Table 3 Pharmacological effects of artemisinin and its derivatives on hepatic diseases in vivo

Effects on oxidative stress and inflammation

 Liver injury

Newborn piglets /

IUGR

DHA

80 mg/kg; orally

↓MDA, H2O2, PC, 8-OhdG, GSSG, GSSG:GSH;

↑T-SOD, T-AOC, GSH, Nrf2, HO-1

[104]

 Liver injury

Adult male Wistar rats/I/R insult

ART

50 mg/kg; i.p

↓NLRP3, NF-κB, TNF-α, IL-18, IL-1β, HMGB1, IL-6

[105]

 Liver fibrosis

Sprague–Dawley rats/multiple pathogenic factors

ART

28.8 mg/kg; orally

↓TNF-α, IL-6, NF-κB p65

[108]

 Autoimmune hepatitis

Male Balb/c mice/ConA

ART

27, 54, 108 mg/kg; oral gavage

↓IL-6, IL-1β, TNF-α, IFN-γ, IL-17, NF-κB p65, p-JNK, p-ERK, p-p38;

↑IL-10

[109]

 Cholestatic hepatitis

Adult male mice/lithocholic acid

Artemisinin

100 mg/kg; oral gavage

↑GSH, MRP2, CRA, FXR

[110]

 Liver fibrosis

Male Sprague–Dawley rats/BDL

DHA

3.5, 7, 14 mg

/kg; i.p

↓liver/body weight, serum AST, ALT, TNF-α, IL-6

[111]

 Liver injury

Newborn piglets/IUGR

DHA

80 mg/kg/d; orally

↓AST/ALT ratio, TNF-α, IL-6, IL-1β, IFN-γ

[113]

 NAFLD

Male C57BL/6 J mice/High-fat diet

AA extract

400 mg/kg/day; orally

↓COX-2, TGF-β1, HMGB1

[114]

 Liver fibrosis

Male Sprague–Dawley rats/CCl4

DHA

3.5, 7, 14 mg

/kg; i.p

↓NF-κB, TNF-α, IL-6, IL-8, NLRP3, IL-1β; ↑IL-4, IL-10, ROS, JNK1/2

[54]

 AFLD

Male Sprague–Dawley rats/alcohol

DHA

7 mg/kg/day; i.p

↓TNF-α, NF-κB, NLRP3

[120]

Effects on lipid metabolism

 NAFLD

Male C57BL/6J mice/High-fat diet

AA extract

400 mg/kg/day; orally

↓body weight, liver weight, TG, ChREBP, SREBP1;

↑p-ACC

[114]

 NAFLD

Female SWISS mice/HFD + LPS

Artemisinin

0.25 mg/kg/day; i.p

↓NOS2;

↑adipolysis

[118]

 Liver injury

Newborn piglets/IUGR

DHA

80 mg/kg/d; orally

↓TC, VLDL-C, NEFA, FAS, ACCβ, SREBP-1;

↑HDL-C, LPL, HL, TL, AMPKα, SIRT1, CPT-1

[113]

 AFLD

Male Sprague–Dawley rats/alcohol

DHA

7 mg/kg/day; i.p

↓TC, TG, FAS, SREBP-1c;

↑PPAR-α, CPT1, FXR

[120]

 AFLD

Male ICR mice/alcohol

DHA

20 mg/kg/day; i.p

↓SREBP-1c, SCD1;

↑PPAR-α, FGF21, FSP27, VNN1

[122]

 AFLD

Male ICR mice/alcohol

DHA

7 mg/kg/day; i.p

↓lipin-1β, FAS, SREBP-1c, SCD;

↑PPAR-α, CPT1α

[123]

Effects on cell apoptosis

Liver fibrosis

Male Sprague–Dawley rats/BDL

DHA

3.5, 7, 14 mg

/kg; i.p

↓Bcl-2, p-ATK, p-PI3K; ↑HSCs apoptosis, Bax, cleaved caspase-9, cleaved caspase-3, cleaved PARP-1, Cyt c

[111]

 AFLD

Male ICR mice/alcohol

DHA

20 mg/kg/day; i.p

↓hepatocytes apoptosis, caspase-9/-3, PUMA, Bim

[122]

 AFLD

Male ICR mice/alcohol

DHA

7 mg/kg/day; i.p

↓hepatocyte lipoapoptosis, caspase-9/3;

↑Bcl-2

[123]

 Liver injury

Adult male Wistar rats/I/R insult

ART

50 mg/kg; i.p

↓hepatocytes apoptosis, Bax;

↑Bcl-2

[105]

 Liver cancer

Mice/Subcutaneous injection of Hep G2 cells

DHA

20 mg/kg; i.p

↓weights of Hep G2 xenografts, Mcl-1,

↑Bak, cleaved caspase 3

[50]

 Liver cancer

Mice/Subcutaneous injection of Hep G2 cells

DHA

5 mg/kg; i.p

↓Mcl-1, p-ERK,

↑PARP, necrosis

[129]

Effects on hepatic fibrogenesis

 Liver fibrosis

Sprague–Dawley rats/multiple pathogenic factors

ART

28.8 mg/kg; orally

↓TLR4, MyD88, TGF-β1, collagen, α-SMA

[108]

 Liver fibrosis

Male Sprague–Dawley rats/bile duct ligation

DHA

3.5, 7, 14 mg/kg; i.p

↓HSC activation, PDGF, PDGF-βR, TGF-βRI, TGF-βRII, EGFR, p-ERK, α-SMA, α1 (I) collagen, fibronectin, TIMP-1;

↑PPARγ

[52]

 Liver fibrosis

Male Sprague–Dawley rats/BDL

DHA

3.5, 7, 14 mg

/kg; i.p

↓Collagen, α-SMA, α1(I) procollagen and fibronectin, TGF-βRII, PDGF-βR, EGFR

[111]

 Liver fibrosis

Male ICR mice/CCl4

ART

50, 100, 200 mg/kg/day; i.p

↓α-SMA, collagen1, fibronectin, desmin

[87]

 Liver fibrosis

Male ICR mice/CCl4

ARM

5, 10, 20 mg/kg; i.p

↓hydroxyproline, α-SMA), α1(I) collagen, fibronectin, PDGF-βR, EGFR

[88]

 Liver fibrosis

Male wistar rats/bovine serum albumin

ART

3.2, 9.6, 28.8, 53.1 mg/kg; oral gavage

↓collagen, α-SMA, type I collagen, MMP-2, MMP-9;

↑ MMP-13

[126]

 Liver fibrosis

Male ICR mice/CCl4

DHA

7 mg/kg/day; i.p

↓α-SMA, fibrotic, nodular;

↑FXR

[127]

Effects on autophagy

 Liver fibrosis

Male Sprague–Dawley rats/CCl4

DHA

3.5, 7, 14 mg

/kg; i.p

↓p62,

↑autophagosome, LC3-II, ROS,

[54]

 Liver fibrosis

Male Sprague–Dawley rats/CCl4

DHA

3.5, 7, 14 mg

/kg; i.p

↓p-mTOR;

↑HSC senescence, p53, p16, GATA6, autophagosome, LC3-II, p-ULK1

[99]

Effects on ferroptosis

 Liver fibrosis

Male ICR mice/CCl4

ART

50, 100, 200 mg/kg/day; i.p

↓GSH;

↑Fe2 + , lipid ROS, Ptgs2

[87]

 Liver fibrosis

Male ICR mice/CCl4

ARM

5, 10, 20 mg/kg; i.p

Small and ruptured mitochondria; ↓Gpx4, SLC7A11;

↑ROS1, P53

[88]

Effects on metastasis

 Liver disease

Male athymic BALB/c nu/nu mice/orthotopic xenografts

Artemisinin

0, 50, 100 mg/kg; oral gavage

↓lung tumors

[82]