Oxidative Medicine and Cellular Longevity / 2015 / Article / Tab 1

Review Article

Sulforaphane Protects against Cardiovascular Disease via Nrf2 Activation

Table 1

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

CVDModelSFN dose Biomarker modulation Reference

HypertensionFemale 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 sproutsFemale 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 M for 6 daysSFN inhibited early-stage adipocyte differentiation [31]
Isolated aortic SMCs from SHRsp rats or controls0.05–1 M 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− diets0.9 mg SFN in 200 mg air-dried broccoli sproutsSHRsp fed a Grn+ diet had a major improvement in the cardiovascular and kidney tissues and reduced hypertension [33]

AtherosclerosisMouse VSMCs incubated with TNF- (10 ng/mL) for 4 and 8 h Pretreatment with 5, 15, and 25 M for 2 hSFN dose-dependently inhibited TNF--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 h1 M, 24 hSFN inhibited TNF--induced VCAM-1 expression and prevented VSMC proliferation
Sprague-Dawley rats subjected to carotid artery balloon injury; VSMCs were exposed to TNF-5 MSFN attenuated neointima formation after balloon injury and intima area ratio and stenosis[36]
HAEC treated with TNF- (100 U/mL) for 4 h 1–4 M pretreatment of HAECs for 1 hSFN suppressed TNF--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- for 24 h or with 10 ng/mL TNF- for 0–48 h 10 M pretreatment for 1 hSFN inhibited TNF-α-mediated induction of endothelial lipase in HUVEC, indicating that SFN may have a beneficial effect on HDL cholesterol levels[38]

I/RIschemia in isolated perfused Langendorff Sprague-Dawley rat hearts 0.5 mg/kg daily i.p. pretreatment for 3 days before ischemiaSFN 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]

DiabetesMale Wistar rats injected with STZ (80 mg/kg) Oral pretreatment with 0.1, 0.25, or 0.5 mg/kgAll SFN doses reduced levels of triacylglycerol, urea, and creatinine, cholesterol, alanine, and aspartate aminotransferase levels[40]
RIN cells treated with IL-1 (2 ng/mL) and IFN- (100 U/mL) to produce H2O22.5–10 M 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 daysPretreatment 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 daysSubcutaneous injection of 0.5 mg/kg, five days per week, for 3 monthsSFN 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 STZAdministration of 0.5 and 1 mg/kg six weeks after diabetesSFN reduced NF-B expression and IB kinase phosphorylation, along with abrogation of inducible nitric oxide synthase, cyclooxygenase-2 expression, and TNF- and IL-6 levels[44]

Diabetic angiopathyHMEC-1 cultured in high glucose medium (30 mM) 4 M for 6–48 hMultiple pathways of biochemical dysfunction in HMEC-1 cells induced by hyperglycemia were reversed by SFN [45]

DCMMice were injected with 50 mg/kg STZ i.p. daily for 5 days0.5 mg/kg subcutaneous injection daily for 3 months after STZ-induced diabetesDiabetes 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 days0.5 mg/kg subcutaneous injection daily for 3 months after STZ-induced diabetesSFN 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 T2DM0.5 mg/kg subcutaneous injection daily five days a week for 4 monthsSFN 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 -cell line RINm5F. SHRsp: spontaneously hypertensive stroke-prone rats. SMC: smooth muscle cell. STZ: streptozocin. TNF-: tumor necrosis factor-. VSMC: vascular smooth muscle cell. T2DM: type 2 diabetes mellitus. VCAM: vascular cell adhesion molecule. HAEC: human aortic endothelial cells. DCM: diabetic cardiomyopathy.