An Overview of the Mechanism of Penthorum chinense Pursh on Alcoholic Fatty Liver

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.