Hyperlipidemia is a risk factor for clinically significant thrombotic events in cardiovascular diseases.Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxi...Hyperlipidemia is a risk factor for clinically significant thrombotic events in cardiovascular diseases.Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxidized lipids in oxidized low-density lipoprotein(ox-LDL)particles,a process that induces atherothrombosis.Sulforaphane(SFN)is a dietary isothiocyanate enriched in cruciferous vegetables and exerts multiple biological activities.The current study sought to investigate the efficacy of SFN on platelet hyperreactivity under hyperlipidemic conditions in vitro and in vivo.Using a series of platelet functional assays in human platelets in vitro,we demonstrated that SFN attenuated ox-LDL-increased platelet aggregation and activation(surface CD62P expression).Mechanistically,studies using pharmacological inhibitors clarified that these inhibitory effects of SFN were mainly modulated by down-regulating CD36-mediated activation of Src kinases,leading to enhanced activation of cyclic adenosine monophosphate/protein kinase A(cAMP/PKA)signaling,and resultant inhibition of NADPH oxidase 2(NOX2)-dependent generation of reactive oxygen species(ROS).Moreover,12-week supplementation of SFN-enriched broccoli sprout extract(BSE,0.06%diet)in hyperlipidemic C57BL/6J mice also decreased platelet hyperreactivity.Studies using pharmacological inhibitors of CD36,protein kinase A(PKA)and NOX2 showed that the efficacy of BSE supplementation was mainly through modulating CD36-mediated the cAMP/PKA/NOX2 signaling.Thus,through modulating the cAMP/PKA/NOX2 pathway and attenuating CD36-mediated platelet hyperreactivity,SFN may play important protective roles in atherothrombosis under hyperlipidemic conditions.展开更多
Prostate cancer is one of the most common tumors in urology.Dietary prophylaxis can effectively reduce prostate cancer incidence and progression.A growing body of research has shown that natural food ingredients such ...Prostate cancer is one of the most common tumors in urology.Dietary prophylaxis can effectively reduce prostate cancer incidence and progression.A growing body of research has shown that natural food ingredients such as Sulforaphane(SFN)can reduce the incidence of prostate cancer.It has a significant inhibitory effect on the progression from local prostate cancer to more aggressive prostate cancer.This article mainly expounds on the prevention mechanism and research progress of sulforaphane in various ways for prostate cancer and provides a reference for its future clinical application.In this review,‘SFN’,‘Prostate Cancer’,and‘PCa’were searched through PubMed,Embase,Web of Science,and other databases.SFN inhibits the occurrence and development of prostate cancer mainly through anti-oxidation,inhibition of fatty acid metabolism,inhibition of glycolysis,inhibition of proinflammatory factors,inhibition of cell proliferation and promotion of apoptosis,reduction of androgen receptors,and influence of epigenetics.Therefore,SFN is a natural compound with great potential for the prevention and treatment of prostate cancer,but the key factors such as effective chemoprevention dose,bioavailability,toxic dose,and response of sulforaphane in the human body need to be further studied in the future.展开更多
AIM: To investigate the effect of sulforaphane (SFN) on regulation of NF-E2-related factor-2 (Nrf2)-antiox-idant response element (ARE) pathway in liver injury induced by intestinal ischemia/reperfusion (I/R). METHODS...AIM: To investigate the effect of sulforaphane (SFN) on regulation of NF-E2-related factor-2 (Nrf2)-antiox-idant response element (ARE) pathway in liver injury induced by intestinal ischemia/reperfusion (I/R). METHODS: Rats were divided randomly into four ex-perimental groups: control, SFN control, intestinal I/R and SFN pretreatment groups (n = 8 in each group). The intestinal I/R model was established by clamping the superior mesenteric artery for 1 h and 2 h reperfu-sion. In the SFN pretreatment group, surgery was performed as in the intestinal I/R group, with intraperitoneal administration of 3 mg/kg SFN 1 h before the op-eration. Intestine and liver histology was investigated. Serum levels of aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured. Liver tissue superoxide dismutase (SOD), myeloperoxidase (MPO), glutathione (GSH) and glutathione peroxidase (GSH-Px) activity were assayed. The liver transcription factor Nrf2 and heme oxygenase-1 (HO-1) were determined by immunohistochemical analysis and Western blotting analysis.RESULTS: Intestinal I/R induced intestinal and liver injury, characterized by histological changes as well as a signif icant increase in serum AST and ALT levels (AST: 260.13 ± 40.17 U/L vs 186.00 ± 24.21 U/L, P < 0.01; ALT: 139.63 ± 11.35 U/L vs 48.38 ± 10.73 U/L, P < 0.01), all of which were reduced by pretreatment with SFN, respectively (AST: 260.13 ± 40.17 U/L vs 216.63 ± 22.65 U/L, P < 0.05; ALT: 139.63 ± 11.35 U/L vs 97.63 ± 15.56 U/L, P < 0.01). The activity of SOD in the liver tissue decreased after intestinal I/R (P < 0.01), which was enhanced by SFN pretreatment (P < 0.05). In ad-dition, compared with the control group, SFN markedly reduced liver tissue MPO activity (P < 0.05) and elevat-ed liver tissue GSH and GSH-Px activity (P < 0.05, P < 0.05), which was in parallel with the increased level of liver Nrf2 and HO-1 expression.CONCLUSION: SFN pretreatment attenuates liver injury induced by intestinal I/R in rats, attributable to the antioxidant effect through Nrf2-ARE pathway.展开更多
Sulforaphane is a type of sulfur-containing isothiocyanates hydrolyzed from glucosinolates by myrosinase found in Brassica plants. Sulforaphane is a naturally occurring inducer of phase II enzymes in human and animal ...Sulforaphane is a type of sulfur-containing isothiocyanates hydrolyzed from glucosinolates by myrosinase found in Brassica plants. Sulforaphane is a naturally occurring inducer of phase II enzymes in human and animal bodies to detoxify cancer-causing chemicals. Glucoraphanin is the precursor of sulforaphane and its content is greatly influenced by plant species and genotype, plant organs, pre-harvest factors, and post-harvest processing, thus sulforaphane formation is also directly influenced. Here, we review the formation mechanism of sulforaphane and the factors influencing sulforaphane formation. In the end, the future directions are also discussed.展开更多
AIM: To evaluate effects of dietary supplementation of sulforaphane(SF)-rich broccoli sprout(BS) extract on hepatic abnormalities in Japanese male participants.METHODS: In a randomized,placebo-controlled,double blind ...AIM: To evaluate effects of dietary supplementation of sulforaphane(SF)-rich broccoli sprout(BS) extract on hepatic abnormalities in Japanese male participants.METHODS: In a randomized,placebo-controlled,double blind trial,male participants with fatty liver received either BS capsules containing glucoraphanin [GR; a precursor of SF(n = 24)] or placebo(n = 28) for 2 mo. Liver function markers,serum levels of aspartate and alanine aminotransferases(AST and ALT,respectively) and γ-glutamyl transpeptidase(γ-GTP) and an oxidative stress marker,urinary levels of 8-hydroxydeoxyguanosine(8-OHd G),were measured and compared in participants before and after the trial period. In an animal model,chronic liver failure was induced in Sprague-Dawley rats by successive intraperitoneal injection with N-nitrosodimethylamine(NDMA) for 4 wk. Concomitantly,rats received AIN-76 diets supplemented with or without BS extract. Thereafter,rats were sacrificed,and their sera and livers were collected to measure serum liver function markers and hepatic levels of thiobarbituric acid reactive substances(TBARS) levels and hepatic glutathione S-transferase(GST) activity,a prototypical phase 2 antioxidant enzyme.RESULTS: Dietary supplementation with BS extract containing SF precursor GR for 2 mo significantly decreased serum levels of liver function markers,ALT [median(interquartile range),before: 54.0(34.5-79.0) vs after supplementation: 48.5(33.3-65.3) IU/L,P < 0.05] and γ-GTP [before: 51.5(40.8-91.3) vs after: 50.0(37.8-85.3) IU/L,P < 0.05],as well as the alkali phosphatase activity. Placebo showed no significant effects on the markers. The urinary level of 8-OHd G,an established oxidative stress marker,was significantly reduced in participants who had received BS capsules but not the placebo [before: 6.66(5.51-9.03) vs after: 5.49(4.89-6.66) ng/mg-creatinine,P < 0.05]. The reduction of urinary 8-OHd G was significantly correlated with decreased levels of both ALT and γ-GTP [?8-OHd G and ?ALT: Spearman r(r) 0.514 and P = 0.012,?8-OHd G and ?γ-GTP: r = 0.496 and P = 0.016]. Intake of BS extract prevented NDMA-induced chronic liver failure in rats,which was attributable to the suppression of the increase in TBARS through induction of hepatic phase 2 antioxidant enzymes including hepatic GST(86.6 ± 95.2 vs 107.8 ± 7.7 IU/g,P < 0.01).CONCLUSION: Dietary supplementation with BS extract containing the SF precursor GR is likely to be highly effective in improving liver function through reduction of oxidative stress.展开更多
Tumorigenicity-inhibiting compounds have been identifled in our daily diet.For example,isothiocyanates(ITCs)found in cruciferous vegetables were reported to have potent cancer=prevention activities.The best characteri...Tumorigenicity-inhibiting compounds have been identifled in our daily diet.For example,isothiocyanates(ITCs)found in cruciferous vegetables were reported to have potent cancer=prevention activities.The best characterized ITC is sulforaphane(SF).SF can simultaneously modulate multiple cellular targets involved in carcinogenesis,including(1)modulating carcinogen-metabolizing enzymes and blocking the action of mutagens;(2)inhibition of cell proliferation and induction of apoptosis;and(3)inhibition of neo-angiogenesis and metastasis.SF targets cancer stem cells through modulation of nuclear factor kappa B(NF-κB),Sonic hedgehog(SHH),epithelial-mesenchymal transition,and Wnt/βcatenin pathways.Conventional chemotherapy/SF combination was tested in several studies and resulted in favorable outcomes.With its favorable toxicological profile,SF is a promising agent in cancer prevention and/or therapy.In this article,we discuss the human metabolism of SF and its effects on cancer prevention,treatment,and targeting cancer stem cells,as well as providing a brief review of recent human clinical trials on SF.展开更多
Innate immunity,particularly macrophages,is critical for intestinal homeostasis.Sulforaphane,a dietary isothiocyanate from cruciferous vegetables,has been reported to protect against intestinal inflammation.However,th...Innate immunity,particularly macrophages,is critical for intestinal homeostasis.Sulforaphane,a dietary isothiocyanate from cruciferous vegetables,has been reported to protect against intestinal inflammation.However,the role of macrophages in sulforaphane mediated intestinal inflammation and the underlying molecular mechanisms have not been studied yet.In this study,sulforaphane effectively attenuated dextran sodium sulphate(DSS)induced intestinal inflammation in murine model.Of note,sulforaphane skewed the switching from classically(M1)to alternatively(M2)activated phenotype both in intestinal and bone marrow-derived macrophages(BMDMs).The expression levels of M1 associated maker genes induced by DSS or lipopolysaccharide(LPS)plus interferon gamma-γ(IFN-γ)were suppressed by sulforaphane while M2 marker gene expression levels were improved.This resulted in alteration of inflammatory mediators,particularly interleukin-10(IL-10),both in colon tissues and culture medium of BMDMs.Subsequently,IL-10 was found to mediate the sulforaphane induced M2 phenotype switching of BMDMs through the activation of STAT3 signaling.This was confirmed by immunofluorescence analysis with increased number of p-STAT3-positive cells in the colon sections.Moreover,anti-IL-10 neutralizing antibody significantly interfered M2 phenotyping of BMDMs induced by sulforaphane with reduced STAT3 phosphorylation.Findings here introduced a potential utilization of sulforaphane for intestinal inflammation treatment with macrophages as the therapeutic targets.展开更多
Background Mastitis not only deteriorates the composition or quality of milk,but also damages the health and pro-ductivity of dairy goats.Sulforaphane(SFN)is a phytochemical isothiocyanate compound with various pharma...Background Mastitis not only deteriorates the composition or quality of milk,but also damages the health and pro-ductivity of dairy goats.Sulforaphane(SFN)is a phytochemical isothiocyanate compound with various pharmacologi-cal effects such as anti-oxidant and anti-inflammatory.However,the effect of SFN on mastitis has yet to be elucidated.This study aimed to explore the anti-oxidant and anti-inflammatory effects and potential molecular mechanisms of SFN in lipopolysaccharide(LPS)-induced primary goat mammary epithelial cells(GMECs)and a mouse model of mastitis.Results In vitro,SFN downregulated the mRNA expression of inflammatory factors(tumor necrosis factor-α(TNF-α),interleukin(IL)-1βand IL-6),inhibited the protein expression of inflammatory mediators(cyclooxygenase-2(COX2),and inducible nitric oxide synthase(iNOS))while suppressing nuclear factor kappa-B(NF-κB)activation in LPS-induced GMECs.Additionally,SFN exhibited an antioxidant effect by increasing Nrf2 expression and nuclear translocation,up-regulating antioxidant enzymes expression,and decreasing LPS-induced reactive oxygen species(ROS)produc-tion in GMECs.Furthermore,SFN pretreatment promoted the autophagy pathway,which was dependent on the increased Nrf2 level,and contributed significantly to the improved LPS-induced oxidative stress and inflammatory response.In vivo,SFN effectively alleviated histopathological lesions,suppressed the expression of inflammatory factors,enhanced immunohistochemistry staining of Nrf2,and amplified of LC3 puncta LPS-induced mastitis in mice.Mechanically,the in vitro and in vivo study showed that the anti-inflammatory and anti-oxidative stress effects of SFN were mediated by the Nrf2-mediated autophagy pathway in GMECs and a mouse model of mastitis.Conclusions These results indicate that the natural compound SFN has a preventive effect on LPS-induced inflam-mation through by regulating the Nrf2-mediated autophagy pathway in primary goat mammary epithelial cells and a mouse model of mastitis,which may improve prevention strategies for mastitis in dairy goats.展开更多
Objective To determine whether sulforaphane （SFN） protects neurons against injury caused by oxygen-glucose deprivation/reoxygenation （OGD/R） and, if so, to investigate the possible mechanisms. Methods Primary cult...Objective To determine whether sulforaphane （SFN） protects neurons against injury caused by oxygen-glucose deprivation/reoxygenation （OGD/R） and, if so, to investigate the possible mechanisms. Methods Primary cultures of neurons were prepared from the cerebral cortex of 1-day-old Sprague-Dawley rats. On days 5-6 in vitro, the neurons were exposed to OGD for 1 h, followed by reoxygenation for 24 h. Cells were treated with 0, 0.1, 0.2, 0.5, 1, 2.5, or 5 μmol/L SFN, with or without 10 μmol/L LY294002, a PI3K-specific inhibitor, during OGD/R （a total of 25 h）. After 24-h reoxygenation, MTT was used to assess viability and injury was assessed by Hoechst 33258/propidium iodide （PI） staining; immunofluorescence staining and Western blot were performed to detect molecular events associated with apoptosis. Results The MTT assay showed that 1 μmol/L SFN significantly increased viability, and Hoechst 33258/PI staining showed that the numbers of injured neurons were reduced significantly in the SFN group. Furthermore, immunofluorescence staining and Western blot showed that SFN increased Bcl-2 and decreased cleaved caspase-3 levels. Moreover, LY294002 inhibited the phosphorylated-Akt expression evoked by SFN, decreased Bcl-2 expression and increased cleaved caspase-3 expression. Conclusion SFN protects neurons against injury from OGD/R and this effect may be partly associated with an anti-apoptosis pathway.展开更多
Objective: To analyze two isothiocyanates(sulforaphene and sulforaphane) and their antiproliferative effect of 11 indigenous cruciferous vegetables.Methods: Phytoconstituents identification was conducted by high perfo...Objective: To analyze two isothiocyanates(sulforaphene and sulforaphane) and their antiproliferative effect of 11 indigenous cruciferous vegetables.Methods: Phytoconstituents identification was conducted by high performance liquid chromatography and gas chromatography-mass spectrometer techniques. The antiproliferation was evaluated in colon cancer cell line HCT116 by MTT assay.Results: Isothiocyanate identification by high performance liquid chromatography showed that broccoli, cabbage, "Khi-Hood"(Raphanus sativus L. var. caudatus Alef) and Chinese radish contained isothiocyanates sulforaphane. Sulforaphene and sulforaphane in broccoli, cabbage and "Khi-Hood" were characterized by the gas chromatography-mass spectrometer analysis. Antiproliferation screening by MTT assay found that the potent plants which possessed IC_(50) below 50 mg/m L were cabbage and "Khi-Hood", while the others had low antiproliferation with IC_(50) higher than 50 mg/m L. Difference in antiproliferation was probably due to difference existed phytochemical constituents in each plant. "Khi-Hood" possessed the highest antiproliferation against HCT116 with the lowest IC_(50)at(9.42 ± 0.46) mg/m L. The IC_(50) of chemotherapeutic drug(mitomycin C)was(19.12 ± 1.00) mg/m L, while both melphalan and 5-fluorouracil possessed the IC_(50) value higher than 50 mg/m L.Conclusions: Commonly consumed cruciferous vegetables exerted varied antiproliferation and isothiocyanate contents. High isothiocyanate content in "Khi-Hood" was contributed to high antiproliferation. Among 11 plants studied, "Khi-Hood" could be an alternative chemopreventive diet.展开更多
Objective Acute liver failure(ALF)is characterized by severe liver dysfunction,rapid progression and high mortality and is difficult to treat.Studies have found that sulforaphane(SFN),a nuclear factor E2-related facto...Objective Acute liver failure(ALF)is characterized by severe liver dysfunction,rapid progression and high mortality and is difficult to treat.Studies have found that sulforaphane(SFN),a nuclear factor E2-related factor 2(NRF2)agonist,has anti-inflammatory,antioxidant and anticancer effects,and has certain protective effects on neurodegenerative diseases,cancer and liver fibrosis.This paper aimed to explore the protective effect of SFN in ALF and it possible mechanisms of action.Methods Lipopolysaccharide and D-galactosamine were used to induce liver injury in vitro and in vivo.NRF2 agonist SFN and histone deacetylase 6(HDAC6)inhibitor ACY1215 were used to observe the protective effect and possible mechanisms of SFN in ALF,respectively.Cell viability,lactate dehydrogenase(LDH),Fe2+,glutathione(GSH)and malondialdehyde(MDA)were detected.The expression of HDAC6,NRF2,glutathione peroxidase 4(GPX4),acyl-CoA synthetase long-chain family member 4(ACSL4)and solute carrier family 7 member 11(SLC7A11)were detected by Western blotting and immunofluorescence.Results Our results show that NRF2 was activated by SFN.LDH,Fe2+,MDA and ACSL4 were downregulated,while GSH,GPX4 and SLC7A11 were upregulated by SFN in vitro and in vivo,indicating the inhibitory effect of SFN on ferroptosis.Additionally,HDAC6 expression was decreased in the SFN group,indicating that SFN could downregulate the expression of HDAC6 in ALF.After using the HDAC6 inhibitor,ACY1215,SFN further reduced HDAC6 expression and inhibited ferroptosis,indicating that SFN may inhibit ferroptosis by regulating HDAC6 activity.Conclusion SFN has a protective effect on ALF,and the mechanism may include reduction of ferroptosis through the regulation of HDAC6.展开更多
AIM:To examine the effects of sulforaphane on fibrotic changes of transforming growth factor(TGFβ2)induced human conjunctival fibroblast(HCon Fs).METHODS:HCon Fs were cultured and divided into control,TGFβ2(1 ng/m L...AIM:To examine the effects of sulforaphane on fibrotic changes of transforming growth factor(TGFβ2)induced human conjunctival fibroblast(HCon Fs).METHODS:HCon Fs were cultured and divided into control,TGFβ2(1 ng/m L),sulforaphane and TGFβ2+sulforaphane groups.Cell viability and apoptosis were detected using the MTT and Apo Tox-Glo Triplex assay.Cell migration was detected using scratch and Transwell assay.Real-time quantitative PCR method was used to evaluate m RNA expression of TGFβ2,matrix metalloproteinase-2(MMP2),myosin light chain kinase(MYLK),integrinαV,integrinα5,fibronectin 1 andα-smooth muscle actin(α-SMA).The protein expression ofα-SMA,p-PI3 K,PI3 K,p-Akt,and Akt were detected by Western blot.RESULTS:The proliferation of HCon Fs was significantly(P<0.05)suppressed by sulforaphane compared to control cells with the increase of the concentration and treatment time.Cell proliferation after 48 h incubation was significantly reduced with 100μmol/L sulforaphane treatment by 17.53%(P<0.05).The Transwell assay showed sulforaphane decreased cell migration by 18.73%compared with TGFβ2-induced HCon F(P<0.05).TGFβ2-induced the increasing expression of fibronectin,type I collagen andα-SMA,and the phosphorylation of PI3 K and Akt were all significantly suppressed by sulforaphane pretreatment.CONCLUSION:Sulforaphane inhibits proliferation,migration,and synthesis of the extracellular matrix in HCon Fs,and inhibiting the PI3 K/Akt signaling pathway.Sulforaphane could be a potential therapeutic drug for prevention of scar formation in filtering bleb after trabeculectomy.展开更多
Neurodegeneration is a key aspect of a large number of diseases that come under the umbrella of＂neurodegenerative diseases＂with the most notable being Parkinson＇s,Alzheimer＇s,and Huntington＇s diseases（AD,PD,HD）...Neurodegeneration is a key aspect of a large number of diseases that come under the umbrella of＂neurodegenerative diseases＂with the most notable being Parkinson＇s,Alzheimer＇s,and Huntington＇s diseases（AD,PD,HD）.They are all incurable and debilitating conditions that result in progressive degeneration and/or death of neurons and are the leading cause of disability in the elderly. The incidence of these diseases is on the rise and yet there is a paucity of effective therapies to treat them.展开更多
Selenocysteine methyltransferase(SMT)is a key enzyme involved in the Se metabolism pathway,and it is responsible for the catalysis of Se-methylselenocysteine(SeMSC)compound formation.Previous studies showed that selen...Selenocysteine methyltransferase(SMT)is a key enzyme involved in the Se metabolism pathway,and it is responsible for the catalysis of Se-methylselenocysteine(SeMSC)compound formation.Previous studies showed that selenium treatment activated SMT expression and promoted the accumulation of glucosinolates(GSLs)and sulforaphane,but the roles and functional mechanisms of SMT in mediating GSLs and sulforaphane synthesis remain unclear.In this study,we identified the BoSMT gene in broccoli and uncovered its roles in mediating GSLs biosynthesis.Transgenic assays revealed that BoSMT is involved in SeMSC biosynthesis in broccoli.More importantly,the contents of GSLs and sulforaphane were significantly increased in the BoSMT-overexpressing broccoli lines but decreased in the knockdown lines,suggesting that BoSMT played a positive role in regulating GSLs and sulforaphane synthesis.Further evidence indicated that BoSMT-mediated overaccumulation of GSLs and sulforaphane might be due to the increase in the endogenous SeMSC content.Compared with the mock(water)treatment,selenite-induced significantly increases of the SeMSC content in the BoSMT-knockdown plants partially compensated the phenotype of GSLs and sulforaphane loss.Compared with the mock treatment,exogenous SeMSC treatment significantly increased the contents of GSL and sulforaphane and activated GSL synthesis-related gene expression,suggesting that SeMSC acted as a positive regulator for GSL and sulforaphane production.Our findings provided novel insights into selenium-mediated GSLs and sulforaphane accumulation.The genetic manipulation of BoSMT might be a useful strategy for improving the dietary nutritional values of broccoli.展开更多
AIM: To investigate the effects of sulforaphane(SFN) on transforming growth factor(TGF)-β2 stimulated migration and epithelial-mesenchymal transition(EMT) in ARPE-19 cells.METHODS: ARPE-19 cells were cultured in the ...AIM: To investigate the effects of sulforaphane(SFN) on transforming growth factor(TGF)-β2 stimulated migration and epithelial-mesenchymal transition(EMT) in ARPE-19 cells.METHODS: ARPE-19 cells were cultured in the presence or absence of SFN or TGF-β2. SFN toxicity was assessed by performing a lactate dehydrogenase assay(LDH) and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium(MTS) assays, and cell migration was evaluated by Transwell migration assay. Actin stress fiber formation in ARPE-19 cells was determined using immunofluorescence analysis. Immunoblotting analysis was used to determine fibronectin and α-smooth muscle actin expressions along with the degree of Smad and Akt phosphorylation.RESULTS: SFN inhibited ARPE-19 migration. Additionally, SFN attenuated TGF-β2-induced appearance of actin stress fibers as well as fibronectin and α-smooth muscle actin expressions in these cells. SFN also hindered the TGF-β2-stimulated phosphorylation of Smad2, Smad3, and Akt. SFN showed no cytotoxicity towards ARPE-19 cells. CONCLUSION: SFN inhibits TGF-β2-stimulated migration and EMT in ARPE-19 cells, probably by preventing the establishment of actin stress fibers and Akt and Smad2/3 signaling.展开更多
Nuclear factor erythroid-derived 2-like 2(Nrf2)is the master regulator of antioxidant defenses.High-intensity interval training(HIIT)has been proposed as a time-efficient training program and has become a substantial ...Nuclear factor erythroid-derived 2-like 2(Nrf2)is the master regulator of antioxidant defenses.High-intensity interval training(HIIT)has been proposed as a time-efficient training program and has become a substantial component of modern training program In the present study,we evaluated the effects of sulforaphane(SFN),a dietary isothiocyanate derived from cruciferous vegetables and a potent Nrf2 activator,on Nrf2-mediated antioxidant defense responses of skeletal muscle induced by exhaustive exercise in HIIT mice.Male C57 BL/6 J mice were randomly allocated into control group,HIIT group,and HIIT pretreated with SFN(HIIT+SFN)group.On the third day after completion of a 6-weeks HIIT protocol,an exhaustive treadmill test was conducted in all mice.Mice were intraperitoneally injected with SFN(HIIT+SFN group)or PBS(HIIT and control mice)4 times in 3 days prior to the exhaustive treadmill test.The results indicated that the 6-weeks HIIT protocol did not increase the antioxidative capacity of skeletal muscle during exhaustive exercise.Importantly,SFN treatment improved anti oxidative capacity of skeletal muscle in response to the acute exhaustive exercise by increasing mRNA and nucleoprotein expression of Nrf2 and these genes involved in antioxidant generation and decreasing blood creatine kinase(CK)and 4-hydroxy-2-nonenal(4-HNE)-modified protein levels in the HIIT mice.展开更多
Sulforaphane(SFN), found in broccoli and other cruciferous vegetables, has a beneficial effect in chemoprevention of prostate cancer, whose incidence and associated mortality have gradually increased worldwide. There ...Sulforaphane(SFN), found in broccoli and other cruciferous vegetables, has a beneficial effect in chemoprevention of prostate cancer, whose incidence and associated mortality have gradually increased worldwide. There is great enthusiasm for bench-to-bedside development of SFN as a potent chemopreventive agent, possibly alone or as an adjunct to existing chemotherapy regimens, in the oncology care setting to reduce toxicity of chemotherapeutics and potentially enhance their cancer cell-kill efficacy. In this review, we appreciate existing knowledge on SFN using a pharmacometrics approach, which is fast becoming a gold standard in discovery research and validation of New Chemical Entities and New Biological Entities in pharmaceutical industry. We discuss the epistemology of SFN target engagement and quantitative systems pharmacology with due emphasis on mechanistic pharmacology, pharmacodynamics, pharmacogenomics and metabolism of SFN. In addition, we explore the quantitative freeway to SFN translational medicine by assessing the preclinical and clinical PK/metabolism aspects of SFN that form the cornerstone of SFN pharmacometric evaluation, as well as the promise of SFN in prostate cancer. Taken together, we share perspectives on the exciting developments in translational cancer chemoprevention, with emphasis on the pharmacometric aspects, of the nutraceutical SFN which is currently in clinical trials, and suggest that the pharmacometric approach holds great promise in the SFN translational pharmacology paradigm for prostate cancer.展开更多
The dietary phytochemicals curcumin （CUR） and sulforaphane （SFN） have shown remarkable cancer chemopreventive effects in many model systems. This study was designed to investigate the induction of Nrf2-mediated an...The dietary phytochemicals curcumin （CUR） and sulforaphane （SFN） have shown remarkable cancer chemopreventive effects in many model systems. This study was designed to investigate the induction of Nrf2-mediated antioxidant enzymes by combining doses of CUR and SFN and the effect of their combination on the Nrf2-ARE （antioxidant response element） response in HepG2-C8 cells. We hypothesized that the combination of the polyphenol CUR and the isothiocyanate SFN could enhance the induction of AREs and Nrf2-target enzymes. HepG2-C8 cells were treated with a combination of low doses of CUR, SFN or both. The induction of Nrf2-mediated antioxidant and phase II detoxifying enzymes-heme oxygenase-1 （HO-I） and UDP-glucuronosyltransferase-1A （UGT1A）-was measured by real-time RT-PCR and western blotting. ARE-luciferase activity was also quantified. Low doses of CUR （10 ~tM） and SFN （12.5 ~tM） significantly induced the expression of HO-1 and UGT 1 A1 proteins. Through the use of chemical inhibitors of mRNA and protein synthesis, the combination of CUR and SFN was shown to affect the transcriptional regulation of both HO-1 and UGT1A1. Additionally, the combination of CUR and SFN synergistically induced the expression of Nrf2- and ARE-luciferase activity in HepG2-C8 cells. Thus, CUR and SFN at low concentrations augment therapeutic effects in HepG2-C8 cells. The enhanced ARE-luciferase activity of combined CUR and SFN treatment could partly explain the significant induction of the Nrf2-target enzymes HO-1 and UGT1A1. Taken together, our results suggest that combining low doses of CUR and SNF could be a promising strategy for cancer chemoprevention in humans.展开更多
The organosulfur compound sulforaphane(SFN;C6H11NOS2)is a potent cytoprotective agent promoting antioxidant,anti-inflammatory,antiglycative,and antimicrobial effects in in vitro and in vivo experimental models.Mitocho...The organosulfur compound sulforaphane(SFN;C6H11NOS2)is a potent cytoprotective agent promoting antioxidant,anti-inflammatory,antiglycative,and antimicrobial effects in in vitro and in vivo experimental models.Mitochondria are the major site of adenosine triphosphate(ATP)production due to the work of the oxidative phosphorylation(OXPHOS)system.They are also the main site of reactive oxygen species(ROS)production in nucleated human cells.Mitochondrial impairment is central in several human diseases,including neurodegeneration and metabolic disorders.In this paper,we describe and discuss the effects and mechanisms of action by which SFN modulates mitochondrial function and dynamics in mammalian cells.Mitochondria-related pro-apoptotic effects promoted by SFN in tumor cells are also discussed.SFN may be considered a cytoprotective agent,at least in part,because of the effects this organosulfur agent induces in mitochondria.Nonetheless,there are certain points that should be addressed in further experiments,indicated here as future directions,which may help researchers in this field of research.展开更多
Sulforaphane, a naturally specialized metabolite, plays significant roles in human disease prevention and plant defense. Myrosinase(MY) is a key gene responsible for the catalysis of sulforaphane formation, but the mo...Sulforaphane, a naturally specialized metabolite, plays significant roles in human disease prevention and plant defense. Myrosinase(MY) is a key gene responsible for the catalysis of sulforaphane formation, but the molecular mechanisms through which MY regulates sulforaphane biosynthesis in plants remains largely unknown. Here, we discovered that the change of sulforaphane content in broccoli sprouts caused by exogenous selenite treatments is positively related to BoMY expression. BoMY overexpression in the Arabidopsis thaliana tgg1 mutants could dramatically increase myrosinase activity and sulforaphane content in the rosette leaves of 35S::BoMY/tgg1 and rescue its phenotypes.Moreover, an obvious increase of myrosinase activity and sulforaphane content was displayed in transgenic BoMY-overexpressed broccoli lines.In addition, a 2 033 bp promoter fragment of BoMY was isolated. Yeast one-hybrid(Y1H) library screening experiment uncovered that one bHLH transcription factor, BoFAMA, could directly bind to BoMY promoter to activate its expression, which was further evidenced by Y1H assay and dual-luciferase reporter assay. BoFAMA is a selenite-responsive transcription factor that is highly expressed in broccoli leaves;its protein is solely localized to nucleus. Additionally, genetic evidence suggested that the knockdown of FAMA gene in Arabidopsis thaliana could significantly decrease sulforaphane yield by inhibiting the expression of myrosinase genes. Interestingly, exogenous selenite supply could partially restore the low level of sulforaphane content in transgenic Arabidopsis FAMA-silencing plants. Our findings uncover a novel function of FAMAMY module in the regulation of selenite-mediated sulforaphane synthesis and provide a new insights into the molecular mechanism by which selenite regulates the accumulation of sulforaphane in plants.展开更多
基金supported by the National Natural Science Foundation of China(82003451 and 82003455)Yunnan Fundamental Research Projects(202101AT070033)the Start-Up Fund for Introduction of High-level Talents to Dali University(YBS2021015).
文摘Hyperlipidemia is a risk factor for clinically significant thrombotic events in cardiovascular diseases.Platelet reactivity in hyperlipidemic conditions is enhanced when platelet scavenger receptor CD36 recognizes oxidized lipids in oxidized low-density lipoprotein(ox-LDL)particles,a process that induces atherothrombosis.Sulforaphane(SFN)is a dietary isothiocyanate enriched in cruciferous vegetables and exerts multiple biological activities.The current study sought to investigate the efficacy of SFN on platelet hyperreactivity under hyperlipidemic conditions in vitro and in vivo.Using a series of platelet functional assays in human platelets in vitro,we demonstrated that SFN attenuated ox-LDL-increased platelet aggregation and activation(surface CD62P expression).Mechanistically,studies using pharmacological inhibitors clarified that these inhibitory effects of SFN were mainly modulated by down-regulating CD36-mediated activation of Src kinases,leading to enhanced activation of cyclic adenosine monophosphate/protein kinase A(cAMP/PKA)signaling,and resultant inhibition of NADPH oxidase 2(NOX2)-dependent generation of reactive oxygen species(ROS).Moreover,12-week supplementation of SFN-enriched broccoli sprout extract(BSE,0.06%diet)in hyperlipidemic C57BL/6J mice also decreased platelet hyperreactivity.Studies using pharmacological inhibitors of CD36,protein kinase A(PKA)and NOX2 showed that the efficacy of BSE supplementation was mainly through modulating CD36-mediated the cAMP/PKA/NOX2 signaling.Thus,through modulating the cAMP/PKA/NOX2 pathway and attenuating CD36-mediated platelet hyperreactivity,SFN may play important protective roles in atherothrombosis under hyperlipidemic conditions.
文摘Prostate cancer is one of the most common tumors in urology.Dietary prophylaxis can effectively reduce prostate cancer incidence and progression.A growing body of research has shown that natural food ingredients such as Sulforaphane(SFN)can reduce the incidence of prostate cancer.It has a significant inhibitory effect on the progression from local prostate cancer to more aggressive prostate cancer.This article mainly expounds on the prevention mechanism and research progress of sulforaphane in various ways for prostate cancer and provides a reference for its future clinical application.In this review,‘SFN’,‘Prostate Cancer’,and‘PCa’were searched through PubMed,Embase,Web of Science,and other databases.SFN inhibits the occurrence and development of prostate cancer mainly through anti-oxidation,inhibition of fatty acid metabolism,inhibition of glycolysis,inhibition of proinflammatory factors,inhibition of cell proliferation and promotion of apoptosis,reduction of androgen receptors,and influence of epigenetics.Therefore,SFN is a natural compound with great potential for the prevention and treatment of prostate cancer,but the key factors such as effective chemoprevention dose,bioavailability,toxic dose,and response of sulforaphane in the human body need to be further studied in the future.
基金Supported by The grants of Chinese National Natural Science Foundation, No. 30872449the grants of the Dalian Scientific Research Foundation, No. 2008E13SF217
文摘AIM: To investigate the effect of sulforaphane (SFN) on regulation of NF-E2-related factor-2 (Nrf2)-antiox-idant response element (ARE) pathway in liver injury induced by intestinal ischemia/reperfusion (I/R). METHODS: Rats were divided randomly into four ex-perimental groups: control, SFN control, intestinal I/R and SFN pretreatment groups (n = 8 in each group). The intestinal I/R model was established by clamping the superior mesenteric artery for 1 h and 2 h reperfu-sion. In the SFN pretreatment group, surgery was performed as in the intestinal I/R group, with intraperitoneal administration of 3 mg/kg SFN 1 h before the op-eration. Intestine and liver histology was investigated. Serum levels of aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured. Liver tissue superoxide dismutase (SOD), myeloperoxidase (MPO), glutathione (GSH) and glutathione peroxidase (GSH-Px) activity were assayed. The liver transcription factor Nrf2 and heme oxygenase-1 (HO-1) were determined by immunohistochemical analysis and Western blotting analysis.RESULTS: Intestinal I/R induced intestinal and liver injury, characterized by histological changes as well as a signif icant increase in serum AST and ALT levels (AST: 260.13 ± 40.17 U/L vs 186.00 ± 24.21 U/L, P < 0.01; ALT: 139.63 ± 11.35 U/L vs 48.38 ± 10.73 U/L, P < 0.01), all of which were reduced by pretreatment with SFN, respectively (AST: 260.13 ± 40.17 U/L vs 216.63 ± 22.65 U/L, P < 0.05; ALT: 139.63 ± 11.35 U/L vs 97.63 ± 15.56 U/L, P < 0.01). The activity of SOD in the liver tissue decreased after intestinal I/R (P < 0.01), which was enhanced by SFN pretreatment (P < 0.05). In ad-dition, compared with the control group, SFN markedly reduced liver tissue MPO activity (P < 0.05) and elevat-ed liver tissue GSH and GSH-Px activity (P < 0.05, P < 0.05), which was in parallel with the increased level of liver Nrf2 and HO-1 expression.CONCLUSION: SFN pretreatment attenuates liver injury induced by intestinal I/R in rats, attributable to the antioxidant effect through Nrf2-ARE pathway.
基金the financial support provided by the National Natural Science Foundation of China (31271912)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
文摘Sulforaphane is a type of sulfur-containing isothiocyanates hydrolyzed from glucosinolates by myrosinase found in Brassica plants. Sulforaphane is a naturally occurring inducer of phase II enzymes in human and animal bodies to detoxify cancer-causing chemicals. Glucoraphanin is the precursor of sulforaphane and its content is greatly influenced by plant species and genotype, plant organs, pre-harvest factors, and post-harvest processing, thus sulforaphane formation is also directly influenced. Here, we review the formation mechanism of sulforaphane and the factors influencing sulforaphane formation. In the end, the future directions are also discussed.
文摘AIM: To evaluate effects of dietary supplementation of sulforaphane(SF)-rich broccoli sprout(BS) extract on hepatic abnormalities in Japanese male participants.METHODS: In a randomized,placebo-controlled,double blind trial,male participants with fatty liver received either BS capsules containing glucoraphanin [GR; a precursor of SF(n = 24)] or placebo(n = 28) for 2 mo. Liver function markers,serum levels of aspartate and alanine aminotransferases(AST and ALT,respectively) and γ-glutamyl transpeptidase(γ-GTP) and an oxidative stress marker,urinary levels of 8-hydroxydeoxyguanosine(8-OHd G),were measured and compared in participants before and after the trial period. In an animal model,chronic liver failure was induced in Sprague-Dawley rats by successive intraperitoneal injection with N-nitrosodimethylamine(NDMA) for 4 wk. Concomitantly,rats received AIN-76 diets supplemented with or without BS extract. Thereafter,rats were sacrificed,and their sera and livers were collected to measure serum liver function markers and hepatic levels of thiobarbituric acid reactive substances(TBARS) levels and hepatic glutathione S-transferase(GST) activity,a prototypical phase 2 antioxidant enzyme.RESULTS: Dietary supplementation with BS extract containing SF precursor GR for 2 mo significantly decreased serum levels of liver function markers,ALT [median(interquartile range),before: 54.0(34.5-79.0) vs after supplementation: 48.5(33.3-65.3) IU/L,P < 0.05] and γ-GTP [before: 51.5(40.8-91.3) vs after: 50.0(37.8-85.3) IU/L,P < 0.05],as well as the alkali phosphatase activity. Placebo showed no significant effects on the markers. The urinary level of 8-OHd G,an established oxidative stress marker,was significantly reduced in participants who had received BS capsules but not the placebo [before: 6.66(5.51-9.03) vs after: 5.49(4.89-6.66) ng/mg-creatinine,P < 0.05]. The reduction of urinary 8-OHd G was significantly correlated with decreased levels of both ALT and γ-GTP [?8-OHd G and ?ALT: Spearman r(r) 0.514 and P = 0.012,?8-OHd G and ?γ-GTP: r = 0.496 and P = 0.016]. Intake of BS extract prevented NDMA-induced chronic liver failure in rats,which was attributable to the suppression of the increase in TBARS through induction of hepatic phase 2 antioxidant enzymes including hepatic GST(86.6 ± 95.2 vs 107.8 ± 7.7 IU/g,P < 0.01).CONCLUSION: Dietary supplementation with BS extract containing the SF precursor GR is likely to be highly effective in improving liver function through reduction of oxidative stress.
文摘Tumorigenicity-inhibiting compounds have been identifled in our daily diet.For example,isothiocyanates(ITCs)found in cruciferous vegetables were reported to have potent cancer=prevention activities.The best characterized ITC is sulforaphane(SF).SF can simultaneously modulate multiple cellular targets involved in carcinogenesis,including(1)modulating carcinogen-metabolizing enzymes and blocking the action of mutagens;(2)inhibition of cell proliferation and induction of apoptosis;and(3)inhibition of neo-angiogenesis and metastasis.SF targets cancer stem cells through modulation of nuclear factor kappa B(NF-κB),Sonic hedgehog(SHH),epithelial-mesenchymal transition,and Wnt/βcatenin pathways.Conventional chemotherapy/SF combination was tested in several studies and resulted in favorable outcomes.With its favorable toxicological profile,SF is a promising agent in cancer prevention and/or therapy.In this article,we discuss the human metabolism of SF and its effects on cancer prevention,treatment,and targeting cancer stem cells,as well as providing a brief review of recent human clinical trials on SF.
基金the financial support provided by“Modern Food Processing,Food Storage,Transportation Technology,and Equipment”State Key Research and Development Plan(2017YFD0400204)the National Science Foundation of China(31972091).
文摘Innate immunity,particularly macrophages,is critical for intestinal homeostasis.Sulforaphane,a dietary isothiocyanate from cruciferous vegetables,has been reported to protect against intestinal inflammation.However,the role of macrophages in sulforaphane mediated intestinal inflammation and the underlying molecular mechanisms have not been studied yet.In this study,sulforaphane effectively attenuated dextran sodium sulphate(DSS)induced intestinal inflammation in murine model.Of note,sulforaphane skewed the switching from classically(M1)to alternatively(M2)activated phenotype both in intestinal and bone marrow-derived macrophages(BMDMs).The expression levels of M1 associated maker genes induced by DSS or lipopolysaccharide(LPS)plus interferon gamma-γ(IFN-γ)were suppressed by sulforaphane while M2 marker gene expression levels were improved.This resulted in alteration of inflammatory mediators,particularly interleukin-10(IL-10),both in colon tissues and culture medium of BMDMs.Subsequently,IL-10 was found to mediate the sulforaphane induced M2 phenotype switching of BMDMs through the activation of STAT3 signaling.This was confirmed by immunofluorescence analysis with increased number of p-STAT3-positive cells in the colon sections.Moreover,anti-IL-10 neutralizing antibody significantly interfered M2 phenotyping of BMDMs induced by sulforaphane with reduced STAT3 phosphorylation.Findings here introduced a potential utilization of sulforaphane for intestinal inflammation treatment with macrophages as the therapeutic targets.
基金supported by Fuping County Dairy Goat High-efficiency Breeding Technology R&D and Extension Application Project(No.K3380216101)the Dairy Goat High-efficiency Breeding Technology Research and Application Project(No.K4040121023).
文摘Background Mastitis not only deteriorates the composition or quality of milk,but also damages the health and pro-ductivity of dairy goats.Sulforaphane(SFN)is a phytochemical isothiocyanate compound with various pharmacologi-cal effects such as anti-oxidant and anti-inflammatory.However,the effect of SFN on mastitis has yet to be elucidated.This study aimed to explore the anti-oxidant and anti-inflammatory effects and potential molecular mechanisms of SFN in lipopolysaccharide(LPS)-induced primary goat mammary epithelial cells(GMECs)and a mouse model of mastitis.Results In vitro,SFN downregulated the mRNA expression of inflammatory factors(tumor necrosis factor-α(TNF-α),interleukin(IL)-1βand IL-6),inhibited the protein expression of inflammatory mediators(cyclooxygenase-2(COX2),and inducible nitric oxide synthase(iNOS))while suppressing nuclear factor kappa-B(NF-κB)activation in LPS-induced GMECs.Additionally,SFN exhibited an antioxidant effect by increasing Nrf2 expression and nuclear translocation,up-regulating antioxidant enzymes expression,and decreasing LPS-induced reactive oxygen species(ROS)produc-tion in GMECs.Furthermore,SFN pretreatment promoted the autophagy pathway,which was dependent on the increased Nrf2 level,and contributed significantly to the improved LPS-induced oxidative stress and inflammatory response.In vivo,SFN effectively alleviated histopathological lesions,suppressed the expression of inflammatory factors,enhanced immunohistochemistry staining of Nrf2,and amplified of LC3 puncta LPS-induced mastitis in mice.Mechanically,the in vitro and in vivo study showed that the anti-inflammatory and anti-oxidative stress effects of SFN were mediated by the Nrf2-mediated autophagy pathway in GMECs and a mouse model of mastitis.Conclusions These results indicate that the natural compound SFN has a preventive effect on LPS-induced inflam-mation through by regulating the Nrf2-mediated autophagy pathway in primary goat mammary epithelial cells and a mouse model of mastitis,which may improve prevention strategies for mastitis in dairy goats.
基金supported by grants from the National Natural Science Foundation of China (30900457 and 81070917)
文摘Objective To determine whether sulforaphane （SFN） protects neurons against injury caused by oxygen-glucose deprivation/reoxygenation （OGD/R） and, if so, to investigate the possible mechanisms. Methods Primary cultures of neurons were prepared from the cerebral cortex of 1-day-old Sprague-Dawley rats. On days 5-6 in vitro, the neurons were exposed to OGD for 1 h, followed by reoxygenation for 24 h. Cells were treated with 0, 0.1, 0.2, 0.5, 1, 2.5, or 5 μmol/L SFN, with or without 10 μmol/L LY294002, a PI3K-specific inhibitor, during OGD/R （a total of 25 h）. After 24-h reoxygenation, MTT was used to assess viability and injury was assessed by Hoechst 33258/propidium iodide （PI） staining; immunofluorescence staining and Western blot were performed to detect molecular events associated with apoptosis. Results The MTT assay showed that 1 μmol/L SFN significantly increased viability, and Hoechst 33258/PI staining showed that the numbers of injured neurons were reduced significantly in the SFN group. Furthermore, immunofluorescence staining and Western blot showed that SFN increased Bcl-2 and decreased cleaved caspase-3 levels. Moreover, LY294002 inhibited the phosphorylated-Akt expression evoked by SFN, decreased Bcl-2 expression and increased cleaved caspase-3 expression. Conclusion SFN protects neurons against injury from OGD/R and this effect may be partly associated with an anti-apoptosis pathway.
基金Supported by Higher Education Research Promotion and National Research University Project of Thailand,Office of the Higher Education Commission,through the Food and Functional Food Research Cluster and Research and Development of Herbal Nutraceutics Subcluster of Khon Kaen University(F-2553-M-11 and NRU541051)
文摘Objective: To analyze two isothiocyanates(sulforaphene and sulforaphane) and their antiproliferative effect of 11 indigenous cruciferous vegetables.Methods: Phytoconstituents identification was conducted by high performance liquid chromatography and gas chromatography-mass spectrometer techniques. The antiproliferation was evaluated in colon cancer cell line HCT116 by MTT assay.Results: Isothiocyanate identification by high performance liquid chromatography showed that broccoli, cabbage, "Khi-Hood"(Raphanus sativus L. var. caudatus Alef) and Chinese radish contained isothiocyanates sulforaphane. Sulforaphene and sulforaphane in broccoli, cabbage and "Khi-Hood" were characterized by the gas chromatography-mass spectrometer analysis. Antiproliferation screening by MTT assay found that the potent plants which possessed IC_(50) below 50 mg/m L were cabbage and "Khi-Hood", while the others had low antiproliferation with IC_(50) higher than 50 mg/m L. Difference in antiproliferation was probably due to difference existed phytochemical constituents in each plant. "Khi-Hood" possessed the highest antiproliferation against HCT116 with the lowest IC_(50)at(9.42 ± 0.46) mg/m L. The IC_(50) of chemotherapeutic drug(mitomycin C)was(19.12 ± 1.00) mg/m L, while both melphalan and 5-fluorouracil possessed the IC_(50) value higher than 50 mg/m L.Conclusions: Commonly consumed cruciferous vegetables exerted varied antiproliferation and isothiocyanate contents. High isothiocyanate content in "Khi-Hood" was contributed to high antiproliferation. Among 11 plants studied, "Khi-Hood" could be an alternative chemopreventive diet.
文摘Objective Acute liver failure(ALF)is characterized by severe liver dysfunction,rapid progression and high mortality and is difficult to treat.Studies have found that sulforaphane(SFN),a nuclear factor E2-related factor 2(NRF2)agonist,has anti-inflammatory,antioxidant and anticancer effects,and has certain protective effects on neurodegenerative diseases,cancer and liver fibrosis.This paper aimed to explore the protective effect of SFN in ALF and it possible mechanisms of action.Methods Lipopolysaccharide and D-galactosamine were used to induce liver injury in vitro and in vivo.NRF2 agonist SFN and histone deacetylase 6(HDAC6)inhibitor ACY1215 were used to observe the protective effect and possible mechanisms of SFN in ALF,respectively.Cell viability,lactate dehydrogenase(LDH),Fe2+,glutathione(GSH)and malondialdehyde(MDA)were detected.The expression of HDAC6,NRF2,glutathione peroxidase 4(GPX4),acyl-CoA synthetase long-chain family member 4(ACSL4)and solute carrier family 7 member 11(SLC7A11)were detected by Western blotting and immunofluorescence.Results Our results show that NRF2 was activated by SFN.LDH,Fe2+,MDA and ACSL4 were downregulated,while GSH,GPX4 and SLC7A11 were upregulated by SFN in vitro and in vivo,indicating the inhibitory effect of SFN on ferroptosis.Additionally,HDAC6 expression was decreased in the SFN group,indicating that SFN could downregulate the expression of HDAC6 in ALF.After using the HDAC6 inhibitor,ACY1215,SFN further reduced HDAC6 expression and inhibited ferroptosis,indicating that SFN may inhibit ferroptosis by regulating HDAC6 activity.Conclusion SFN has a protective effect on ALF,and the mechanism may include reduction of ferroptosis through the regulation of HDAC6.
基金Supported by National Natural Science Foundation of China(No.81700813)Beijing Municipal Administration of Hospitals Qingmiao Projects(No.QML20180205)the Priming Scientific Research Foundation for the Junior Researcher in Beijing Tongren Hospital。
文摘AIM:To examine the effects of sulforaphane on fibrotic changes of transforming growth factor(TGFβ2)induced human conjunctival fibroblast(HCon Fs).METHODS:HCon Fs were cultured and divided into control,TGFβ2(1 ng/m L),sulforaphane and TGFβ2+sulforaphane groups.Cell viability and apoptosis were detected using the MTT and Apo Tox-Glo Triplex assay.Cell migration was detected using scratch and Transwell assay.Real-time quantitative PCR method was used to evaluate m RNA expression of TGFβ2,matrix metalloproteinase-2(MMP2),myosin light chain kinase(MYLK),integrinαV,integrinα5,fibronectin 1 andα-smooth muscle actin(α-SMA).The protein expression ofα-SMA,p-PI3 K,PI3 K,p-Akt,and Akt were detected by Western blot.RESULTS:The proliferation of HCon Fs was significantly(P<0.05)suppressed by sulforaphane compared to control cells with the increase of the concentration and treatment time.Cell proliferation after 48 h incubation was significantly reduced with 100μmol/L sulforaphane treatment by 17.53%(P<0.05).The Transwell assay showed sulforaphane decreased cell migration by 18.73%compared with TGFβ2-induced HCon F(P<0.05).TGFβ2-induced the increasing expression of fibronectin,type I collagen andα-SMA,and the phosphorylation of PI3 K and Akt were all significantly suppressed by sulforaphane pretreatment.CONCLUSION:Sulforaphane inhibits proliferation,migration,and synthesis of the extracellular matrix in HCon Fs,and inhibiting the PI3 K/Akt signaling pathway.Sulforaphane could be a potential therapeutic drug for prevention of scar formation in filtering bleb after trabeculectomy.
基金supported by MIUR-FIRB(project RBAP11HSZS)Fondazione del Monte di Bologna e Ravenna(ITALY)
文摘Neurodegeneration is a key aspect of a large number of diseases that come under the umbrella of＂neurodegenerative diseases＂with the most notable being Parkinson＇s,Alzheimer＇s,and Huntington＇s diseases（AD,PD,HD）.They are all incurable and debilitating conditions that result in progressive degeneration and/or death of neurons and are the leading cause of disability in the elderly. The incidence of these diseases is on the rise and yet there is a paucity of effective therapies to treat them.
基金the Projects of International Cooperation National Key R&D Program of China(Grant No.2022YFE0108300)the National Key Research and Development Program of China(Grant No.2022YFF1003000)the National Natural Science Foundation of China(Grant Nos.32372682,32272747,32072585,32072568).
文摘Selenocysteine methyltransferase(SMT)is a key enzyme involved in the Se metabolism pathway,and it is responsible for the catalysis of Se-methylselenocysteine(SeMSC)compound formation.Previous studies showed that selenium treatment activated SMT expression and promoted the accumulation of glucosinolates(GSLs)and sulforaphane,but the roles and functional mechanisms of SMT in mediating GSLs and sulforaphane synthesis remain unclear.In this study,we identified the BoSMT gene in broccoli and uncovered its roles in mediating GSLs biosynthesis.Transgenic assays revealed that BoSMT is involved in SeMSC biosynthesis in broccoli.More importantly,the contents of GSLs and sulforaphane were significantly increased in the BoSMT-overexpressing broccoli lines but decreased in the knockdown lines,suggesting that BoSMT played a positive role in regulating GSLs and sulforaphane synthesis.Further evidence indicated that BoSMT-mediated overaccumulation of GSLs and sulforaphane might be due to the increase in the endogenous SeMSC content.Compared with the mock(water)treatment,selenite-induced significantly increases of the SeMSC content in the BoSMT-knockdown plants partially compensated the phenotype of GSLs and sulforaphane loss.Compared with the mock treatment,exogenous SeMSC treatment significantly increased the contents of GSL and sulforaphane and activated GSL synthesis-related gene expression,suggesting that SeMSC acted as a positive regulator for GSL and sulforaphane production.Our findings provided novel insights into selenium-mediated GSLs and sulforaphane accumulation.The genetic manipulation of BoSMT might be a useful strategy for improving the dietary nutritional values of broccoli.
基金Supported by the National Science Foundation of China (No.81770889)the Natural Science Foundation of Guangdong Province (No.2018A030313428)Administration of Traditional Chinese Medicine of Guangdong Province (No. 20201070)。
文摘AIM: To investigate the effects of sulforaphane(SFN) on transforming growth factor(TGF)-β2 stimulated migration and epithelial-mesenchymal transition(EMT) in ARPE-19 cells.METHODS: ARPE-19 cells were cultured in the presence or absence of SFN or TGF-β2. SFN toxicity was assessed by performing a lactate dehydrogenase assay(LDH) and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H-tetrazolium(MTS) assays, and cell migration was evaluated by Transwell migration assay. Actin stress fiber formation in ARPE-19 cells was determined using immunofluorescence analysis. Immunoblotting analysis was used to determine fibronectin and α-smooth muscle actin expressions along with the degree of Smad and Akt phosphorylation.RESULTS: SFN inhibited ARPE-19 migration. Additionally, SFN attenuated TGF-β2-induced appearance of actin stress fibers as well as fibronectin and α-smooth muscle actin expressions in these cells. SFN also hindered the TGF-β2-stimulated phosphorylation of Smad2, Smad3, and Akt. SFN showed no cytotoxicity towards ARPE-19 cells. CONCLUSION: SFN inhibits TGF-β2-stimulated migration and EMT in ARPE-19 cells, probably by preventing the establishment of actin stress fibers and Akt and Smad2/3 signaling.
基金supported by Winter Sports Nutrition Research Center in Beijing Sport University supported by Herbalife Nutrition~(TM)Scientific Research Program Funded by Shaanxi Provincial Education Department(20JK0993 to Y.X.)Exercise and Physical Fitness,the Key Laboratory of Ministry of Education in Beijing Sport University。
文摘Nuclear factor erythroid-derived 2-like 2(Nrf2)is the master regulator of antioxidant defenses.High-intensity interval training(HIIT)has been proposed as a time-efficient training program and has become a substantial component of modern training program In the present study,we evaluated the effects of sulforaphane(SFN),a dietary isothiocyanate derived from cruciferous vegetables and a potent Nrf2 activator,on Nrf2-mediated antioxidant defense responses of skeletal muscle induced by exhaustive exercise in HIIT mice.Male C57 BL/6 J mice were randomly allocated into control group,HIIT group,and HIIT pretreated with SFN(HIIT+SFN)group.On the third day after completion of a 6-weeks HIIT protocol,an exhaustive treadmill test was conducted in all mice.Mice were intraperitoneally injected with SFN(HIIT+SFN group)or PBS(HIIT and control mice)4 times in 3 days prior to the exhaustive treadmill test.The results indicated that the 6-weeks HIIT protocol did not increase the antioxidative capacity of skeletal muscle during exhaustive exercise.Importantly,SFN treatment improved anti oxidative capacity of skeletal muscle in response to the acute exhaustive exercise by increasing mRNA and nucleoprotein expression of Nrf2 and these genes involved in antioxidant generation and decreasing blood creatine kinase(CK)and 4-hydroxy-2-nonenal(4-HNE)-modified protein levels in the HIIT mice.
基金Institutional funds from Amrita Vishwa Vidyapeetham University,India,and Rutgersthe State University of New Jersey,USARO1 CA118947 and RO1 CA152826 from the National Institutes of Health(NIH),USA
文摘Sulforaphane(SFN), found in broccoli and other cruciferous vegetables, has a beneficial effect in chemoprevention of prostate cancer, whose incidence and associated mortality have gradually increased worldwide. There is great enthusiasm for bench-to-bedside development of SFN as a potent chemopreventive agent, possibly alone or as an adjunct to existing chemotherapy regimens, in the oncology care setting to reduce toxicity of chemotherapeutics and potentially enhance their cancer cell-kill efficacy. In this review, we appreciate existing knowledge on SFN using a pharmacometrics approach, which is fast becoming a gold standard in discovery research and validation of New Chemical Entities and New Biological Entities in pharmaceutical industry. We discuss the epistemology of SFN target engagement and quantitative systems pharmacology with due emphasis on mechanistic pharmacology, pharmacodynamics, pharmacogenomics and metabolism of SFN. In addition, we explore the quantitative freeway to SFN translational medicine by assessing the preclinical and clinical PK/metabolism aspects of SFN that form the cornerstone of SFN pharmacometric evaluation, as well as the promise of SFN in prostate cancer. Taken together, we share perspectives on the exciting developments in translational cancer chemoprevention, with emphasis on the pharmacometric aspects, of the nutraceutical SFN which is currently in clinical trials, and suggest that the pharmacometric approach holds great promise in the SFN translational pharmacology paradigm for prostate cancer.
基金Institutional FundsR01-CA118947,R01-CA152826,from the National Cancer Institute(NCI)R01-AT007065 from the National Center for Complementary and Alternative Medicines(NCCAM)and the Office of Dietary Supplements(ODS)
文摘The dietary phytochemicals curcumin （CUR） and sulforaphane （SFN） have shown remarkable cancer chemopreventive effects in many model systems. This study was designed to investigate the induction of Nrf2-mediated antioxidant enzymes by combining doses of CUR and SFN and the effect of their combination on the Nrf2-ARE （antioxidant response element） response in HepG2-C8 cells. We hypothesized that the combination of the polyphenol CUR and the isothiocyanate SFN could enhance the induction of AREs and Nrf2-target enzymes. HepG2-C8 cells were treated with a combination of low doses of CUR, SFN or both. The induction of Nrf2-mediated antioxidant and phase II detoxifying enzymes-heme oxygenase-1 （HO-I） and UDP-glucuronosyltransferase-1A （UGT1A）-was measured by real-time RT-PCR and western blotting. ARE-luciferase activity was also quantified. Low doses of CUR （10 ~tM） and SFN （12.5 ~tM） significantly induced the expression of HO-1 and UGT 1 A1 proteins. Through the use of chemical inhibitors of mRNA and protein synthesis, the combination of CUR and SFN was shown to affect the transcriptional regulation of both HO-1 and UGT1A1. Additionally, the combination of CUR and SFN synergistically induced the expression of Nrf2- and ARE-luciferase activity in HepG2-C8 cells. Thus, CUR and SFN at low concentrations augment therapeutic effects in HepG2-C8 cells. The enhanced ARE-luciferase activity of combined CUR and SFN treatment could partly explain the significant induction of the Nrf2-target enzymes HO-1 and UGT1A1. Taken together, our results suggest that combining low doses of CUR and SNF could be a promising strategy for cancer chemoprevention in humans.
基金Project supported by the National Council for Scientific and Technological Development(CNPq,No.301273/2018-9),Brazil。
文摘The organosulfur compound sulforaphane(SFN;C6H11NOS2)is a potent cytoprotective agent promoting antioxidant,anti-inflammatory,antiglycative,and antimicrobial effects in in vitro and in vivo experimental models.Mitochondria are the major site of adenosine triphosphate(ATP)production due to the work of the oxidative phosphorylation(OXPHOS)system.They are also the main site of reactive oxygen species(ROS)production in nucleated human cells.Mitochondrial impairment is central in several human diseases,including neurodegeneration and metabolic disorders.In this paper,we describe and discuss the effects and mechanisms of action by which SFN modulates mitochondrial function and dynamics in mammalian cells.Mitochondria-related pro-apoptotic effects promoted by SFN in tumor cells are also discussed.SFN may be considered a cytoprotective agent,at least in part,because of the effects this organosulfur agent induces in mitochondria.Nonetheless,there are certain points that should be addressed in further experiments,indicated here as future directions,which may help researchers in this field of research.
基金funded by the National Key Research and Development Program of China (Grant Nos.2022YFF1003000,2022YFE0108300)the Natural Science Foundation of China (Grant Nos.32272747,32072585,32072568)+1 种基金the Natural Science Foundation of Hunan Province (Grant Nos.2021JJ30324,2021JJ30345)the Outstanding Youth Project of Educational Department of Hunan Province (Grant No.20B275)。
文摘Sulforaphane, a naturally specialized metabolite, plays significant roles in human disease prevention and plant defense. Myrosinase(MY) is a key gene responsible for the catalysis of sulforaphane formation, but the molecular mechanisms through which MY regulates sulforaphane biosynthesis in plants remains largely unknown. Here, we discovered that the change of sulforaphane content in broccoli sprouts caused by exogenous selenite treatments is positively related to BoMY expression. BoMY overexpression in the Arabidopsis thaliana tgg1 mutants could dramatically increase myrosinase activity and sulforaphane content in the rosette leaves of 35S::BoMY/tgg1 and rescue its phenotypes.Moreover, an obvious increase of myrosinase activity and sulforaphane content was displayed in transgenic BoMY-overexpressed broccoli lines.In addition, a 2 033 bp promoter fragment of BoMY was isolated. Yeast one-hybrid(Y1H) library screening experiment uncovered that one bHLH transcription factor, BoFAMA, could directly bind to BoMY promoter to activate its expression, which was further evidenced by Y1H assay and dual-luciferase reporter assay. BoFAMA is a selenite-responsive transcription factor that is highly expressed in broccoli leaves;its protein is solely localized to nucleus. Additionally, genetic evidence suggested that the knockdown of FAMA gene in Arabidopsis thaliana could significantly decrease sulforaphane yield by inhibiting the expression of myrosinase genes. Interestingly, exogenous selenite supply could partially restore the low level of sulforaphane content in transgenic Arabidopsis FAMA-silencing plants. Our findings uncover a novel function of FAMAMY module in the regulation of selenite-mediated sulforaphane synthesis and provide a new insights into the molecular mechanism by which selenite regulates the accumulation of sulforaphane in plants.
