TABLE 1.

Protective effect of isoflavones and triterpenoid saponins from pueraria lobata on liver diseases

Active ingredients	Model	Efficacy	Dose/Concentrations	Targets/Pathway/Mechanism	Reference
Puerarin	Alcoholic liver injury in rats	Reduces intestinal permeability and prevents alcohol absorption	3 g/kg/d (Crude extract of puerarin; purity, 58.9%)	Protects intestinal tight junction protein ZO−1	(Zhang et al., 2009)
Puerarin	Alcoholic liver injury in rats	Promotes alcohol metabolism	30, 60, 120 mg /kg/d	Increases the activity of ADH and ALDH; Reduces CYP2E1, CYP1A2, and CYP3A levels	(Chen et al., 2013)
Puerarin	Alcoholic liver injury in mice	Alleviates oxidative stress	200 mg/kg/d	Increases GSH, SOD, and GPX levels	(Zhao et al., 2010)
Puerarin	Alcoholic liver injury in rats	Regulates inflammatory response	30, 60, 120 mg /kg/d	Decreases IL−1 β, IL−6, PGE2, and TNF‐α levels; inhibits GSK−3β/NF‐κB pathway	(Li et al., 2013)
Puerarin	The rat hepatoma cell line H4IIE treated with ethanol	Restores hepatocyte autophagy; regulates lipid homeostasis	60, 120 μM	Activates AMPK/mTOR pathway	(Noh et al., 2011)
Puerarin	Pb‐induced liver injury in rats	Alleviates oxidative stress; antiapoptotic	400 mg/kg/d	Increases the activity of GPx, CAT, SOD, and GSH; decreases caspase−3 level	(Liu et al., 2012)
Puerarin	Ni‐induced liver injury in mice	Alleviates oxidative stress; reduces inflammation	400 mg/kg/d	Promotes the expression of MT protein; decreases TNF‐α, IL−6, PGE2, and COX−2 levels; inhibits TLR4/p38/CREB pathway	(Liu et al., 2016)
Puerarin	CCl4‐induced liver injury in mice	Alleviates oxidative stress; reduces lipid peroxidation	200, 400 mg/kg/d	Activates JNK/c‐jun/CYP7A1 pathway	(Ma et al., 2014)
Puerarin	Type 2 diabetes mellitus in mice	Alleviates oxidative stress; improves liver energy metabolism	650 mg/kg/d	Upregulates bcl−2 expression; increases the activity of SOD, GSH‐Px, Na(+)‐K(+)‐ATPase	(Shuo Yang et al., 2009)
Puerarin	Nonalcoholic fatty liver disease induced by a high‐fat diet in rats	Improves liver steatosis	400, 800 mg/kg/d	Activates JAK2/STAT3 pathway	(Zheng et al., 2009)
Puerarin	Nonalcoholic fatty liver disease induced by a high‐fat diet in rats	Improves liver steatosis	50, 100, 200 mg/kg/d	Upregulates hepatic PPAR‐γ and IR expression levels	(Zhao et al., 2016)
Puerarin	Steatohepatitis induced by a methionine‐ and choline‐deficient diet in mice	Regulates the early stages of lipid metabolism	900 mg/kg/d	Increases the expression of PPAR‐γ	(Yunliang Wang et al., 2014)
Puerarin	CCl4‐induced liver injury in rats	Reverses liver fibrosis	400, 800 mg/kg/d	Down‐regulates bcl−2 mRNA expression; induces apoptosis of activated HSC cells	(Zhang et al., 2006)
Puerarin	CCl4‐induced liver injury in mice	Reverses liver fibrosis; alleviates oxidative stress	100, 200 mg/kg/d	Inhibits the expression of PARP−1	(Wang et al., 2016)
Puerarin	CCl4‐induced liver injury in rats	Reverses liver fibrosis	200, 400, 800 mg/kg/d	Upregulates the PPAR‐γ expression; blocks the PI3K/Akt pathway	(Guo et al., 2013)
Puerarin	CCl4‐induced liver injury in rats	Reverses liver fibrosis	400 mg/kg/d	Inhibits Wnt1/β‐catenin pathway; inhibits the activation of hepatic stellate cells	(Huang et al., 2018)
Puerarin	Dimethylnitrosamine‐induced liver injury in rats	Reverses liver fibrosis	500 mg/kg/d	Inhibits TGF‐β/Smad pathway	(Xu et al., 2013)
Puerarin	Thioacetamide‐induced liver injury in rats	Reverses liver fibrosis; Reduces inflammation	200 mg/kg/d	Inhibits TGF‐β/ERK1/2 pathway	(Xiuqing Li et al., 2019)
Puerarin	LPS/D‐Gal‐induced liver injury in mice	Restores the autophagy; reduces inflammation	200 mg/kg/d	Increases the ratio of LC3B‐II/I and the protein level of Beclin−1; decreases the level of p62 protein expression	(Li et al., 2018)
Puerarin	2‐AAF/PH‐induced liver injury in mice	Reduces apoptosis	200 mg/kg/d	Inhibits mTOR pathway via inactivation of AKT	(Zhou et al., 2018)
Daidzein	7,12‐dimethylbenz[a]‐anthracene‐induced liver injury in mice	Alleviates oxidative stress; reduces apoptosis	5, 25 mg/kg/d	Increases SOD, CAT, GSH‐Px, and GR levels; Decreases caspase−3 level and increases Bcl−2 level	(Choi et al., 2009)
Daidzein	D‐Gal‐induced liver injury in rats	Alleviates oxidative stress	100 mg/kg/d	Increases SOD activity; decreases MDA level	(Wong et al., 2007)
Daidzein	Cisplatin‐induced liver injury in rats	Alleviates oxidative stress	20, 40 mg/kg/d	Increases SOD, GSH, and CAT activity; Decreases MDA level	(Karale et al., 2017)
Daidzein	The rat hepatoma cell line H4IIE treated with H2O2	Alleviates oxidative stress	200, 300 μM	Increases CAT and GPx levels	(Röhrdanz et al., 2002)
Daidzein/Genistein	Western‐style diet‐induced obesity in mice	Regulates lipid metabolism	160 mg/kg/d	Activates liver X receptor	(Luo et al., 2018)
Daidzein	Nonalcoholic fatty liver disease induced by a high‐fat diet in mice	Regulates lipid metabolism	100, 500 mg/kg/d	Promotes leptin and adiponectin mRNA expression; activates AMPK/PPARα pathway	(Kim et al., 2011)
Daidzein	Nonalcoholic fatty liver disease induced by a high‐fat diet in rats	Reduces steatosis	50 mg/kg/d	Promotes leptin and adiponectin mRNA expression; activates PPARα and PPARγ	(Crespillo et al., 2011)
Daidzein	Human hepatocellular carcinoma cells SK‐HEP−1	Induces the apoptosis	200, 400, 600 μM	Increases the release of mitochondrial cytochrome c and the activation of APAF−1, caspase9, and caspase−3 through the bcl−2 family	(Park et al., 2013)
Formononetin	APAP‐induced liver injury in mice	Alleviates oxidative stress	50, 100 mg/kg/d	Increases GSH activity; activates Nrf2 pathway	(Jin et al., 2017)
Formononetin	Ritonavir‐induced liver injury in rats	Modulates the oxidative stress, inflammation, apoptosis and reversing the tissue degeneration	100 mg/kg/d	Attenuates the RIT‐induced Bax, caspase−3, NFκB, and eNOS activation; upregulates the Bcl−2 and pAkt level	(Alauddin et al., 2018)
Formononetin	Naphthalene isothiocyanate‐induced liver injury in mice	Ameliorates cholestasis; reduces inflammation	10, 20, 50 mg/kg/d	Activates SIRT1; regulates PPARα/JNK pathway	(Shu Yang et al., 2019)
Formononetin	Nonalcoholic fatty liver disease induced by a high‐fat diet in mice	Regulates lipid metabolism; promotes autophagy	100 mg/kg/d	Activates AMPK/TFEB pathway; facilitates TFEB‐mediated lysosome biogenesis	(Yan Wang et al., 2019)
Genistein	D‐GalN‐induced liver injury in rats	Improves liver fibrosis	5 mg/kg/d	Modulates the expression of Smad2/3 and Smad7; activates Smad/TGF‐β pathway	(Ganai et al., 2017)
Genistein	Liver injury by prolonged biliary obstruction in rats	Decreases liver fibrosis and cholestasis	25 mg/kg/d	Increases Matrigel and collagen type I degradation	(Salas et al., 2007)
Genistein	Schistosomiasis‐induced liver granuloma and fibrosis in mice	Reduces liver granuloma and fibrosis	25, 50 mg/kg/d	Decreases MCP−1, TNFα, IL1β, IL4, CXCL1 and IL10 mRNA levels; inhibits NF‐κB pathway	(Wan et al., 2017)
Genistein	APAP‐induced liver injury in mice	Alleviates oxidative stress	50, 100, 200 mg/kg/d	Increases the activities of GSH, UGTs, GSH‐PX, and TAC; inhibits CYP2E1; activates UDP‐glucuronosyltransferase; accelerates the glucuronidation of APAP	(Fan et al., 2013)
Genistein	Morphine‐induced liver injury in mice	Reduces liver damage	25, 50 mg/kg/d	Reduces serum AST, ALT, ALP, and NO levels	(Salahshoor et al., 2018)
Genistein/Puerarin	Alcoholic liver injury in mice	Alleviates oxidative stress; inhibits lipid peroxidation; reduces apoptosis	0.3 mmol/kg/d	Increases HO−1, CAT, SOD, GSH, and GSH‐Px levels; decreases NF‐κB p65, TGF‐β1, COX−2, MCP−1, TNF‐α, and IL−6 levels	(Zhao et al., 2016)
Genistein	Nonalcoholic fatty liver disease induced by a high‐fat diet in rats	Improves liver steatosis	4, 8 mg/kg/d	Activates AMPK/PPARα pathway; decreases the expression of SREBP−1c	(Liu et al., 2017)
Soyasaponins	BRL cells treated with H2O2	Alleviates oxidative stress	25–800 μg/mL	Increases SOD, GSH‐Px, GSH, and CAT levels; reduces ROS	(Chen et al., 2014)
Soyasaponins	precancerous lesion of liver in rats	Increases antioxidant activity	100 mg/kg/d	Increases CAT, SOD, and GSH‐Px levels; Decreases MDA and NO levels	(Hui‐ et al., 2012)
Soyasaponins	D‐GalN‐induced liver injury in mice	Reduces inflammation and immune response	5 mg/kg/d	Diminishes YB−1 phosphorylation and Nlrp3‐ inflammasome priming	(Wang et al., 2020)
Soyasaponins	Alcoholic liver injury in mice	Alleviates oxidative stress; improves liver steatosis	300, 600, 1200 mg/kg/d	Reduces TC, TG, and MDA levels; increases SOD, GSH‐Px, and GSH levels	(Yang et al., 2011)