Sulforaphane

==Nom de la substance==
Sulforaphane
==Famille moléculaire==
Isothiocyanate (dérivé de glucosinolate), produit par l'hydrolyse de la glucoraphanine
==Source végétale==
* Présent dans les crucifères (Brassicaceae), surtout les légumes (brocoli, choux-fleur, cressons)
** La myrosinase transforme la glucoraphanine, un glucosinolate, en sulforaphane
** Lorsque les tissus de plantes à glucosinolates sont lésés, ils sont hydrolysés par une enzyme, la “myrosinase” toujours présente dans ce type de plantes qui produit du Soufre et des isothiocyanates
 
==Propriétés==
* Anti-inflammatoire, inhibe la prolifération des tumeurs et déclenche l’apoptose, effet antidiabétique par amélioration de la tolérance au glucose, effet anti-obésité en réduisant l’accumulation de graisse, neuroprotecteur (adjuvant dans Alzheimer, Parkinson, sclérose en plaques) Schepici G, Bramanti P, Mazzon E. Efficacy of Sulforaphane in Neurodegenerative Diseases. Int J Mol Sci. 2020 Nov 16;21(22):8637. doi: 10.3390/ijms21228637. PMID 33207780; PMCID: PMC7698208.
* Active le Nrf2 Calabrese EJ, Kozumbo WJ. The phytoprotective agent sulforaphane prevents inflammatory degenerative diseases and age-related pathologies via Nrf2-mediated hormesis. Pharmacol Res. 2021 Jan;163:105283. doi: 10.1016/j.phrs.2020.105283. Epub 2020 Nov 4. PMID 33160067., un facteur de transcription régulant le stress oxydatif et l'inflammation, protecteur contre les composés toxiques Baralić K, Živanović J, Marić Đ, Bozic D, Grahovac L, Antonijević Miljaković E, Ćurčić M, Buha Djordjevic A, Bulat Z, Antonijević B, Đukić-Ćosić D. Sulforaphane-A Compound with Potential Health Benefits for Disease Prevention and Treatment: Insights from Pharmacological and Toxicological Experimental Studies. Antioxidants (Basel). 2024 Jan 25;13(2):147. doi: 10.3390/antiox13020147. PMID 38397745; PMCID: PMC10886109.
* Propriétés chimiopréventives, le sulforaphane cible la voie de signalisation Keap1-Nrf2 impliquée dans la réponse cellulaire au stress Kensler TW, Egner PA, Agyeman AS, Visvanathan K, Groopman JD, Chen JG, Chen TY, Fahey JW, Talalay P. Keap1-nrf2 signaling: a target for cancer prevention by sulforaphane. Top Curr Chem. 2013;329:163-77. doi: 10.1007/128_2012_339. PMID 22752583; PMCID: PMC3553557.
** La voie Nrf2 par activation de la réponse antioxydante pourrait être un mécanisme central, intégratif et sous-jacent de l'hormésis, réponse de stimulation des défenses biologiques à des doses très faibles de certains toxiques 
* Anti-arthritique, régulateur de processus auto-immuns Moon SJ, Jhun J, Ryu J, Kwon JY, Kim SY, Jung K, Cho ML, Min JK. The anti-arthritis effect of sulforaphane, an activator of Nrf2, is associated with inhibition of both B cell differentiation and the production of inflammatory cytokines. PLoS One. 2021 Feb 16;16(2):e0245986. doi: 10.1371/journal.pone.0245986. Erratum in: PLoS One. 2021 Aug 19;16(8):e0256716. PMID 33592002; PMCID: PMC7886167.
* Détoxifiant par inhibition des enzymes de phase 1 et augmentation des enzymes de phase 2 Abel EL, Boulware S, Fields T, McIvor E, Powell KL, DiGiovanni J, Vasquez KM, MacLeod MC. Sulforaphane induces phase II detoxication enzymes in mouse skin and prevents mutagenesis induced by a mustard gas analog. Toxicol Appl Pharmacol. 2013 Feb 1;266(3):439-42. doi: 10.1016/j.taap.2012.11.020. PMID 23201461, Boddupalli S, Mein JR, Lakkanna S, James DR. Induction of phase 2 antioxidant enzymes by broccoli sulforaphane: perspectives in maintaining the antioxidant activity of vitamins A, C, and E. Front Genet. 2012 Jan 24;3:7. doi: 10.3389/fgene.2012.00007. eCollection 2012. PMID 22303412, James D, Devaraj S, Bellur P, Lakkanna S, Vicini J, Boddupalli S. Novel concepts of broccoli sulforaphanes and disease: induction of phase II antioxidant and detoxification enzymes by enhanced-glucoraphanin broccoli. Nutr Rev. 2012 Nov;70(11):654-65. doi: 10.1111/j.1753-4887.2012.00532.x. PMID 23110644, Fahey JW, Talalay P. Antioxidant functions of sulforaphane: a potent inducer of Phase II detoxication enzymes. Food Chem Toxicol. 1999 Sep-Oct;37(9-10):973-9. PMID 10541453, Trinh K, Moore K, Wes PD, Muchowski PJ, Dey J, Andrews L, Pallanck LJ. Induction of the phase II detoxification pathway suppresses neuron loss in Drosophila models of Parkinson's disease. J Neurosci. 2008 Jan 9;28(2):465-72. doi: 10.1523/JNEUROSCI.4778-07.2008. PMID 18184789, chimioprotection du cancer par induction d'enzymes de phase 2 Talalay P. Chemoprotection against cancer by induction of phase 2 enzymes. Biofactors. 2000;12(1-4):5-11. doi: 10.1002/biof.5520120102. PMID 11216505., Talalay P, Fahey JW, Holtzclaw WD, Prestera T, Zhang Y. Chemoprotection against cancer by phase 2 enzyme induction. Toxicol Lett. 1995 Dec;82-83:173-9. doi: 10.1016/0378-4274(95)03553-2. PMID 8597048.
** Inhibiteur de cytochromes P-450 et inducteur des glutathion transférases Maheo K, Guillouzo A. Effets de deux agents chimioprotecteurs, l'oltipraz et le sulforaphane, sur l'expression des cytochromes p-450 et des glutathion transférases hépatiques en situation normale et inflammatoire. Thèse Université de Rennes 1, 1998. 178 p. http://cat.inist.fr/?aModele=afficheN&cpsidt=188662
* Antioxydant de Figueiredo SM, Filho SA, Nogueira-Machado JA, Caligiorne RB. The anti-oxidant properties of isothiocyanates: a review. Recent Pat Endocr Metab Immune Drug Discov. 2013 Sep;7(3):213-25. Review. PMID 23978168, de Figueiredo SM, Binda NS, Nogueira-Machado JA, Vieira-Filho SA, Caligiorne RB. The antioxidant properties of organosulfur compounds (sulforaphane). Recent Pat Endocr Metab Immune Drug Discov. 2015;9(1):24-39. doi: 10.2174/1872214809666150505164138. PMID 25944116.
* Prévention des complications vasculaires du diabète Yamagishi S, Matsui T. Protective role of sulphoraphane against vascular complications in diabetes. Pharm Biol. 2016 Oct;54(10):2329-39. doi: 10.3109/13880209.2016.1138314. PMID 26841240.
* Prévention nutritionnelle de cancers Kaiser AE, Baniasadi M, Giansiracusa D, Giansiracusa M, Garcia M, Fryda Z, Wong TL, Bishayee A. Sulforaphane: A Broccoli Bioactive Phytocompound with Cancer Preventive Potential. Cancers (Basel). 2021 Sep 25;13(19):4796. doi: 10.3390/cancers13194796. PMID 34638282; PMCID: PMC8508555., prévention du développement de certains cancers Bayat Mokhtari, R., Baluch, N., Homayouni, T. S., Morgatskaya, E., Kumar, S., Kazemi, P., & Yeger, H. (2018). The role of Sulforaphane in cancer chemoprevention and health benefits: a mini-review. Journal of cell communication and signaling, 12(1), 91–101. https://doi.org/10.1007/s12079-017-0401-y PMID 28735362, induction de l‘apoptose, suppression de la progression tumorale, inhibition de l’angiogenèse et activité anti-inflammatoire Juge N, Mithen RF, Traka M. Molecular basis for chemoprevention by sulforaphane: a comprehensive review. Cell Mol Life Sci. 2007 May;64(9):1105-27. PMID 17396224, Parul Gupta, Bonglee Kim, Sung-Hoon Kim, Sanjay K. Srivastava. Molecular targets of isothiocyanates in cancer: Recent advances. Molecular Nutrition & Food Research, Volume 58, Issue 8, pages 1685–1707, August 2014. DOI: 10.1002/mnfr.201300684 texte intégral, inhibe la progression du taux de PSA dans le cancer de la prostate Bernard G Cipolla, Eric Mandron, Jean Marc Lefort, Yves Coadou, Emmanuel Della Negra, Luc Corbel, Romuald Le Scodan, Nicolas Mottet. First double-blind placebo-controlled, multicenter, randomized trial of stabilized natural sulforaphane in men with rising PSA following radical prostatectomy. 2014 ASCO Annual Meeting, Poster Highlights Session, Genitourinary (Prostate) Cancer, Abstract Number: 5032. J Clin Oncol 32:5s, 2014 (suppl; abstr 5032), limite l’élévation du PSA ("récidive biologique") après prostatectomie radicale Cipolla BG, Mandron E, Lefort J, Coadou Y, Della Negra E, Corbel L, Le Scodan R, Azzouzi AR, Mottet N. Effect of Sulforaphane in Men with Biochemical Recurrence after Radical Prostatectomy. Cancer Prev Res (Phila). 2015 Aug;8(8):712-9. doi: 10.1158/1940-6207.CAPR-14-0459. PMID 25968598, diminue la cancérogénicité de l'estradiol Yager JD. Mechanisms of estrogen carcinogenesis: The role of E2/E1-quinone metabolites suggests new approaches to preventive intervention - A review. Steroids. 2014 Aug 24. pii: S0039-128X(14)00199-8. doi: 10.1016/j.steroids.2014.08.006. PMID 25159108, inhibition de la croissance de cellules de cancer de vessie Abbaoui B, Riedl KM, Ralston RA, Thomas-Ahner JM, Schwartz SJ, Clinton SK, Mortazavi A. Inhibition of bladder cancer by broccoli isothiocyanates sulforaphane and erucin: characterization, metabolism, and interconversion. Mol Nutr Food Res. 2012 Nov;56(11):1675-87. doi: 10.1002/mnfr.201200276. PMID 23038615, comme l'érucine
* Anticancéreux par activité spécifique sur les cellules souches cancéreuses, qui peuvent former des masses tumorales très hétérogènes, très peu sensibles aux agents chimiothérapiques cytostatiques conventionnels Coutinho Leandro de Lima , Junior Tharcísio Citrangulo Tortelli , Rangel Maria Cristina. Sulforaphane: An emergent anti-cancer stem cell agent. Frontiers in Oncology, 13, 2023, https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1089115
* Neuroprotecteur Morroni F, Tarozzi A, Sita G, Bolondi C, Zolezzi Moraga JM, Cantelli-Forti G, Hrelia P. Neuroprotective effect of sulforaphane in 6-hydroxydopamine-lesioned mouse model of Parkinson's disease. Neurotoxicology. 2013 May;36:63-71. doi: 10.1016/j.neuro.2013.03.004. PMID 23518299, Klomparens EA, Ding Y. The neuroprotective mechanisms and effects of sulforaphane. Brain Circ. 2019 Apr-Jun;5(2):74-83. doi: 10.4103/bc.bc_7_19. PMID 31334360; PMCID: PMC6611193., protecteur des cellules dopaminergiques Tarozzi A, Morroni F, Merlicco A, Hrelia S, Angeloni C, Cantelli-Forti G, Hrelia P. Sulforaphane as an inducer of glutathione prevents oxidative stress-induced cell death in a dopaminergic-like neuroblastoma cell line. J Neurochem. 2009 Dec;111(5):1161-71. doi: 10.1111/j.1471-4159.2009.06394.x. PMID 19780897, Han JM, Lee YJ, Lee SY, Kim EM, Moon Y, Kim HW, Hwang O. Protective effect of sulforaphane against dopaminergic cell death. J Pharmacol Exp Ther. 2007 Apr;321(1):249-56. PMID 17259450, protège de la neurotoxine endogène 5-S-cystéinyl-dopamine Vauzour D, Buonfiglio M, Corona G, Chirafisi J, Vafeiadou K, Angeloni C, Hrelia S, Hrelia P, Spencer JP. Sulforaphane protects cortical neurons against 5-S-cysteinyl-dopamine-induced toxicity through the activation of ERK1/2, Nrf-2 and the upregulation of detoxification enzymes. Mol Nutr Food Res. 2010 Apr;54(4):532-42. doi: 10.1002/mnfr.200900197. PMID 20166144, protège de la neuro-inflammation constatée dans les troubles du spectre de l'autisme Singh K, Connors SL, Macklin EA, Smith KD, Fahey JW, Talalay P, Zimmerman AW. Sulforaphane treatment of autism spectrum disorder (ASD). Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15550-5. doi: 10.1073/pnas.1416940111. Epub 2014 Oct 13. PMID 25313065; PMCID: PMC4217462.
* Anti-Helicobacter pylori Yanaka A, Fahey JW, Fukumoto A, Nakayama M, Inoue S, Zhang S, Tauchi M, Suzuki H, Hyodo I, Yamamoto M. Dietary sulforaphane-rich broccoli sprouts reduce colonization and attenuate gastritis in Helicobacter pylori-infected mice and humans. Cancer Prev Res (Phila). 2009 Apr;2(4):353-60. doi: 10.1158/1940-6207.CAPR-08-0192. PMID 19349290, Fahey JW, Haristoy X, Dolan PM, Kensler TW, Scholtus I, Stephenson KK, Talalay P, Lozniewski A. Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumors. Proc Natl Acad Sci U S A. 2002 May 28;99(11):7610-5. PMID 12032331, Galan, M. V., Kishan, A. A., & Silverman, A. L. (2004). Oral broccoli sprouts for the treatment of Helicobacter pylori infection: a preliminary report. Digestive diseases and sciences, 49(7-8), 1088–1090. https://doi.org/10.1023/b:ddas.0000037792.04787.8a PMID 15387326, Yanaka A. (2017). Role of Sulforaphane in Protection of Gastrointestinal Tract Against H. pylori and NSAID-Induced Oxidative Stress. Current pharmaceutical design, 23(27), 4066–4075. https://doi.org/10.2174/1381612823666170207103943 PMID 28176666, Haristoy, X., Angioi-Duprez, K., Duprez, A., & Lozniewski, A. (2003). Efficacy of sulforaphane in eradicating Helicobacter pylori in human gastric xenografts implanted in nude mice. Antimicrobial agents and chemotherapy, 47(12), 3982–3984. https://doi.org/10.1128/aac.47.12.3982-3984.2003 PMID 14638516
* Après prise alimentaire de brocolis, riches en sulforaphane, on retrouve des thiocyanates dans l'articulation, avec induction de modifications histologiques du cartilage Davidson R, Gardner S, Jupp O, Bullough A, Butters S, Watts L, Donell S, Traka M, Saha S, Mithen R, Peffers M, Clegg P, Bao Y, Cassidy A, Clark I. Isothiocyanates are detected in human synovial fluid following broccoli consumption and can affect the tissues of the knee joint. Sci Rep. 2017 Jun 13;7(1):3398. doi: 10.1038/s41598-017-03629-5. PMID 28611391; PMCID: PMC5469854.
* Potentialités dans les accidents vasculaires cérébraux ischémiques : en cas d’AVC ischémique, l’efficacité de l'activateur tissulaire du plasminogène (qui réduit la taille du caillot) passe de 20 % à 60 % lorsque le médicament est co-administré avec le sulforaphane Guan IA, Liu JST, Sawyer RC, Li X, Jiao W, Jiramongkol Y, White MD, Hagimola L, Passam FH, Tran DP, Liu X, Schoenwaelder SM, Jackson SP, Payne RJ, Liu X. Integrating Phenotypic and Chemoproteomic Approaches to Identify Covalent Targets of Dietary Electrophiles in Platelets. ACS Cent Sci. 2024 Jan 29;10(2):344-357. doi: 10.1021/acscentsci.3c00822. PMID 38435523 PMCID: PMC10906253.
==Effet thérapeutique==
* Cancers Fimognari C, Hrelia P. Sulforaphane as a promising molecule for fighting cancer. Mutat Res. 2007 May-Jun;635(2-3):90-104. PMID 17134937, surtout de la prostate, intérêt chez des patients atteints de cancer de la prostate localisé en récidive biologique après prostatectomie 
* Maladie de Parkinson (?) Beal MF. Therapeutic approaches to mitochondrial dysfunction in Parkinson's disease. Parkinsonism Relat Disord. 2009 Dec;15 Suppl 3:S189-94. doi: 10.1016/S1353-8020(09)70812-0. PMID 20082988 
* Accidents vasculaires cérébraux ischémiques 
* DMLA Wang S, Tang YJ. Sulforaphane ameliorates amyloid-β-induced inflammatory injury by suppressing the PARP1/SIRT1 pathway in retinal pigment epithelial cells. Bioengineered. 2021 Dec;12(1):7079-7089. doi: 10.1080/21655979.2021.1976503. PMID 34982643; PMCID: PMC8973853.
==Effets indésirables==
* Très bonne tolérance
* Inhibiteur des cytochromes P-450 CYP2B et CYP3A2
* La surgélation et la cuisson à haute température détruiraient le sulforaphane Dosz EB, Jeffery EH. Modifying the processing and handling of frozen broccoli for increased sulforaphane formation. J Food Sci. 2013 Sep;78(9):H1459-63. doi: 10.1111/1750-3841.12221. PMID 23915112, Edward B. Dosz, Elizabeth H. Jeffery, Commercially produced frozen broccoli lacks the ability to form sulforaphane. Journal of Functional Foods, Volume 5, Issue 2, April 2013, Pages 987–990. DOI: 10.1016/j.jff.2013.01.033
==Bibliographie==
* Yeh CT, Yen GC. Effect of sulforaphane on metallothionein expression and induction of apoptosis in human hepatoma HepG2 cells. Carcinogenesis. 2005 Dec;26(12):2138-48. PMID 16033772
* Cook AL, Vitale AM, Ravishankar S, Matigian N, Sutherland GT, Shan J, Sutharsan R, Perry C, Silburn PA, Mellick GD, Whitelaw ML, Wells CA, Mackay-Sim A, Wood SA. NRF2 activation restores disease related metabolic deficiencies in olfactory neurosphere-derived cells from patients with sporadic Parkinson's disease. PLoS One. 2011;6(7):e21907. doi: 10.1371/journal.pone.0021907. PMID 21747966
* Niso-Santano M, González-Polo RA, Bravo-San Pedro JM, Gómez-Sánchez R, Lastres-Becker I, Ortiz-Ortiz MA, Soler G, Morán JM, Cuadrado A, Fuentes JM; Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED). Activation of apoptosis signal-regulating kinase 1 is a key factor in paraquat-induced cell death: modulation by the Nrf2/Trx axis. Free Radic Biol Med. 2010 May 15;48(10):1370-81. doi: 10.1016/j.freeradbiomed.2010.02.024. PMID 20202476
Catégorie:principes actifs