Novel insights into the mechanisms whereby isoflavones protect against fatty liver disease

Table 1 Effects of soy, kudzu and red clover isoflavones on fatty liver disease in rodents

Experimental model	Treatment	Effects	Ref.
Mice fed high-fat diet	Genistein	Alleviates NAFLD by stimulating hepatic fatty acid β-oxidation and increasing antioxidative enzyme	Lee et al[24]
Rats fed high-fat diet	Genistein	Prevents emergence of NASH by attenuating oxidative stress	Yalniz et al[25]
Rats fed MCD diet	Soy isoflavone	Prevents liver damage by decreasing lipid peroxidation in NASH model	Ustundag et al[26]
Rats fed high-fructose diet	Genistein	Reduces NAFLD via activation of antioxidant profiles and decreases IL-6 and TNF-α	Mohamed Salih et al[27]
Mice fed high-fat diet	Genistein	Reduces NAFLD by regulating adipocyte fatty acid β-oxidation and adipogenesis	Kim et al[28]
Rats fed high-fat diet	Genistein	Slows down NASH progression by inhibiting IκB-α phosphorylation, nuclear translocation of NF-κB p65 subunit, and activation of JNK	Ji et al[29]
Rats provided with ethanol	Genistein	Ameliorates alcoholic liver injury and liver fibrosis by reducing lipid peroxidation, recruiting the anti-oxidative defense system, inhibiting CYP2El activity, and promoting extracellular matrix degradation	Huang et al[30]
ApoE-/- mice fed high-fat diet	Genistein	Alleviates metabolic abnormalities including hypercholesterolemia and NASH in ApoE-/- mice	Kwon et al[31]
Mice fed high-fat diet	Daidzein	Prevents NAFLD through the direct regulation of hepatic de novo lipogenesis and insulin signaling, and the indirect control of adiposity and adipocytokines	Kim et al[32]
Rats fed high-fat diet	Daidzein	Reduces weight gain and fat content in liver by affecting PPARα/γ and stearoyl coenzyme A desaturase 1	Crespillo et al[33]
Rats fed high-fat diet	Puerarin	Reduces NAFLD via hepatic leptin signaling activation (leptin receptor/JAK2/STAT3)	Zheng et al[34]
Rats provided with ethanol	Puerarin	Prevents acute alcoholic liver injury by inhibiting oxidative stress	Zhao et al[35]
Mice provided with ethanol	Tectoridin	Protects against ethanol-induced liver steatosis by modulating disturbance of PPARα pathway and ameliorating mitochondrial function	Xiong et al[36]
Hepatocytes treated with ethanol	Puerarin	Restores viability of cells and reduces lipid accumulation in ethanol-treated hepatocytes by activating autophagy via AMPK/mTOR-mediated signaling	Noh et al[37]
Mice fed high-fat diet	Puerariae flower extract (isoflavone-rich)	Exerts anti-fatty liver effects by suppressing lipogenesis in the liver	Kamiya et al[38]
Rats provided with the Liber-DeCarli liquid diet	Puerarin	Alleviates chronic alcoholic liver injury by inhibiting endotoxin gut leakage, Kupffer cell activation, and endotoxin receptors expression	Peng et al[39]
db/db diabetic mice	Red clover extract (isoflavone-rich)	Reduces liver TG and cholesterol levels by activating hepatic PPARα and inhibiting hepatic fatty acid synthase	Qiu et al[40]
Mice fed cholesterol-enriched diet	2-heptyl-formononetin, formononetin	Induces hepatic steatosis, but decreases markers of inflammation and liver injury	Andersen et al[42]
Mice fed MCD diet	Red clover extract (isoflavone-rich)	Improves hepatic steatosis, but does not alleviate liver inflammation	Qiu et al[41]

AMPK: Adenosine 5‘-monophosphate-activated protein kinase; IκB: Inhibitor of NF-κB; JAK2: Janus kinase 2; mTOR: Mammalian target of rapamycin; STAT3: Signal transducer and activator of transcription 3; NAFLD: Non-alcoholic fatty liver disease; NASH: Non-alcoholic steatohepatitis; TNF: Tumor necrosis factor; IL: Interleukin; MCD: Methionine-choline-deficient; PPAR: Peroxisome proliferator-activated receptor.