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Sulforaphane Protects against Cardiovascular Disease via Nrf2 Activation.

Bai Y, Wang X, Zhao S, Ma C, Cui J, Zheng Y - Oxid Med Cell Longev (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: The Cardiac Surgery Department, The First Hospital of Jilin University, Changchun 130021, China ; The Jilin Province People's Hospital, Changchun 130021, China.

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.

No MeSH data available.


Related in: MedlinePlus

Glucoraphanin is the major glucosinolate in broccoli. Under neutral conditions, Grn is hydrolyzed by myrosinase to yield glucose, sulfate, and sulforaphane (SFN).
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fig1: Glucoraphanin is the major glucosinolate in broccoli. Under neutral conditions, Grn is hydrolyzed by myrosinase to yield glucose, sulfate, and sulforaphane (SFN).

Mentions: SFN [1-isothiocyanate-(4R)-(methylsulfinyl) butane] [12] is the hydrolysis product of glucoraphanin (Grn), the main glucosinolate (GLS) in broccoli [13, 14]. GLS (β-thioglucose N-hydroxysulfates) are relatively stable biosynthetic precursors along with SFN [15]. GLS exist in association with but structurally segregated from the myrosinase enzyme (β-thioglucoside glucohydrolase); this is released upon plant cell injury (e.g., by chewing) and cleaves GLS to produce SFN, sulfate, and glucose [16, 17] (Figure 1). Ahn et al. [18] showed that 24 synthetic sulfoxythiocarbamate analogs that retained the important structural features of SFN analogs, demonstrating efficacy for phase II enzyme induction in a range of cell lines. In order to eliminate chemicals, drug-metabolizing enzymes initially metabolize the compounds (phase I reaction) and then detoxify electrophiles and oxidants (phase II reaction). A group of heterogeneous enzymes carry out the phase II reactions including glutathione-S-transferase (GST), epoxide hydrolase, UDP-glucuronosyltransferase and sulfotransferase, and NAD(P)H: quinone oxidoreductase 1 (NQO1). The antioxidant systems of phase II reactions can detoxify ROS directly [19, 20]. GST catalyzes the conjugation of glutathione (GSH) with electrophilic compounds making them more water soluble and facilitating their removal from the body. It is well known that ITC-GSH conjugates are exported out to extracellular. This continous conjugation and efflux of the conjugate can cause intracellular GSH level to drop. ITC can also induce GST scavenge ROS [21]. Shibata et al. examined the effect of sulfhydryl molecules on cellular responses induced by 6-methylsulfinylhexyl isothiocyanate (6-HITC), an analog of SFN isolated from broccoli. Significant induction of heme oxygenase-1 (HO-1) was observed when cells were treated with 6-HITC, even in the presence of GSH [22]. It was also demonstrated that the main mechanism of action of SFN involves regulation of the nuclear factor erythroid-derived 2- (NF-E2) related factor 2- (Nrf2-) antioxidant response element (ARE) pathway; this in turn upregulates the expression of a range of antioxidant enzymes including HO-1, NQO1, GST, γ-glutamyl cysteine ligase (GCL), and glutathione reductase (GR) [23]. Therefore, SFN has been considered to act as an indirect antioxidant and a highly potent inducer of phase II cytoprotective enzymes. The resultant detoxification of electrophiles and oxidants can protect against carcinogens, oxidative stress, and inflammation.


Sulforaphane Protects against Cardiovascular Disease via Nrf2 Activation.

Bai Y, Wang X, Zhao S, Ma C, Cui J, Zheng Y - Oxid Med Cell Longev (2015)

Glucoraphanin is the major glucosinolate in broccoli. Under neutral conditions, Grn is hydrolyzed by myrosinase to yield glucose, sulfate, and sulforaphane (SFN).
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4637098&req=5

fig1: Glucoraphanin is the major glucosinolate in broccoli. Under neutral conditions, Grn is hydrolyzed by myrosinase to yield glucose, sulfate, and sulforaphane (SFN).
Mentions: SFN [1-isothiocyanate-(4R)-(methylsulfinyl) butane] [12] is the hydrolysis product of glucoraphanin (Grn), the main glucosinolate (GLS) in broccoli [13, 14]. GLS (β-thioglucose N-hydroxysulfates) are relatively stable biosynthetic precursors along with SFN [15]. GLS exist in association with but structurally segregated from the myrosinase enzyme (β-thioglucoside glucohydrolase); this is released upon plant cell injury (e.g., by chewing) and cleaves GLS to produce SFN, sulfate, and glucose [16, 17] (Figure 1). Ahn et al. [18] showed that 24 synthetic sulfoxythiocarbamate analogs that retained the important structural features of SFN analogs, demonstrating efficacy for phase II enzyme induction in a range of cell lines. In order to eliminate chemicals, drug-metabolizing enzymes initially metabolize the compounds (phase I reaction) and then detoxify electrophiles and oxidants (phase II reaction). A group of heterogeneous enzymes carry out the phase II reactions including glutathione-S-transferase (GST), epoxide hydrolase, UDP-glucuronosyltransferase and sulfotransferase, and NAD(P)H: quinone oxidoreductase 1 (NQO1). The antioxidant systems of phase II reactions can detoxify ROS directly [19, 20]. GST catalyzes the conjugation of glutathione (GSH) with electrophilic compounds making them more water soluble and facilitating their removal from the body. It is well known that ITC-GSH conjugates are exported out to extracellular. This continous conjugation and efflux of the conjugate can cause intracellular GSH level to drop. ITC can also induce GST scavenge ROS [21]. Shibata et al. examined the effect of sulfhydryl molecules on cellular responses induced by 6-methylsulfinylhexyl isothiocyanate (6-HITC), an analog of SFN isolated from broccoli. Significant induction of heme oxygenase-1 (HO-1) was observed when cells were treated with 6-HITC, even in the presence of GSH [22]. It was also demonstrated that the main mechanism of action of SFN involves regulation of the nuclear factor erythroid-derived 2- (NF-E2) related factor 2- (Nrf2-) antioxidant response element (ARE) pathway; this in turn upregulates the expression of a range of antioxidant enzymes including HO-1, NQO1, GST, γ-glutamyl cysteine ligase (GCL), and glutathione reductase (GR) [23]. Therefore, SFN has been considered to act as an indirect antioxidant and a highly potent inducer of phase II cytoprotective enzymes. The resultant detoxification of electrophiles and oxidants can protect against carcinogens, oxidative stress, and inflammation.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: The Cardiac Surgery Department, The First Hospital of Jilin University, Changchun 130021, China ; The Jilin Province People's Hospital, Changchun 130021, China.

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.

No MeSH data available.


Related in: MedlinePlus