Table 3.

Hepatoprotective effects of polydatin.

Study Type	Biological Effects	Animal Types, Cell Lines	Doses	References
In vitro, in vivo	↓CYP2Y3, CYP3A65, HMGCRa, HMGCRb, FASN, lipid and ethanol metabolism, hepatic fat accumulation, oxidative stress, DNA damage↑CHOP and GADD45aa expression	Zebrafish larvae	6.25, 12.5, 25 μg/mL for 48 h	[153]
In vivo	⇅TLR4 and NF-κB activity, ↓TNF-α, IL-1β, IL-6, CYP2E1, and ROS levels, ↑Nrf2/HO-1, SOD activity, GSH-Px, CAT, ADH, and ALDH activity	Rat	25, 50, 100 mg/kg/day orally for 7 days	[48,155]
In vivo	↓lipid peroxidation, TNF-α expression, lipogenesis	Rat	30, 90 mg/kg/day orally for 8 weeks	[156]
In vivo, in vitro	┬mTOR signaling activity, ↑TFEB expression, autophagic flux	Mice, human hepatocyte cell line (LO2)	100 mg/kg every other day orally for 4 weeks, 24 μM for 24 h	[154]
In vivo, in vitro	↓NOX4 enzymes, oxidative stress, CD68, FAS, SREBP-1c, LDH, cleaved caspase-3, annexin V, ALT, AST levels, ┬TLR-4/NF-κB p65 signaling pathway activity,	Mice, human hepatocellular carcinoma cell line (HepG2)	5 mg/kg, every other day, i.p. injection for 4 weeks, 5, 10, 20 μM for 24 h	[157]
In vivo, in vitro	↑Sirt1/Nrf2 pathway activity, ↓serum aminotransferase levels, hepatic pathological damage	Mice, human hepatocyte cell line (L02)	100, 200, 400 mg/kg/day orally for 7 days, 50 μM for 24 h	[158]
In vivo	↓4-HNE production, NOX4 expression	Mice	5 mg/kg i.p. injection	[159]
In vivo	↓AST, ALT, MDA, TNF-α, IL-1β, COX-2, iNOs, NF-κB, ↑GSH content, GST, SOD, CAT, and GSH-Px activity, hepatic TGF-b1 expression	Mice	25, 50, 100 mg/kg/day orally for 5 days	[70]
In vivo	┬NF-κB activation, ↓TNF-α expression, MPO activity, ICAM-l and ECAM-l expression, caspase-3 activity	Mice	10, 30,100 mg/kg i.p. injection	[55,161]

↓: decrease, ↑: increase, ┬: inhibit, ⇅: regulate, μg: microgram, μM: micromole, μM: microgram, 4-HNE: 4-hydroxy-2-nonenal, ADH: alcohol dehydrogenase, ALDH: aldehyde dehydrogenase, ALT: alanine transaminase, AST: aspartate transaminase, CAT: catalase, CD68: cluster of differentiation 68, COX-2: cyclooxygenase-2, CYP: cytochrome P450, DNA: deoxyribonucleic acid, ECAM-1: epithelial cell adhesion molecule-1, FASN: fatty acid synthase, GADD45αa: growth arrest and DNA-damage-inducible alpha a, GSH: glutathione, GSH-Px: glutathione peroxidase, GST: glutathione transferase, HMGCRa: hydroxymethylglutaryl-CoA reductase a, HMGCRb: hydroxymethylglutaryl-CoA reductase b, HO-1: heme oxygenase-1, i.p.: intraperitoneal, ICAM-1: intercellular adhesion molecule 1, IL-1β: interleukin-1β, IL-6: interleukin-6, iNOs: inducible nitric oxide synthase, kg: kilogram, LDH: lactate dehydrogenase, MDA: malondialdehyde, mg: milligram, MPO: myeloperoxidase, mTOR: mammalian target of rapamycin, NF-κB: nuclear factor-kappa B, ROS: reactive oxygen species, NOX4: NADPH oxidase 4, Nrf2: nuclear factor erythroid 2-related factor 2, Sirt1: sirtuin1, SOD: superoxide dismutase, SREBP-1c: sterol regulatory element-binding protein 1c, TFEB: transcription factor EB, TGF-β1: transforming growth factor-beta1, TNF-α: tumor necrosis factor-α, TLR4: Toll-like receptor 4.