/HFD模型	每日100 mg·kg^-1/口服/12周	促进脂肪酸氧化和能量消耗，降低脂质积累	[28]
糖类和苷类Sugars and glycosides
五味子多糖 Schisandra polysaccharides	五味子	雄性C57BL/6小鼠/HFD模型	每日100 mg·kg^-1/口服/12周	下调SREBPs的表达，抑制肝脂质积累	[29]
枸杞多糖 Lycium barbarum polusaccharide	枸杞	雄性C57BL/6J小鼠/HFD模型	每日100 mg·kg^-1/口服/24周	激活AMPK通路，抑制SREBP-1c表达	[30]
海参皂苷 Sea cucumber saponins	海参	Wistar大鼠/HFD模型	0.15%、1%饮食持续10 d	改善小鼠血脂异常和肝脂质积累，促进胆汁酸排泄	[31]
灵芝多糖Ganoderan	灵芝	雄性C57BL6/J小鼠/HFD模型	每日100、400 mg·kg^-1/口服/8周	改善小鼠血脂异常和肝脂质积累	[32]
柴胡皂苷Saikoside	柴胡	雄性C57BL/6J小鼠/HFD模型	2 mg·kg^-1/口服/8周	改善小鼠血脂异常和肝脂质积累	[33]

表 1

表 2

抗氧化应激的天然活性物质"

类别 Category	天然活性物质 Natural active substances	来源 Source	试验模型 Model	剂量/给药途径/给药时间 Dose/Route/Duration	效果/作用机制 Effect/Mechanisms	参考文献 References
黄酮类 Flavone	茶黄素Theaflavin	红茶	雄性C57BL/6小鼠/HFD模型	每日30 mg·kg^-1/腹腔注射/5d	抑制肝氧化应激，降低ROS的产生	[41]
	枇杷叶黄酮 Loquat leaf flavonoids	枇杷叶	雄性ICR小鼠/PM_2.5模型	每日50、100、200 mg·kg^-1/口服/7 d/35 d	抑制肝和脂肪氧化应激，提高抗氧化酶活性	[42]
	柚皮素 Naringenin	葡萄柚	BALB/c小鼠/药物损伤模型	每日50或100 mg·kg^-1/灌胃/14 d	减少肝氧化应激损伤，提高抗氧酶活性	[43]
	水飞蓟素 Silymarin	水飞蓟	雄性Wistar白化大鼠/果糖诱导模型	每日200、400 mg·kg^-1/口服/8周	减少肝氧化应激损伤，提高抗氧酶活性	[44]
	芦丁Rutin	水果	雄性C57BL/小鼠/HFD模型	每日200 mg·kg^-1/腹腔注射/8周	减少氧化应激，降低肝损伤	[45]
萜类 Terpene	栀子苷 Geniposide	栀子花果实	雄性Nrf2-/C57BL/6小鼠/HFD模型	每日50、75、100 mg·kg^-1/腹腔注射/18 h	减少肝氧化应激损伤，提高抗氧酶活性	[46]
	龙胆苦苷 Gentiopicroside	龙胆科植物根茎	雌性C57BL/6小鼠/药物损伤模型	每日20、40、80 mg·kg^-1/腹腔注射/12 h	上调Nrf2抗氧化途径缓解氧化损伤和脂质积累	[47]
	番茄红素 Lycopene	红色蔬菜和水果	雄性Wistar大鼠/HFD模型	每日5、10、20 mg·kg^-1/口服/6周	减少肝氧化应激损伤，提高抗氧酶活性	[48]
	脱氢枞酸 Dehydroabietic acid	针叶植物	雄性C57BL/6J小鼠/HFD模型	每日10、20 mg·kg^-1/口服/9周	改善体内氧化应激和脂质过氧化，提高抗氧化酶活性	[49]
生物碱类 Polyphenols	桑枝生物碱 Moricine	桑树枝	C57BL/6J小鼠HFD模型	每日100、200、300、400 mg·kg^-1/腹腔注射/6周	减少肝氧化应激损伤，提高抗氧酶活性	[50]
生物碱类 Polyphenols	苦参碱 Sophocarpidine	豆科植物	C57BL/6J小鼠/HFD模型	每日0.5、2.5、10 mg·kg^-1/口服/6周	通过影响SERCA通路改善氧化应激和脂质代谢紊乱	[51]

表 2

表 3

改善炎症反应的天然活性物质"

天然活性物质 Natural active substances	来源 Source	试验模型 Model	剂量/给药途径/给药时间 Dose/Route/Duration	效果/作用机制 Effect/Mechanisms	参考文献 References
黄酮类Flavone
姜黄素Curcumin	姜黄根茎	雄性C57BL/6J小鼠/HFD模型	每日2 g·kg^-1口服/24周	抑制炎性细胞浸润和减少炎性细胞因子表达	[57]
藏红花素Crocin	藏红花	雄性C57BL/6J小鼠/HFD模型	每日10、30、50 mg·kg^-1/口服/10周	抑制肝损伤，减少炎性细胞因子表达	[58]
芹菜素Apigenin	水果、蔬菜	雄性C57BL/6J小鼠/LPS诱导模型	每日50 mg·kg^-1/口服/8周	抑制NLRP3/NF-κB信号通路，降低炎症反应	[59]
萜类Terpene
芍药苷Paeoniflorin	牡丹	雄性Sprague-Dawley大鼠/HFD模型	每日20mg·kg^-1/口服/4周	抑制ROCK/NF-κB通路缓解炎症反应，降低肝损伤	[60]
虾青素Astaxanthin	虾等海洋生物	雄性C57BL /6J小鼠/HFD模型	0.02%含量高脂饮食/口服/10周	减少促炎型巨噬细胞和增加抑炎型巨噬细胞的量	[61]
姜黄醇Turmerol	姜黄	雄性SD大鼠/HFD模型	25、50、100 mg/kg/每3 d腹腔注射1次/21d	调节TLR4/NF-κB通路缓解炎症反应	[62]
多酚类Polyphenols
蔓越莓多酚Cranberry polyphenols	蔓越莓	雄性C57BL/6J小鼠/HFD模型	每日0.5~7 g/口服/10周	抑制TLR4/NF-κB通路，降低炎症反应	[63]
绿茶多酚Green tea polyphenols	绿茶	雄性Zucker大鼠/HFD模型	每日200 mg·kg^-1/口服/8周	抑制肝损伤，减少炎性细胞因子表达	[64]
白藜芦醇Resveratrol	葡萄	雄性FVB/N小鼠/HFD模型	每日30 mg·kg^-1/口服/60 d	调节SIRT1通路，抑制炎症反应	[65]
芒果苷Mangiferin	芒果	雄性C57BL/6J小鼠/HFD模型	每日25、50、100 mg·kg^-1/口服/12周	抑制NLRP3炎症小体表达，减轻炎症损伤	[66]

表 3

表 4

改善肠道菌群的天然活性物质"

类别 Category	天然活性物质 Natural active substances	来源 Source	试验模型 Model	剂量/给药途径/给药时间 Dose/Route/Duration	效果/作用机制 Effect/Mechanisms	参考文献 References
多酚类 Polyphenols	金银花多酚 Honeysuckle polyphenol	金银花	雄性C57BL/6N小鼠/HFD模型	每日0.5、1 g·kg^-1/口服/35 d	改善肠道微生物菌群结构，降低血清内毒素水平	[74]
	柑橘多酚 Citrus polyphenol	柑橘皮粉	Sprague-Dawley大鼠/HFD模型	每日1 g·kg^-1/口服/12周	改善肠道微生物菌群结构，抑制炎症反应	[75]
	绿原酸 Chlorogenic acid	杜仲等植物	雄性C57BL/6小鼠/HFD模型	每日60 mg·kg^-1/口服/12周	改善肠道微生物菌群结构，降低血清内毒素水平	[76]
糖类和苷类 Sugars and glycosides	黄芪多糖 Astragalus polysaccharide	黄芪	雄性C57BL/6J小鼠/HFD模型	每日2%、4%、8%/口服/14周	逆转肠道微生物结构和功能以及肠道代谢物的变化	[77]
	灵芝菌丝体多糖 Ganoderma lucidum mycelium polysaccharide	灵芝	雄性C57BL/6N小鼠/HFD模型	每日100 μL/口服/2月	预防肠道菌群失调和肥胖相关代谢紊乱	[78]
	绞股蓝多糖 Gynostemma Pentaphyllum	绞股蓝	雄性C57BL/6小鼠/蛋氨酸和胆碱缺乏模型	每日150、300 mg·kg^-1/口服/4周	调节肠道菌群和TLR2/NLRP3通路改善NASH	[79]
	云芝多糖 Coriolus versicolor polysaccharide	云芝	雄性C57BL/6J小鼠/HFD模型	每日100、400 mg·kg^-1/口服/40 d	改善肠道微生物菌群结构，缓解肝脂肪变性	[80]
	三七皂苷 Notoginsenoside	三七	雄性C57BL/6小鼠/HFD模型	每日400、800 mg·kg^-1/口服/7周	改善肠道微生物菌群结构，缓解肝脂肪变性	[81]
生物碱类 Polyphenols	甜菜碱 Betaine	甜菜	C57BL/6J小鼠/HFD模型	1%水溶液自由饮水/13周	改善肠道微生物菌群结构，提高短链脂肪酸的浓度	[82]
生物碱类 Polyphenols	小檗碱和吴茱萸碱 Berberine and evodiine	黄檗和吴茱萸	雄性Sprague-Dawley大鼠/HFD模型	每日18、36、72 mg·kg^-1/口服/4周	调节肠道微生物群和保护肠道屏障	[83]

表 4

表 5

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天然活性物质 Natural active substances	来源 Source	试验模型 Model	剂量/给药途径/给药时间 Dose/Route/Duration	效果/作用机制 Effect/Mechanisms	参考文献 References
黄酮类Flavone
金丝桃苷 Hyperin	山楂	10周龄雄性大鼠/HFD模型	每日0.6、1.5 mg·kg^-1/口服/20 d	上调FXR/LXRα通路，促进胆汁酸排泄和抑制脂肪生成	[86]
柑橘的总黄酮提取物 Citrus flavone extract	柑橘	雄性C57BL/6J小鼠/HFD模型	每日50 mg·kg^-1/口服/7周	促进胆汁酸代谢和调节肠道菌群紊乱	[87]
萜类Terpene
甘草甜素 Glycyrrhizin	甘草	雄性C57BL/6小鼠/蛋氨酸和胆碱缺乏模型	每日50 mg·kg^-1/腹腔注射/8周	调节胆汁酸排泄和胆固醇代谢	[88]
绞股蓝皂苷 Gypenosides	绞股蓝	雄性C57BL/6小鼠/HFD模型	每日10 mg·kg^-1/口服/4周	促进胆汁酸合成并介导胆汁酸代谢，参与脂质代谢	[89]
多酚类Polyphenols
儿茶素 Catechin	绿茶	雄性C57BL/6J小鼠/HFD模型	每日3.2 g·kg^-1/口服/32周	降低小鼠胆汁酸和脂质吸收	[90]
茶褐素 Theabrownin	普洱茶	13名健康男性	每日50 mg·kg^-1/静脉输液/4周	促进胆汁酸排泄和胆固醇代谢	[91]
原花青素 Procyanidine	葡萄籽	雄性Wistar大鼠/高果糖诱导模型	每日250 mg每日/口服/7 d	促进胆汁酸排泄和总脂质排泄	[92]

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