Table 1.

Summary of Nrf2 and PPARγ pathway activators studied for their potential protective effects on various disease models. Nrf2 and PPARγ pathway activators are categorized based on their target specificities and origin of synthesis. Their compound names, target diseases, effects on experimental models, effect on Nrf2, PPARγ, and other relevant molecules, and their related references are listed accordingly. Abbreviations used within the table are as follows. Nrf2: nuclear factor erythroid 2p45-related factor 2; PPARγ: peroxisome proliferator-activated receptor γ; HO-1: heme oxygenase-1; CNS: central nerve system; ARE-luc: antioxidant response element-containing luciferase reporter; PI3K: phosphatide 3-kinase; PKC: protein kinase C; LPS: lipopolysaccharide; NF-κB: nuclear factor kappa B; COX-2: cyclooxygenase-2; MAPK: mitogen-activated protein kinase; iNOS: inducible nitric oxide synthase; GST-α: glutathione S-transferase-α; ABCA1: ATP-binding cassette transporter 1; MAPKAPK: mitogen-activated protein kinase-activated protein kinase; Bcl-xL: B-cell lymphoma-extra large; NQO-1: NAD(P)H quinone oxidoreductase-1; SOD: superoxide dismutase; GPX: glutathione peroxidase; GST: glutathione; TNF-α: tumor necrosis factor-α; MDA: malondialdehyde; CAT: catalase; NO: nitric oxide; SIRT1: silent information regulator 2 (Sir2) protein 1; γ-GCL: γ-glutamyl cysteine ligase.

Category	Compound name	Target disease	Effects on experimental models	Effect on Nrf2	Effect on PPARγ	Effect on others	Reference
Nrf2 activators	Bardoxolone methyl	Kidney disease	Amelioration of ischemic acute kidney injury in mice	Nrf2 ↑	PPARγ ↑	HO-1 ↑	Wu et al. [69]
	Curcumin	Malaria	Increased nonopsonic phagocytosis of Plasmodium falciparum in monocytes/macrophages and hepatoma cells	Nrf2 ↑	PPARγ ↑	CD36 ↑	Mimche et al. [73]
Endogenous PPARγ activators	15-Deoxy-D12, 14-prostaglandin J2	CNS disease	Protection against homocysteic acid-induced oxidative death in neurons	ARE-luc ↑	Independent	HO-1 ↑	Haskew-Layton et al. [75]
		Not specified	Attenuation of cell death in RAW264.7 mouse macrophages	Nrf2 ↑	Independent	HO-1 ↑	Gong et al. [76]
	Nitroalkene fatty acids	Not specified	Activation of Nrf2 and PPARγ pathways in human MCF7 breast cancer cells	Nrf2 ↑ (<1 μM)	PPARγ ↑ (>1 μM)	PI3K, PKC ↑	Bates et al. [78]
	Nitrated fatty acids	Respiratory disease	Decreased severity of LPS-induced acute lung injury in mice	Nrf2 ↑	PPARγ ↑	NF-κB ↓	Reddy et al. [80]
Synthetic PPARγ activators	Rosiglitazone	Diabetes	Protection against high glucose-induced toxicity in hepatocytes	Nrf2, ARE ↑	Independent	HO-1 ↑ PKC, COX-2 ↓	Wang et al. [67]
		Respiratory disease	Protection against paraquat-induced acute lung injury in rats	Nrf2 ↑	PPARγ ↑	NF-κB ↓	Liu et al. [83]
	Troglitazone and cyanidin	Liver disease	Protection against H2O2-induced cytotoxicity in human hepatoblastoma HepG2 and rat normal hepatocytes	Nrf2 and ARE ↑	PPARγ ↑	MAPK ↑	Shih et al. [84]
	Arylidene-thiazolidinedione	Diabetes	Blockage of LPS-induced inflammation and oxidative stress in RAW mouse macrophages	Independent	PPARγ ↑	CD36, HO-1 ↑ iNOS, COX-2 ↓	Faine et al. [82]
Natural PPARγ activators	Carotenoids	Cancer	Inhibition of proliferation of K562 myelogenous leukemia cells	Nrf2 ↑	PPARγ ↑	p21 ↑, cyclin D1 ↓	Zhang et al. [85]
	Monascin	Diabetes	Protection against methylglyoxal-induced toxicity in HepG2 cells and rats	Nrf2 ↑	PPARγ ↑	PKC ↓	Hsu et al. [88]
							Hsu et al. [87]
	Ankaflavin	Diabetes	Protection against methylglyoxal-induced toxicity in HepG2 cells and rats	Nrf2 ↑	PPARγ ↑	Glyoxalase, HO-1 ↑	Lee et al. [90]
							Hsu and Pan [89]
Dual Nrf2 and PPARγ activators	Genistein	Atherosclerosis	Attenuation of H2O2-induced endothelial cell injury in transformed human umbilical vein endothelial cells	Nrf2 ↑	PPARγ ↑	HO-1 ↑	Zhang et al. [92]
	Vitamin E	Atherosclerosis	Protection against hypercholesterolemia-induced atherosclerosis in rabbit aortae	Nrf2 ↑	PPARγ ↑	GST, ABCA1 ↑	Bozaykut et al. [94]
	Olmesartan	Kidney disease	Protection against oxidative and inhibition of inflammation in daunorubicin-induced nephrotoxicity in rats	Nrf2 ↑	PPARγ ↑	MAPKAPK, caspase-12, p47, p67 ↓ Bcl-xL, GST ↑	Gounder et al. [96]
	α-Methylene-γ-lactones	Kidney disease	Activation of Nrf2 and PPARγ pathways in mouse peritoneal macrophages from normal and PPARγ-knockout mice against	Nrf2 ↑	PPARγ ↑	Dectin-1, CD36, NQO-1, HO-1 ↑	Le Lamer et al. [97]
	18β-Glycyrrhetinic acid	Kidney disease	Protection against methotrexate-induced kidney injury in rats	Nrf2 ↑	Independent	GSH, SOD, GPX, GST, HO-1 ↑, TNF-α, MDA, NO ↓	Abd El-Twab et al. [100]
		Liver disease	Protection against cyclophosphamide-induced hepatotoxicity in rats	Nrf2 ↑	PPARγ ↑	MDA, NF-κB, iNOS ↓, GSH, GPX, SOD, CAT ↑	Mahmoud and Al Dera [102]
	(−)-Epigallocatechin-3-gallate	Kidney disease	Protection against crescentic glomerulonephritis induced by administration of rabbit anti-mouse glomerular basement membrane antibody in mice	Nrf2 ↑	PPARγ ↑	SIRT1, γ-GCL, GPX1, NQO-1↑, AKT, JNK, ERK, p38 ↓	Ye et al. [103]
	Mangiferin	Gastrointestinal disease	Protection against gastric ulcer in ischemia/reperfused rats	Nrf2 ↑	PPARγ ↑	HO-1 ↑, NF-κB ↓	Mahmoud-Awny et al. [104]
	3-O-Lauryl glyceryl ascorbate	Skin disease	Suppression of oxidative damage induced by H2O2 and UVB in normal human epidermal keratinocytes	Nrf2 ↑	PPARγ ↑	γ-GCS, HO-1, NQO-1, GSH ↑	Katsuyama et al. [105]
	Umbelliferone	Liver disease	Protection against cyclophosphamide-induced hepatotoxicity in rats	Nrf2 ↑	PPARγ ↑	HO-1 ↑	Mahmoud et al. [106]
	Graptopetalum paraguayense and resveratrol	Diabetes	Protection against carboxymethyllysine-induced pancreas dysfunction and hyperglycemia in mice	Nrf2 ↑	PPARγ ↑	PDX-1, GSH, GCL ↑	Lee et al. [109]
	Cyanidin-3-glucose and resveratrol	Gastrointestinal disease	Protection against cytokine-stimulated oxidative stress in human colon cancer cells	Nrf2 ↑	PPARγ ↑	HO-1, γ-GCS, GSH ↑	Serra et al. [110]