Table 1.

Summary of in  vivo and in  vitro studies of sulforaphane- (SFN-) mediated protection against cardiovascular disease (CVD).

CVD	Model	SFN dose	Biomarker modulation	Reference
Hypertension	Female SHRsp rats on the Grn+ and Grn diets (1st generation), and the offspring (2nd generation)	0.9 mg SFN in 200 mg air-dried broccoli sprouts	Female SHRsp on a Grn+ diet had decreased hypertension. Their offspring had lower blood pressure in adulthood, regardless of diet, and the best health outcomes	[29]
	Female SHRsp rats, oral gavage of SFN in corn oil	1.77 mg/kg	Mean arterial pressure was 20% higher in vehicle-treated SHRsp and SFN administration to SHRsp improved blood pressure	[30]
	3T3-L1 preadipocytes, cultured with SFN	20 μM for 6 days	SFN inhibited early-stage adipocyte differentiation	[31]
	Isolated aortic SMCs from SHRsp rats or controls	0.05–1 μM for 24 h	SFN induced concentration-dependent increases in cellular GSH levels and HO-1 protein content and decreased oxidative stress	[32]
	Male SHRsp and Sprague-Dawley rats on control, Grn+, and Grn− diets	0.9 mg SFN in 200 mg air-dried broccoli sprouts	SHRsp fed a Grn+ diet had a major improvement in the cardiovascular and kidney tissues and reduced hypertension	[33]
Atherosclerosis	Mouse VSMCs incubated with TNF-α (10 ng/mL) for 4 and 8 h	Pretreatment with 5, 15, and 25 μM for 2 h	SFN dose-dependently inhibited TNF-α-induced protein expression of VCAM-1 and intracellular ROS, which may have beneficial effects on inflammation within the atherosclerotic lesion	[34]
	Male C57BL/6 or Nrf2−/− mice aortic EC were stained at susceptible and protected sites	Pretreatment with 5 mg/kg for 4 h or 24 h	SFN activation of Nrf2 reduced endothelial activation at atherosusceptible sites	[35]
	Confluent HUVEC exposed to unidirectional laminar shear for 24 h	1 μM, 24 h	SFN inhibited TNF-α-induced VCAM-1 expression and prevented VSMC proliferation
	Sprague-Dawley rats subjected to carotid artery balloon injury; VSMCs were exposed to TNF-α	5 μM	SFN attenuated neointima formation after balloon injury and intima area ratio and stenosis	[36]
	HAEC treated with TNF-α (100 U/mL) for 4 h	1–4 μM pretreatment of HAECs for 1 h	SFN suppressed TNF-α-induced VCAM-1 protein expression, suggesting that SFN may be a useful treatment for inflammatory diseases	[37]
	HUVEC treated with 0–40 ng/mL TNF-α for 24 h or with 10 ng/mL TNF-α for 0–48 h	10 μM pretreatment for 1 h	SFN inhibited TNF-α-mediated induction of endothelial lipase in HUVEC, indicating that SFN may have a beneficial effect on HDL cholesterol levels	[38]
I/R	Ischemia in isolated perfused Langendorff Sprague-Dawley rat hearts	0.5 mg/kg daily i.p. pretreatment for 3 days before ischemia	SFN significantly improved coronary flow and reduced I/R-induced increases in LDH level and infarct size, showing that SFN protected against I/R injury	[39]
Diabetes	Male Wistar rats injected with STZ (80 mg/kg)	Oral pretreatment with 0.1, 0.25, or 0.5 mg/kg	All SFN doses reduced levels of triacylglycerol, urea, and creatinine, cholesterol, alanine, and aspartate aminotransferase levels	[40]
	RIN cells treated with IL-1β (2 ng/mL) and IFN-γ (100 U/mL) to produce H2O2	2.5–10 μM pretreatment for 3 h	Pretreatment with SFN resulted in concentration-dependent protection against the toxic effect of cytokines, with increased survival of RIN cells	[41]
Diabetic nephropathy	Eight-week-old mice received STZ (50 mg/kg) i.p. for 5 consecutive days	Pretreatment with 12.5 mg/kg i.p. three times a week for 16 weeks	SFN significantly attenuated common metabolic disorder symptoms, improved renal performance, and minimized pathological alterations in the glomerulus of STZ-Nrf2+/+ mice	[42]
	Mice were injected i.p. with 50 mg/kg STZ daily for 5 days	Subcutaneous injection of 0.5 mg/kg, five days per week, for 3 months	SFN prevented diabetes-induced renal inflammation and oxidative stress and also prevented renal structural changes and fibrosis	[43]
Diabetic neuropathy	Diabetic neuropathy was induced in rats using STZ	Administration of 0.5 and 1 mg/kg six weeks after diabetes	SFN reduced NF-κB expression and IκB kinase phosphorylation, along with abrogation of inducible nitric oxide synthase, cyclooxygenase-2 expression, and TNF-α and IL-6 levels	[44]
Diabetic angiopathy	HMEC-1 cultured in high glucose medium (30 mM)	4 μM for 6–48 h	Multiple pathways of biochemical dysfunction in HMEC-1 cells induced by hyperglycemia were reversed by SFN	[45]
DCM	Mice were injected with 50 mg/kg STZ i.p. daily for 5 days	0.5 mg/kg subcutaneous injection daily for 3 months after STZ-induced diabetes	Diabetes induced significant increases in oxidative stress and inflammation in the aorta at both 3 and 6 months, and fibrotic response at 6 months. SFN completely prevented these pathogenic changes	[46]
	Mice were injected with 50 mg/kg STZ i.p. daily for 5 days	0.5 mg/kg subcutaneous injection daily for 3 months after STZ-induced diabetes	SFN significantly reduced hypertension and cardiac dysfunction at both 3 and 6 months and also prevented cardiac hypertrophy and fibrosis. SFN also almost completely prevented cardiac oxidative damage and inflammation	[47]
	Mice were fed a high-fat diet for 3 months, then treated with 100 mg/kg STZ i.p. to induce T2DM	0.5 mg/kg subcutaneous injection daily five days a week for 4 months	SFN significantly inhibited cardiac lipid accumulation improved cardiac inflammation oxidative stress and fibrosis induced by T2DM	[48]

Notes. EC: endothelial cells. Grn: glucoraphanin. GSH: glutathione. HMEC: human microvascular endothelial cells. HUVEC: human umbilical vein endothelial cells. IL: interleukin. i.p.: intraperitoneal injection. I/R: ischemia-reperfusion. i.v.: intravenous injection. RIN cells: rat pancreatic β-cell line RINm5F. SHRsp: spontaneously hypertensive stroke-prone rats. SMC: smooth muscle cell. STZ: streptozocin. TNF-α: tumor necrosis factor-α. VSMC: vascular smooth muscle cell. T2DM: type 2 diabetes mellitus. VCAM: vascular cell adhesion molecule. HAEC: human aortic endothelial cells. DCM: diabetic cardiomyopathy.