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Thursday, 31 October 2013

Phytochemicals in Foods - 11 Health Benefits of Sulphoraphane

Sulphoraphane are phytochemicals in the class of Dithiolthiones, belonging to group of Organosulfides, found abundantly in broccoli, Brussels sprouts or cabbages, etc.

Health Benefits
1. Prostate cancer
In the investigation of the effects of Sulforaphane (SFN) on DNA methylation status of cyclin D2 promoter, and how alteration in promoter methylation impacts cyclin D2 gene expression in LnCap cells, found that SFN significantly decreased the expression of DNA methyltransferases (DNMTs), especially DNMT1 and DNMT3b. Furthermore, SFN significantly decreased methylation in cyclin D2 promoter regions containing c-Myc and multiple Sp1 binding sites. Reduced methlyation of cyclin D2 promoter corresponded to an increase in cyclin D2 transcript levels, suggesting that SFN may de-repress methylation-silenced cyclin D2 by impacting epigenetic pathways, according to "Promoter de-methylation of cyclin D2 by sulforaphane in prostate cancer cells" by Hsu A, Wong CP, Yu Z, Williams DE, Dashwood RH, Ho E.(1)

2. Breast cancer
In the evaluation of sulforaphane, a natural compound derived from broccoli/broccoli sprouts, for its efficacy to inhibit breast CSCs and its potential mechanism, found that Sulforaphane inhibits breast CSCs and downregulates the Wnt/beta-catenin self-renewal pathway. These findings support the use of sulforaphane for the chemoprevention of breast cancer stem cells and warrant further clinical evaluation, according to "Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells" by Li Y, Zhang T, Korkaya H, Liu S, Lee HF, Newman B, Yu Y, Clouthier SG, Schwartz SJ, Wicha MS, Sun D.(2)

3. Aging and aging related diseases
In the elucidating the modulatory role of nutrition in aging and age-related disease development, indicated that nutrients can act as the source of epigenetic modifications and can regulate the placement of these modifications. Nutrients involved in one-carbon metabolism, namely folate, vitamin B12, vitamin B6, riboflavin, methionine, choline and betaine, are involved in DNA methylation by regulating levels of the universal methyl donor S-adenosylmethionine and methyltransferase inhibitor S-adenosylhomocysteine. Other nutrients and bioactive food components such as retinoic acid, resveratrol, curcumin, sulforaphane and tea polyphenols can modulate epigenetic patterns by altering the levels of S-adenosylmethionine and S-adenosylhomocysteine or directing the enzymes that catalyse DNA methylation and histone modifications, according to "Nutritional influences on epigenetics and age-related disease" by Park LK, Friso S, Choi SW.(3)

4. Human brain microvascular endothelial cells (HBMECs)
In the delineation of a unique brain endothelial phenotype in that MMP-9 secretion is increased upon phorbol 12-myristate 13-acetate (PMA) treatment of HBMEC, indicated that Sulforaphane (SFN), an isothiocyanate present in broccoli which exhibits chemopreventive properties, selectively inhibited the secretion of MMP-9 but not that of MMP-2. The decrease in MMP-9 gene expression correlated with a decrease in the expression of the mRNA stabilizing factor HuR protein triggered by SFN. PMA-induced HBMEC migration was also antagonized by SFN. Silencing of the MMP-9 gene inhibited PMA-induced MMP-9 secretion, cell migration, and in vitro tubulogenesis on Matrigel. While SFN inhibited the chemoattractive abilities of brain tumor-derived growth factors, it failed to inhibit PMA-induced tubulogenesis, according to "The diet-derived sulforaphane inhibits matrix metalloproteinase-9-activated human brain microvascular endothelial cell migration and tubulogenesis" by Annabi B, Rojas-Sutterlin S, Laroche M, Lachambre MP, Moumdjian R, Béliveau R.(4)

5. Oxidative stress
In the investigation of anti oxidative stress of Sulforaphane [1-isothiocyanate-(4R)-(methylsulfinyl)butane] is a natural dietary isothiocyanate produced by the enzymatic action of the myrosinase on glucopharanin, a 4-methylsulfinylbutyl glucosinolate contained in cruciferous vegetables of the genus Brassica such as broccoli, brussel sprouts, and cabbage, found that Sulforaphane is considered an indirect antioxidant; this compound is able to induce many cytoprotective proteins, including antioxidant enzymes, through the Nrf2-antioxidant response element pathway. Heme oxygenase-1, NAD(P)H: quinone oxidoreductase, glutathione-S-transferase, gamma-glutamyl cysteine ligase, and glutathione reductase are among the cytoprotective proteins induced by sulforaphane. In conclusion, sulforaphane is a promising antioxidant agent that is effective to attenuate oxidative stress and tissue/cell damage in different in vivo and in vitro experimental paradigms, according to "Protective effect of sulforaphane against oxidative stress: Recent advances" by Guerrero-Beltrán CE, Calderón-Oliver M, Pedraza-Chaverri J, Chirino YI.(5)

6. Anti nephrotoxicity
In the evaluation of whether SFN induces a cytoprotective effect on the CDDP-induced nephrotoxicity, found that The renoprotective effect of SFN on CDDP-induced nephrotoxicity was associated with the attenuation in oxidative/nitrosative stress and the preservation of antioxidant enzymes, according to "Sulforaphane protects against cisplatin-induced nephrotoxicity" by Guerrero-Beltrán CE, Calderón-Oliver M, Tapia E, Medina-Campos ON, Sánchez-González DJ, Martínez-Martínez CM, Ortiz-Vega KM, Franco M, Pedraza-Chaverri J.(6)

7. Liver protection
In the investigation of the effect of sulforaphane (SFN) on regulation of NF-E2-related factor-2 (Nrf2)-antioxidant response element (ARE) pathway in liver injury induced by intestinal ischemia/reperfusion (I/R), showed that SFN pretreatment attenuates liver injury induced by intestinal I/R in rats, attributable to the antioxidant effect through Nrf2-ARE pathway, according to "Sulforaphane protects liver injury induced by intestinal ischemia reperfusion through Nrf2-ARE pathway" by Zhao HD, Zhang F, Shen G, Li YB, Li YH, Jing HR, Ma LF, Yao JH, Tian XF.(7)

8. Antibacterial Effects
In the evaluation of the effects of various glucosinolate-derived hydrolysis products (HP) as antibacterial compounds against Enterobacteriaceae and Enterococcaceae isolated from intestinal segments of healthy pigs collected directly from slaughter-houses in the North of Portugal, found that the glucosinolates-derived HPs were very effective in vitro inhibitors of bacterial growth. The natural products, and specifically the isothiocyanates, should be evaluated as potential alternative control agents for potentially pathogenic bacteria (e.g., dietary amendment of pig foods with glucosinolate-containing plants), according to "Antibacterial Effects of Glucosinolate-Derived Hydrolysis Products Against Enterobacteriaceae and Enterococci Isolated from Pig Ileum Segments" by Saavedra MJ, Dias CS, Martinez-Murcia A, Bennett RN, Aires A, Rosa EA.(8)

9. Anti-inflammatory Effects
In the investigation of the anti-inflammatory effects of two dietary compounds, nobiletin (NBN) and sulforaphane (SFN), in combination. Noncytotoxic concentrations of NBN, SFN, and their combinations were studied in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophage cells, indicated that low doses of NBN and SFN in combination significantly suppressed LPS-induced upregulation of IL-1 mRNA levels and synergistically increased HO-1 mRNA levels. Overall, our results demonstrated that NBN and SFN in combination produced synergistic effects in inhibiting LPS-induced inflammation in RAW 264.7 cells, according to "Synergistic Anti-inflammatory Effects of Nobiletin and Sulforaphane in Lipopolysaccharide-Stimulated RAW 264.7 Cells" by Guo S, Qiu P, Xu G, Wu X, Dong P, Yang G, Zheng J, McClements DJ, Xiao H.(9)

10. Hypertension
In the determination of whether the metabolite of glucoraphanin, sulforaphane, was responsible for this improved blood pressure and whether this is associated with normalization of renal methylated DNA, showed that Sulforaphane administration rectified pathological abnormalities in SHRSP kidneys and significantly improved blood pressure. This was associated with normalization of global kidney DNA methylation suggesting that DNA methylation could be associated with hypertension, according to "The dietary phase 2 protein inducer sulforaphane can normalize the kidney epigenome and improve blood pressure in hypertensive rats" by Senanayake GV, Banigesh A, Wu L, Lee P, Juurlink BH.(10)

11. Diabetic symptoms
In the determination of whether dietary compounds targeting NFE2-related factor 2 (Nrf2) activation used to attenuate renal damage and preserve renal function during the course of streptozotocin (STZ)-induced diabetic nephropathy, showed that SF or CA significantly attenuated common metabolic disorder symptoms associated with diabetes in Nrf2(+/+) but not in Nrf2(-/-) mice, indicating SF and CA function through specific activation of the Nrf2 pathway. Furthermore, SF or CA improved renal performance and minimized pathological alterations in the glomerulus of STZ-Nrf2(+/+) mice. Nrf2 activation reduced oxidative damage and suppressed the expression of TGF-β1, extracellular matrix proteins and p21 both in vivo and in HRMCs. In addition, Nrf2 activation reverted p21-mediated growth inhibition and hypertrophy of HRMCs under hyperglycemic conditions, according to "Therapeutic potential of Nrf2 activators in streptozotocin-induced diabetic nephropathy" by Zheng H, Whitman SA, Wu W, Wondrak GT, Wong PK, Fang D, Zhang DD.(11)

12. Etc.
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Sources
(1) http://www.ncbi.nlm.nih.gov/pubmed/22303414
(2) http://www.ncbi.nlm.nih.gov/pubmed/20388854
(3) http://www.ncbi.nlm.nih.gov/pubmed/22051144
(4) http://www.ncbi.nlm.nih.gov/pubmed/18435488
(5) http://www.ncbi.nlm.nih.gov/pubmed/21129940
(6) http://www.ncbi.nlm.nih.gov/pubmed/19913604
(7) http://www.ncbi.nlm.nih.gov/pubmed/20572303
(8) http://www.ncbi.nlm.nih.gov/pubmed/22356572
(9) http://www.ncbi.nlm.nih.gov/pubmed/22335189
(10) http://www.ncbi.nlm.nih.gov/pubmed/22052072
(11) http://www.ncbi.nlm.nih.gov/pubmed/22025779

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