Sulforaphane Protects against Cardiovascular Disease via Nrf2 Activation

Abstract

Cardiovascular disease (CVD) causes an unparalleled proportion of the global burden of disease and will remain the main cause of mortality for the near future. Oxidative stress plays a major role in the pathophysiology of cardiac disorders. Several studies have highlighted the cardinal role played by the overproduction of reactive oxygen or nitrogen species in the pathogenesis of ischemic myocardial damage and consequent cardiac dysfunction. Isothiocyanates (ITC) are sulfur-containing compounds that are broadly distributed among cruciferous vegetables. Sulforaphane (SFN) is an ITC shown to possess anticancer activities by both in vivo and epidemiological studies. Recent data have indicated that the beneficial effects of SFN in CVD are due to its antioxidant and anti-inflammatory properties. SFN activates NF-E2-related factor 2 (Nrf2), a basic leucine zipper transcription factor that serves as a defense mechanism against oxidative stress and electrophilic toxicants by inducing more than a hundred cytoprotective proteins, including antioxidants and phase II detoxifying enzymes. This review will summarize the evidence from clinical studies and animal experiments relating to the potential mechanisms by which SFN modulates Nrf2 activation and protects against CVD.

Cruciferous and Total Vegetable Intakes Are Inversely Associated With Subclinical Atherosclerosis in Older Adult Women

“…Isothiocyanates are organosulfur compounds that have been extensively researched for their anticancer properties 14, 54, 55, 56. However, accumulating evidence suggests sulforaphane, a compound within the isothiocyanate group, may have beneficial effects on vascular damage via the blockade of oxidative stress and/or inhibition of advanced glycation end products 57, 58. There was strong evidence that intake of cruciferous vegetables was inversely associated with mean CCA‐IMT in this cohort, even after further adjustment for noncruciferous vegetables and other food and nutrients thought to be associated with cardiovascular health.…”

Sulforaphane induces neurovascular protection against a systemic inflammatory challenge via both Nrf2-dependent and independent pathways

“…Through interactions with the cysteine residues of Keap1, SFN may induce the release of Nrf2 allowing for its nuclear localization where it binds to the antioxidant response element in a variety of different genes [11–13]. As such, in order to establish whether the observed influence over cerebral leukocyte recruitment was dependent on Nrf2 activation, we conducted experiments using Nrf2-KO mice.…”

“…Sulforaphane (SFN) is a sulfur-based isothiocyanate found naturally in cruciferous vegetables such as broccoli, brussel sprouts, cabbage and cauliflower [11]. SFN has been shown to induce anti-oxidative mechanisms, and protect against cell inflammatory stress via activation of the NF-erythroid 2-related factor 2 (Nrf2) transcription factor [12].…”

Consumption of Fruit or Fiber-Fruit Decreases the Risk of Cardiovascular Disease in a Mediterranean Young Cohort

“…Bendinelli [9] analyzed the association between fruit and vegetable consumption and CHD in a Mediterranean cohort of women, and found an inverse association with green leafy vegetables, which was consistent with other studies [32,44,45], but did not report the results for cruciferous vegetables alone. Cruciferous vegetables contain sulforaphane [7], the most widely studied and best characterized isothiocyanate [46] which is a long-acting antioxidant, but also has anti-inflammatory activity by inhibition of cytokine production. The relationship between sulforaphane and the atherosclerosis process seems to be clear [46].…”