TABLE 1.

Main preclinical studies of PPARα-related modulators for liver fibrosis

Agent	Models	Mechanisms	Effects	Refs.
Bezafibrate	Rat	Prevention of HSC activation		207
Feno fibrate	Human	Regulation of vanin-1		208
	Human hepatocytes/Mice	Reduction of cholestasis		(14, 82, 129)
	Mice	Regulation of fatty acid metabolism		209
	Rat	Enhancement of catalase activity		55
	Rat	Modulation of inflammatory cytokines		210
	Mice	Reduction of hepatic iron accumulation		211
Pemafibrate	Mice	—		212
WY14643	Mice	Enhancement of catalase activity		66, 213
	Mice	Inhibition of insulin resistance		214
	Human hepatocytes	Control of catabolism of cytotoxic bile acids		(14, 129)
	Mice	Amelioration of hepatic cell death		215
PPARα/γ agonist
Elafibranor	Mice/Rat	PPARa-dependent and -independent mechanisms		216
ZLY16	Mice	Enhancement of antioxidant enzymes activity		217
MHY2013	Mice	—		218
Triazo lone derivatives	Mice	—		219
PPARα/γ agonist
Chiglitazar	Rat	Improvement of insulin resistance and dyslipidemia		220
Aleglitazar	Rat	Modulation of inflammatory cytokines		221
Saroglitazar	Mice/Rat	Improvement of insulin resistance, modulation of inflammatory cytokines ang adiponectin		222, 223
Pan-PPAR agonist
Lanifibranor	Mice	Reduction of proinflammatory macrophages activation		224, 225
MBT1805	Mice	Reduction of cholestasis		226
Quadruple agonist
RLA8	Mice	Reduction of lipotoxicity and oxidative stress		227
ZLY18	Mice	Reduction of lipotoxicity and oxidative stress		228
Chemical or oligonucleotide
Oleoylethanolamide	Mice	Suppression of SMAD2/3 phosphorylation, α-SMA expression, and myofibroblast transformation		(186)
Pirfenidone	Mice	Activation of SIRTl/LKBl/pAMPK		229, 230
Melatonin	Mice	Regulation of circadian clocks		(75)
Ascorbic acid	Mice	—		231
Chicory seed extract	Rat/HepG2 cells	—		232
Syringic acid	Mice	Reduction of lipotoxicity		233
Glycyrrhizic acid	Mice	—		234
2,3,5,4'-tetrahydroxy stilbene-2-O-β-d-glu coside	Mice	Regulation of key regulators of lipid metabolism, inflammation, fibrosis, and oxidative stress		235
4-O'-methylhonokiol	Mice	Induction of MMPs, AEA, and NAEs and prevention of HSC activation,		(78)
Iso-alpha acids	Mice	Reduction of HSC activation and oxidative stress		236
Baicalin	Mice	Regulation of key regulators of lipid metabolism, proinflammatory cytokines, fibrosis markers		237
Betanin	Mice	Downregulation of SREBP-lc		238
Calycosin	Mice	Activation of farnesoid X receptor		239
Naringenin	Mice	Activation of hepatic SIRT1-mediated signaling cascades		240
Conophylline	Mice	Inhibition of hepatic TGF-β level		241
Curcumin	Rat	Regulation of oxidative stress, autophagy and epithelial-mesenchymal transition		242
Quercetin	Rat	Downregulation of the transcription of miR-21		243
Perfluorooctanoate	Mice	—		244
Alisol B 23-acetate	Mice	Activation of farnesoid X receptor		245
Telmisartan	Mice	Regulation of inflammatory- and fibrosis-related responses		246
Periostin antisense oligonucleotide	Mice	Downregulation of the hepatic periostin expression		247
CircRNA_0046367	HepG2 cells.	Reduction of miR-34a’s inhibitory effect on PPARα		348
miRNA
miR-21	Mice	Inhibition of PPARα expression		249
miR-27	Huh7 cells	Repression of PPARα signaling		(33)
miR-33a	Hepatic stellate cells LX-2	Regulation of HSCs trans differentiation and proliferation		(192)
miR-155	Mice	Enhancement of PPRE and PPARα binding and decreased		65
miR-540	Primary hepatocytes of mice	Inhibition of PPARα expression		250

: positive effect on injury (), steatosis (), inflammation (), or fibrosis ().

: neutral or non-available effect on injury (), steatosis (), inflammation (), or fibrosis ().

: negative effect on injury (), steatosis (), inflammation (), or fibrosis ().

Abbreviations: PPRE, peroxisome proliferators response elements; PPARα, peroxisome proliferator-activated receptor alpha; Refs., references.