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Things To Know & Note
Sulforaphane content in Broccoli and cooked vegetables is sensitive to heat
How to Take Sulforaphane
Recommended dosage, active amounts, other details
Although an ideal dosage is not known, supplementation of 0.1-0.5mg/kg sulforaphane to rats has been noted to be bioactive. This is an estimated human dose of:
7-34 mg for a 150lb person
9-45 mg for a 200lb person
11-57 mg for a 250lb person
These low quantities are likely attainable via raw broccoli or cruciferious vegetable products, while higher doses may be further beneficial. The optimal supplemental dose of sulforaphane is unknown.
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Scientific Research on Sulforaphane
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Sulforaphane exists in food in its foodbound form known as Glucoraphanin, a glycoside (bound to a sugar) or sulforaphane that is commonly seen as a prodrug or storage form of Sulforaphane. Glucoraphanin is one of a few molecules known as isothiocyanates, existing mostly in cruciferous vegetables alongside Sinigrin (metabolized into Allyl Isothiocyanate), Glucotropaeolin (metabolized into Benzyl Isothiocyanate), Gluconasturtiin (metabolized into Phenethylisothiocyanate) and Glucobrassicin (metabolized into Diindolylmethane).
Sources of sulforaphane and/or glucoraphanin include:
Sulforaphane is an active isothiocyanate, found in food via its storage form of Glucoraphanin
As sulforaphane tends to exist in foods as Glucoraphanin (4-methylsulphinylbutyl glucosinolate) which has its glucose moiety removed by Myrosinase (Thioglucoside glucohydrolase), an enzyme occurring in the broccoli family of plants that also mediates the conversion of other glucosinolates such as glucobrassicin to Indole-3-Carbinol (which proceeds to turn into Diindolylmethane).
When Myrosinase acts on Glucoraphanin, it produces an unstable intermediate; if epithiospecifier protein (ESP) is active it can convert this intermediate to a sulforaphane nitrile (5-methylsulfinylpentane nitrile) that has no anti-cancer activity. If ESP is low-active, then the only other alternate pathway for this unstable intermediate to progress to is towards production of Sulforaphane
Heating for a short period of time denatures ESP and can enhance sulforaphane production in broccoli due to reducing the alternate metabolic fate of Glucoraphanin while excessive heat application appears to denature Myrosinase itself and abolish all sulforaphane content; as inactivation of Myrosinase during food preparation by excessive heat would mean a lack of sulforaphane absorption (except for perhaps a small content from the colon) preparing broccoli via heat treatment for the purpose of Sulforaphane preservation appears to be a balancing act. This balancing act exists since ESP is more sensitive to heat than Myrosinase.
The application of heat can enhance the absorption of Sulforaphane, but excessive application of heat can prevent most sulforaphane from being absorbed; a balancing act exists
With microwaving, 3 minutes in an 800W microwave (with 150mL water) depletes sulforaphane with peak sulforaphane content at 1 minute. A 900W microwave between 0.5-0.75 minutes appears to maximize Sulforaphane while minimizing nitrile formation, with 1 minute highly depleting nitrile formation but also sulforaphane starting to be affected.
Boiling broccoli in 1.5L water appears to inactive myrosinase after 1 minute, with the authors of this study concluding that without dipping broccoli into ice water after 30s of heating (to reduce heat application after being removed from liquid) that boiling is unlikely to be an effective method of preparation.
With steaming sulforaphane peaks at 1-3 minutes while being depleted at 5, but nitrile formation does not appear to exist to any sufficient level with steaming.
Steaming appears to be the best preservation method, with microwaving coming in second place; boiling broccoli appears to be a highly ineffective way to preserve sulforaphane content
When comparing the bioavailability of Sulforaphane from broccoli that has been purchased frozen against fresh, it appears that the fresh broccoli has 10-fold the Sulphoraphane content; this was credited to blanching processes pre-freezing destroying Myrosinase.
Hydrogen sulfide is one of three major gasotransmitters in the human body (transmitting molecules which happen to be gasses) alongside nitric oxide and carbon monoxide, and is the major underlying factor in garlic supplementation. Cruciferous vegetables are known to confer a smell of H2S when cooked, and since garlic has its cardioprotective effects mediated by sulfur and sulforaphane has similar protective effects it was investigated if there was a connection and it was found that, in prostatic cancer cells and mouse liver homogenate at 10µM, sulforaphane releases H2S. It is thought that any molecule with an isothiocyanate group (-N=C=S) can act as a sulfur donating molecule for the production of H2S.
Sulforaphane may release hydrogen sulfide in the body following oral ingestion, suggesting that many of its mechanisms would parallel that of garlic or SAMe (another H2S releasing supplement)
Sulforaphane appears to be well absorbed, as numerous studies in humans following the consumption of broccoli have noted increased urinary metabolites of Sulforaphane. In humans, bioavailability of sulforaphane appears to be 74% and primarily absorbed in the jejunum.
Appears to be well absorbed from the intestines after oral administration
In rats, an oral dose of 50umol (8.8mg; which is 58-73mg/kg) appears in the blood within 1 hour and peaks 4 hours after consumption, reaching 20uM; this does is accompanied by a 2.2 hour half-life and reaching close to baseline levels 12 hours after consumption.
Can be elevated to levels in serum that are used in many in vitro studies, suggesting applicability of those results to practical interventions
Sulforaphane appears to rapidly enter and accumulate into cells where it is rapidly conjugated, with Glutathione and Glutathione-S-Transferase contributing to its accumulation; Sulforaphane undergoes conjugation with glutathione readily to form dithiocarbamate conjugates such as Glutathione-Sulforaphane, a process accelerated by Glutathione-S-Transferase. Cellular concentrations may exceed serum concentrations, as one study incubating cultures with 0.028-0.28mM sulforaphane noted cellular concentrations of 4.4-13.3mM, said to be 47-145fold accumulation within 2 hours when counting both Sulforaphane and conjugated Sulforaphane. This study noted that over the next four hours an 8% decline occurred when the cells remained in medium, but had rapid export of Sulforaphane-Glutathione conjugates when the medium contained no Sulforaphane; this efflux was inhibited potently by MRP protein inhibitors (retaining 54-73% within the cell) and weakly by P-Glycoprotein inhibitors (38-39%; control retained 30%).
Rapid accumulation into cells, which may exceed serum values; efflux out of cells is mediated mostly by MRP proteins and to a lesser extent by P-Glycoproteins
When fed to rats, sulforaphane is detected in all measure tissues with a significant dose and time interaction in brain, prostate, liver, colon, lung, kidney, and the small intestine mucosa as well as plasma. The liver, brain, and kidney had peaks at 2 hours after gavage with slight attenuation at 4 hours while the lungs had rapid elimination at 4 hours; all other tissues noted elevations at 2 hours and higher concentrations at 4 hours, with all tissues being depleted of most sulforaphane by 24 hours post-ingestion. Tissue concentrations varied, however, with brain concentrations being quite low relative to other organs; over 100-fold variability was noted.
Sulforaphane is able to inhibit CYP1A1 (Aromatase) induction induced by benzo(a)pyrene compounds when incubated at 0.5-2.5uM in HepG2 cells, and is ineffective on CYP1A1/2 in Mcf7 cells when the sulforaphane and the benzopyrene compounds are introduced at the same time; sulforaphane appeared to attenuate the increase in CYP1A induced by previous concentrations of benzo(a)pyrenes. The maximum inhibition appeared to be 30% of CYP1A at 0.5uM and 14% of CYP1B at 1uM.
The attenuation of aromatase was deemed secondary to preventing nuclear translocation of the Aryl Hydrocarbon Receptor (AhR) at concentrations of 0.5-1uM. Sulforaphane is a weak agonist (less than 10% the potency of the control drug TCDD) yet a non-competitive antagonist of the Aryl Hydrocarbon receptor, and by preventing binding of more potent agonists to the AhR Sulforaphane reduces genetic transcription of AhR on its reporter (Arnt) and prevents agonist-induced upregulation of aromatase and any cancerous process mediated via AhR. This antagonism is not concentration dependent.
The role of Sulforaphane, as it pertains to Aromatase, is as a selective AhR modulator; preventing strong agonists from activating AhR (and upregulating Aromatase) while weakly activating the AhR itself when no strong agonist is present
The enzyme CYP2A6 (responsible for metabolism of nicotine) may be regulated via Sulforaphane's ability to induce Nrf2, which has been induced up to 1.4fold control levels with 10uM Sulforaphane, and CYP2A6 has been noted to be increased after 6 days of broccoli sprout consumption at 500g per day by a variable 1.4-5.5 fold increase. Variances may be due to differing activity of the Antioxidant Response Element (ARE1) that Nrf2 activation works via.
Sulforaphane can be detected in the neural tissue of rats after oral administration of 5umol (0.88mg; 19.36mg/kg) and 20umol (3.52mg; 77.44mg/kg) at both 2 hours and 6 hours post-ingestion, with correlations between brain concentrations and serum concentrations at all points between 0.72-0.77, with 0.59 at the lower dose at 6 hours when sulforaphane was being depleted from the body; no sulforaphane is detected in the brain at these doses (estimated human equivalence of 1.55mg/kg and 6.2mg/kg; respectively) 24 hours after ingestion.
Despite this high correlation with serum, neural concentrations of oral sulforaphane seem low; ranging between 0.002-0.003mg/g wet weight in response to the above doses.
Concentrations in the brain correlate well with concentrations in the blood, but there may be problems in crossing the blood brain barrier as the concentrations in the brain of rats in response to oral sulforaphane seem low
Incubation of nerve cells with sulforaphane appears to be able to offer oxidative protection from high glucose concentrations secondary to induction of Nrf2 and its downstream targets of HO-1 and NOQ1, and antiinflammatory attenuation via inhibition of Nf-kB; both of which were confirmed in vivo when rats were fed 0.5-1mg/kg sulforaphane and the sciatic nerve measured after 6 weeks.
HDAC inhibition is shown to reduce cocaine cravings in mice (with no influence on sucrose cravings) which has been noted with Trichostatin A (a common reference used in some sulforaphane studies). At this moment in time, however, no studies have been conducted assessing the ability of sulforaphane in inhibiting cocaine addiction.
There is mechanistic plausibility for sulforaphane in inhibiting cocaine addiction, but this has not yet been studied
Mechanisms of Sulforaphane related to anti-aging appear to be centralized around inducing the Proteasome activity and reducing cellular build-up of modified proteins; a reduction in the activity of this system induces cellular aging (senesence).
Sulforaphane has been found to activate the Heat Shock Response via selective overexpression of HSP27 at 7.5-10uM concentration via Hsf1 translocation, which increases HSP27. It should be noted that heat-shock was found to not induce Nrf2 activity.
Activation of the 26S proteasome subunit PSMB5 by Sulforaphane is a consequence of Nrf2 activation working via the Genomic Antioxidant Response Element (ARE); the commonest mechanism of Sulforaphane.
The proteasome activity induced by Sulforaphane appears to be chymotrypsin-like and caspase-like, but not trypsin-like, in multiple cell lines without any apparent apoptosis and to almost 2-fold that of control. As silencing of HSP27 inhibits the increase and potency is correlated to the degree of HSP27 induction in vitro, it appears that HSP27 modulates Sulforaphane-induced Proteasome activity.
Sulforaphane appears to be able to increase the rate of glycerol release into medium (lipolysis) in a concentration-dependent manner up to 10uM concentration, coupled with an increase in Hormone Sensitive Lipase (HSL) mRNA and CPT1A mRNA (approximately 1.6-fold control) and no effect on Perilipin or ATGL mRNA. Sulforaphane appears to be associated with phorphorylation of HSL at Ser563, which may be indirect through inactivating AMPK via phorphorylating Thr172 and indirectly activating HSL; Sulforaphane's effects on glycerol release are attenuated when coincubated with AMPK activators, and phosphorylated AMPK was reduced to around 20% of control at 5-10uM Sulforaphane.
AMPK is able to directly induce glycerol release and cause fat loss, but its inhibition may do the same secondary to increased CPT1A, as evidenced by Compound C (an AMPK inhibitor).
May have fat burning potential secondary to AMPK, but in the opposite direction that most plant extracts influence AMPK; by inhibition rather than activation. Practical significance is unknown
Other studies indicate Nrf2, a target of sulforaphane that is antioxidative in nature (by activating the genetic antioxidant response elemant ARE), appears to be involved in the regulation of adipocytes (or possibly just thought to be so due to contradicting evidence) with both knockout and overexpression reducing adipocyte growth (which may be accompanied by adverse health events such as insulin resistance). Downstream of Nrf2, a protein called NAD(P)H:quinone oxidoreductase (not to be confused with NADPH oxidase, a target of Spirulina) which, when activated up to 10.5-fold higher with Sulforaphane at 5-20uM can reduce triglyceride accumulation in fat cells independent of fat cell differentiation.
Possible anti-obesity effects, but this is also understudied with unknown practical significance
Possibly secondary to its ability to act as a Histone Deacetylase Inhibitor, Sulforaphane may repress Myostatin transcription and attenuate negative feedback on Myostain suppression in porcine satellite cells. It has been noted elsewhere in liver fibrosis pathology that neither NQO1 and HO-1 (downstream of Nrf2) but Nrf2 itself disrupted signalling from TGF-β to Smad proteins, via inhibiting nuclear accumulation of Smad3; one of the proteins which mediate the actions of Myostatin in the nucleus. However, application of these mechanisms to satellite cells may not be valid as Sulforaphane appears to regulate TGF-β/Smad signalling differentially depending on the cellular conditions.
The aforementioned study in pigs noted that both Sulforphane and the reference drug 5-aza-2′-deoxycytidine suppressed Myostatin, but not trichostatin A (another Histone Deacetylase Inhibitor). Sulforaphane at 5, 10, and 15uM concentration (achieveable with oral intake) failed to increase Follistatin concentrations (natural antagonist to Myostatin) but increases in Smad7 and Smurf1 mRNA was noted, with most significance at 5uM. miRNAs that increase Myostatin signalling did not appear to be downregulated, with only suppression in miR-29a and miR-29b.
One study in skeletal muscle satellite cells noting an attenuation of Myostatin signalling (an anabolic event), possibly due to interactions with Sulforaphane's HDAC or Nrf2 inhibitor actions; practical relevance for muscle hypertrophy unclear
Interestingly, this study noted a significant reduction in MyoD mRNA levels at 10uM concentration (5uM not tested) in these porcine satellite cells, coupled with diminished binding to the Myostatin promoter via hypoacetylation of the binding site.
In an animal model of type 1 diabetes (streptozotocin-induced) oral doses of 0.1, 0.25, or 0.5mg/kg sulforaphane for three days prior to injections of streptozotocin noted that, in the week following injections, that Sulforaphane was able to attenuate the changes to liver weight and changes in body weight and wholly normalized changes in blood glucose and insulin sensitivity.
Sulforaphane appears to act on the prototypical anti-inflammatory mechanism of inhibiting NF-kB translocation, a mechanism which disrupts inflammatory signals to the nucleus. In a study using Macrophages (RAW 264.7 cell line), LPS-induced inflammation was attenuated with Sulforaphane with IC50 values on inhibiting NO release, TNF-α release, and PGE2 production being 0.7uM, 7.8uM, and 1.4uM; respectively.
The mechanism of sulforaphane inhibiting NF-kB translocation does not appear to be via directly influencing the inhibitory unit IκB-β (which holds NF-kB in an inactive position]) but instead attenuates the production of IκB-α. Sulforaphane may also directly prevent NF-kB from forming complexes when in the nucleus.
Anti-inflammatory effects of Sulforaphane are mediated by preventing NF-kB from translocating to the nucleus, which disrupts pro-inflammatory signals from the cytosol and serum from acting in the nucleus
Sulforaphane appears to be an inhibitor of thioredoxin reductase in LPS-stimulated macrophages, which may be upstream of its effects on NF-kB as thioredoxin may increase NF-kB activity in pro-inflammatory conditions. Sulforaphane appears to be synergistic in this regard with the agent CDNB, an irreversible thioredoxin reductase inactivator.
In non-immune cells not stimulated with LPS, thioredoxin can be increased secondary to activation of the anti-oxidant response element (ARE) from Nrf2 activation; induction of thioredoxin has been seen with injections of 0.5mg/kg sulforaphane (physiologically relevant concentrations).
Thioredoxin reductase is also a molecular target of pyrroloquinoline quinone, but interactions with Sulforaphane are unknown.
Some cross-over from Sulforaphane's antioxidant actions may influence inflammatory properties due to some proteins that act in both pathways
Rheumatoid Arthritis is characterized by inflammation and rapidly proliferating synoviocytes, and commonly seen as a treatment target.
Sulforaphane appears to be able to, in vitro in cultered synoviocytes, suppress TNF-α induced inflammation and proliferation when pre-incubated (secondary to activating Nrf2) and induce apoptosis in cultures already stimulated with TNF-α.
The potency of sulforaphane at 15uM appears to be as effective as the standard drug trichostatin A at 100ng/mL, with additive benefits when both were coincubated; as they do not influence Histone Deacetylase protein content nor β-catenin (content or translocation), it appears they work by depressing the TOPflash promoter resulting in up to a doubling of acetylation as measured by histone H3 and H4.
Sulforaphane itself does not work in this regard, but appears to work via metabolites, with sulforaphane-cysteine and sulforaphane-NAC being effective in a concentration dependent manner.
Sulforaphane acts as a Histone Deacetylase inhibitor at concentrations that can be achieved in serum
Oral administration of Sulforaphane can reach the prostate at concentrations between 0.07-0.1mg/g wet weight between 2-6 hours after ingestion of (human dose equivalent extrapolated from mice) 1.55-6.2mg/kg; although in a manner that does not correlate with serum values.
Sulforaphane is confirmed to reach the prostate following oral ingestion, and it appears to bioaccumulate in the concentrations required for its mechanisms of action
Sulforaphane is able to release free hydrogen sulfide (H2S) in prostatic cancer cells, and 5-50µM sulforaphane causes concentration dependent H2S release (via cystathionine γ-lyase) and reductions in cellular viability in a manner that is partially blocked by scavenging H2S. H2S, as well as sulforaphane, activated all three major MAPKs (ERK, JNK, p38) and inhibiting the activation of these MAPKs blocked the effects of H2S.
It seems that the activatin of MAPKs in prostatic cancer cells from sulforaphane is due to sulforaphane releasing hydrogen sulfide (H2S)
Histone deacetylase 6 (HDAC6) is a protein that appears to disrupt a cytoplasmic chaperone called HSP90, and this disruption dysregulates the androgen receptor and attenuates signalling through the androgen receptor at 10-20µM concentration; this is mediated via HSP90 hyperacetylation from inhibiting HDAC6. Transcriptional activiy was not ablated with sulforaphane, indicating that inhibition came post-transcription and was thought to be through a reduction in Androgen Receptor content in both LNCaP and VCaP prostatic cancer cell lines, as well as BPH-1 and PC-3 cells most of which mimick the elevation of androgen receptor during prostate cancer.
Mechanistically, sulforaphane inhibits the activation of HDAC6 which then reduces the ability of androgens to signal through the prostate. Since androgens can act to make prostatic cancer cells survive, this is an antisurvival mechanisms
Interestingly, there is a synthetic analogue of Sulforaphane called D,L-Sulforaphane that is currently being investigated for its usage against prostate cancers; which appears to be promising.
Possibly secondary to these mechanisms, Sulforaphane has been found to inhibit cancerous cell growth and induce apoptosis of cancer cells in vitro.
One study assessing possible nutrient interactions noted, with curcumin and EGCG form green tea catechins tested in LNCaP cells alongside Sulforaphane, that pairing either of two two nutraceuticals with Sulforaphane showed efficacy in reducing cell proliferation relative to control and combining all three trended to be more significant.
Nonsignificant additive beneficial effects of Curcumin, EGCG, and Sulforaphane in reducing prostatic cell growth
One study using Caco-2 cells noted that incubation of sulforaphane increased mRNA content of the TGF-β receptor, its two subunits (receptors I and II), and enhanced SMAD2/3 signalling when this receptor was stimulated which contributed to apoptotic effects in these cells as assessed by phosporylation and SBE4luc transluciferase activity. Previously, broccoli extracts have been implicated in suppressing Smad2 phosphorylation and contest these results.
In response to oral sulforaphane, kidney concentrations of sulforaphane appear to range from 0.06-0.07mg/g wet weight betwen 4-6 hours after ingestion; suggesting that oral supplementation can load in the kidneys.
Sulforaphane, at an oral dose of 0.5mg/kg bodyweight in mice for 3 months, was able to significantly attenuate the progression of renal disease (as assessed by kidney weight the albumin:creatinine ratio, normalizing the difference between diabetic and control mice by 41% and 37.7% respectively) in diabetic mice only when it was being consumed; with benefits ceasing upon cessation of Sulforaphane. These effects were mediated by Nrf2 activation preventing oxidative and inflammatory stressors, which also appears to underlie protection of the kidneys from organotoxins (with similar potency as curcumin), unilateral ureteral obstruction, diabetic nephropathy, ischemia/reperfusion, and cisplatin.
Appears to be an effective kidney protective compound during periods of toxin or physical stressors to the kidneys, with protection only existing during periods of Sulforaphane consumption
One study using streptozotocin to induce type 1 diabetes noted that sulforaphane at 0.05-0.5mg/kg of the diet prior to injections exacerbated some damage to the liver, increasing AST (but not ALT) and total cholesterol (but not HDL-C nor hepatic Triglycerides; serum TGs was beneficially reduced to control levels).
Sulforaphane appears to be synergistic with Curcumin in regards to anti-inflammatory actions in Macrophages, as the level of antiinflammatory effects exerted by either alone is matched by their combination when concentrations are dropped to 40%. This synergism is not at the level of proinflammatory mRNA induction, but rather at the level of inducing antioxidative protein mRNA of HO-1 and NQO1.
Phenethyl Isothiocyanate (PEITC) is another compound found in Brassica vegetables alongside Diindolylmethane and Sulforaphane (SFN), and appears to be synergistic with the latter. In a study on cultured macrophages (RAW 264.7, immune cells) it was found that PEITC was equally effective as curcumin in isolation on inhibiting inflammation from the macrophage (measured by Nitric Oxide; IC80 of 5uM each) while SFN was more potent with an IC80 of 1uM; the synergism between PEITC and SFN at these concentrations was more potent than the synergism betwen SFN and Curcumin, and the combination with 40% of the concentration (2uM PEITC and 0.4uM SFN) was as effective as either alone at higher concentrations.
Neoglucobrassicin is another glucosinolate from broccoli alongside PEITC and Sulforaphane, with relatively low contents in Broccoli sprouts and higher levels in mature Broccoli where it is similar to that of Sulforaphane. In vitro, Neoglucobrassicin and its metabolites appear to compete with and inhibit signalling of Sulforaphane via Nrf2, when assessing glutathione induction. These metabolites do not stimulate Nrf2 themselves, and inhibition ranges from absolute to practically insignificant in vitro depending on the promoter measured.
Practical relevance unknown, but may reduce the benefits of Sulforaphane on Nrf2 (where it mediates a good deal of antioxidant effects)
Glucoraphanin gets hydrolyzed by the myrosinase enzyme and then produces one of two metabolites, either 5-methylsulfinylpentane nitrile (via the ESP enzyme) or sulforaphane. While heating at low temperatures can enhance sulforaphane production from inactivating ESP higher temporatures also inhibit myrosinase and prevent either metabolite from being formed. Due to this balancing act (of which practical cooking techniques tend to denature myrosinase), the addition of mustard to the cooking of broccoli has been investigated as mustard (sinapsis alba) has a form of myrosinase that is much more heat resistant whereas broccoli tends to have a heat sensitive form. Due to this, when mustard seed powder is mixed with broccoli powder (1-2%; or 12-25mg per 250mg broccoli powder) the sulforaphane availability is increased when cooked, and the losses that would normally occur beyond 60°C instead occur above 90°C and cooking at a temperature that normally abolishes sulforaphane formation (8-12 minutes of boiling sous vide) has three-fold more sulforaphane when it is mixed with mustard seed.
The mixture of mustard seeds alongside broccoli powder during cooking can increase sulforaphane bioavailability since mustard has a more heat-resistant form of the enzyme that makes sulforaphane. That being said, the study mixed powders of both foods rather than cooking with the whole food products; this information may not apply to placing mustard seeds alongside broccoli florets
- Variation in content of bioactive components in broccoli.
- Perocco P, et al. Glucoraphanin, the bioprecursor of the widely extolled chemopreventive agent sulforaphane found in broccoli, induces phase-I xenobiotic metabolizing enzymes and increases free radical generation in rat liver. Mutat Res. (2006)
- Nakagawa K, et al. Evaporative light-scattering analysis of sulforaphane in broccoli samples: Quality of broccoli products regarding sulforaphane contents. J Agric Food Chem. (2006)
- Thangstad OP, et al. The myrosinase (thioglucoside glucohydrolase) gene family in Brassicaceae. Plant Mol Biol. (1993)
- Matusheski NV, et al. Epithiospecifier protein from broccoli (Brassica oleracea L. ssp. italica) inhibits formation of the anticancer agent sulforaphane. J Agric Food Chem. (2006)
- Matusheski NV, Jeffery EH. Comparison of the bioactivity of two glucoraphanin hydrolysis products found in broccoli, sulforaphane and sulforaphane nitrile. J Agric Food Chem. (2001)
- Matusheski NV, et al. Preparative HPLC method for the purification of sulforaphane and sulforaphane nitrile from Brassica oleracea. J Agric Food Chem. (2001)
- Matusheski NV, Juvik JA, Jeffery EH. Heating decreases epithiospecifier protein activity and increases sulforaphane formation in broccoli. Phytochemistry. (2004)
- Saha S, et al. Isothiocyanate concentrations and interconversion of sulforaphane to erucin in human subjects after consumption of commercial frozen broccoli compared to fresh broccoli. Mol Nutr Food Res. (2012)
- Furniss CS, et al. Polyamine metabolism and transforming growth factor-beta signaling are affected in Caco-2 cells by differentially cooked broccoli extracts. J Nutr. (2008)
- Wang GC, Farnham M, Jeffery EH. Impact of Thermal Processing on Sulforaphane Yield from Broccoli ( Brassica oleracea L. ssp. italica). J Agric Food Chem. (2012)
- Benavides GA, et al. Hydrogen sulfide mediates the vasoactivity of garlic. Proc Natl Acad Sci U S A. (2007)
- Dietary approach to attenuate oxidative stress, hypertension, and inflammation in the cardiovascular system.
- Pei Y, et al. Hydrogen sulfide mediates the anti-survival effect of sulforaphane on human prostate cancer cells. Toxicol Appl Pharmacol. (2011)
- Conaway CC, et al. Disposition of glucosinolates and sulforaphane in humans after ingestion of steamed and fresh broccoli. Nutr Cancer. (2000)
- Vermeulen M, van Rooijen HJ, Vaes WH. Analysis of isothiocyanate mercapturic acids in urine: a biomarker for cruciferous vegetable intake. J Agric Food Chem. (2003)
- Petri N, et al. Absorption/metabolism of sulforaphane and quercetin, and regulation of phase II enzymes, in human jejunum in vivo. Drug Metab Dispos. (2003)
- In Vivo Pharmacokinetics and Regulation of Gene Expression Profiles by Isothiocyanate Sulforaphane in the Rat.
- Zhang Y, Talalay P. Mechanism of differential potencies of isothiocyanates as inducers of anticarcinogenic Phase 2 enzymes. Cancer Res. (1998)
- Role of glutathione in the accumulation of anticarcinogenic isothiocyanates and their glutathione conjugates by murine hepatoma cells.
- Zhang Y, Callaway EC. High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate. Biochem J. (2002)
- Isothiocyanates as substrates for human glutathione transferases: structure-activity studies.
- Clarke JD, et al. Metabolism and tissue distribution of sulforaphane in Nrf2 knockout and wild-type mice. Pharm Res. (2011)
- Skupinska K, et al. Sulforaphane and its analogues inhibit CYP1A1 and CYP1A2 activity induced by benzo(a)pyrene. J Biochem Mol Toxicol. (2009)
- Anwar-Mohamed A, El-Kadi AO. Sulforaphane induces CYP1A1 mRNA, protein, and catalytic activity levels via an AhR-dependent pathway in murine hepatoma Hepa 1c1c7 and human HepG2 cells. Cancer Lett. (2009)
- Abdull Razis AF, et al. The naturally occurring aliphatic isothiocyanates sulforaphane and erucin are weak agonists but potent non-competitive antagonists of the aryl hydrocarbon receptor. Arch Toxicol. (2012)
- Kalpana Deepa Priya D, Gayathri R, Sakthisekaran D. Role of sulforaphane in the anti-initiating mechanism of lung carcinogenesis in vivo by modulating the metabolic activation and detoxification of benzo(a)pyrene. Biomed Pharmacother. (2011)
- Benzo(a)pyrene carcinogenicity is lost in mice lacking the aryl hydrocarbon receptor.
- The Aryl Hydrocarbon Receptor Nuclear Translocator (Arnt) is required for tumor initiation by benzo(a)pyrene.
- Yokota S, et al. Human CYP2A6 is regulated by nuclear factor-erythroid 2 related factor 2. Biochem Pharmacol. (2011)
- Hakooz N, Hamdan I. Effects of dietary broccoli on human in vivo caffeine metabolism: a pilot study on a group of Jordanian volunteers. Curr Drug Metab. (2007)
- Negi G, Kumar A, Sharma SS. Nrf2 and NF-κB modulation by sulforaphane counteracts multiple manifestations of diabetic neuropathy in rats and high glucose-induced changes. Curr Neurovasc Res. (2011)
- Romieu P, et al. Histone deacetylase inhibitors decrease cocaine but not sucrose self-administration in rats. J Neurosci. (2008)
- Host L, et al. Cocaine self-administration alters the expression of chromatin-remodelling proteins; modulation by histone deacetylase inhibition. J Psychopharmacol. (2011)
- Stadtman ER. Protein oxidation and aging. Science. (1992)
- Gan N, et al. Sulforaphane activates heat shock response and enhances proteasome activity through up-regulation of Hsp27. J Biol Chem. (2010)
- Wu C. Heat shock transcription factors: structure and regulation. Annu Rev Cell Dev Biol. (1995)
- Kwak MK, et al. Role of increased expression of the proteasome in the protective effects of sulforaphane against hydrogen peroxide-mediated cytotoxicity in murine neuroblastoma cells. Free Radic Biol Med. (2007)
- Kwak MK, et al. Antioxidants enhance mammalian proteasome expression through the Keap1-Nrf2 signaling pathway. Mol Cell Biol. (2003)
- Kwak MK, Kensler TW. Induction of 26S proteasome subunit PSMB5 by the bifunctional inducer 3-methylcholanthrene through the Nrf2-ARE, but not the AhR/Arnt-XRE, pathway. Biochem Biophys Res Commun. (2006)
- Dinkova-Kostova AT, et al. Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proc Natl Acad Sci U S A. (2002)
- Keum YS. Regulation of the Keap1/Nrf2 system by chemopreventive sulforaphane: implications of posttranslational modifications. Ann N Y Acad Sci. (2011)
- Yeh CT, Yen GC. Effect of sulforaphane on metallothionein expression and induction of apoptosis in human hepatoma HepG2 cells. Carcinogenesis. (2005)
- Lee JH, et al. Sulforaphane induced adipolysis via hormone sensitive lipase activation, regulated by AMPK signaling pathway. Biochem Biophys Res Commun. (2012)
- Garton AJ, Yeaman SJ. Identification and role of the basal phosphorylation site on hormone-sensitive lipase. Eur J Biochem. (1990)
- Gaidhu MP, Fediuc S, Ceddia RB. 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside-induced AMP-activated protein kinase phosphorylation inhibits basal and insulin-stimulated glucose uptake, lipid synthesis, and fatty acid oxidation in isolated rat adipocytes. J Biol Chem. (2006)
- Identification of a novel Nrf2-regulated antioxidant response element (ARE) in the mouse NAD(P)H:quinone oxidoreductase 1 gene: reassessment of the ARE consensus sequence.
- Vomhof-Dekrey EE, Picklo MJ Sr. The Nrf2-antioxidant response element pathway: a target for regulating energy metabolism. J Nutr Biochem. (2012)
- Deficiency in the Nuclear factor E2-related factor 2 transcription factor results in impaired adipogenesis and protects against diet-induced obesity.
- Xu J, et al. Enhanced Nrf2 Activity Worsens Insulin Resistance, Impairs Lipid Accumulation in Adipose Tissue, and Increases Hepatic Steatosis in Leptin-Deficient Mice. Diabetes. (2012)
- Vomhof-DeKrey EE, Picklo MJ. NAD(P)H:quinone oxidoreductase 1 activity reduces hypertrophy in 3T3-L1 adipocytes. Free Radic Biol Med. (2012)
- Fan H, et al. Sulforaphane causes a major epigenetic repression of myostatin in porcine satellite cells. Epigenetics. (2012)
- Oh CJ, et al. Sulforaphane attenuates hepatic fibrosis via NF-E2-related factor 2-mediated inhibition of transforming growth factor-β/Smad signaling. Free Radic Biol Med. (2012)
- Zhu X, et al. Myostatin signaling through Smad2, Smad3 and Smad4 is regulated by the inhibitory Smad7 by a negative feedback mechanism. Cytokine. (2004)
- Kaminski BM, et al. Isothiocyanate sulforaphane inhibits protooncogenic ornithine decarboxylase activity in colorectal cancer cells via induction of the TGF-β/Smad signaling pathway. Mol Nutr Food Res. (2010)
- de Souza CG, et al. Metabolic effects of sulforaphane oral treatment in streptozotocin-diabetic rats. J Med Food. (2012)
- Heiss E, et al. Nuclear factor kappa B is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms. J Biol Chem. (2001)
- The IκB Kinase Complex (IKK) Contains Two Kinase Subunits, IKKα and IKKβ, Necessary for IκB Phosphorylation and NF-κB Activation.
- The IKK Complex, a Central Regulator of NF-κB Activation.
- Heiss E, Gerhäuser C. Time-dependent modulation of thioredoxin reductase activity might contribute to sulforaphane-mediated inhibition of NF-kappaB binding to DNA. Antioxid Redox Signal. (2005)
- Lillig CH, Holmgren A. Thioredoxin and related molecules--from biology to health and disease. Antioxid Redox Signal. (2007)
- Arnér ES, Björnstedt M, Holmgren A. 1-Chloro-2,4-dinitrobenzene is an irreversible inhibitor of human thioredoxin reductase. Loss of thioredoxin disulfide reductase activity is accompanied by a large increase in NADPH oxidase activity. J Biol Chem. (1995)
- Tanito M, et al. Sulforaphane induces thioredoxin through the antioxidant-responsive element and attenuates retinal light damage in mice. Invest Ophthalmol Vis Sci. (2005)
- Bartok B, Firestein GS. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis. Immunol Rev. (2010)
- Fragoulis A, et al. Sulforaphane has opposing effects on TNF-alpha stimulated and unstimulated synoviocytes. Arthritis Res Ther. (2012)
- Ocker M, Schneider-Stock R. Histone deacetylase inhibitors: signalling towards p21cip1/waf1. Int J Biochem Cell Biol. (2007)
- Myzak MC, et al. A novel mechanism of chemoprotection by sulforaphane: inhibition of histone deacetylase. Cancer Res. (2004)
- Bali P, et al. Inhibition of histone deacetylase 6 acetylates and disrupts the chaperone function of heat shock protein 90: a novel basis for antileukemia activity of histone deacetylase inhibitors. J Biol Chem. (2005)
- Gibbs A, et al. Sulforaphane destabilizes the androgen receptor in prostate cancer cells by inactivating histone deacetylase 6. Proc Natl Acad Sci U S A. (2009)
- Chen L, et al. Chemical ablation of androgen receptor in prostate cancer cells by the histone deacetylase inhibitor LAQ824. Mol Cancer Ther. (2005)
- Myzak MC, et al. Sulforaphane inhibits histone deacetylase activity in BPH-1, LnCaP and PC-3 prostate epithelial cells. Carcinogenesis. (2006)
- Friedlander TW, Ryan CJ. Targeting the androgen receptor. Urol Clin North Am. (2012)
- Kim SH, Singh SV. D,L-Sulforaphane causes transcriptional repression of androgen receptor in human prostate cancer cells. Mol Cancer Ther. (2009)
- Hahm ER, et al. Notch activation is dispensable for d, L-sulforaphane-mediated inhibition of human prostate cancer cell migration. PLoS One. (2012)
- Chiao JW, et al. Sulforaphane and its metabolite mediate growth arrest and apoptosis in human prostate cancer cells. Int J Oncol. (2002)
- Farooqi AA, et al. Shattering the underpinnings of neoplastic architecture in LNCap: synergistic potential of nutraceuticals in dampening PDGFR/EGFR signaling and cellular proliferation. J Exp Ther Oncol. (2011)
- Cui W, et al. Prevention of diabetic nephropathy by sulforaphane: possible role of nrf2 upregulation and activation. Oxid Med Cell Longev. (2012)
- Alp H, et al. Effects of sulforophane and curcumin on oxidative stress created by acute malathion toxicity in rats. Eur Rev Med Pharmacol Sci. (2012)
- Chung SD, et al. Activating nrf-2 signaling depresses unilateral ureteral obstruction-evoked mitochondrial stress-related autophagy, apoptosis and pyroptosis in kidney. PLoS One. (2012)
- Zheng H, et al. Therapeutic potential of Nrf2 activators in streptozotocin-induced diabetic nephropathy. Diabetes. (2011)
- Yoon HY, et al. Sulforaphane protects kidneys against ischemia-reperfusion injury through induction of the Nrf2-dependent phase 2 enzyme. Biochem Pharmacol. (2008)
- Guerrero-Beltrán CE, et al. Sulforaphane protects against cisplatin-induced nephrotoxicity. Toxicol Lett. (2010)
- Cheung KL, Khor TO, Kong AN. Synergistic effect of combination of phenethyl isothiocyanate and sulforaphane or curcumin and sulforaphane in the inhibition of inflammation. Pharm Res. (2009)
- Sutaria D, et al. Chemoprevention of pancreatic cancer using solid-lipid nanoparticulate delivery of a novel aspirin, curcumin and sulforaphane drug combination regimen. Int J Oncol. (2012)
- Shapiro TA, et al. Chemoprotective glucosinolates and isothiocyanates of broccoli sprouts: metabolism and excretion in humans. Cancer Epidemiol Biomarkers Prev. (2001)
- Broccoli sprouts: An exceptionally rich source of inducers of enzymes that protect against chemical carcinogens.
- Haack M, et al. Breakdown products of neoglucobrassicin inhibit activation of Nrf2 target genes mediated by myrosinase-derived glucoraphanin hydrolysis products. Biol Chem. (2010)
- Temperature and pressure stability of mustard seed (Sinapis alba L.) myrosinase.
- Thermal and high hydrostatic pressure inactivation of myrosinase from green cabbage: A kinetic study.
- Ludikhuyze L, et al. Kinetic study of the irreversible thermal and pressure inactivation of myrosinase from broccoli (Brassica oleracea L. Cv. italica). J Agric Food Chem. (1999)
- Ghawi SK, Methven L, Niranjan K. The potential to intensify sulforaphane formation in cooked broccoli (Brassica oleracea var. italica) using mustard seeds (Sinapis alba). Food Chem. (2013)