Table 1.

PPAR ligands suppressing biological actions of HMGB1.

PPAR ligands	PPAR types	Possible involved HMGB1 signaling or expression	Effects on biological actions of HMGB1	Cell lines	Animal model	Potential applied diseases	References
EPA	PPAR-γ	HMGB1/TLR9 signaling	EPA inhibits HMGB1/TLR9 pathway and downregulates HMGB1 expression in brain cortex.	—	Ovariectomized rat model of cerebral ischemia	Ischemic brain damage and ischemic stroke	[39]
Telmisartan	PPAR-γ	—	Telmisartan decreases plasma HMGB1 levels and suppresses the expression of HMGB1 in macrophages or microglial cells.	—	Mice model of focal cerebral ischemia	Postischemic injury	[38]
Troglitazone	PPAR-γ	Transcriptional activity of HMGB1 promoter and NF-κB or AP-1 signaling	Troglitazone inhibits HMGB1 expression in endothelial cells.	Vascular endothelial cells	—	Sepsis, arthritis, and atherosclerosis	[41]
		miRNA-based regulation	Troglitazone inhibits HMGB1 expression through upregulation of miR-142-3p.	THP-1 cells	Mice model of endotoxemia	Sepsis	[42]
Rosiglitazone	PPAR-γ	HMGB1/TLR4 signaling	Rosiglitazone decreases LPS-induced plasma HMGB1 levels and inhibits HMGB1 release of RAW264.7 cells.	RAW264.7 cells	Mice model of endotoxemia	Sepsis	[43]
		HMGB1/RAGE signaling	Rosiglitazone reverses LPS-induced elevation of HMGB1 in bronchoalveolar lavage fluid.	—	Mice model of ALI	ALI and ARDS	[44, 45]
Pioglitazone	PPAR-γ	HMGB1/TLR4 and HMGB1/RAGE signaling	Pioglitazone reverses AGEs-induced elevation of HMGB1 expression in OA chondrocytes.	Chondrocytes	—	OA	[46]
		HMGB1/RAGE signaling	Pioglitazone downregulates HMGB1 expression and inhibits HMGB1/RAGE signaling in HCC cells.	SMMC-7721 and HepG2 cells	—	Hepatocellular carcinoma	[47]
Fenofibrate	PPAR-α	—	Fenofibrate reverses basal and LPS-induced HMGB1 expression, as well as modulating its cellular localization.	Cardiomyocytes	Mice model of hypertrophic myocardium	Cardiac hypertrophy	[48]

EPA: eicosapentaenoic acid; LPS: lipopolysaccharide; TLR: Toll-like receptor; RAGE: receptor for advanced glycation end-products; ALI: acute lung injury; ARDS: acute respiratory distress syndrome; AGEs: advanced glycation end-products; OA: osteoarthritis; HCC: hepatocellular carcinoma.