Table 2.

The potential antifibrotic mechanisms of some polyphenols.

Effects	Polyphenol	Model	Mechanisms	Ref.
Inhibition of HSC activation	Apigenin	In vitro HSCs	Upregulating C1QTNF2 expression	[107]
	EGCG	In vitro HSCs & thioacetamide-treated animal	Upregulating miR-221 to accelerate osteopontin degradation	[108]
	Quercetin	Rats with CCl4-induced fibrosis	Activation of MMPs and regulating profibrogenic/antifibrogenic molecules balance	[109]
	Icaritin	In vitro HSC-T6 and LX-2 HSC lines & rats with CCl4 or CBDL-induced fibrosis	Dependent on mitochondrial-activated apoptosis	[110]
	Curcumin	In vitro HSCs & animal model	Suppressing membrane translocation and gene expression of GLUT2; inhibiting PPARγ via regulation of DLK1 protein partly mediated by interruption of Shh signaling pathway	[111, 112]
	Resveratrol	Rats with N′-nitrosodimethylamine-induced liver fibrosis	Relieving oxidative damage	[113]
Induce HSC apoptosis	Hyperoside	In vitro human LX-2 HSCs	Inhibiting the DNA-binding activity of NF-κB and altered genes related to apoptosis	[125]
	Morin	In vitro HSCs	Suppressing canonical NF-κB signaling
	Gallic acid	In vitro HSCs	Regulating TNF-α signaling pathway	[114]
	Quercetin	In vitro HSCs	Dependent on activation of ER stress	[115]
Inhibit proliferation and profibrogenesis-related genes in HSCs	Chrysin	Mice with CCl4-induced fibrosis	Suppressing TGF-β1/Smad pathway	[116]
	Tricin	In vitro human HSC line LI90	Blocking tyrosine phosphorylation of PDGF receptor	[117]
	Chlorogenic acid	In vitro HSCs & CCl4-treated rats	Improving antioxidant capacity via activation of Nrf2 pathway and suppressing profibrotic action via inhibition of NOX/ROS/MAPK pathway	[118]
	Luteolin	In vitro rat HSCs and HSC-T6 cells & rat models induced by CCl4, DMN, and BDL	Increasing caspase 3 activity and p53 expression; inducing G1 arrest with the decreased expression of bcl-2, cyclin E, and p-Cdk-2; suppressing PDGF and TGF1-simulated phosphorylation of AKT and Smad pathway	[126]
	Resveratrol	In vitro human LX-2 HSCs & mice with CCl4-induced fibrosis	Suppressing the activation of NF-κB and Akt	[119]
	EGCG	In vitro HSC LX-2 & BDL rats	Inhibiting PI3K/Akt/Smad pathway	[120]
	Wogonoside	In vitro HSC T6 cells & mice with CCl4-induced fibrosis	Inhibiting PI3K/Akt/mTOR/p70S6K	[121]
Attenuate liver injury and antifibrosis	Morin	Rats with CCl4-induced fibrosis	Reducing oxidative stress, inflammatory responses, and fibrogenic markers	[122]
	Chlorogenic acid	Rats with CCl4-induced fibrosis	Inhibition of TLR4/MyD88/NF-κB signaling pathway	[123]
	Curcumin	Mice with type 2 diabetes mellitus	Suppressing the AGEs-mediated induction of RAGE gene expression by increasing PPARγ and stimulating GSH	[124]
	Total flavonoids of Astmgali Radix	Rats with fibrosis	Regulating PPAR signal pathway and the interaction with FXR	[127]