Sulforaphane Overview

1) Conditions Studied for Sulforaphane

Sulforaphane, a compound found in cruciferous vegetables like broccoli, has been studied for its potential effects on a variety of health conditions. These include:

• Cancer prevention and therapy
• Neurodegenerative diseases (e.g., Alzheimer's and Parkinson's disease)
• Cardiovascular health
• Diabetes and metabolic syndrome
• Inflammatory conditions
• Autism spectrum disorder
• Age-related decline in health and function

2) Efficacy in Treating Conditions

While sulforaphane shows promise in preclinical studies, human studies are less conclusive. Here's what current research suggests:

• In cancer research, sulforaphane has demonstrated anti-cancer properties in laboratory and animal studies, but human data is limited and more research is needed to confirm these effects.
• For neurodegenerative diseases, some studies indicate potential protective effects, yet robust clinical trials are necessary to determine its efficacy.
• There are mixed results regarding cardiovascular health and diabetes; while some studies show benefit, others do not.
• Its impact on autism spectrum disorder has shown some positive results in small-scale trials but is not yet widely recognized as a treatment.

3) Health Benefits

Reported health benefits of sulforaphane include:

• Antioxidant and detoxification promotion
• Anti-inflammatory effects
• Enhancement of brain function
• Possible protective effect against certain types of cancer
• Potential to improve glucose control in type 2 diabetes

4) Downsides

Although sulforaphane is generally considered safe when consumed through diet, there are potential downsides, especially when taken in supplement form:

• Possible gastrointestinal distress
• Interactions with medication, especially for those with thyroid issues
• Insufficient data on long-term safety of supplements
• Rare cases of allergic reactions

5) Genetic Variations and Sulforaphane

The benefits or harms of sulforaphane may vary depending on genetic makeup. For instance:

• Individuals with certain mutations in genes related to glutathione S-transferase, an enzyme involved in sulforaphane metabolism, may not experience the same detoxification benefits.
• Genetic variations in the Nrf2 pathway, which is activated by sulforaphane, could influence the extent of antioxidant and anti-inflammatory effects experienced by an individual.

It is important to note that research in this area is ongoing, and personalized dietary recommendations based on genetic profiles are not yet fully established.

Sulforaphane Research Summary

Sulforaphane, a compound found in cruciferous vegetables, has been the focus of various studies due to its potential anticancer properties and ability to influence important biological processes.

Gene Expression and Biological Impact

Research has shown that sulforaphane can alter gene expression in intestinal cells, affecting genes involved in polyamine catabolism and the transforming growth factor-beta (TGF-beta) signaling pathway. It also influences the concentration of specific polyamines and reduces the induction of phosphorylated Smad 2.

Cancer Prevention and Therapeutic Potential

Sulforaphane has been studied for its effects on prostate cancer cells, demonstrating reduced activation of growth factor receptors and cell proliferation. It activates genes responsible for detoxification and antioxidant defense by inducing the transcription factor Nrf2, potentially altering its regulation through posttranslational modifications.

Myrosinase Stability and Sulforaphane Bioavailability

The stability of myrosinase, an enzyme crucial for sulforaphane formation, is sensitive to both heat and pressure. The bioavailability of sulforaphane is significantly reduced in frozen broccoli due to the loss of myrosinase activity during commercial processing.

Protective Effects Against Cancer and Other Diseases

Sulforaphane shows protective effects against lung cancer initiation by modulating enzyme activity involved in carcinogen metabolism. It also exhibits potent anticarcinogenic effects by activating detoxification enzymes, inhibiting carcinogen-activating enzymes, and promoting cell death (apoptosis).

Regulation of Proteasomes and Detoxification Enzymes

Studies have indicated that sulforaphane can stimulate the activity of proteasomes responsible for degrading misfolded proteins and activate phase 2 detoxification enzymes through the Nrf2 pathway, providing protection against cellular damage.

Role in Disease Prevention and Treatment

Sulforaphane has been suggested as a potential mechanism for preventing diabetic nephropathy and aging-related diseases, and for alleviating inflammatory conditions. Its effects on phase I enzymes, which can activate carcinogens, highlight the complexity of its biological activity and the need for further research.

Conclusion

The body of research on sulforaphane underscores its multifaceted role in health and disease, emphasizing its potential as a dietary compound with chemopreventive and therapeutic benefits.

References:

1. Polyamine metabolism and transforming growth factor-beta signaling are affected in Caco-2 cells by differentially cooked broccoli extracts
2. Shattering the underpinnings of neoplastic architecture in LNCap: synergistic potential of nutraceuticals in dampening PDGFR/EGFR signaling and cellular proliferation
3. Regulation of the Keap1/Nrf2 system by chemopreventive sulforaphane: implications of posttranslational modifications
4. Kinetic study of the irreversible thermal and pressure inactivation of myrosinase from broccoli (Brassica oleracea L. Cv. italica)
5. Isothiocyanate concentrations and interconversion of sulforaphane to erucin in human subjects after consumption of commercial frozen broccoli compared to fresh broccoli
6. Role of sulforaphane in the anti-initiating mechanism of lung carcinogenesis in vivo by modulating the metabolic activation and detoxification of benzo(a)pyrene
7. High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate
8. Myostatin signaling through Smad2, Smad3 and Smad4 is regulated by the inhibitory Smad7 by a negative feedback mechanism
9. Cocaine self-administration alters the expression of chromatin-remodelling proteins; modulation by histone deacetylase inhibition
10. Prevention of diabetic nephropathy by sulforaphane: possible role of Nrf2 upregulation and activation
11. Sulforaphane activates heat shock response and enhances proteasome activity through up-regulation of Hsp27
12. Breakdown products of neoglucobrassicin inhibit activation of Nrf2 target genes mediated by myrosinase-derived glucoraphanin hydrolysis products
13. Analysis of isothiocyanate mercapturic acids in urine: a biomarker for cruciferous vegetable intake
14. Protein oxidation and aging
15. Comparison of the bioactivity of two glucoraphanin hydrolysis products found in broccoli, sulforaphane and sulforaphane nitrile
16. Time-dependent modulation of thioredoxin reductase activity might contribute to sulforaphane-mediated inhibition of NF-kappaB binding to DNA
17. Hydrogen sulfide mediates the anti-survival effect of sulforaphane on human prostate cancer cells
18. Sulforaphane and its analogues inhibit CYP1A1 and CYP1A2 activity induced by benzo[a]pyrene
19. 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
20. Effects of sulforophane and curcumin on oxidative stress created by acute malathion toxicity in rats
21. The naturally occurring aliphatic isothiocyanates sulforaphane and erucin are weak agonists but potent non-competitive antagonists of the aryl hydrocarbon receptor
22. Chemical ablation of androgen receptor in prostate cancer cells by the histone deacetylase inhibitor LAQ824
23. Notch activation is dispensable for D, L-sulforaphane-mediated inhibition of human prostate cancer cell migration
24. Thioredoxin and related molecules--from biology to health and disease
25. Therapeutic potential of Nrf2 activators in streptozotocin-induced diabetic nephropathy
26. Nuclear factor kappa B is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms
27. Metabolic effects of sulforaphane oral treatment in streptozotocin-diabetic rats
28. 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
29. Sulforaphane induced adipolysis via hormone sensitive lipase activation, regulated by AMPK signaling pathway
30. Chemoprotective glucosinolates and isothiocyanates of broccoli sprouts: metabolism and excretion in humans
31. Activating Nrf-2 signaling depresses unilateral ureteral obstruction-evoked mitochondrial stress-related autophagy, apoptosis and pyroptosis in kidney
32. Sulforaphane protects kidneys against ischemia-reperfusion injury through induction of the Nrf2-dependent phase 2 enzyme
33. Histone deacetylase inhibitors: signalling towards p21cip1/waf1
34. Sulforaphane inhibits histone deacetylase activity in BPH-1, LnCaP and PC-3 prostate epithelial cells
35. Absorption/metabolism of sulforaphane and quercetin, and regulation of phase II enzymes, in human jejunum in vivo
36. Targeting the androgen receptor
37. Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants
38. Impact of thermal processing on sulforaphane yield from broccoli ( Brassica oleracea L. ssp. italica)
39. Antioxidants enhance mammalian proteasome expression through the Keap1-Nrf2 signaling pathway
40. D,L-Sulforaphane causes transcriptional repression of androgen receptor in human prostate cancer cells
41. Sulforaphane and its metabolite mediate growth arrest and apoptosis in human prostate cancer cells
42. Evaporative light-scattering analysis of sulforaphane in broccoli samples: Quality of broccoli products regarding sulforaphane contents
43. Nrf2 and NF-κB modulation by sulforaphane counteracts multiple manifestations of diabetic neuropathy in rats and high glucose-induced changes
44. Metabolism and tissue distribution of sulforaphane in Nrf2 knockout and wild-type mice
45. Heat shock transcription factors: structure and regulation
46. A novel mechanism of chemoprotection by sulforaphane: inhibition of histone deacetylase
47. Histone deacetylase inhibitors decrease cocaine but not sucrose self-administration in rats
48. Hydrogen sulfide mediates the vasoactivity of garlic
49. Heating decreases epithiospecifier protein activity and increases sulforaphane formation in broccoli
50. NAD(P)H:quinone oxidoreductase 1 activity reduces hypertrophy in 3T3-L1 adipocytes
51. Sulforaphane protects against cisplatin-induced nephrotoxicity
52. Isothiocyanate sulforaphane inhibits protooncogenic ornithine decarboxylase activity in colorectal cancer cells via induction of the TGF-β/Smad signaling pathway
53. Human CYP2A6 is regulated by nuclear factor-erythroid 2 related factor 2
54. Preparative HPLC method for the purification of sulforaphane and sulforaphane nitrile from Brassica oleracea
55. The Nrf2-antioxidant response element pathway: a target for regulating energy metabolism
56. Mechanism of differential potencies of isothiocyanates as inducers of anticarcinogenic Phase 2 enzymes
57. Sulforaphane has opposing effects on TNF-alpha stimulated and unstimulated synoviocytes
58. Induction of 26S proteasome subunit PSMB5 by the bifunctional inducer 3-methylcholanthrene through the Nrf2-ARE, but not the AhR/Arnt-XRE, pathway
59. Disposition of glucosinolates and sulforaphane in humans after ingestion of steamed and fresh broccoli
60. Effects of dietary broccoli on human in vivo caffeine metabolism: a pilot study on a group of Jordanian volunteers
61. Synergistic effect of combination of phenethyl isothiocyanate and sulforaphane or curcumin and sulforaphane in the inhibition of inflammation
62. Enhanced Nrf2 activity worsens insulin resistance, impairs lipid accumulation in adipose tissue, and increases hepatic steatosis in leptin-deficient mice
63. Chemoprevention of pancreatic cancer using solid-lipid nanoparticulate delivery of a novel aspirin, curcumin and sulforaphane drug combination regimen
64. Sulforaphane causes a major epigenetic repression of myostatin in porcine satellite cells
65. The myrosinase (thioglucoside glucohydrolase) gene family in Brassicaceae
66. Sulforaphane destabilizes the androgen receptor in prostate cancer cells by inactivating histone deacetylase 6
67. Sulforaphane attenuates hepatic fibrosis via NF-E2-related factor 2-mediated inhibition of transforming growth factor-β/Smad signaling
68. Sulforaphane induces thioredoxin through the antioxidant-responsive element and attenuates retinal light damage in mice
69. 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
70. Identification and role of the basal phosphorylation site on hormone-sensitive lipase
71. Effect of sulforaphane on metallothionein expression and induction of apoptosis in human hepatoma HepG2 cells
72. Sulforaphane induces CYP1A1 mRNA, protein, and catalytic activity levels via an AhR-dependent pathway in murine hepatoma Hepa 1c1c7 and human HepG2 cells
73. 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
74. Role of increased expression of the proteasome in the protective effects of sulforaphane against hydrogen peroxide-mediated cytotoxicity in murine neuroblastoma cells
75. Epithiospecifier protein from broccoli (Brassica oleracea L. ssp. italica) inhibits formation of the anticancer agent sulforaphane
76. The potential to intensify sulforaphane formation in cooked broccoli (Brassica oleracea var. italica) using mustard seeds (Sinapis alba)
77. Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis
78. Sulforaphane regulates Nrf2-mediated antioxidant activity and downregulates TGF-β1/Smad pathways to prevent radiation-induced muscle fibrosis
79. Therapeutic effects of sulforaphane in ulcerative colitis: effect on antioxidant activity, mitochondrial biogenesis and DNA polymerization
80. Sulforaphane Ameliorates the Severity of Psoriasis and SLE by Modulating Effector Cells and Reducing Oxidative Stress
81. Anti-Obesogenic Effects of Sulforaphane-Rich Broccoli ( Brassica oleracea var. italica) Sprouts and Myrosinase-Rich Mustard ( Sinapis alba L.) Seeds In Vitro and In Vivo
82. Modulation of endoplasmic reticulum stress via sulforaphane-mediated AMPK upregulation against nonalcoholic fatty liver disease in rats
83. Nrf2 regulates the arginase 1+ microglia phenotype through the initiation of TREM2 transcription, ameliorating depression-like behavior in mice
84. Oxidative Stress and NRF2/KEAP1/ARE Pathway in Diabetic Kidney Disease (DKD): New Perspectives
85. Sulforaphane alleviates high fat diet-induced insulin resistance via AMPK/Nrf2/GPx4 axis
86. Supplementation of the Diet by Exogenous Myrosinase via Mustard Seeds to Increase the Bioavailability of Sulforaphane in Healthy Human Subjects after the Consumption of Cooked Broccoli
87. Effects of sulforaphane intake on processing speed and negative moods in healthy older adults: Evidence from a randomized controlled trial
88. Sulforaphane promotes white matter plasticity and improves long-term neurological outcomes after ischemic stroke via the Nrf2 pathway
89. Isothiocyanate from Broccoli, Sulforaphane, and Its Properties
90. The Anticancer Potential of Plant-Derived Nutraceuticals via the Modulation of Gene Expression
91. Sulforaphane Increase Mitochondrial Biogenesis-Related Gene Expression in the Hippocampus and Suppresses Age-Related Cognitive Decline in Mice
92. Phytochemicals in Skeletal Muscle Health: Effects of Curcumin (from Curcuma longa Linn) and Sulforaphane (from Brassicaceae) on Muscle Function, Recovery and Therapy of Muscle Atrophy

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