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

From: Anti-malarial drug: the emerging role of artemisinin and its derivatives in liver disease treatment

Hepatic disease Animals/stimulation (model) Drug Dosage/administration route Variations Ref
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]
  1. i.p. Intraperitoneal injection