The Role of Nrf2 in Cardiovascular Function and Disease

Table 2

The effect of Nrf2 activation on CVD.

Activator	Animal model/cell line	Effects	Reference
Bardoxolone methyl derivative dh404	Male Akita mice at 26 weeks of age & human aortic endothelial cells (HAECs)	Attenuation of endothelial dysfunction; Downregulation of inflammatory and prooxidant genes; Reduction in systemic and vascular oxidative stress	[188]
	Streptozotocin- (STZ-) induced diabetic ApoE^−/− mice	Prevention of atherosclerosis	[189]
Sulforaphane	Vascular smooth muscle cells (VSMCs)	Suppression of VSMC proliferation	[190]
	HUVECs	Protection against oxidized low-density lipoprotein- (oxLDL-) induced endothelial damage	[191]
	High-fat diet- (HFD-) induced type 2 diabetic mice	Prevention of aortic damage	[192]
	Low-dose STZ diabetic mice	Prevention of diabetic cardiomyopathy	[154]
	Multiple low dose STZ-induced type 1 diabetic mice	Prevents aortic oxidative damage, fibrosis, and inflammation	[193]
Miltirone	EA.hy926 endothelial cells	Protects against oxLDL-derived oxidative stress	[194]
Epigallocatechin-3-gallate	HUVECs	Protects against PM2.5-induced oxidative stress	[195]
Barleria lupulina alkyl catechols (4-ethylcatechol, 4-vinylcatechol, and 4-methylcatechol)	Human dermal microvascular endothelial cells	Improves organization of the cytoskeleton; Organizes tight cell junctions; Reduces inflammation and vascular leakage	[196]
Small molecule glycomimetics	HUVECs	Attenuates palmitate-induced oxidative stress and endothelial dysfunction.; Increases NO production.	[104]
Rutin	HUVECs	Prevents hydrogen peroxide- (H2O2-) induced oxidative stress	[197]
1,25-Dihydroxycholecalciferol	HUVECs	Prevents leptin-induced oxidative stress and inflammation	[198]
Willow bark extract	HUVECs and Caenorhabditis elegans	Prevents ROS-induced cytotoxicity of HUVECs and death of C. elegans	[199]
Aged garlic extract	HUVECs	Enhances HO-1 and glutamate-cysteine ligase modifier subunit expression (GCLM)	[200]
Celastrol	HUVECs	Attenuates angiotensin II mediated endothelial damage	[201]
Paeotang	HUVECs	Prevents TNF-α-induced vascular inflammation	[202]
Cyanidin-3-O-glucoside	HUVECs	Ameliorates palmitate-induced insulin resistance and endothelial derived vasoactive factors	[203]
		Attenuates palmitate-induced inflammation	[204]
	EA.hy926 endothelial cells	Attenuates angiotensin II-induced oxidative stress and inflammation	[205]
Piceatannol	HUVECs	Attenuates homocysteine-induced endoplasmic reticulum stress and cell damage	[206]
Equol	ApoE^−/− mice	Attenuates atherosclerosis and inhibits endoplasmic reticulum stress	[207]
	HUVECs	Abrogates apoptosis induced by t-BHP
Sheep/goat whey protein	EA.hy926 endothelial cells	Increases antioxidant defences	[208]
Quercetin	HAECs	Inhibits LPS-induced adhesion molecule expression and ROS production	[209]
Panax notoginseng saponins and Ginsenoside Rb1	HUVECs	Suppresses monocyte adhesion and inhibits ROS	[210]
Bortezomib	Human microvascular endothelial cells (HMECs)	Induces expression of HO-1	[211]
Sofalcone	HUVECs	Suppresses endothelial dysfunction	[212]
Salidroside	HUVECs	Suppresses ROS-induced damage	[213]
Caffeic acid	HUVECs	Attenuates high glucose-induced endothelial dysfunction	[214]
Myricitrin	H9c2 cardiomyocytes	Attenuates high glucose-induced apoptosis	[215]
	STZ-induced diabetic mice & AGE-induced H9c2 cardiomyocytes	Alleviates oxidative stress-induced inflammation, apoptosis, and cardiomyopathy	[216]
Andrographolide	EA.hy926 endothelial cells	Inhibits hypoxia-induced HIF-1α-driven endothelin 1 secretion	[217]
Tanshinone IIA	HUVECs	Inhibits cyclic strain-induced expression of interleukin 8	[218]
Lycopene	HUVECs	Inhibits cyclic strain-induced endothelin-1 expression and oxidative stress	[219]
Withaferin A	EA.hy926 endothelial cells & HUVECs	Induces HO-1 expression	[220]
Copper diethyldithiocarbamate	Bovine aortic endothelial cells	Inhibits proteasome and Nrf2 binding to Kelch-like ECH-associated protein 1	[221]
Clopidogrel	HAECs	Hinders TNF-α-induced VCAM-1 expression	[222]
Hericium erinaceus	EA.hy926 endothelial cells	Inhibits TNF-α-induced angiogenesis and ROS generation	[223]
Andrographolide	Primary cerebral endothelial cells	Prevents middle cerebral artery occlusion- (MCAO-) induced ischemic stroke	[224]
Butin	C57/BL6J diabetic mice	Prevents ischemia/reperfusion-induced myocardial injury	[225]
Aspalathin	H9c2 cardiomyocytes and diabetic db/db mice	Protects against hyperglycemia-induced oxidative damage and apoptosis	[146]
Broccoli sprout	Diabetic db/db mice	Prevents diabetic cardiomyopathy	[226]
Oleuropein	Spontaneously hypertensive rats	Attenuates oxidative stress and improves mitochondrial function in the hypothalamic paraventricular nucleus	[227]
Aralia taibaiensis	H9c2 cardiomyocytes	Protects against high glucose-induced oxidative stress and apoptosis	[228]
Compound C66	STZ-induced diabetic mice aorta	Prevents oxidative and nitrative stress, inflammation, apoptosis, cell proliferation, and fibrosis	[229]
Dimethyl fumarate	VSMCs	Attenuates vascular calcification	[127]
Gemigliptin	VSMCs	Prevents proliferation and migration of VSMCs	[230]
L6H9 (chalcone)	H9c2 cardiomyocytes	Prevents hyperglycemia-induced oxidative stress and inflammation	[231]
Magnesium lithospermate B	VSMCs	Prevents proliferation and migration of VSMCs	[232]
4-O-methylhonokiol	HFD-induced obese mice	Prevents cardiac pathogenesis	[233]
Resveratrol	Coronary arterial endothelial cells	Protects against high glucose-induced endothelial protection	[234]
	VSMCs	Ameliorates vascular calcification	[126]
	db/db mice	Ameliorates vascular inflammation	[235]
	STZ-induced type 2 diabetic rats	Ameliorates vascular inflammation	[236]
MG132	OVE26 type 1 diabetic mice	Prevents aortic oxidative damage and inflammatory response	[237]
		Prevents cardiomyopathy	[238]