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

Table 2

Mechanisms of protection of hepatocytes from apoptosis by medicinal plants.

Plants	Bioactive compounds and/or extracts	Types of study	Cell lines/animals used	Apoptosis inducers	Mechanisms of protection of hepatocytes from apoptosis
C. longa	Curcumin	I [55]	PCRH	Ethanol	LPO, cytochrome c release
		I [56]	PCRH	FeNTA	Bcl-2, Bcl-XL, ROS, caspase-3 and NF-B
		I [57]	PCRH	HFFAs	ROS, ATP, PEPCK, G6Pase, mtDNA copy number, PGC1, NRF1, Tfam, MMP and NF-B p65
S. marianum	Silymarin	I [58]	PCRH	t-BHP	NOS-2 and HO-1
G. biloba	G. biloba extract	II [59]	Rats	CCl4	LPO
	G. biloba extract	II [60]	SD rats	Ethanol	GSH, LPO, SOD, GPx, CAT and HO-1
	G. biloba	II [61]	Wistar rats	^99mTc	P53/Bcl-2 ratio and LPO
S. miltiorrhiza	Tanshinone IIA	I [62]	PCRH	LPS and ethanol	ROS, RNS, fatty acid synthesis, fatty acid oxidation, SCD1 and RXR-
		II [63]	Kunming mice	TAA	IGFBP7
		I [64]	PCRH	CCl4	MMP
	Danshen	II [65]	Kunming mice	Iron dextran	LPO, GPx and SOD
	PF2401-SF, tanshinone II, tanshinone IIA, cryptotanshinone	I [66]	PCRH	GDCD	ROS, JNK phosphorylation and p38 phosphorylation
	PF2401-SF and cryptotanshinone	I [67]	PCRH	LPS and ethanol	lipid accumulation and activation, SREBP1 nuclear translocation
	Extract of S. miltiorrhiza	I [68]	SD rats	BDL	p53 cytoplasmic sequestration, Bax and Bcl-2
	salvianolic acid B	I, II [69]	Mice and HL-7702	Death receptor (I) and LPS + D-GalN (II)	TNFR1, Bcl-2, cytochrome release and caspase-3
G. glabra	Glycyrrhizin	I [70]	PCRH	t-BHP	GSH, ROS, SOD, LPO, MMP, cytochrome release, caspase-3 and caspase-9
		II [71]	SD rats	CCl4	caspase-3, p53, Bax/Bcl-2 ratio, caspase-9, Smac, cytochrome release and Smac release
		I [72]	PCRH	BCG vaccine + LPS	NO and ICAM-1
		II [73]	Wistar rats	LPS	caspase-3 and cytochrome release
		II [74]	Balb/c mice	LPS + D-GalN	IL-18
		I [75]	Huh-BAT	HMGB1	cytochrome release and p38 activation
	18-glycyrrhetinic acid	I [76]	PCRH	GDCD	ROS, caspase-3, caspase-9, caspase-10, PARP cleavage, JNK, MMP and cytochrome c release
		I, II [77]	HepG2 and SD rats	HFFAs (I) and HFD (II)	Stabilize lysosomal membrane, cathepsin B, cytochrome c release and oxidative stress
S. baicalensis	Baicalin	I, II [78]	PCRH and Balb/c mice	TNF- + (Act D) (I) and Con A (II)	TNF-, IFN-, IL-6, MPO, LPO and SOD
Phyllanthus species	35 kD P. niruri protein	I [79]	PCMH	FeSO4	GSH, 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 mice	Ethanol	LPO, protein carbonylation, CAT, SOD, GPx, GR, PARP cleavage, Bax and Bcl-2
	Protein from P. niruri	I [81]	PCMH	t-BHP	SOD GSH/GSSG ratio, MMP, Bax, Bcl-2,; caspase-3, caspase-9 and cytochrome c release
B. aristata	Berberine	I [82]	L02	H2O2	caspase-3, PARP, FasL, Bim and SIRT1
P. kurroa	Picroside II	II [83]	Kunming mice	CCl4, D-GalN and AP	LPO, SOD, GPx, ATPase, swelling extent of mitochondria
		I, II [84]	PCRH and Kunming mice	TNF- + Act D (I) and LPS + D-GalN	LPO, SOD, Bcl-2 and Bax
Ginseng species	Ginseng extract from P. ginseng Meyer	II [85]	SD rats	AFB1	SOD, CAT, GPx and LPO
A. paniculata	Andrographolide	II [86]	C57BL/6 mice	Con A	LDH, 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.