Letter to the editor
Current potential health benefits of sulforaphane
Jae Kwang Kim1, Sang Un Park21Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon, 406-772, Korea
2Department of Crop Science, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 305-764, Korea
EXCLI J 2016;15:Doc571
Sulforaphane [SFN: 1-isothiocyanato-4-(methylsulfinyl)butane] belongs to the isothiocyanate class of phytochemicals. Glucoraphanin, a glucosinolate precursor of SFN, is a glucosinolate found in cruciferous vegetables such as broccoli, cabbage, cauliflower, and kale. All glucosinolates are composed of a basic structure consisting of a β-D-thioglucose group, a sulfonated oxime group, and an amino acid-derived side chain. Glucosinolates are activated by enzyme-dependent hydrolysis to their respective isothiocyanates. SFN (molecular formula C6H11NOS2) is the biologically active isothiocyanate produced by the metabolism of glucoraphanin by the enzyme myrosinase (Fahey et al., 2015).
SFN is one of the most frequently studied plant-derived isothiocyanate organosulfur compounds. It has been reported to exhibit a wide range of biological effects including antioxidant (Fahey and Talalay, 1999), antimicrobial (Johansson et al., 2008), anticancer (Amjad et al., 2015), anti-inflammatory (Greaney et al., 2016), anti-aging (Sikdar et al., 2016), neuroprotective (Tarozzi et al., 2013), and antidiabetic (Lee et al., 2012).
SFN shows a range of biological activities and health benefits in humans, has been found to be a very promising chemopreventive agent against not only a variety of cancers such as breast, prostate, colon, skin, lung, stomach, and bladder but also against cardiovascular and neurodegenerative diseases and diabetes (Yang et al., 2016). In this present study, we reviewed the most recent studies on the biological and pharmacological activities of SFN (Table 1(Tab. 1)) (References in Table 1: Pal and Konkimalla, 2016; Zhao et al., 2016; Wu et al., 2016; Sasaki et al., 2016; Jiang et al., 2016; Hernández-Rabaza et al., 2016; Sikdar et al., 2016; Li et al., 2016; Thaler et al., 2016; Lan et al., 2016; Shehatou and Suddek, 2016; Townsend and Johnson, 2016; Qi et al., 2016; Abbas et al., 2016; Kikuchi et al., 2015; Atwell et al., 2015; Ma et al., 2015; Kim et al., 2015; Wang et al., 2015; Lubecka-Pietruszewska et al., 2015; Brown et al., 2015; Carrasco-Pozo et al., 2015; Ambrecht et al., 2015; Lavich et al., 2015; Waston et al., 2015; Shirai et al., 2015; Prasad and Mishra, 2015; Li et al., 2015; Cipolla et al., 2015; Angeloni et al., 2015; Oguz et al., 2015; Noh et al., 2015; Shang et al., 2015; Horwacik et al., 2015; Shokeir et al., 2015; Alzoubi et al., 2015; Gabriel et al., 2015; Kee et al., 2015; Rizzo et al., 2014; Pan et al., 2014; Sayed et al., 2014; Singh et al., 2014; Maeda et al., 2014; Zhang et al., 2014; Lee et al., 2014; Fimognari et al., 2014; Jo et al., 2014).
This work was supported by Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries (IPET) through Agri-Bio Industry Technology Development Program, funded by Ministry of Agriculture, Food and Rural Affairs (MAFRA) (316006-5).
Conflict of interest
The authors declare no conflict of interest
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13. Gabriel D, Roedl D, Gordon LB, Djabali K. Sulforaphane enhances progerin clearance in Hutchinson–Gilford progeria fibroblasts. Aging Cell. 2015;14:78-91.
14. Greaney AJ, Maier NK, Leppla SH, Moayeri M. Sulforaphane inhibits multiple inflammasomes through an Nrf2-independent mechanism. J Leukoc Biol. 2016;99:189-99.
15. Hernández-Rabaza V, Cabrera-Pastor A, Taoro-González L, Malaguarnera M, Agustí A, Llansola M, et al. Hyperammonemia induces glial activation, neuroinflammation and alters neurotransmitter receptors in hippocampus, impairing spatial learning: reversal by sulforaphane. J Neuroinflamm. 2016;13:1.
16. Horwacik I, Gaik M, Durbas M, Boratyn E, Zając G, Szychowska K, et al. Inhibition of autophagy by 3-methyladenine potentiates sulforaphane-induced cell death of BE (2)-C human neuroblastoma cells. Mol Med Rep. 2015;12:535-42.
17. Jiang LL, Zhou SJ, Zhang XM, Chen HQ, Liu W. Sulforaphane suppresses in vitro and in vivo lung tumorigenesis through downregulation of HDAC activity. Biomed Pharmacother. 2016;78:74-80.
18. Jo GH, Kim GY, Kim WJ, Park KY, Choi YH. Sulforaphane induces apoptosis in T24 human urinary bladder cancer cells through a reactive oxygen species-mediated mitochondrial pathway: the involvement of endoplasmic reticulum stress and the Nrf2 signaling pathway. Int J Oncol. 2014;45:1497-506.
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20. Kee HJ, Kim GR, Kim IK, Jeong MH. Sulforaphane suppresses cardiac hypertrophy by inhibiting GATA4/GATA6 expression and MAPK signaling pathways. Mol Nutr Food Res. 2015;59:221-30.
21. Kikuchi M, Ushida Y, Shiozawa H, Umeda R, Tsuruya K, Aoki Y, et al. Sulforaphane-rich broccoli sprout extract improves hepatic abnormalities in male subjects. World J Gastroenterol. 2015;21:12457.
22. Kim DH, Sung B, Kang YJ, Hwang SY, Kim MJ, Yoon JH, et al. Sulforaphane inhibits hypoxia-induced HIF-1α and VEGF expression and migration of human colon cancer cells. Int J Oncol. 2015;47:2226-32.
23. Lan F, Yang Y, Han J, Wu Q, Yu H, Yue X. Sulforaphane reverses chemo-resistance to temozolomide in glioblastoma cells by NF-κB-dependent pathway downregulating MGMT expression. Int J Oncol. 2016;48:559-68.
24. Lavich I, De Freitas B, Kist L, Falavigna L, Dargél V, Köbe L, et al. Sulforaphane rescues memory dysfunction and synaptic and mitochondrial alterations induced by brain iron accumulation. Neuroscience. 2015;301:542-52.
25. Lee JH, Jeong JK, Park SY. Sulforaphane-induced autophagy flux prevents prion protein-mediated neurotoxicity through AMPK pathway. Neuroscience. 2014;278:31-9.
26. Lee JH, Moon MH, Jeong JK, Park YG, Lee YJ, Seol JW, et al. Sulforaphane induced adipolysis via hormone sensitive lipase activation, regulated by AMPK signaling pathway. Biochem Biophys Res Commun. 2012;426:492-7.
27. Li B, Tian S, Liu X, He C, Ding Z, Shan Y. Sulforaphane protected the injury of human vascular endothelial cell induced by LPC through up-regulating endogenous antioxidants and phase II enzymes. Food Funct. 2015;6:1984-91.
28. Li YP, Wang SL, Liu B, Tang L, Kuang RR, Wang XB, et al. Sulforaphane prevents rat cardiomyocytes from hypoxia/reoxygenation injury in vitro via activating SIRT1 and subsequently inhibiting ER stress. Acta Pharmacol Sin. 2016;37:344-53.
29. Lubecka-Pietruszewska K, Kaufman-Szymczyk A, Stefanska B, Cebula-Obrzut B, Smolewski P, Fabianowska-Majewska K. Sulforaphane alone and in combination with clofarabine epigenetically regulates the expression of DNA methylation-silenced tumour suppressor genes in human breast cancer cells. J Nutrigenet Nutrigenom. 2015;8:91-101.
30. Ma LL, Xing GP, Yu Y, Liang H, Yu TX, Zheng WH, et al. Sulforaphane exerts neuroprotective effects via suppression of the inflammatory response in a rat model of focal cerebral ischemia. Int J Clin Exp Med. 2015;8:17811.
31. Maeda S, Matsui T, Ojima A, Takeuchi M, Yamagishi SI. Sulforaphane inhibits advanced glycation end product–induced pericyte damage by reducing expression of receptor for advanced glycation end products. Nutr Res. 2014;34:807-13.
32. Noh JR, Kim YH, Hwang JH, Choi DH, Kim KS, Oh WK, et al. Sulforaphane protects against acetaminophen-induced hepatotoxicity. Food Chem Toxicol. 2015;80:193-200.
33. Oguz A, Kapan M, Kaplan I, Alabalik U, Ulger BV, Uslukaya O, et al. The effects of sulforaphane on the liver and remote organ damage in hepatic ischemia-reperfusion model formed with pringle maneuver in rats. Int J Surg. 2015;18:163-8.
34. Pal S, Konkimalla VB. Sulforaphane regulates phenotypic and functional switching of both induced and spontaneously differentiating human monocytes. Int Immunopharmacol. 2016;35:85-98.
35. Pan H, He M, Liu R, Brecha NC, Yu ACH, Pu M. Sulforaphane protects rodent retinas against ischemia-reperfusion injury through the activation of the Nrf2/HO-1 antioxidant pathway. PloS One. 2014;9:e114186.
36. Prasad AK, Mishra P. Mechanism of action of sulforaphane as a superoxide radical anion and hydrogen peroxide scavenger by double hydrogen transfer: a model for iron superoxide dismutase. J Phys Chem B. 2015;119:7825-36.
37. Qi T, Xu F, Yan X, Li S, Li H. Sulforaphane exerts anti-inflammatory effects against lipopolysaccharide-induced acute lung injury in mice through the Nrf2/ARE pathway. Int J Mol Med. 2016;37:182-8.
38. Rizzo B, Maltese G, Paraskevi MP, Hrelia S, Mann G, Siow R. OP1-6-Induction of antioxidant genes by sulforaphane and klotho in human aortic smooth muscle cells. Free Rad Biol Med. 2014;75:S14-5.
39. Sasaki M, Shinozaki S, Shimokado K. Sulforaphane promotes murine hair growth by accelerating the degradation of dihydrotestosterone. Biochem Biophys Res Commun. 2016;472:250-4.
40. Sayed RH, Khalil WK, Salem HA, El-Sayeh BM. Sulforaphane increases the survival rate in rats with fulminant hepatic failure induced by D-galactosamine and lipopolysaccharide. Nutr Res. 2014;34:982-9.
41. Shang G, Tang X, Gao P, Guo F, Liu H, Zhao Z, et al. Sulforaphane attenuation of experimental diabetic nephropathy involves GSK-3 beta/Fyn/Nrf2 signaling pathway. J Nutr Biochem. 2015;26:596-606.
42. Shehatou GS, Suddek GM. Sulforaphane attenuates the development of atherosclerosis and improves endothelial dysfunction in hypercholesterolemic rabbits. Exp Biol Med. 2016;241:426-36.
43. Shirai Y, Fujita Y, Hashimoto R, Ohi K, Yamamori H, Yasuda Y, et al. Dietary intake of sulforaphane-rich broccoli sprout extracts during juvenile and adolescence can prevent phencyclidine-induced cognitive deficits at adulthood. PloS One. 2015;10:e0127244.
44. Shokeir AA, Barakat N, Hussein AM, Awadalla A, Harraz A, Khater S, et al. Activation of Nrf2 by ischemic preconditioning and sulforaphane in renal ischemia/reperfusion injury: a comparative experimental study. Physiol Res. 2015;64:313.
45. Sikdar S, Papadopoulou M, Dubois J. What do we know about sulforaphane protection against photoaging? J Cosmet Dermatol. 2016;15:72-7.
46. Singh K, Connors SL, Macklin EA, Smith KD, Fahey JW, Talalay P, et al. Sulforaphane treatment of autism spectrum disorder (ASD). Proc Natl Acad Sci USA. 2014;111:15550-5.
47. Tarozzi A, Angeloni C, Malaguti M, Morroni F, Hrelia S, Hrelia P. Sulforaphane as a potential protective phytochemical against neurodegenerative diseases. Oxid Med Cell Longev. 2013;2013:415078.
48. Thaler R, Maurizi A, Roschger P, Sturmlechner I, Khani F, Spitzer S, et al. Anabolic and antiresorptive modulation of bone homeostasis by the epigenetic modulator sulforaphane, a naturally occurring isothiocyanate. J Biol Chem. 2016;291:6754-71.
49. Townsend BE, Johnson RW. Sulforaphane induces Nrf2 target genes and attenuates inflammatory gene expression in microglia from brain of young adult and aged mice. Exp Gerontol. 2016;73:42-8.
50. Wang W, He Y, Yu G, Li B, Sexton DW, Wileman T, et al. Sulforaphane protects the liver against CdSe quantum dot-induced cytotoxicity. PloS One. 2015;10:e0138771.
51. Watson GW, Wickramasekara S, Fang Y, Palomera‐Sanchez Z, Maier CS, Williams DE, et al. Analysis of autophagic flux in response to sulforaphane in metastatic prostate cancer cells. Mol Nutr Food Res. 2015;59:1954-61.
52. Wu J, Han J, Hou B, Deng C, Wu H, Shen L. Sulforaphane inhibits TGF-β-induced epithelial-mesenchymal transition of hepatocellular carcinoma cells via the reactive oxygen species-dependent pathway. Oncol Rep. 2016;35:2977-83.
53. Yang L, Palliyaguru DL, Kensler TW. Frugal chemoprevention: targeting Nrf2 with foods rich in sulforaphane. Semin Oncol. 2016;43:146-53.
54. Zhang R, Zhang J, Fang L, Li X, Zhao Y, Shi W, et al. Neuroprotective effects of sulforaphane on cholinergic neurons in mice with Alzheimer’s disease-like lesions. Int J Mol Sci. 2014;15:14396-410.
55. Zhao Z, Liao G, Zhou Q, Lv D, Holthfer H, Zou H. Sulforaphane attenuates contrast-induced nephropathy in rats via Nrf2/HO-1 pathway. Oxid Med Cell Longev. 2016;2016:9825623.
Table 1: Recent studies on biological and pharmacological activities of sulforaphane (SFN)