Benefits of Sulforaphane on Antioxidation

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• The widespread belief that oxidative damage plays a major role in cancer, ageing, and in a number of chronic diseases and is widely believed to contribute to the etiology and progression of many age-related chronic degenerative diseases. This view focuses the attention of science and the public on the search and development of antioxidants.

  Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, has cytoprotective effects against oxidative stress. Substantial and growing evidence that SFN administration acts indirectly to increase the antioxidant capacity of animal cells and their abilities to cope with oxidative stress. SFN has been shown to induce expression of antioxidant genes via activation of a transcription factor, nuclear factor erythroid-2 related factor 2 (Nrf2). And a number of in vitro and animals studies have provided further supportive evidence of SFN’s role not only on induction of quinone oxidoreductase 1 (NQO1) but of other antioxidant response element (ARE)-dependent enzyme family members.                                         

  1.Academic Research

  In 2004, Professor Paul Talalay’s team found that the phase 2 genes induced by SFN can protect retinal pigment epithelial cells from photooxidative damage. SFN treatment also protected retinal pigment epithelial (RPE) cells against the photooxidative toxicity of retinaldehyde. Prior treatment of human adult RPE cells (ARPE-19) with SFN (1.25-5.0μM) for 24h resulted in substantial concentration-dependent protection against exposure to retinaldehyde and light, and the survival of ARPE-19 cells improved as the concentration of SFN was raised[1].

  2. Animal models

  2004，researchers at the University of Saskatchewan in Canada used GRA-rich broccoli sprouts to treat spontaneously hypertensive stroke-pr rats. After each rat took 5.5 μmol per day, they had significantly decreased oxidative stress in cardiovascularand kidney tissues, as shown by increased alutathione (GSH) content and decreased oxidized GSH, decreased protein nitrosylation, as well as ingreased GSH reductase and GSH peroxidase activities. The results show that intake of broccoli sprouts high in GRA, whose metabolite SFN is a potent phase 2 protein inducer, decreased oxidative stress and inflammation in kidneys and the cardiovascular system[2].

  In 2005, a study tested whether pretreatment with SFN protects against light-induced retinal damage in mice. The results showed that both intraperitoneal and oral SFN induced thioredoxin (Trx) protein in neural retina and retinal pigment epithelial cells (RPE). Trx is a multifunctional endogenous redox regulator that protects cells against various types of cellular or tissue stresses. SFN induced Trx in mouse retina, which can effectively reduce retinal light damage[3].

  In 2010, a study reported that SFN activated endogenous biological antioxidant defense system. In the study, pretreatment with SFN effectively reduced cerebral infarct volume of neonatal hypoxia ischemia (HI) rats through inducing the expressions of Nrf2 and HO-1, which may indirectly act as therapeutic antioxidants by selectively reducing cytotoxic oxygen radicals. Therefore, activation of endogenous antioxidant system by SFN may offer an alternative route in clinical management of neonatal hypoxia ischemia brain injury[4].

  In 2010, Donghoo Kim et al. studied the effect of SFN on mechanical allodynia and thermal pain in mice injured by spinal nerve transection (SNT). SFN injection 5 min before SNT injury reduced mechanical allodynia by 70%, and almost completely inhibited the induction of thermal hyperalgesia. In addition, SFN injection 1 h post injury was able to inhibit mechanical allodynia. Intrathecal administration of sulforaphane reduced oxidative stress and proinflammatory cytokine expression caused by spinal nerve transection and inhibited the development of neuropathic pain[5].

  In a report in 2012, SFN provided protection at all doses of UVA radiatior tested (up to 20 J/cm²) in mice under both basal conditions and after 6-TG (a surrogate for the immunosuppressive and anti-inflammatory agent azathioprine) treatment. Protection correlates with increased levels of NQO1 and GSH, and requires transcription factor Nrf2. That implicated the indirect antioxidant activity of SFN, via induction of Nrf2-dependent genes, as the major protective mechanism[6].

  3.Clinical trials

  In 2008, a placebo-controlled dose escalation trial studied the in vivo effects of SFN on the expression of glutathione-s-transferase MI (GSTM1), glutathione-s-transferase P1 (GSTP1), NADPH quinone oxidoreductase (NQO1), and hemoxygenase-1 (HO-1) in the upper airway of human subjects. Study subjects consumed oral SFN doses contained in a standardized broccoli sprout homogenate (BSH). RNA expression for selected Phase II enzymes was measured in nasal lavage cells by RT-PCR before and after SFN dosing. Results showed that increased Phase II enzyme expression in nasal lavage cells occurred in a dose-dependent manner. Significant increases were seen in all sentinel Phase II enzymes RNA expression compared to baseline. These indicate that oral SFN increases Phase II antioxidant enzymes in the human upper airway[7].

  In 2015, Japanese researchers recruited 55 male outpatients with fatty liver for clinical trials. They received either 3 BS capsules containino 30 mg of GRA, the precursor of SFN, or the placebo for 2 mo. Dietary supplementation with BS extract containing SFN precursor GRA for 2 mo significantly decreased serum levels of liver function markers, and placebo showed no significant effects on the markers. Among them, the urinary level of 8-OHdG, an established oxidative stress marker, was significantly reduced. The researchers thought that dietary supplementation with BS extract containing the SFN precursor GRA is likely to be highly effective in improving liver function through reduction of oxidative stress[8].

  In 2015, Chang, Y. W, et al. From Korea and others investigated whether a broccoli sprout extract containing SFN (BSES) inhibited the Helicobacter pylori infection density and exerted an antioxidative effect on gastric mucosa damage. The results showed that BSES treatment did significantly reduce mucosal malondialdehyde (MDA, an oxidative damage biomarker) concentrations. BSES prevented lipid peroxidation in the gastric mucosa and may play a cytoprotective role in H. pylori-induced gastritis[9].

  Excessive exercise increases the production of reactive oxygen species in skeletal muscles. In 2021, researchers from University of Tsukuba evaluated the effect of SFN supplement intake in humans regarding the delayed onset muscle soreness (DOMS) after eccentric exercise. SFN supplement intake for 2 weeks increased NQO1 mRNA expression in peripheral blood mononuclear cells (PBMCs). Muscle soreness on palpation and range of motion (ROM) were significantly lower 2 days after exercise in the SFN group compared with the control group. Serum MDA showed significantly lower levels 2 days after exercise in the SFN group compared with the control group[10].

  
  

  
  

  References（obtained by email info@sanherb.com）

  
  

  
  

  [1]X., et al. "Induction of phase 2 genes by sulforaphane protects retinal pigment epithelial cells against photooxidative damage." Proceedings of the National Academy of Sciences 101.28(2004):10446-10451.

  [2]Wu, L. Y. , et al. "Dietary approach to attenuate oxidative stress, hypertension, and inflammation in the cardiovascular system." Proceedings of the National Academy of Sciences 101.18(2004).

  [3]Masaki, Tanito , et al. "Sulforaphane Induces Thioredoxin through the Antioxidant-Responsive Element and Attenuates Retinal Light Damage in Mice." Invest Ophthalmol Vis 46.3(2005):979-987.

  [4]Zhang, et al. "Sulforaphane protects brains against hypoxic–ischemic injury through induction of Nrf2-dependent phase 2 enzyme." Brain Research (2010).

  [5]D, Kim, B, et al. NADPH oxidase 2-derived reactive oxygen species in spinal cord microglia contribute to peripheral nerve injury-induced neuropathic pain[J]. Proceedings of the National Academy of Sciences, 2010.

  [6]Benedict, et al. "The indirect antioxidant sulforaphane protects against thiopurine-mediated photooxidative stress." CARCINOGENESIS 2012,33(12).-(2012):2457-2466.

  [7]Riedl M A , Saxon A , Diaz-Sanchez D . Oral sulforaphane increases Phase II antioxidant enzymes in the human upper airway[J]. Clinical Immunology, 2009, 130(3):244-251.

  [8]Masahiro Kikuchi Yusuke Ushida Hirokazu Shiozawa Rumiko Umeda Kota Tsuruya Yudai Aoki Hiroyuki Suganuma Yasuhiro Nishizaki. Sulforaphane-rich broccoli sprout extract improves hepatic abnormalities in male subjects[J]. World J Gastroenterol 2015 November 21; 21(43): 12457-12467.

  [9]Chang Y W , Jang J Y , Yong H K , et al. The Effects of Broccoli Sprout Extract Containing Sulforaphane on Lipid Peroxidation and Helicobacter pylori Infection in the Gastric Mucosa[J]. Gut & Liver, 2015, 9(4):486-493.

  [10]Komine S, Miura I, Miyashita N, Oh S, Tokinoya K, Shoda J, Ohmori H. Effect of a sulforaphane supplement on muscle soreness and damage induced by eccentric exercise in young adults: A pilot study. Physiol Rep. 2021 Dec;9(24):e15130. doi: 10.14814/phy2.15130. PMID: 34927380; PMCID: PMC8685487.