Table 1: Mechanisms of induction of hepatic stellate cells apoptosis by medicinal plants.

PlantsBioactive compounds and/or extractsTypes of studyCell lines/animals used (fibrogenic inducers)Mechanisms of induction of HSC apoptosis

C. longa CurcuminI [25]PCR-HSCcaspase-3, Bcl-2, PPAR- and NF-B
I [26]PCR-HSCPPAR-, Bax, Bcl-2 and caspase-3
I [28]PCR-HSCBax, Bcl-2, PPAR-, ERK, JNK and PI-3K/AKT
I [29]PCR-HSCPPAR-, Bax, Bcl-2 and NF-B p65
I, II [30]PCR-HSC and SD rats (CCl4) caspase-3
I [31]HSC-T6 (TGF-1)cytochrome release
I [32]Human telomerase reverse transcriptase HSC Modulate BAX and FLIP and Wnt signaling pathway components AXIN2 and FRA1

S. miltiorrhiza IH764-3I [33]CFSCcaspase-3
I [34]HSC (H2O2)ERK
II [35]SD rats (BDL)FAK, p-FAK, ERK and p-ERK
Tanshinone II [36]T-HSC/Cl-6caspase-3, PARP, cytochrome release and MMP
Tanshinone IIAI [37]T-HSC/Cl-6caspase-3, PARP, cytochrome release, Bax, Bcl-2 and MMP
I, II [38]HSC-T6 and Wistar rats (DMN)prohibitin, C-Raf membrane tanslocation, pERK, AKT phosphorylation, Bax, Bcl-2, cytochrome c release, caspase-3, caspase-9 and PARP cleavage.
Salvianolic acid AI [39]HSC-T6 (PDGF-BB)AKT phosphorylation, caspase-3 and Bcl-2
PF2401-SFI, II [40]T-HSC/Cl-6 and SD rats (CCl4)caspase-3, caspase-8, caspase-9, PARP cleavage, Bax and Bcl-2
Root of S. miltiorrhiza I [41]HSC-T6Bax, Fas and Bcl-XL

G. glabra 18-glycyrrhizinI, II [23]CFSC and SD rats (CCl4)NF-B

B. falcatum Saikosaponin A and DI [42]HSC-T6ERK

P. notoginseng 20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiolI [43]T-HSC/Cl-6MMP, caspase-3 and PARP cleavage
25-OCH3-PPDI [44]T-HSC/Cl-6 (TNF-)caspase-3, survivin, Bcl-2, c-FLIPL, c-FLIPS, XIAP, NF-B p65 nuclear translocation and IB-

Abbreviations: : inductor effect, : inhibitor effect; I: in vitro; II: in vivo; AKT: protein kinase B; Bax: Bcl-2-associated X protein; Bcl-2: B-cell lymphoma 2; Bcl-XL: B-cell lymphoma-extralarge; BDL: bile duct ligation; c-FLIPL: cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein (isoform L); c-FLIPS: cellular FLICE- (FADD-like IL-1β-converting enzyme-) inhibitory protein (isoform S); CCl4: carbon tetrachloride; CFSC: hepatic stellate cell line; DMN: dimethylnitrosamine; ERK: extracellular signal-regulated kinases; FAK: focal adhesion kinase; H2O2: hydrogen peroxide; HSC: hepatic stellate cells; HSC-T6: immortalized rat liver stellate cell line; IκB-α: inhibitor of nuclear factor kappaB alpha; JNK: c-Jun N-terminal kinases; MMP: mitochondrial membrane potential; NF-κB: nuclear factor kappaB; NF-κB p65: p65 subunit of nuclear factor kappaB; p-ERK: phosphorylated extracellular signal-regulated kinases; p-FAK: phosphorylated focal adhesion kinase; PARP: poly ADP ribose polymerase; PCR-HSC: primary cultured rat hepatic stellate cells; PDGF-BB: platelet derived growth factor-BB; PI-3K/AKT: phosphatidylinositide 3-kinases/protein kinase B; PPAR-γ: peroxisome proliferator-activated receptor gamma; SD: Sprague-Dawley; TGF-β1: transforming growth factor beta 1; T-HSC/Cl-6: rat hepatic stellate cells transformed by simian virus 40; TNF-α: tumor necrosis factor alpha; XIAP: X-linked inhibitor of apoptosis protein.