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Table 2 Pharmacological effects of artemisinin and its derivatives on hepatic diseases in vitro

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

Hepatic disease Cell lines Drug Dosage Variations Refs.
Effects on cell cycle
 HCC HepG2 cells, PLC/PRF/5 cells, Hep3B cells DHA 20–40 μM ↓cyclin B, CDC25C; ↑P21, G2/M phase [50]
  HepG2 cells, Hep3B cells ART, DHA 0–50  μM ↓E2F1, CDK2
, CDK3, cyclin D1, cyclin E;
↑G1 phase, Kip1/p27, Cip/p21
[51]
Liver fibrosis HSCs DHA 15–50 μM ↓cyclin A, CDK2;
↑S phase, p53, p21
[52]
Effects on cell proliferation
 HCC HepG2215 cells DHA 50–200  μM ↓cell proliferation [55]
  HepG2215 cells DHA 5–20  μM ↓cell proliferation, colony formation [56]
  HepG2 cells DHA 0–200  μM ol/L ↓cell proliferation;
↑ROS, [Ca2+]
[58]
  HCCLM6 cells DHA 1–100  μM ↓cell proliferation, E2F1, BCL, PCNA, MKI67, CCNE2 [59]
  HCCLM3 cells, MHCC97H cells ART 0–100  μM ↓cell growth, colony formation; cell cycle arrest [60]
 CCA HUCCT-1 cells, FRH201 cells DHA 20  μM ol/L ↓cell proliferation [57]
 Liver fibrosis HSCs ART 125–225  μM ol/L ↓cell proliferation [63]
  LX-2 cells ART 0–50 ug/ml ↓cell proliferation [64]
Effects on cell apoptosis
 Liver fibrosis LX-2 cells ART 12.5–50 ug/ml ↓Bcl-2;
↑Bax/Bcl-2
[64]
  HSCs ART 150–200  μM ol/L ↑p53 [63]
 HCC SMMC-7721 cells Artemisinin 100–200  μM ol/L ↑apoptotic rate [65]
  HepG2 cells ART and DHA 0–50  μM ↓Bcl-2, PARP;
↑Bax, caspase-3, p53, MDM2
[51]
  HepG2 cells ART 0.5–8 mg/L ↓p-STAT3; ↑Fas [69]
  HepG2, cells DHA 0–200  μM ol/L ↓Bcl-2;
↑GADD153, Bax,
[58]
  HepG2 cells DHA 0–100 μM ↑cleaved PARP, caspase-3 [71]
  SK-Hep-1 cells DHA 20–60  μM ↓PARP, Sp1;
↑caspase8, caspase9, caspase3
[72]
  HepG2 and Huh-7 cells DHA 0–150  μM ↓ΔΨm, Mcl-1;
↑Bim, cytochrome c, caspase8, caspase9,caspase3, ROS, Bak
[73]
  Hep3B and Huh-7 cells ART 10–150  μM ↑ROS, Bax, MOMP, cytochrome c, caspase 9, caspase3 [74]
  HepG2 cells ART 10–150  μM ↓ΔΨm, Bcl-2/Bcl-xl; ↑Bax, caspase8, ROS, caspase9, caspase3 [75]
  HuH-7 cells and PLC/PRF/5 cells ART 1–300 μM ↓Bcl-2;
↑Bax, caspase-3/7, cleaved PARP1
[76]
CCA QBC939 cells, HUCCT-1 and FRH201 cells DHA 20  μM ol/L ↑Mcl-1S, Mcl-1S/Mcl-1L, apoptotic rate [57, 77]
Effects on angiogenesis, invasion, metastasis
 HCC SK‐HEP1, SM7721, HepG2, and Huh7 cells ART 100  μM ↓N/E-cadherin, MMP9, vimentin, EMT [81]
  HepG2215 cells DHA 100  μM ↓Migration ability; [55]
  HCCLM3 and MHCC97H cells ART 25–100  μM ↓N-cadherin, MMP2, MMP9, Snail, E-cadherin [60]
  HCCLM6 cells DHA 50–100  μM ↓FN1, ITGB1 [59]
  HepG2 and SMMC-7721 cells ART 12.5–75  μM ↓MMP2;
↑TIMP2
[82]
  HepG2 cells ART 6.25–50 mmol/L ↓VEGF, PIGF [83]
  HepG2 and Huh7 cells ART 25  μM , 125  μM ↓Cell migration [84]
Effects on hepatic stellate cells
 Liver fibrosis Mouse HSCs and LX-2 cells ART 25–75  μM ↓Cell vaibility, GSH, GPX4, NADPH, α-SMA, collagen 1, fibronectin, desmin, FTH1, NCOA4, p62;
↑cell death, Fe2+ accumulation, LPO, MDA, ROS, ferroptosis,
LC3; mitochondria morphology change
[87]
  HSC-T6 cells ARM 10–40 ug/ml ↓α-SMA, collagen 1, fibronectin, TGF-β, PDGF-β, EGF, cell viability, GSH, NADPH, Gpx4, SLC7A11;
↑cell death, Fe2+, ROS1, ferroptosis, p53; mitochondria morphology change
[88]
  LX-2 cells ARM 10–40 ug/ml ↓cell activation;
↑cell death, Fe2+, ROS, MDA, LPO, ferroptosis, IRP2
[89]
  LX-2 cells ART 12.5–50 ug/ml ↓cell activation, α-SMA, collagen 1, p-Akt, p-FAK, p-GSK-3β [64]
  LX-2 cells ART 350umol/L ↓hydroxyproline;
↑ceramide synthase protein, ceramide, PPAR-γ, caspase-3
[90]
  LX-2 cells ART 50–200  μM ↓cell viability, Col1a1, Col3a1, OGDH, CS, IDH2, mitochondrial function, NDUFB8, UQCRC2;
↑Cell apoptosis
[91]
Effects on cell autophagy
 Liver fibrosis Primary rat HSCs DHA 5–20  μM ↓P62, inflammatory factors, GSH/GSSG; ↑autophagosome, autophagic flux, LC3-II, ROS, p-JNK1/2 [54]
  Primary rat HSCs DHA 5–20  μM ↑autophagosome, p-ULK1, p-mTOR, Atg6/Beclin1, LC3-II, p53, GATA6, cell senescence [99]
 HCC HepG2215 cells DHA 100  μM ↓p-AKT, p-mTOR, p-p70S6K, p-4EBP1;
↑LC3, p-AMPK, p62
[55]
  HepG2215 cells DHA 21.5  μM ↓p62/SQSTM1;
↑LC3B-II
[56]
Effects on chemsensitization to chemotherapeutic agents
 HCC SM-7721, SK-hep1 cells ART 50  μM Chemosensitize with Sor, ↓IC50, cell viability, p-RAF, p-ERK, p-AKT, p-mTOR;
↑cell apoptosis, p-PARP
[93]
  HepG2 cells
Huh7 cells
ART 25 μM
125 μM
Chemosensitize with Sor, ↓IC50, VEGFR2;
↑cell apoptosis, cleaved caspase-9, cleaved PARP
[84]
  HepG2 and Hep3B cells ART and DHA 10 μmol/L Chemosensitize with gemcitabine, ↓cell survival [51]
  Hep3B cells DHA 5 μM Chemosensitize with ADM, ↓cell viability, clone, P-gp, p-ERK1/2, p65;
↑cell apoptosis
[95]