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Review
. 2015:2015:407580.
doi: 10.1155/2015/407580. Epub 2015 Oct 25.

Sulforaphane Protects against Cardiovascular Disease via Nrf2 Activation

Yang Bai  1 , Xiaolu Wang  2 , Song Zhao  3 , Chunye Ma  4 , Jiuwei Cui  5 , Yang Zheng  4
Affiliations
Review

Sulforaphane Protects against Cardiovascular Disease via Nrf2 Activation

Yang Bai et al. Oxid Med Cell Longev. 2015.

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.

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Figures

Figure 1
Figure 1
Glucoraphanin is the major glucosinolate in broccoli. Under neutral conditions, Grn is hydrolyzed by myrosinase to yield glucose, sulfate, and sulforaphane (SFN).
Figure 2
Figure 2
The Kelch-like chicken erythroid-derived cap “n” collar homology factor-associated protein 1- (Keap1-) NF-E2-related factor 2- (Nrf2) antioxidant response element (ARE) signaling pathway. (a) Keap1-Nrf2 interactions are mediated via the high affinity ETGE motif “hinge” site and the lower affinity DLG motif “latch” site within the Nrf2 Neh2 domain. Under normal cellular conditions, Nrf2 first interacts with the Keap1 dimer through the ETGE hinge and subsequently with the cullin-3- (Cul3-) ring box 1 (Rbx1) complex via the DLG latch motif, which leads to the ubiquitination and degradation of Nrf2. During cellular stress, the hinge and the latch of Nrf2 may be disrupted by changes to Keap1 homodimer formation and translocation to nucleus. (b) The structure of Nrf2, including Neh1–6 domains. (c) Keap1 is composed of distinct structural domains, including the N terminal region (NTR), Broad complex, Tramtrack, and bric-a-brac (BTB) domain, intervening region (IVR), double glycine repeat (DGR; Nrf2 binding region), and C terminal region (CTR).
Figure 3
Figure 3
Sulforaphane (SFN) activation of Nrf2 signaling. SFN activates three mitogen-activated protein kinases (MAPKs): extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK), and p38; these may stimulate Nrf2 activation. SFN may also activate protein kinase C (PKC), which directly phosphorylates Nrf2. Alternatively SFN activates Nrf2 through phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT). Ultimately, Nrf2 phosphorylation triggers nuclear translocation and induction of antioxidant-response element- (ARE-) mediated gene transcription, reducing oxidative stress.
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