Table 2: Mechanisms of protection of hepatocytes from apoptosis by medicinal plants.

PlantsBioactive compounds and/or extractsTypes of studyCell lines/animals usedApoptosis inducersMechanisms of protection of hepatocytes from apoptosis

C. longa CurcuminI [55]PCRHEthanolLPO, cytochrome c release
I [56]PCRHFeNTABcl-2, Bcl-XL, ROS, caspase-3 and NF-B
I [57]PCRH HFFAsROS, ATP, PEPCK, G6Pase, mtDNA copy number, PGC1, NRF1, Tfam, MMP and NF-B p65

S. marianum SilymarinI [58]PCRH t-BHPNOS-2 and HO-1

G. biloba G. biloba extractII [59]Rats CCl4LPO
G. biloba extract II [60]SD ratsEthanolGSH, LPO, SOD, GPx, CAT and HO-1
G. biloba II [61]Wistar rats 99mTcP53/Bcl-2 ratio and LPO

S. miltiorrhiza Tanshinone IIAI [62]PCRHLPS and ethanolROS, RNS, fatty acid synthesis, fatty acid oxidation, SCD1 and RXR-
II [63]Kunming miceTAAIGFBP7
I [64]PCRHCCl4MMP
DanshenII [65]Kunming miceIron dextranLPO, GPx and SOD
PF2401-SF, tanshinone II, tanshinone IIA, cryptotanshinoneI [66]PCRHGDCDROS, JNK phosphorylation and p38 phosphorylation
PF2401-SF and cryptotanshinoneI [67]PCRHLPS and ethanollipid accumulation and activation, SREBP1 nuclear translocation
Extract of S. miltiorrhiza I [68]SD ratsBDLp53 cytoplasmic sequestration, Bax and Bcl-2
salvianolic acid BI, II [69]Mice and HL-7702 Death receptor (I) and LPS + D-GalN (II)TNFR1, Bcl-2, cytochrome release and caspase-3

G. glabra GlycyrrhizinI [70]PCRHt-BHPGSH, ROS, SOD, LPO, MMP, cytochrome release, caspase-3 and caspase-9
II [71]SD ratsCCl4caspase-3, p53, Bax/Bcl-2 ratio, caspase-9, Smac, cytochrome release and Smac release
I [72]PCRHBCG vaccine + LPSNO and ICAM-1
II [73]Wistar ratsLPS caspase-3 and cytochrome release
II [74]Balb/c miceLPS + D-GalNIL-18
I [75]Huh-BATHMGB1cytochrome release and p38 activation
18-glycyrrhetinic acidI [76]PCRHGDCDROS, caspase-3, caspase-9, caspase-10, PARP cleavage, JNK, MMP and cytochrome c release
I, II [77]HepG2 and SD ratsHFFAs (I) and HFD (II)Stabilize lysosomal membrane, cathepsin B, cytochrome c release and oxidative stress

S. baicalensis BaicalinI, II [78]PCRH and Balb/c miceTNF- + (Act D) (I) and Con A (II)TNF-, IFN-, IL-6, MPO, LPO and SOD

Phyllanthus species 35 kD P. niruri proteinI [79]PCMHFeSO4GSH, GSSG, SOD, CAT, GST, GR, GPx, protein carbonylation, LPO, MMP, cytochrome release, caspase, PARP cleavage, PI3k/Akt, NF-B phosphorylation, MAPK and ERK
Geraniin and amariin from P. amarus II [80]Cultured liver slices of miceEthanolLPO, protein carbonylation, CAT, SOD, GPx, GR, PARP cleavage, Bax and Bcl-2
Protein from P. niruri I [81]PCMHt-BHPSOD GSH/GSSG ratio, MMP, Bax, Bcl-2,
caspase-3, caspase-9 and cytochrome c release

B. aristata BerberineI [82]L02 H2O2caspase-3, PARP, FasL, Bim and SIRT1

P. kurroa Picroside IIII [83]Kunming miceCCl4, D-GalN and APLPO, SOD, GPx, ATPase, swelling extent of mitochondria
I, II [84]PCRH and Kunming miceTNF- + Act D (I) and LPS + D-GalNLPO, SOD, Bcl-2 and Bax

Ginseng speciesGinseng extract from P. ginseng MeyerII [85]SD rats AFB1SOD, CAT, GPx and LPO

A. paniculata AndrographolideII [86]C57BL/6 miceCon ALDH, MPO, COX2, Glut1, HIF-1, HO-1, SOD1, iNOS and TNF-α

Abbreviations: : inductor effect, : inhibitor effect; I: in vitro; II: in vivo; 99mTc: technetium 99mTc; Act D: actinone D; AFB1: aflatoxin B1; AP: acetaminophen; ATP: adenosine triphosphate; ATPase: adenosinetriphosphatase; BDL: bile duct ligation; Bim: Bcl-2-interacting mediator; CAT: catalase; CCl4: carbon tetrachloride; Con A: concanavalin A; COX2: cyclooxygenase 2; D-GalN: D-galactosamine; FasL: Fas ligand; FeNTA: ferric nitrilotriacetate; FeSO4: iron (II) sulfate; G6Pase: glucose-6-phosphatase; GDCD: glycochenodeoxycholic acid; Glut1: glucose transporter 1; GPx: gluthatione peroxidase; GR: glutathione reductase; GSH: glutathione; GSSG: glutathione disulfide; GST: glutathione S-transferase; H2O2: hydrogen peroxide; HFD: high fat diet; HFFAs: high free fatty acids; HIF-1α: hypoxia-inducible factor 1-alpha; HMGB1: high-mobility group box 1; HO-1: heme oxygenase 1; ICAM-1: intercelular adhesion molecule 1; IFN-γ: interferon-gamma; IGFBP7: insulin-like growth factor binding protein 7; IL-6: interleukine-6; IL-18: interleukine-18; iNOS: inducible nitric oxide synthase; JNK: c-Jun-NH2-terminal kinase; LDH: lactate dehydrogenase; LPO: lipid peroxidation; LPS: lipopolysaccharide; MAPK: mitogen activated protein kinases; MMP: mitochondrial membrane potential; MPO: myeloperoxidase; mtDNA: mitochondrial DNA; NF-κB: nuclear factor kappaB; NO: nitric oxide; NOS-2: nitric oxide synthase 2; NRF1: nuclear respiratory factor 1; PARP: poly ADP ribose polymerase; PCMH: primary cultured mouse hepatocytes; PCRH: primary cultured rat hepatocytes; PEPCK: phosphoenol pyruvate carboxykinase; PGC1α: peroxisome proliferator-activated receptor gamma coactivator 1 alpha; PI3k/Akt: phosphatidylinositide 3-kinases/protein kinase B; RNS: reactive nitrosative species; ROS: reactive oxygen species; RXR-α: retinoid-X receptor-alpha; SCD1: stearoyl-CoA desaturase-1; SD: Sprague-Dawley; SIRT1: sirtuin 1; Smac: second mitochondria derived activator of caspases; SOD: superoxide dismutase; SREBP1: sterol regulatory element binding protein-1; t-BHP: tert-butylhydroperoxide; TAA: thioacetamide; Tfam: mitocondrial transcription factor A; TNF-α: tumor necrosis factor alpha; TNFR1: tumor necrosis factor alpha receptor type 1.