TABLE 3.

Summarization of the effects of drugs acting on PPARγ in cerebral IRI.

Drugs act on PPARγ	IRI models	Main effects	Conclusion	Reference
15 daysPGJ2 a	Male Long-Evans rats	Suppressed apoptosis and necrosis, and increased PPARγ, HO-1 expression	15 days-PGJ2 improves cerebral IRI insult, and decreases apoptosis and necrosis via a PPARγ-dependent way	Lin et al. (2006)
15 days-PGJ2 a	Neuronal cells derived from the neocortices of E15 embryos in pregnant female C57BL/6 J mice	Protected neurons against cell death and inhibited neuronal autophagy	15 days-PGJ2 protects neurons partially by inhibiting autophagy via up-regulating Bcl-2 and inhibiting beclin1–Bcl2 heterodimer dissociation	Qin et al. (2015)
12-HETE b	Adult male Sprague–Dawley rats weighing 280–330 g	Suppressed iNOS expression, protected cortical neurons, and activated PPARγ	12-HETE exerts neuroprotective effect through PPARγ activation via the 12/15-lox pathway	Han et al. (2015)
Bexarotene b	Adult male Sprague–Dawley rats (280–320 g)	Improved neurobehavioral deficits and reduced brain edema, effects of microglia/macrophage activation and neutrophil infiltration	Bexarotene protects the brain at least in part through PPARγ/SIRT6/FoxO3, a signaling pathway	Zuo et al. (2019)
d-allose b	Male BALB/c mice weighing 20–25 g	Inhibited apoptosis, various inflammatory cytokines, and inflammation-related molecules	d-allose has therapeutic implication that may involve in the PPARγ-dependent activation	Huang et al. (2016)
Aleglitazar b	Fetal C57BL/6 N mice (E15) cerebral cortex	Anti-inflammation and reduction in NO production, release of pro-inflammatory cytokines, migration, and phagocytosis	Aleglitazar can be a clinical stroke therapy with short-term treatment	Boujon et al. (2019)
Icariin (ICA) b	Sprague–Dawley rats (4 months, 250–280 g)	Decreased neurological deficit score, diminished the infarct volume, and reduced the levels of IL-1β and TGF-β1	ICA has neuroprotective effects by inhibiting NF-κB, PPARα, and PPARγ mediate inflammation	Xiong et al. (2016)
Mifepristone b	Male Sprague–Dawley rats weighing 250–280 g	Reduced the levels of TNF-α, IL-1β, IL-6, MMP-2, and MMP-9, and increased TIMP-1 protein	Mifepristone relieves cerebral IRI by restoring the balance between MMPs and TIMPs and inhibiting inflammatory cytokines by activating PPARγ	Wu et al. (2018)
Rosiglitazone c	Female Sprague–Dawley rats weighing 250–300 g, aged 3 months	Reduced cerebral infarct volume, brain edema, attenuated IL-1β, IL-6, TNF-α, LC3-II/LC3-I and Beclin-1 level	Rosiglitazone may protect brain through inhibiting neuroinflammation and autophagic neuronal death	Shao and Liu (2015)
Umbelliferone b	Male Sprague–Dawley rats weight 220–270 g	Reduced MDA, IL1β, and IL-18; increased SOD, PPARγ level; suppressed the expression of NLRP3 inflammasome and TXNIP induction	Umbelliferone ameliorates cerebral IRI, may be partly related with the inhibition of NLRP3 inflammasome in the brain, and upregulation of PPARγ expression	Wang et al. (2015)

HO-1, heme oxygenase-1; E15, embryonic day 15; iNOS, inducible NO synthase; 12-HETE, 12-hydroxyeicosatetraenoic acid; SIRT6P, the endogenous retinoid X receptor and sirtuin 6; FoxO3a, forkhead box O3a; BBB, blood–brain barrier; MMP-2, , tissue inhibitor of metalloproteinase 1; TXNIP, thioredoxin interacting protein; MDA, malondialdehyde; NLRP3, nod-like receptor family, pyrin domain containing 3.

^aPPARγ natural ligand.

^bPPARγ agonist.

^cPPARγ synthetic ligand.