Advances in Pharmacological and Pharmaceutical Sciences

Review Article

Liver Fibrosis and Protection Mechanisms Action of Medicinal Plants Targeting Apoptosis of Hepatocytes and Hepatic Stellate Cells

Table 1

Mechanisms of induction of hepatic stellate cells apoptosis by medicinal plants.


Plants	Bioactive compounds and/or extracts	Types of study	Cell lines/animals used (fibrogenic inducers)	Mechanisms of induction of HSC apoptosis

C. longa	Curcumin	I [25]	PCR-HSC	caspase-3, Bcl-2, PPAR- and NF-B
		I [26]	PCR-HSC	PPAR-, Bax, Bcl-2 and caspase-3
		I [27]	PCR-HSC	PPAR-
		I [28]	PCR-HSC	Bax, Bcl-2, PPAR-, ERK, JNK and PI-3K/AKT
		I [29]	PCR-HSC	PPAR-, 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	IH764-3	I [33]	CFSC	caspase-3
		I [34]	HSC (H₂O₂)	ERK
		II [35]	SD rats (BDL)	FAK, p-FAK, ERK and p-ERK
	Tanshinone I	I [36]	T-HSC/Cl-6	caspase-3, PARP, cytochrome release and MMP
	Tanshinone IIA	I [37]	T-HSC/Cl-6	caspase-3, PARP, cytochrome release, Bax, Bcl-2 and MMP
	Tanshinone IIA	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 A	I [39]	HSC-T6 (PDGF-BB)	AKT phosphorylation, caspase-3 and Bcl-2
	PF2401-SF	I, 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-T6	Bax, Fas and Bcl-XL

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

B. falcatum	Saikosaponin A and D	I [42]	HSC-T6	ERK

P. notoginseng	20-O-beta-D-glucopyranosyl-20(S)-protopanaxadiol	I [43]	T-HSC/Cl-6	MMP, caspase-3 and PARP cleavage
P. notoginseng	25-OCH₃-PPD	I [44]	T-HSC/Cl-6 (TNF-)	caspase-3, survivin, Bcl-2, c-FLIP_L, c-FLIP_S, 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-FLIP_L: cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein (isoform L); c-FLIP_S: 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.