Potential Effects of Dietary Isoflavones on Drug-Induced Liver Injury

Table 1

Hepatoprotective effects of isoflavone and extracts.

Isoflavone and extracts	Drugs	Injury	Mechanism	Refs
Biochanin A	Arsenic	Hepato/hematotoxicity	Increasing free radical scavenging properties	[57]
	CCl4	Acute liver injury	Increasing antioxidant	[60]
	LSP/D-GalN	Acute liver injury	Activation of the Nrf2 pathway	[69]
Formononetin	APAP	Hepatotoxicity	Enhancing Nrf2 activity	[68]
Calycosin	TAA	Oxidative stress	Reducing ROS and expression of CYP2E1	[62]
	APAP	NASH	Activating FXR	[85]
	HFD	NAFLD	Activating FXR	[86]
	CCl4	Acute liver injury	Activating FXR/increasing expressions of STAT3, Bcl-xl, and SOCS3	[87]
Daidzein	LSP/D-GalN	Hepatic failure	Suppressing production of TNF-α; increasing caspase-3 activity	[56]
	D-GalN	Liver injury	Activating PG-liposome-based system	[67]
	DMBA	Liver oxidative injury	Activation of antioxidant enzymes and Bcl-2; upregulation of caspase-3 and Bax	[74]
	Cisplatin	Hepato/hematotoxicity	Increasing free radical scavenging properties; reducing bone marrow suppression	[82]
Puerarin	CCl4	Liver oxidative injury/hyperlipidaemia	Inhibiting JNK/c-Jun/CYP7A1 pathway/ROS generation	[63]
	Alcohol	Acute liver injury	Decreasing activity of oxidant enzyme (MDA)/increasing activity of antioxidant enzymes (SOD and GPX)	[66]
	Lead	Liver oxidative injury/hyperlipidaemia	Reducing ROS production/hepatic metabolism genes expression; increasing activation of antioxidant enzymes	[73]
	Alcohol	Chronic liver injury	Inhibiting GSK-3β/NF-κB pathway	[78]
	Nickel	Liver oxidative stress/immunotoxicity	Inhibiting TLR4/p38/CREB pathway	[79]
Genistein	TAA	Liver inflammatory/fibrosis	Inhibiting tyrosine kinase/activation of HSC	[61]
	APAP	Liver injury	Increasing expression of UGTs; inhibiting CYP2E1	[64]
	Alcohol	Hepatic injury/fibrosis	Increasing activities of ADH and ALDH; downregulating expression of TIMP-1, MMP-2, and Bcl-2	[75]
	Endotoxin	Shock/MODS	Decreasing expression of iNOS and COX-2 protein; attenuating the vascular hyporeactivity to NA; inhibiting the activity of protein tyrosine kinase	[84]
	Fructose	NAFLD	Activating AMPK and suppressing SREBP-1 cleavage processing and de novo lipogenesis in hepatocytes	[88]
Kakkalide	Ethanol	Hepatic injury	Orally administered kakkalide and intraperitoneally administered irisolidone have the protective effect; kakkalide can be metabolized to form the bioactive irisolidone by intestinal microflora	[71, 72]
Tectorigenin	TBHQ	Apoptosis in liver injury	Inhibiting β-glucuronidase activity	[77]
	Ethanol	Liver steatosis	Increasing expression of PPAR-α; ameliorating mitochondrial function	[89]
Flemingia macrophylla	CCl4	Acute hepatotoxicity	Inhibiting ROS generation; preventing lipid peroxidation; strengthening antioxidant systems	[58]
Fraxin isolated from Acer tegmentosum	CCl4	Acute hepatotoxicity	Lowering AST and ALT	[91]
GFSE	TBHQ	Hepatotoxicity	Downregulating NOX4; upregulating the mRNA levels of antioxidant enzymes	[59]
Butea monosperma	TAA	Liver injury	Deregulation of PI3K/Akt/mTOR signaling	[81]

AST: aspartate aminotransferase; ALT: alanine aminotransferase; ADH: alcohol dehydrogenase; ALDH: aldehyde dehydrogenase; APAP: acetaminophen; CCl4: carbon-tetrachloride; CYP2E1: cytochromeP450, family 2, subfamily E, polypeptide1; COX: cyclooxygenase; DMBA: 7,12-dimethylbenz[a]-anthracene; FXR: farnesoid X receptor; GFSE: germinated and fermented soybean extract; GSK-3β/NF-κB pathway: glycogen synthase kinase-3β/nuclear factor kappa-B pathway; HFD: high-fat diet; iNOS: inducible nitric oxide synthase; JNK/c-Jun/CYP7A1 pathway: c-Jun NH2-terminal kinase/c-Jun protein/cholesterol 7a-hydroxylase pathway; LSP/D-GalN: lipopolysaccharide/D-galactosamine; LPO: lipid peroxides; MMP-2: matrix metalloproteinases; MODS: multiple organ dysfunction syndrome; NASH: nonalcoholic steatohepatitis; NAFLD: nonalcoholic fatty liver disease; NOX4: nicotinamide adenine dinucleotide phosphate oxidase 4; PI3K/Akt/mTOR: phosphatidylinositol 3-kinase/Akt/mammalian; SOCS3: suppressor of cytokine signaling 3; STAT3: signal transducer and activator of transcription 3; TAA: thioacetamide; TLR4/p38/CREB pathway: Toll-like receptor 4/cAMP response element-binding protein; TIMP-1: tissue inhibitors of metalloproteinases; TBHQ: tert-butyl hyperoxide.