Table 1.
Therapeutic effects of PCP and its active ingredients on alcohol fatty liver disease and related mechanisms.
| Animal model | Medicine | Dose/treatment | Effect | Mechanism | Reference |
|---|---|---|---|---|---|
| Mice fed with high fat diet and alcohol at the dose of 3 g/kg | PCP (95% ethanol) | 20, 40, 80 mg/kg 21 d |
TG, TC, ALT, AST↓ ↑MDA |
Antilipogenesis | [19] |
| L02 feed with 1.5% FeSO4 with 50% ethanol | PCP (50% ethanol) | 40 μg/mL 12 d |
TG, ALT, AST↓ | Antilipogenesis | [20] |
| Feed with 1.5% FeSO4 and 50% ethanol for rats | PCP (95% ethanol) quercetin | 4000, 2000 mg/kg 50 mg/kg 6 w |
TG, TC, ALT, AST↓ P. chinense Pursh played a more significant role than quercetin |
Antilipogenesis | [21] |
| Feed with high fat iron with 52% ethanol, 15% sugar for rats | PCP (35, 75, 95% ethanol) | 3 g/kg 4 w |
TC, TG, LDL-C, AST↓ 75%, 95% ethanol extract P. chinense Pursh played a more significant role |
Antilipogenesis | [22] |
| Rats fed with 1.5% FeSO4 and 45% ethanol | PCP (aqueous) | 1.67, 8.4, 4.2 g/kg 6 w |
TG, CHO, LDL-C, NEAF↓ ALT, AST, TBIL↓ ↑HDL-C |
Antilipogenesis | [23] |
| 1.5% ferrous sulfate feed, 50% 8 g/kg alcohol | PCP (aqueous) total flavonoids | 2000 mg/kg 800 mg/kg 14 d |
TG, TC, ALT, AST↓ total flavonoids played a more significant role than P. chinense Pursh | Antilipogenesis | [24] |
| Fatty acids, cholesterol, neutral lipids, phospholipids, and very-low-density lipoproteins (VLDL) were investigated in rat hepatocyte | Quercetin | 50–25 μM | TG, VLDL↓ HMG-CoA-R, ACC↓ |
Antilipogenesis | [25] |
| Lipid accumulation in human hepatoma (HepG2 cells) | Quercetin | 10 μM 24 h, 48 h |
TC, TG, ABCA1↓ HMGCR, SREBP-1c↓ ↑CYP7A1, AMPKα2, |
Antilipogenesis | [26] |
| Adipogenesis in 3T3-L1cell | Quercetin | 100 Mm 24 h, 48 h |
PPARγ, C/EBPα↓ ↑AMPK ACC↓ ↑MAPK/ERK1/2 Cytochrome c↓ |
Antilipogenesis Autophagy |
[27] |
| Adipogenesis and apoptosis in 3T3-L1 cells | Quercetin | 10, 20, 40, 80 μM 5, 15, 45, 135 μM 4 w |
PPARγ, C/EBPα↓ SREBP-1c↓ |
Antilipogenesis | [28] |
| Rats ingesting 65% ethanol solution | Resveratrol | 250 mg/kg 4 w |
TG, ALT, AST↓ | Antilipogenesis | [29] |
| HepG2 cells with 100 μM oleic acid and 87 mM alcohol | Resveratrol | 5, 15, 45, 135 μM 24 h |
TG↓ ↑AMPK ACC, SREBP-1c, PGC-1α↓ ↑PPAR-α, Lipin1 |
Antilipogenesis Antiadipogenic |
[30] |
| Rats ingesting 10% ethanol solution | Quercetin | 10 mg/kg 2 w |
↑Insulin, adiponectin ↑AMPK ACC↓ |
Antiadipogenic | [31] |
| Vitro model of a normal rat's liver cell (BRL-3A). | PCP (ethanol) (70% ethanol) |
6.25–100 mg/kg | 70% ethanol extract P. chinense Pursh played a more significant role than aqueous extract | Antioxidant | [20] |
| HepG2 cells were induced by free fatty acid (FFA) | Effective flavonone | PCB, MPG (1, 10, 100 μM) PCBG (0.1, 1, 10 μM) |
ALT, AST↓ ↑AMPK/SRIT1 ↑PPAR-α FAS, ACC, SCD1↓ ↑MDA, GSH-Px |
Antioxidant Antilipogenesis |
[32] |
| ABTS, hydroxyl radical scavenging, DPPH tests | PCP (75% ethanol) | 0.5–50 mg/kg | DPPH, ABTS, and hydroxyl radicals scavenging↓ lipid peroxidation↓ | Antioxidant Antilipogenesis |
[12] |
| t-BHP-induced liver damage in LO2 cells | PCP (aqueous) | 100, 200, 400 mg/kg 12 h |
Caspase-9, caspase-3↓ ↑PARP, Bcl-xl, Bcl-2 |
Antioxidant Antiapoptotic |
[33] |
| t-BHP-induced liver damage in LO2 cells | PCP (aqueous) | 50 mg/kg 12 h |
↑Nrf2, HO-1, SOD-2 KEAP-1↓ ↑Bcl-2 E50M60 subfraction was more significant than P. chinense at 200 μg/mL |
Antioxidant Antiapoptotic |
[34] |
| Ethanol gavage (4.7 g/kg) every 12 h for a total of three doses | PCP (aqueous) | 5.2, 10.3 g/kg 7 d |
TG, ATGL, ALT, AST↓ CYP2E1↓ ↑MDA, GSH, SOD, CAT TNF-α, IL-6↓ |
Antilipogenesis Antioxidant Anti-inflammatory |
[35] |
| Mice were fed a Lieber-De Carli liquid diet containing alcohol | PCP (aqueous) | 5, 10, 30 g/kg 4 w |
ALT, AST↓ TNF-α, IL-6↓ ↑MDA, GSH, SOD, GPx CYP2E1↓ ↑Nrf2/HO-1 |
Antioxidant Anti-inflammatory |
[36] |
| RAW264.7 cell with LPS (1 ng/mL) | PCP (80% ethanol) PCPP, PCPP1a |
15, 30, 60, 120 μg/mL 24 h |
NO, TNF-α, IL-1β↓ | Anti-inflammatory | [14] |
| Human LX-2 cells and rat HSC-T6 cells | PCP (aqueous) | 25, 50, 100 mg/kg 24 h |
Collagen I, α-SMA, TGF-β1↓ ↑SIRT3, SOD2, GSK3β PI3K-Akt↓ |
Antioxidant | [35] |
| Male C57BL/6J mice fed Lieber-De Carli diets containing ethanol (30% of total calories) hepatocytes with ethanol (100 mM) | Quercetin | 100 μM 24 h |
TC, TG, ALT, AST↓ ↑GSH, MDA, TfR1 ↑BMP6/SMAD4, ↑hepcidin |
Antioxidant Autophagy |
[37] |
| Chronic alcohol (30% of total calories) or iron (0.2%)-fed adult male C57BL/J mice | Quercetin | 100 μM | ↑Metal transporter 1, zinc transporter member 14, mucolipin 1, transferrin receptor 1 | Hepatoprotective Antioxidant |
[38] |
| Mouse primary hepatocytes were incubated with ethanol (100 mM) | Quercetin | 100 μM | ALT↓ ↑HDL ↑ROS, SOD, MDA, GSH |
Hepatoprotective Antioxidant |
[39] |
| Male C57BL/6J mice fed Lieber-De Carli diets containing ethanol | Quercetin | 100 μM | AST, ALT, LDH↓ ↑MDA, GSH, GSSH caspase-3↓ |
Antiapoptosis | [40] |
| MS rats with 30% sucrose in drinking water | Quercetin | 0.95 mg/kg | TG, HOMA↓ ↑GSH, Nrf2 |
Antioxidant | [41] |
| Ethanol (4.0 g/kg) to rats | Quercetin | 100 mg/kg 9 d |
AST, LDH↓ CYP2E1↓ ↑MDA, GST, GPx, CAT, ↑HO-1 |
Antioxidant | [42] |
| Ethanol-incubated primary rat hepatocytes (100 mM) | Quercetin | 50 μM 2 h |
AST, LDH↓ ↑MDA, GSH, SOD, CAT ↑Nrf-2/HO-1 |
Antioxidant | [43] |
| HepG2 cell model induced by ethanol in vitro | Quercetin | 25 μM | CYP2E1↓ ↑MDA, 4-HNE, GPx ↑Nrf2/HO-1 |
Antioxidant | [44] |
| RAW 264.7 cells with LPS (100 ng/ml) | Quercetin | 20 μM 24 h |
TNF-α, IL-1β, IL-6, MyD88, PGE2, iNOS, COX-2↓ ↑HO–1 PI3K/Akt/NF-κB, TRAF6 JNK, p38MAPK↓ |
Anti-inflammatory Antioxidant |
[45] |
| Mice fed with 35%, 40%, 52% v/v ethanol (3 g/kg) | Quercetin | 60 mg/kg 3 w |
ALT, AST, TG↓ ↑TBIL TNF-α, IL-1β, IL-2, IL-6↓ ↑IL-10 ↑SOD, GSH-Px, MDA ↑Bcl-xl, Bcl-2 Caspase-3↓ PI3K/Akt/NF-κB↓ ↑STAT3, PARP |
Antioxidant Anti-inflammatory Antilipophagy Antiapoptosis |
[46] |
| Ethanol-dosed adult male Balb/c mice (5.0 g/kg) or primary rat hepatocytes (100 mM) | Quercetin | 2.5 mg/kg | AST, ALT, LDH↓ ↑GSH, SOD, MDA TNF-α, IL-6↓ p38 MAPK↓ ↑HO-1 |
Antioxidant Anti-inflammatory |
[43] |
| Treated with 5% alcohol for 24 h HepG2 cells | Quercetin | 10, 20 μM 1 h |
ALT, AST↓ ↑ROS, MDA, GSH NO, TNF-α↓ ↑Nrf2/HO-1 |
Antioxidant Anti-inflammatory |
[44] |
| 25 patients with AH/rats with 50% (v/v) ethanol 5 g/kg body weight every 12 h three times | Quercetin | 100 mg/kg 14 d |
ALT, AST↓ ↑MDA, GSH-Px TNF-α, IL-1β, IL-18, NLRP3↓ ↑IL-10 ↑Nrf2/HO-1 ASC, caspase-1↓ |
Antioxidant Anti-inflammatory |
[47] |
| Pregnant rats received 1 ml/day of 40% v/v ethanol (4 g/kg) | Quercetin | 50 mg/kg 21 d |
↑MDA, PC, GSH, SOD, CAT TNF-α, IL-1β, IL-6, NF-κB↓ |
Antioxidant Anti-inflammatory |
[48] |
| BALB/c mice had induced liver fibrosis by carbon tetrachloride (CCl4) | Quercetin | 50 mg/kg 8 w |
TNF-α, IL-1β, IL-6, MCP-1↓ | Anti-inflammatory | [45] |
| Peripheral blood of 15 healthy male and female nonsmoking and nondrinking donors | Resveratrol | 5, 25, 50 μM | ↑ADH1B, ALDH2 | Antioxidant | [49] |
| Mice fed with 3 gavages of calories of dextrin-maltose (MP biomedicals) or ethanol at 3.5 g/kg | Resveratrol | 50 μM | AST, ALT, TG↓ ↑ADH, NADH/NAD+ ↑SIRT1, AMPK, ChREBP, FAS, SCD1↓ |
Antioxidant | [50] |
| Rats were fed either control or ethanol liquid diets containing 0.8, 1.6, and 2.4 g/kg ethanol | Resveratrol | 100 mg/kg 22 w |
↑ALDH2, ADH, SIRT1 CYP2E1↓ |
Antioxidant | [51] |
| Ethanol-induced oxidative DNA damage in human peripheral lymphocytes | Resveratrol | 5, 25, 50 μM | ↑ADH1B, ALDH2 | Antioxidant | [52] |
| t-BHP-induced liver damage in LO2 cells | Resveratrol | 25, 50, 75 μM | ↑SOD, GPx, GR, NQO1, GST, ↑Nrf2 |
Antioxidant | [53] |
| Mice administered alcohol in drinking 10% up to 40% v/v | Resveratrol | 10 mg/ml 4 w |
TG↓ TNF-α, IL-1↓ |
Anti-inflammatory | [30] |
| Lipopolysaccharides-induced rats' model | Resveratrol | 3.125, 6.25, 12, 5 μM 25 h |
ALT, AST, ALP, CHO↓ NF-κB/p65, TLR4, MyD88, TRAF6↓ TNF-α, IL-1, IL-1β, IL-6↓ NO, iNOS, COX-2↓ ↑MAPKs ↑IL-10 PI3K/Akt↓ |
Anti-inflammatory | [54] |
| Mice with carbon tetrachloride (CCl4) induced liver fibrosis | Resveratrol | 10, 20, 30 mg/kg | ALT, AST↓ NLRP3, IL-1β, IL-18↓ ↑Caspase1 |
Anti-inflammatory | [55] |
| Mice with carbon tetrachloride (CCl4) induced liver fibrosis | Resveratrol | 50 mg/kg | ALT, AST↓ TNF-α, Akt/NF-κB (IκB)↓ |
Anti-inflammatory | [56] |
| Male Foxo3a/mice administered 33% (v/v) ethanol at a total dose of 4.5 g/kg | Resveratrol | 6, 12 mg/kg 16 h |
↑Ulk1, Atg5, 7, 14 ↑Vps34, LC3II, beclin 1 ↑FoxO3a |
Autophagy | [57] |
| AFL mice fed with an ethanol Lieber-De Carli liquid diet, and HepG2 cells in the presence of oleic acid and alcohol | Resveratrol | 10, 30, 100 mg/kg | ALT, AST, TG, LDL-C↓ ↑HDL-C ↑LC3-II, P62 |
Autophagy | [58] |
| Mice were fed 30% Lieber-De Carli liquid diet containing alcohol | Quercetin | 100 mg/kg 15 w |
↑LC3II, parkin, p62 ↑VDAC1, FoxO3a ↑AMPK, ERK2 |
Autophagy | [59] |
| Pair fed with liquid diets containing ethanol (28% of total calories) and treated mice | Quercetin | 100 mg/kg 12 w |
ALT, AST, TC, TG↓ ↑AMPK, ERK, PLIN2 ↑LC3II, p62 |
Autophagy | [60] |
| t-BHP-induced liver damage in LO2 cells | Quercetin | 50 μM 12 h |
↑Nrf2, HO-1, SOD-2 KEAP-1↓ ↑BcL-2 |
Autophagy | [61] |
| Mice administered alcohol in drinking 6% up to 20% v/v | Resveratrol | 250 mg/kg 16 w |
ALT, AST↓ ↑MDA, SOD, CAT, GPX CYP2E1↓ caspase 3↓ |
Antioxidant Antiapoptotic |
[62] |
| Human hepatocyte Chang cell line induced by ethanol | Resveratrol | 10 μM 6 h |
↑SIRT1 Caspase-12↓ ↑ADH-2, ALDH-2, ↑GRP78, p-IRE1α, p-eIF2α p-PERK, ATF4↓ caspase-3/12↓ ↑CHOP, Bcl-xl |
Antiapoptotic | [51, 63] |
Note: TG, triglyceride; TC, serum total cholesterol; TBil, total bilirubin; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; VLDL, very low-density lipoprotein cholesterol; VDACT1, voltage-dependent anion channel; DBIL, direct bilirubin; HMGCR, 3-hydroxy-3-methylglutaryl-coenzyme A reductase; ALT, alanine aminotransferase; AST, aspartate transaminase; ADH, alcohol dehydrogenase; ALDH, aldehyde dehydrogenase; CYP2E1, cytochrome P450 2E1; ABCA1, ATP-binding cassette transporter; CYP7A1, cholesterol 7-hydroxylase; MDA, malondialdehyde; FAS, fatty acid synthase; ACC, acetyl coenzyme A carboxylase; SCD1, stearoyl coenzyme A desaturase 1; GSH, glutathione; SOD, superoxide dismutase; CAT, catalase; GPx, glutathione peroxidation chemotaxis; HO-1, heme oxygenase; NQO1, NADPH quinone oxidoreductase 1; COX-2, cyclooxygenase-2; IL-1, interleukin-1; IL-6, interleukin-6; IL-10, interleukin-10; TNF-α, tumor necrosis factor alpha; TLR4, toll-like receptor 4; TRAF6, tumor necrosis factor receptor-associated factor; AMPK, AMP-activated protein kinase; SIRT1, sirtuin1; ERK, extracellular signal-regulated kinase; PPAR-α, proliferator-activated receptor alpha; C/EBP, CCAAT/enhancer-binding protein; HA, hyaluronic acid; LN, laminin; PC III, procollagen III; PCIII, type III pre-collagen; LC3-II, light chain 3-II; Bcl2, B-cell lymphoma.