Liver Fibrosis and Mechanisms of the Protective Action of Medicinal Plants Targeting Inflammation and the Immune Response

Table 2

Anti-inflammatory properties of medicinal plants observed in animals treated with a subacute or chronic administration of a hepatotoxic agent.

Plants	Bioactive compounds and/or extracts	Animals used	Profibrogenic agents	Anti-inflammatory mechanisms
C. longa	Curcumin	Male Wistar rats [79]	Fish oil + ethanol	NF-κB, ↑IκBα, ↓TNF-α, ↓IL-12, ↓MCP-1, ↓MIP-2, ↓COX-2, and ↓iNOS
		Female C57BL6/J mice [80]	MCD	↓NF-κB, ↓ICAM-1, ↓COX-2, and ↓MCP-1
		Male C57BL6/J mice [81]	MCD	↓MCP-1 and ↓CD11b
		Male SD rats [144]	CCl4	↓IFN-γ, ↓TNF-α, and ↓IL-6
		Male SD rats [77]	CCl4	↓TNF-α, ↓IL-6, ↓MCP-1, ↓HMGB1, ↓TLR4, and ↓TLR2
		SD rats [110]	CCl4	↓NF-κB, ↓TNF-α, ↓IL-1β, ↓IL-6, and ↑IL-10
		Male C57BL6/J mice [145]	CCl4	↓IL-6 and ↓TNF-α
		Rats [111]	CCl4	↓NF-κB, ↓IL-6, and ↓TNF-α
		Male BALB/c mice [95]	TAA	↓TNF-α and ↓macrophages
		Male ob/ob C57BL/6J mice [82]		↓TNF-α, ↓IL-6, ↓MCP-1, ↓NF-κB, and ↓macrophages
S. marianum	Silymarin	Male Wistar rats [96]	CCl4	↓mast cells
		Male SD rats [88]	DMN	↓iNOS, ↓ICAM-1, and ↓NF-κB
		Male OLETF rats [131]	MCD	↓TNF-α, ↑Nrf2, and ↓ERK
		Male CD-1 Swiss albino mice [97]	S. mansoni	↓mast cells
G. biloba	EGB	Rats [112]	HFD	↓NF-κB p65, ↓NF-κB
		Male Wistar albino rats [98]	BDL	↓TNF-α and ↓neutrophils
		Male SD rats [146]	Ethanol	↓TNF-α
		Rats [113]	HFD	↓NF-κB p65
S. miltiorrhiza	S. miltiorrhiza	Male SD rats [147]	CCl4	↓NOSII
		Male Kunming mice [148]	Iron dextran	↓TNF-α and ↓IL-1α
	Salvianolic acid A and salvianolic acid B	Male SD rats [130]	TAA	↓HO-1, ↓iNOS, ↓TNF-α, ↓IL-6, and ↓IL-1β
	Salvianolic acid B	SD rats [99]	CCl4	↓TNF-α and ↓CD14
		Male SD rats [114]	CCl4	↓NF-κB, ↑IκBα
G. glabra	Glycyrrhizin	Male SD rats [115]	CCl4 + ethanol	↓NF-κB
		Female BALB/c mice [100]	ConA	↓Th1, ↓Th2, ↓Th17, ↓Treg, ↑IFN-γ, and ↑IL-10
S. baicalensis	Baicalin	Male SD rats [149]	CCl4	↓TNF-α, ↓IL-6, and ↑IL-10
		Male SD rats [116]	Ethanol + I/R	↓TLR-4, ↓MyD88, ↓NF-κB p65, ↑IκBα, ↓TNF-α, ↓IL-6, ↓iNOS, and ↓COX-2
B. falcatum	Saikosaponin D	Male SD rats [117]	CCl4	↓TNF-α, ↓IL-6, ↓NF-κB p65, and ↑IκBα
	Saikosaponin A	Male SD rats [110]	CCl4	↓NF-κB, ↓TNF-α, ↓IL-6, ↓IL-1β, and ↑IL-10
B. aristata	Berberine	Mice [150]	CCl4	↓TNF-α
Ginseng species	P. notoginseng saponins	Male SD rats [151]	CCl4	↓TNF-α, ↓IL-6, and ↑IL-10
A. paniculata	Andrographolide	Male SD rats [152]	BDL	↓TNF-α and ↓IL-1β
		Male SD rats [101]	Copper sulfate	↓TNF-α and ↓Kupffer cells
Coffeespecies	Coffee	Male SD rats [153]	DMN	↓TNF-α, ↓IL-1β, and ↓iNOS
	Caffeine	Male Kunming mice [83]	Ethanol	↓TNF-α, ↓IL-6, ↓MCP-1, ↓IFN-γ, and ↓IL-1β
		Male SD rats [102]	TAA	↓inflammatory cells
	Decaffeinated coffee, polyphenols, and melanoidins	Male Wistar rats [154]	HFD	↓TNF-α, ↑IL-6, ↓IFN-γ, ↓IL-1α, ↓IL-1β, ↑IL-4, ↑IL10, and ↑adipo-R2
	Chlorogenic acid	SD rats [118]	CCl4	↓TLR4, ↓MyD88, ↓iNOS, ↓COX-2, ↑Bambi, ↓TNF-α, ↓IL-6, ↓IL-1β, ↑IκBα, and ↓NF-κB

Note: ↓: inhibitory effect, ↑: inductor effect, adipo-R2: adiponectin receptor 2, Bambi: bone morphogenetic protein and activin membrane-bound inhibitor, BDL: bile duct ligation, CCl₄: carbon tetrachloride, CD11b: cluster of differentiation 11b, CD14: cluster of differentiation 14, ConA: concanavalin, COX-2: cyclooxygenase-2, DMN: dimethylnitrosamine, EGB: G. biloba extract, standardized extract of the leaves of G. biloba, a mixture mainly composed of flavonoid glycosides (24%) and terpenoides (6%), including ginkgolides and bilobalide, ERK: extracellular signal regulated kinases, HFD: high fat diet, HMGB1: high mobility group protein B1, HO-1: heme oxygenase-1, I/R: ischemia/reperfusion, IκBα: IkappaBalpha (NF-κB inhibitor), ICAM-1: intracellular adhesion molecule-1, IFN-γ: interferon gamma, IL: interleukin, iNOS: inducible nitric oxide synthase, MCD: methionine and choline deficient diet, MCP-1: monocyte chemotactic protein-1, MIP-2: macrophage inflammatory protein-2, MyD88: myeloid differentiation primary response 88, NF-κB: nuclear factor kappaB, NF-κB p65: p65 subunit of nuclear factor kappaB, NOSII: nitric oxide synthase II, Nrf2: nuclear factor erythroid 2-related factor 2, OLETF: Otsuka Long Evans Tokushima Fatty, SD: Sprague-Dawley, TAA: thioacetamide, Th1: T helper 1, Th2: T helper 2, Th17: T helper 17, Treg: regulatory T cells, TLR: Toll-like receptor, and TNF-α: tumor necrosis factor alpha.