Table 2.

Effects of curcumin: in vitro hepatocyte studies.

Cell	Curcumin Concentration/Duration	Effect	Reference
Hepatic stellate cells	30 µM; 2 h	↓ Cell proliferation ↑ Apoptosis ↓ α1(I) collagen, α-SMA and fibronectin mRNA ↑ p21 and p27 protein ↑ Caspase-3 activity ↓ Bcl-2 mRNA ↑ NF-κB activity	[71]
Primary mice isolated hepatocytes	25 µM; 120 min	↓ Hepatic glycogenolysis ↓ Hepatic gluconeogenesis ↓ G6Pase activity ↓ PEPCK activity ↑ Phospho-AMPK	[72]
H4IIE rat hepatoma and Hep3B human hepatoma cells	2–50 µM; 30 min	↓ Hepatic gluconeogenesis ↓ PEPCK activity ↓ G6Pase activity ↑ AMPK activation	[73]
Hepatic stellate cells	0–30 µM; 1 h	↓ HSC activation ↑ HSC apoptosis ↓ PDGF-βR and EGFR ↓ α-SMA and α-II-collagen ↑ PPARγ ↓ Bcl-2 ↑ Bax ↓ ROS levels ↑ GSH protein ↑ GSH/GSSG ratio ↑ GCL activity ↓ Phospho-InsR, -ERK1/2, -JNK, -PI3K and -Akt	[74]
Isolated rat hepatocytes	1 and 10 µM; 30 min	1 µM ↓ Lipid peroxidation ↓ Cytochrome c translocation 10 µM ↑ Oxidative stress ↑ Hepatocytoxicity ↑ Necrosis ↑ Apoptosis ↑ Glutathione depletion ↑ Caspase-3 activity	[75]
Rat HSCs and immortalized human hepatocytes	20 µM; 1 h	↓ Glucose levels ↓ GLUT4 membrane translocation ↑ Glucokinase activity ↑ Glucose-6-phosphate levels ↓ Phospho-IRS-1 ↓ Phospho-PI3K ↓ Phospho-Akt	[76]
Huh7 cells	20 µM; 48 h	↑ PON1 transactivation ↑ PON1 mRNA and protein	[77]
L02 hepatocytes	-	↓ Oxidative stress ↓ Insulin resistance ↓ ROS production ↓ Glutathione depletion ↓ MDA levels ↓ LDH activity ↓ AST activity	[78]
Primary rat hepatocytes	10 µM; 12 h	↓ Lipo-apoptosis ↓ ROS production ↓ ATP depletion ↓ PEPCK levels ↓ G6Pase levels ↑ Mitochondrial DNA ↑ PGC1α, NRF1 and Tfam mRNA ↑ MMP ↓ NF-kB p65 mRNA	[79]
AML-12 cells	50 µM; 2 h	↑ Insulin response ↑ Phospho-PKB ↓ ROS levels ↓ MDA levels ↓ Phospho-JNK ↓ Phospho-p38	[80]
Primary rat hepatocytes	15 µM; 24 h	↓ Lipid formation ↑ APOBEC-1 mRNA and protein ↑ ApoB mRNA editing ↓ Apo-B lipid formation	[81]
HepG2 cells	30 µM; 2 h	↓ Cholesterol cell content ↓ Endosome/lysosome size and localization ↑ Cholesterol β-hexosaminidase enzyme level ↑ Lysosomal β-hexosaminidase enzyme level ↑ Flotillin-2-positive granules ↑ CD63-positive granules	[82]
HepG2 cells	5–20 µM; 24 h	↑ Hypolipidemic activity ↑ LDL uptake ↑ LDL receptor expression ↑ LDL receptor activity ↓ PCSK9 mRNA and protein ↓ PCSK9 promoter activity ↓ HNF-1α mRNA and protein ↓ HNF-1α nuclear promoter	[83]
L02 cells	2.5 and 5 µM; 2 h	↓ Oxidative stress ↑ Cell viability ↓ DNA-fragments ↓ Micronuclei formation ↓ ROS production ↑ SOD activity ↑ GSH levels	[84]
Primary mice hepatocytes	25 µM; 6 h	↓ Glucose production ↑ FGF21 protein ↑ Phospho-Akt	[85]
L02 cells	5 µM; 2 h	↓ QCT-induced inflammatory response ↓ QCT-induced oxidative stress ↓ Mitochondrial dysfunction ↓ Apoptosis ↓ iNOS activity ↓ NO production ↓ NF-κB mRNA ↑ Nrf2 and HO-1 mRNA	[86]
HepG2 cells	30 µM; 24 h	↓ Hepatic steatosis ↑ Leptin resistance ↓ Lipid deposition ↓ SREBP-1c, SCD-1 and CD36 mRNA ↑ ACC, ACOX1, CPT-1 and PPARα mRNA ↑ Phospho-AMPK ↑ Phospho-ACC	[87]
Primary mouse hepatocytes	1 µM; 4 h	↑ Lipogenesis ↑ ChREBP activation ↑ ChREBP mRNA ↑ Lpk, Fas, Acc1, Scd1 and Me1 mRNA ↑ ChREBP-LUC activity ↓ Oct-1-ChREBP binding	[88]
HepG2 and primary mouse hepatocytes	2 µM; 6 h	↓ Fgf21 resistance ↑ Fgf21 activity ↑ Fgf21 mRNA ↑ PPARα mRNA ↑ Fgf21-LUC activity ↑ PPARα-Fgf21 binding	[89]
HepG2 cells	5 µM; 5 days	↓ Insulin resistance ↑ Glucose consumption ↓ Oxidative stress ↑ Phospho-IR ↑ Phospho-Akt ↓ MDA levels ↓ IL-6 levels ↓ TNF-α levels ↓ Phospho-JNK and p38 ↓ Phospho-IKKβ and IκB-α	[90]
Human LX-2 HSCs	40 µM; 24 h	↓ Fibrotic myofibroblastic phenotype ↑ Lipocyte phenotype ↑ Lipid droplet abundance ↑ Lipid metabolism ↑ Triglyceride content ↑ Nrf2 protein and nuclear translocation ↑ C/EBPα, PPARγ, RXRα and RXRβ protein ↓ PPARα protein	[91]
Primary mice hepatocytes	10 µM; 24 h	↓ Palmitate-induced steatosis ↑ CYP7A and CYP3A protein ↓ SREBP-1c protein	[92]
HepG2 cells and primary mice hepatocytes	10 µM; 30 and 120 min	↓ Glucose production ↓ Mitochondrial complex I activity ↓ cAMP accumulation ↑ PDE4B induction ↑ Phospho-AMPK ↓ Acetyl CoA accumulation ↓ PDK4 mRNA ↓ PDH activity ↓ PC protein	[93]
BRL-3A and HepG2 cells	2.5 µM; 8 and 12 h	↓ Fructose-induced inflammation ↓ NLRP3 inflammasome activity ↑ miR-200a level ↓ NLRP3 and ASC protein ↓ Caspase-1 and IL-1β protein ↓ TXNIP protein ↓ ROS production ↓ H2O2 levels	[94]
HepG2 cells	10 µM; 24 h	↓ Lipotoxicity ↓ Lipid vacuole accumulation ↓ ROS production ↓ SREBP-1, PPAR-γ2 and PARP levels ↓ Cleaved caspase 3 levels	[95]
HepG2 cells	10 µM; 1 h	↓ Palmitate-induced inflammatory injury ↓ Palmitate-induced fibrosis ↓ TNF-α, IL-6, IL-1β and COX-2 mRNA ↓ ICAM, VCAM-1 and MCP-1 mRNA↓ α-SMA, COL-1, COL-4 and TGF-β mRNA ↓ α-SMA protein	[96]