Prenatal brain development is particularly sensitive to chemicals that can disrupt synapse formation and cause neurodevelopmental disorders. In most cases, such chemicals increase cellular oxidative stress. For example, prenatal exposure to the anti-epileptic drug valproic acid (VPA), induces oxidative stress and synaptic alterations, promoting autism spectrum disorders (ASD) in humans and autism-like behaviors in rodents. Using VPA to model chemically induced ASD, we tested whether activation of cellular mechanisms that increase antioxidant gene expression would be sufficient to prevent VPA-induced synaptic alterations. As a master regulator of cellular defense pathways, the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) promotes expression of detoxification enzymes and antioxidant gene products. To increase NRF2 activity, we used the phytochemical and potent NRF2 activator, sulforaphane (SFN). In our models of human neurodevelopment, SFN activated NRF2, increasing expression of antioxidant genes and preventing oxidative stress. SFN also enhanced expression of genes associated with synapse formation. Consistent with these gene expression profiles, SFN protected developing neural networks from VPA-induced reductions in synapse formation. Furthermore, in mouse cortical neurons, SFN rescued VPA-induced reductions in neural activity. These results demonstrate the ability of SFN to protect developing neural networks during the vulnerable period of synapse formation, while also identifying molecular signatures of SFN-mediated neuroprotection that could be relevant for combatting other environmental toxicants.

Autism spectrum disorder (ASD) has become an increasingly prominent global health issue. Sulforaphane is a phytochemical with multiple functions that target many of the same biochemical and molecular pathways (biomarkers) associated with ASD. This study aimed to conduct a meta-analysis based on sulforaphane's effect on Aberrant Behavior Checklist (ABC) and Social Responsiveness Scale (SRS) in patients with ASD. We conducted comprehensive searches in the PubMed, Medline, Cochrane, EMBASE, and Web of Science databases from their inception. The modified Cochrane risk of bias tool was used to check the risk of bias of the included studies. Review Manager 5.3 software was used to conduct this meta-analysis. The results of this meta-analysis showed that sulforaphane significantly improved irritability and hyperactivity symptoms, suggesting that sulforaphane has the potential for the combined treatment of autism. Additional studies are needed to confirm and explore the effect of sulforaphane.

The Qidong Liver Cancer Institute (QDLCI) and the Qidong Cancer Registry were established in 1972 with input from doctors, other medical practitioners, and non-medical investigators arriving from urban centers such as Shanghai and Nanjing. Medical teams were established to quantify the extent of primary liver cancer in Qidong, a corn-growing peninsula on the north side of the Yangtze River. High rates of liver cancer were documented and linked to several etiologic agents, including aflatoxins. Local corn, the primary dietary staple, was found to be consistently contaminated with high levels of aflatoxins, and bioassays using this corn established its carcinogenicity in ducks and rats. Observational studies noted a positive association between levels of aflatoxin in corn and incidence of liver cancer across townships. Biomarker studies measuring aflatoxin B1 and its metabolite aflatoxin M1 in biofluids reflected the exposures. Approaches to decontamination of corn from aflatoxins were also studied. In 1993, investigators from Johns Hopkins University were invited to visit the QDLCI to discuss chemoprevention studies in some townships. A series of placebo-controlled clinical trials were conducted using oltipraz (a repurposed drug), chlorophyllin (an over-the-counter drug), and beverages prepared from 3-day-old broccoli sprouts (rich in the precursor phytochemical for sulforaphane). Modulation of biomarkers of aflatoxin DNA and albumin adducts established proof of principle for the efficacy of these agents in enhancing aflatoxin detoxication. Serendipitously, by 2012, aflatoxin exposures quantified using biomarker measurements documented a many hundred-fold reduction. In turn, the Cancer Registry documents that the age-standardized incidence rate of liver cancer is now 75% lower than that seen in the 1970s. This reduction is seen in Qidongese who have never received the hepatitis B vaccination. Aflatoxin mitigation driven by economic changes switched the dietary staple of contaminated corn to rice coupled with subsequent dietary diversity leading to lower aflatoxin exposures. This 50-year effort to understand the etiology of liver cancer in Qidong provides the strongest evidence for aflatoxin mitigation as a public health strategy for reducing liver cancer burden in exposed, high-risk populations. Also highlighted are the challenges and successes of international team science to solve pressing public health issues.

General pathways were devised to synthesize ω-methylsulfinyl- and ω-methylsulfonylalkyl glucosinolates, which represent an important class of structurally homogeneous plant specialized metabolites. The first approach was based on the selective S-oxidation of ω-methylsulfanyl analogs previously obtained in our laboratory, producing the corresponding sulfoxide or sulfone counterparts in moderate yields. In an alternative approach, previously prepared ω-nitroalkyl methylsulfide precursors were selectively oxidized either to sulfoxides or to sulfones. The key-thiofunctionalized hydroximoyl chloride intermediates were prepared in situ from sulfoxides or sulfones using a nitronate chlorination strategy. A coupling reaction with 1-thio-β-d-glucopyranose was directly applied, followed by O-sulfation of the intermediate thiohydroximates. The final deprotection of the sugar moiety produced the target compounds, including renowned glucoraphanin and homologs, intended for further bioactivity investigations.

Sulforaphane is a main bioactive component in several edible cruciferous vegetables. It acquires several benefits to health in addition to its considered antibacterial and antivirulence activities. Herein, we aimed at evaluating the antivirulence activity of sulforaphane against the worldwide clinically important enteric pathogen Salmonella enterica serovar Typhimurium. The influence of sulforaphane on bacterial adhesion, invasion, biofilm formation, and intracellular replication was assayed. Additionally, the effect of sulforaphane on the type III secretion system (TTSS) in S. enterica was quantified. The outcome of the combination with different antibiotics was assessed, and an in vivo protection assay was conducted to assess the influence on S. enterica pathogenesis. The results showed the significant antibiofilm activity of sulforaphane at subinhibitory effect in addition to its significant reduction in bacterial invasion and intracellular replication inside the host cells. The in vivo findings emphasized the decreased capacity of S. enterica to induce pathogenesis in the presence of sulforaphane. Our finding attributed these antivirulence activities to the interference of sulforaphane with TTSS-type II and the downregulation of its encoding genes. In a nutshell, the edible cruciferous vegetable bioactive sulforaphane is a safe adjunct therapy that can be administrated alongside traditional antibiotics for treating clinically significant enteric pathogens as S. enterica.

Iodine is a key micronutrient essential for the synthesis of thyroid hormone, which regulates metabolic processes and maintains overall health. Despite its importance, iodine deficiency is a global health issue, leading to disorders such as goiter, hypothyroidism, and developmental abnormalities. Biofortification of crops with iodine is a promising strategy to enhance the dietary iodine intake, providing an alternative to iodized salt. Curly kale (Brassica oleracea var. sabellica) is a nutrient-rich vegetable high in vitamins A, C, K; minerals; fiber; and bioactive compounds with antioxidant, anti-inflammatory, and detoxifying properties. This study evaluates the effects of diets containing iodine-biofortified curly kale ('Oldenbor F1' and 'Redbor F1') on iodine content, tissue iodine levels, and various biochemical parameters in laboratory rats. The biofortified curly kale was enriched with 5,7-diiodo-8-quinolinol. The iodine content in the AIN-93G (control) diet and the non-biofortified curly kale diets did not differ significantly. However, diets with 5,7-diiodo-8-quinolinol biofortified kale showed significantly higher iodine levels compared with the control diets. Tissue analysis revealed the highest iodine concentrations in the liver and kidneys of rats fed diets with biofortified curly kale, indicating better iodine bioavailability. Biochemical analysis showed that rats fed the biofortified kale diet had lower total cholesterol (TC) and triglyceride (TG) levels compared with rats fed the control diet. Additionally, the biofortified diet improved the liver function markers (ALAT, ASAT) and reduced oxidative stress markers (TBARS). The study also investigated the expression of thyroid-related genes (Slc5A5, Tpo, Dio1, Dio2) in response to diets containing biofortified kale. The results demonstrated significant changes in gene expression, indicating adaptive mechanisms to dietary iodine levels and the presence of bioactive compounds in the biofortified kale. The study also observed variations in uric acid levels, with lower concentrations in rats fed a diet with biofortified curly kale. Biofortified curly kale supports thyroid function and improves liver and kidney health by reducing oxidative stress and modulating key biochemical and genetic markers. These findings suggest that biofortified curly kale can effectively increase dietary iodine intake as a nutritional intervention to address iodine deficiency and promote overall health.

Sprouts and microgreens which belong to the Brassicaceae family contain significantly more glucosinolates than mature vegetables, and their composition often differs too. These plant growth stages can be a valuable supplement of the aforementioned compounds in the diet. The content and proportion of individual glucosinolates in sprouts and microgreens can be regulated by modifying the length and temperature of cultivation, the type of light, the use of mineral compounds, elicitation, primming, and cold plasma as well as storage conditions. The way in which sprouts are prepared for consumption affects the yield of glucosinolate hydrolysis. Genetic variation leading to different plant responses to the same factors (e.g., type of light) makes it necessary to conduct detailed studies involving species and variety diversity. Heat stress and the use of cold plasma appear to be fairly universal methods for increasing glucosinolate content. Studies on the use of light at different wavelengths do not provide unequivocal results. Despite experiments on the use of seed soaking solutions (e.g., sulfur and selenium compounds), there are no studies in the available literature on the effects of chemical and thermal seed disinfection methods on the glucosinolate content of the obtained sprouts and microgreens.

Broccoli is recognized for its health benefits, attributed to the high concentrations of glucoraphanin (GR). GR must be hydrolyzed by myrosinase (Myr) to form the bioactive sulforaphane (SF). The primary challenge in delivering SF in the upper gastrointestinal (GI) tract- is improving hydrolysis of GR to SF. Here, we optimized the formulation and delivery methods to improve GR conversion and SF bioavailability. We investigated whether the combination of GR-rich broccoli seed extract powder (BSE[GR]) with Myr-rich mustard seed powder (MSP[Myr]), ± ascorbic acid (AA, a co-factor of Myr), delivered as free powder or encapsulated powder, can: (i) facilitate GR hydrolysis to SF during dynamic in vitro gastric digestion and static in vitro small intestinal digestion, and (ii) increase SF bioavailability in Caco-2 cell monolayers, a model of human intestinal epithelium. Addition of exogenous Myr increased the conversion of GR to SF in free powder during small intestinal digestion, but not during gastric digestion, where Myr activity was inhibited by the acidic environment. Capsule delivery of BSE[GR]/MSP[Myr] (w/w ratio 4 : 1) resulted in a 2.5-fold higher conversion efficiency compared to free powder delivery (72.1% compared to 29.3%, respectively). AA combined with MSP[Myr] further enhanced the conversion efficiency in small intestinal digestion and the bioavailability of SF in Caco-2 cell monolayers. Bioavailability of GR as SF, SF metabolites, and GR was 74.8% in Caco-2 cell monolayers following 30 min gastric digestion and 60 min small intestinal digestion. This study highlights strategies to optimize GR bioconversion in the upper GI tract leading to enhanced SF bioavailability.

Helicobacter pylori (Hp) infection is highly prevalent globally and poses a significant public health challenge due to its link with chronic gastritis, peptic ulcers, and gastric malignancies. Hp's persistence within the gastric environment, particularly in case of infection with virulent strains, triggers chronic inflammatory responses and mucosal damage. Antibiotic therapy is the primary approach for Hp eradication, but antibiotic resistance and adverse effects hinder treatment efficacy. Emerging evidence suggests that Brassicaceae-derived metabolites could serve as adjunctive therapy for Hp infection, offering potential antimicrobial and anti-inflammatory benefits.

A systematic literature review was conducted following PRISMA guidelines to assess the impact of Brassicaceae-rich diets on Hp infection control. Searches were performed in MEDLINE PubMed, Web of Science, and the Cochrane Library until 18 October 2023, without language or date restrictions. Eligible studies meeting PICOS criteria were included, encompassing populations infected with Hp or Hp-infected human cell cultures, interventions involving Brassicaceae consumption or its bioactive molecules, and outcomes related to Hp infection control, antibiotic therapy interactions, reduction of antibiotic side effects, and inflammation mitigation. Animal studies, cell line experiments, reviews unrelated to the research objectives, and studies on Hp-related gastric cancer were excluded.

Available evidence indicates that Brassicaceae consumption exhibits the potential to reduce Hp colonization but achieving complete eradication of the pathogen remains challenging. Conflicting results regarding the efficacy of broccoli in Hp treatment emerge, with certain investigations suggesting limited effectiveness. Other studies point to a potential for heightened eradication rates when combined with standard triple therapy. Furthermore, promising outcomes are observed with broccoli extract supplements, indicating their role in mitigating Hp-induced gastric mucosal damage. In fact, it is noteworthy that sulforaphane and its derivatives manifest notable reductions in pro-inflammatory markers, indicative of their anti-inflammatory properties. Adverse events associated with antibiotic therapy seem unaffected by sulforaphane derivatives or probiotics. However, individual responses to these treatments vary, underscoring the unpredictability of their efficacy in ameliorating antibiotic therapy-related side effects.

Our systematic review highlights the potential of Brassicaceae-rich diets as adjunctive therapy for Hp infection, offering synergistic interactions with antibiotics and possibly mitigating antibiotic side effects and inflammation. Further research, particularly well-designed randomized trials, is warranted to elucidate the therapeutic efficacy and optimal utilization of Brassicaceae-derived metabolites in managing human Hp-related diseases.

Alzheimer's disease (AD) is a polygenic, multifactorial neurodegenerative disorder and remains the most prevalent form of dementia, globally. Despite decades of research efforts, there is still no effective cure for this debilitating condition. AD research has increasingly focused on transcription factor NRF2 (nuclear factor erythroid 2-related factor 2) as a potential therapeutic target. NRF2 plays a crucial role in protecting cells and tissues from environmental stressors, such as electrophiles and reactive oxygen species. Recently, an increasing number of studies have demonstrated that NRF2 is a key regulator in AD pathology. NRF2 is highly expressed in microglia, resident macrophages in the central nervous system, and contributes to neuroinflammation, phagocytosis and neurodegeneration in AD. NRF2 has been reported to modulate microglia-induced inflammation and facilitate the transition from homeostatic microglia to a disease-associated microglia subset. Genetic and pharmacological activation of NRF2 has been demonstrated to improve cognitive function. Here, we review the current understanding of the involvement of NRF2 in AD and the critical role that NRF2 plays in microglia in the context of AD. Our aim is to highlight the potential of targeting NRF2 in the microglia as a promising therapeutic strategy for mitigating the progression of AD.

Particulate matter (PM) is an environmental pollutant that negatively affects human health, particularly skin health. In this study, we investigated the inhibitory effects of broccoli sprout extract (BSE) on PM-induced skin aging and inflammation in human keratinocytes.

HaCaT keratinocytes were pretreated with BSE before exposure to PM. Cell viability was assessed using the MTT assay. The expression of skin aging and inflammation markers (MMP-1, COX-2, IL-6) was measured using Western blot, ELISA, and qRT-PCR. Reactive oxygen species levels were determined using the DCF-DA assay. Kinase assays and pull-down assays were conducted to investigate the interaction between BSE and p38α MAPK.

Our findings demonstrate that BSE effectively suppressed the expression of MMP-1, COX-2, and IL-6-critical skin aging and inflammation markers-by inhibiting p38 MAPK activity. BSE binds directly to p38α without competing with ATP, thereby selectively inhibiting its activity and downstream signaling pathways, including MSK1/2, AP-1, and NF-κB.

These results suggest that BSE is a potential functional ingredient in skincare products to mitigate PM-induced skin damage.

Prenatal ethanol exposure can cause a broad range of abnormalities in newborns known as Fetal Alcohol Spectrum Disorder (FASD). Despite significant progress in understanding the disease mechanisms of FASD, there remains a strong global need for effective therapies. To evaluate the therapeutic potential of sulforaphane (SFN), an active compound extracted from cruciferous vegetables, in preventing FASD, ethanol-exposed zebrafish embryos were pretreated, co-treated, or post-treated with various concentrations of SFN. The FASD-like morphological features, survival rate, hatching rate, and vascular development were then assessed in the zebrafish embryos. It was found that pretreatment with 2 μM SFN during 3-24 hpf had no noticeable protective effects against teratogenicity induced by subsequent 1.5% ethanol exposure during 24-48 hpf. In contrast, co-treatment with 2 μM SFN and 1.5% ethanol during 3-24 hpf significantly alleviated a range of ethanol-induced malformations, including reduced body length, small eyes, reduced brain size, small otic vesicle, small jaw, and pericardial edema. Post-treatment with 3 μM SFN for 4 days following 1.5% ethanol exposure during 3-24 hpf also significantly reduced the characteristic features of FASD, decreasing the mortality rate and restoring body length, eye size, brain size, and otic vesicle circumference. Moreover, we found that ethanol, even at a low dose (0.5%), causes vascular development deficit in the zebrafish embryos, which were also largely rescued by SFN treatment. These data indicated that SFN has great potential to be used in the prevention and treatment of FASD.

Chronic inflammatory diseases pose a substantial health challenge globally, significantly contributing to morbidity and mortality. Addressing this issue requires the use of effective anti-inflammatory strategies with fewer side effects than those provoked by currently used drugs. In this study, a range of phytochemicals (phenolic di-caffeoylquinic acid (Di-CQA), flavonoid cyanidin-3,5-diglucoside (Cy3,5DiG), aromatic isothiocyanate sinalbin (SNB) and aliphatic isothiocyanate sulforaphane (SFN)) sourced from vegetables and fruits underwent assessment for their potential anti-inflammatory activity. An in vitro model of human macrophage-like cells treated with a low dose of LPS to obtain a low degree of inflammation that emulates a chronic inflammation scenario revealed promising results. Cell viability and production of the key pro-inflammatory cytokines were assessed in the presence of various phytochemicals. The compounds Di-CQA and Cy-3,5-DiG, within low physiologically relevant doses, demonstrated notable anti-inflammatory effects by significantly reducing the production of key pro-inflammatory cytokines TNF-α and IL-6 without affecting cell viability. These findings underscore the potential of plant-derived bioactive compounds as valuable contributors to the prevention or treatment of chronic inflammatory diseases. These results suggest that these compounds, whether used individually or as part of natural mixtures, hold promise for their inclusion in nutritional interventions designed to mitigate inflammation in associated pathologies.

Constant exposure to harmful substances from both inside and outside the body can mess up the body's natural ways of keeping itself in balance. This can cause severe skin damage, including basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and melanoma. However, plant-derived compounds found in fruits and vegetables have been shown to protect against skin cancer-causing free radicals and other harmful substances. It has been determined that these dietary phytochemicals are effective in preventing skin cancer and are widely available, inexpensive, and well-tolerated. Studies have shown that these phytochemicals possess anti-inflammatory, antioxidant, and antiangiogenic properties that can aid in the prevention of skin cancers. In addition, they influence crucial cellular processes such as angiogenesis and cell cycle control, which can halt the progression of skin cancer. The present paper discusses the benefits of specific dietary phytochemicals found in fruits and vegetables, as well as the signaling pathways they regulate, the molecular mechanisms involved in the prevention of skin cancer, and their drawbacks.

Neuroinflammation in response to environmental stressors is an important common pathway in a number of neurological and psychiatric disorders. Responses to immune-mediated stress can lead to epigenetic changes and the development of neuropsychiatric disorders. Isothiocyanates (ITC) have shown promise in combating oxidative stress and inflammation in the nervous system as well as organ systems. While sulforaphane from broccoli is the most widely studied ITC for biomedical applications, ITC and their precursor glucosinolates are found in many species of cruciferous and other vegetables including moringa. In this review, we examine both clinical and pre-clinical studies of ITC on the amelioration of neuropsychiatric disorders (neurodevelopmental, neurodegenerative, and other) from 2018 to the present, including documentation of protocols for several ongoing clinical studies. During this time, there have been 16 clinical studies (9 randomized controlled trials), most of which reported on the effect of sulforaphane on autism spectrum disorder and schizophrenia. We also review over 80 preclinical studies examining ITC treatment of brain-related dysfunctions and disorders. The evidence to date reveals ITC have great potential for treating these conditions with minimal toxicity. The authors call for well-designed clinical trials to further the translation of these potent phytochemicals into therapeutic practice.

Sulforaphane (SFaN) is a food-derived compound with several bioactive properties, including atherosclerosis, diabetes, and obesity treatment. However, the mechanisms by which SFaN exerts its various effects are still unclear. To elucidate the mechanisms of the various effects of SFaN, we explored novel SFaN-binding proteins using SFaN beads and identified acyl protein thioesterase 2 (APT2). We also found that SFaN binds to the APT2 via C56 residue and attenuates the palmitoylation of APT2, thereby reducing plasma membrane localization of APT2. This study reveals a novel bioactivity of SFaN as a regulator of APT2 protein palmitoylation.

"Cancer chemoprevention" is a term referring to the slowing or reversal of this disease, using nontoxic natural or synthetic compounds. For about 50 years, there has been a strong scientific interest in discovering plant-derived compounds to prevent cancer, and strategies for this purpose using a concerted series of in vitro, ex vivo, and in vivo laboratory bioassays have been developed. Five examples of the more thoroughly investigated agents of this type are described herein, which are each supported by detailed literature reports, inclusive of ellagic acid, isoliquiritigenin, lycopene, trans-resveratrol, and sulforaphane. In addition, extracts of the plants avocado (Persea americana), noni (Morinda citrifolia), açai (Euterpe oleracea), and mangosteen (Garcinia mangostana) have all shown inhibitory activity in an in vivo or ex vivo bioassay using a carcinogen and germane to cancer chemoprevention, and selected in vitro-active constituents are described for each of these 4 species.

Considering a growing, aging population, the need for interventions to improve the healthspan in aging are tantamount. Diet and nutrition are important determinants of the aging trajectory. Plant-based diets that provide bioactive phytonutrients may contribute to offsetting hallmarks of aging and reducing the risk of chronic disease. Researchers now advocate moving toward a positive model of aging which focuses on the preservation of functional abilities, rather than an emphasis on the absence of disease. This narrative review discusses the modulatory effect of nutrition on aging, with an emphasis on promising phytonutrients, and their potential to influence cellular, organ and functional parameters in aging. The literature is discussed against the backdrop of a recent conceptual framework which describes vitality, intrinsic capacity and expressed capacities in aging. This aims to better elucidate the role of phytonutrients on vitality and intrinsic capacity in aging adults. Such a review contributes to this new scientific perspective-namely-how nutrition might help to preserve functional abilities in aging, rather than purely offsetting the risk of chronic disease.

Sicklepod [Cassia obtusifolia L. syn Senna obtusifolia (L.) H.S. Irwin & Barneby, Fabaceae] sprouts are promising ingredients with health-promoting benefits. Notwithstanding, the pharmacologically active compounds in sicklepod sprouts have not been studied or analysed in detail.

This study aimed to isolate and structurally identify phytochemicals showing α-glucosidase inhibitory activity in sicklepod sprouts and simultaneously quantify the compounds in the sprouts to determine the optimal cultivation method and germination time to maximise active compounds.

A simultaneous high-performance liquid chromatography-ultraviolet (HPLC-UV) method with high sensitivity and accuracy was developed and used to analyse time-dependent changes in anthraquinone content during sicklepod germination.

Thirteen anthraquinones were isolated and identified, of which six-chrysoobtusin, emodin, 1-O-methyl-2-methoxychrysophanol, 7-O-methylobtusin, chrysophanol, and physcion-showed moderate α-glucosidase inhibitory activity. The maximum content of anthraquinones in a sprout was observed on Day 5 under both light and dark conditions.

The findings of this study revealed that sicklepod sprouts which are promising functional food materials contain a variety of anthraquinones.

Skin aging is an inevitable and intricate process instigated, among others, by oxidative stress. The search for natural sources that inhibit this mechanism is a promising approach to preventing skin aging. The purpose of our study was to evaluate the composition of phenolic compounds in the micellar extract of Phaseolus vulgaris sprouts. The results of a liquid chromatography-mass spectrometry (LC-MS) analysis revealed the presence of thirty-two constituents, including phenolic acids, flavanols, flavan-3-ols, flavanones, isoflavones, and other compounds. Subsequently, the extract was assessed for its antioxidant, anti-inflammatory, anti-collagenase, anti-elastase, anti-tyrosinase, and cytotoxic properties, as well as for the evaluation of collagen synthesis. It was demonstrated that micellar extract from common bean sprouts has strong anti-aging properties. The performed WST-8 (a water-soluble tetrazolium salt) assay revealed that selected concentrations of extract significantly increased proliferation of human dermal fibroblasts compared to the control cells in a dose-dependent manner. A similar tendency was observed with respect to collagen synthesis. Our results suggest that micellar extract from Phaseolus vulgaris sprouts can be considered a promising anti-aging compound for applications in cosmetic formulations.

The contributions of cruciferous vegetables to human health are widely recognised, particularly at the molecular level, where their isothiocyanates play a significant role. However, compared to the well-studied isothiocyanate 4-(methylsulfinyl)butyl isothiocyanate (sulforaphane) produced from broccoli sprouts, less is known about the pharmacological effects of other isothiocyanates and the stage of vegetables preferable to obtain their benefits. We analysed the quantity and quality of isothiocyanates produced in both the sprouts and mature stages of eight cruciferous vegetables using gas chromatography-mass spectrometry (GC-MS). Additionally, we investigated the hepatoprotective effects of isothiocyanates in a mouse model of acute hepatitis induced by carbon tetrachloride (CCl4). Furthermore, we explored the detoxification enzyme-inducing activities of crude sprout extracts in normal rats. Among the eight cruciferous vegetables, daikon radish (Raphanus sativus L.) sprouts produced the highest amount of isothiocyanates, with 4-(methylsulfinyl)-3-butenyl isothiocyanate (sulforaphene) being the dominant compound. The amount of sulforaphene in daikon radish sprouts was approximately 30 times that of sulforaphane in broccoli sprouts. Sulforaphene demonstrated hepatoprotective effects similar to sulforaphane in ameliorating CCl4-induced hepatic injury in mice. A crude extract of 3-day-old daikon radish sprouts upregulated the detoxifying enzyme glutathione S-transferase (GST) in the liver, whereas the crude extract of broccoli sprouts showed limited upregulation. This study highlights that daikon radish sprouts and sulforaphene have the potential to serve as functional food materials with hepatoprotective effects. Furthermore, daikon radish sprouts may exhibit more potent hepatoprotective effects compared to broccoli sprouts.

We previously found that feeding rats with broccoli or cauliflower leads to the formation of characteristic DNA adducts in the liver, intestine and various other tissues. We identified the critical substances in the plants as 1-methoxy-3-indolylmethyl (1-MIM) glucosinolate and its degradation product 1-MIM-OH. DNA adduct formation and the mutagenicity of 1-MIM-OH in cell models were drastically enhanced when human sulfotransferase (SULT) 1A1 was expressed. The aim of this study was to clarify the role of SULT1A1 in DNA adduct formation by 1-MIM-OH in mouse tissues in vivo. Furthermore, we compared the endogenous mouse Sult1a1 and transgenic human SULT1A1 in the activation of 1-MIM-OH using genetically modified mouse strains. We orally treated male wild-type (wt) and Sult1a1-knockout (ko) mice, as well as corresponding lines carrying the human SULT1A1-SULT1A2 gene cluster (tg and ko-tg), with 1-MIM-OH. N2-(1-MIM)-dG and N6-(1-MIM)-dA adducts in DNA were analysed using isotope-dilution UPLC-MS/MS. In the liver, caecum and colon adducts were abundant in mice expressing mouse and/or human SULT1A1, but were drastically reduced in ko mice (1.2-10.6% of wt). In the kidney and small intestine, adduct levels were high in mice carrying human SULT1A1-SULT1A2 genes, but low in wt and ko mice (1.8-6.3% of tg-ko). In bone marrow, adduct levels were very low, independently of the SULT1A1 status. In the stomach, they were high in all four lines. Thus, adduct formation was primarily controlled by SULT1A1 in five out of seven tissues studied, with a strong impact of differences in the tissue distribution of mouse and human SULT1A1. The behaviour of 1-MIM-OH in these models (levels and tissue distribution of DNA adducts; impact of SULTs) was similar to that of methyleugenol, classified as "probably carcinogenic to humans". Thus, there is a need to test 1-MIM-OH for carcinogenicity in animal models and to study its adduct formation in humans consuming brassicaceous foodstuff.

Variations in the concentration of glucoraphanin (GRA) and glucoerucin (GER), as well as the corresponding breakdown products, isothiocyanates (ITCs) and nitriles, were investigated during the growth of broccoli sprouts. The concentrations of GRA and GER decreased sharply from 33.66 µmol/g to 11.48 µmol/g and 12.98 µmol/g to 8.23 µmol/g, respectively, after seed germination. From the third to the seventh day, both GRA and GER were maintained as relatively stable. The highest concentrations of sulforaphane (17.16 µmol/g) and erucin (12.26 µmol/g) were observed on the first day. Hereafter, the concentrations of nitrile hydrolyzed from GRA or GER were higher than those of the corresponding ITCs. Moreover, the ratio of sulforaphane to sulforaphane nitrile decreased from 1.35 to 0.164 from 1 d to 5 d, with a similar trend exhibited for erucin/erucin nitrile after 2 d. RNA-seq analysis showed that BolMYB28 and BolCYP83A1, involved in aliphatic glucosinolate (GSL) biosynthesis, remained largely unexpressed until the third day. In contrast, the genes operating within the GSL-myrosinase hydrolysis pathway were highly expressed right from the beginning, with their expression levels increasing significantly after the third day. Additionally, we identified two BolESPs and six BolNSPs that might play important roles in promoting the production of nitriles during the development of broccoli sprouts.

The concept of green chemoprevention was introduced in 2012 by Drs. Jed Fahey and Thomas Kensler as whole-plant foods and/or extract-based interventions demonstrating cancer prevention activity. Refining concepts and research demonstrating proof-of-principle approaches are highlighted within this review. Early approaches included extensively investigated whole foods, including broccoli sprouts and black raspberries showing dose-responsive effects across a range of activities in both animals and humans with minimal or no apparent toxicity. A recent randomized crossover trial evaluating the detoxification of tobacco carcinogens by a broccoli seed and sprout extract in the high-risk cohort of current smokers highlights the use of a dietary supplement as a potential next-generation green chemoprevention or green cancer prevention approach. Challenges are addressed, including the selection of dose, duration and mode of delivery, choice of control group, and standardization of the plant food or extract. Identification and characterization of molecular targets and careful selection of high-risk cohorts for study are additional important considerations when designing studies. Goals for precision green cancer prevention include acquiring robust evidence from carefully controlled human studies linking plant foods, extracts, and compounds to modulation of targets for cancer risk reduction in individual cancer types.

Tomato consumption is associated with many health benefits including lowered risk for developing certain cancers. It is hypothesized that tomato phytochemicals are transported to the liver and other tissues where they alter gene expression in ways that lead to favorable health outcomes. However, the effects of tomato consumption on mammalian liver gene expression and chemical profile are not well defined.

The study hypothesizes that tomato consumption would alter mouse liver transcriptomes and metabolomes compared to a control diet. C57BL/6J mice (n = 11-12/group) are fed a macronutrient matched diet containing either 10% red tomato, 10% tangerine tomato, or no tomato powder for 6 weeks after weaning. RNA-Seq followed by gene set enrichment analyses indicates that tomato type and consumption, in general, altered expression of phase I and II xenobiotic metabolism genes. Untargeted metabolomics experiments reveal distinct clustering between control and tomato fed animals. Nineteen molecular formulas (representing 75 chemical features) are identified or tentatively identified as steroidal alkaloids and isomers of their phase I and II metabolites; many of which are reported for the first time in mammals.

These data together suggest tomato consumption may impart benefits partly through enhancing detoxification potential.

Introduction: Broccoli is a cruciferous vegetable that has been shown to have numerous potential therapeutic benefits because of its bioactive compounds. Methods: In this study, we compared the bioactive efficacy of cooked and uncooked (fresh) stems and florets of broccoli extracted with three different solvents: acetonitrile, methanol, and aqueous extracts. The extraction yield and antioxidant and antibacterial potential of different broccoli extracts were examined. Results: Fresh and boiled floret stem extracts increased the extraction yield. The extraction yields were higher for the methanol and acetonitrile extracts than for the aqueous extracts. The antioxidant efficacy of the different extracts was studied using ABTS, DPPH, and metal ion reduction assays. The acetonitrile and aqueous extracts exhibited higher antioxidant activities than the methanolic extracts in different antioxidant assays. In addition, increased antioxidant activity was observed in fresh florets and boiled broccoli stems. TPC and TFC contents were higher in the methanolic extracts than in the aqueous extracts. Similar to antioxidant activities, anti-inflammatory activities were found to be higher in the acetonitrile and aqueous extracts, particularly in boiled stems and fresh florets. Broccoli extracts have been shown to be active against Bacillus subtilis and moderately effective against Pseudomonas aeruginosa and Staphylococcus aureus. Conclusions: Acetonitrile and aqueous extraction of broccoli might be an ideal choice for extraction methods, which show increased extraction yield and antioxidant and anti-inflammatory potentials. Utilization of phytomolecules from natural sources is a promising alternative approach to synthetic drug development.

To our knowledge, IL-10-KO mice have not previously been used to investigate the interactions of host, microbiota, and broccoli, broccoli sprouts, or broccoli bioactives in resolving symptoms of CD. We showed that a diet containing 10% raw broccoli sprouts increased the plasma concentration of the anti-inflammatory compound sulforaphane and protected mice to varying degrees against disease symptoms, including weight loss or stagnation, fecal blood, and diarrhea. Younger mice responded more strongly to the diet, further reducing symptoms, as well as increased gut bacterial richness, increased bacterial community similarity to each other, and more location-specific communities than older mice on the diet intervention. Crohn's disease disrupts the lives of patients and requires people to alter dietary and lifestyle habits to manage symptoms. The current medical treatment is expensive with significant side effects, and a dietary intervention represents an affordable, accessible, and simple strategy to reduce the burden of symptoms.

Pain is a worldwide problem requiring an effective, affordable, non-addictive therapy. Using the edible plant broccoli, a growth protocol was developed to induce a concentrated combinatorial of potential anti-inflammatories in seedlings.

A growth method was utilized to produce a phenylpropanoid-rich broccoli sprout extract, referred to as Original Extract (OE). OE was concentrated and then resuspended for study of the effects on inflammation events. A rabbit disc model of inflammation and degeneration, and, a mouse model of pain behavior were used for in vivo and in vitro tests. To address aspects of mammalian metabolic processing, the OE was treated with the S9 liver microsome fraction derived from mouse, for use in a mouse in vivo study. Analytical chemistry was performed to identify major chemical species. Continuous variables were analyzed with a number of methods including ANOVA, and two-tailed t tests, as appropriate.

In a rabbit spine (disc) injury model, inflammatory markers were reduced, and levels of regenerative markers were increased as a result of OE treatment, both in vivo and in vitro. In a mouse pain behavioral model, after treatment with S9 liver microsome fraction, the resultant extract significantly reduced early and late pain behavior in response to a pain stimulus. The OE itself reduced pain behavior in the mouse pain model, but did not achieve the level of significance observed for S9-treated extract. Analytical chemistry undertaken on the extract constituents revealed identities of the chemical species in OE, and how S9 liver microsome fraction treatment altered species identities and proportions.

In vitro and in vivo results indicate that the OE, and S9-treated OE broccoli extracts are worthwhile materials to develop a non-opiate inflammation and pain-reducing treatment.

In the combat of treating cancer recent therapeutic approaches are focused towards enzymatic targets as they occupy a pivotal participation in the cascade of oncogenesis and malignancy. There are several enzymes that modulate the epigenetic pathways and chromatin structure related to cancer mutation. Among several epigenetic mechanisms such as methylation, phosphorylation, and sumoylation, acetylation status of histones is crucial and is governed by counteracting enzymes like histone acetyl transferase (HAT) and histone deacetylases (HDAC) which have contradictory effects on the histone acetylation. HDAC inhibition induces chromatin relaxation which forms euchromatin and thereby initiates the expression of certain transcription factors attributed with apoptosis, which are mostly correlated with the expression of the p21 gene and acetylation of H3 and H4 histones. Most of the synthetic and natural HDAC inhibitors elicit antineoplastic effect through activation of various apoptotic pathways and promoting cell cycle arrest at various phases. Due to their promising chemo preventive action and low cytotoxicity against normal host cells, bioactive substances like flavonoids, alkaloids, and polyphenolic compounds from plants have recently gained importance. Even though all bioactive compounds mentioned have an HDAC inhibitory action, some of them have a direct effect and others enhance the effects of the standard well known HDAC inhibitors. In this review, the action of plant derived compounds against histone deacetylases in a variety of in vitro cancer cell lines and in vivo animal models are articulated.

The aggressive and incurable diffuse gliomas constitute 80% of malignant brain tumors, and patients succumb to recurrent surgeries and drug resistance. Epidemiological research indicates that substantial consumption of fruits and vegetables diminishes the risk of developing this tumor type. Broccoli consumption has shown beneficial effects in both cancer and neurodegenerative diseases. These effects are partially attributed to the isothiocyanate sulforaphane (SFN), which can regulate the Keap1/Nrf2/ARE signaling pathway, stimulate detoxifying enzymes, and activate cellular antioxidant defense processes. This study employs a C6 rat glioma model to assess the chemoprotective potential of aqueous extracts from broccoli seeds, sprouts, and inflorescences, all rich in SFN, and pure SFN as positive control. The findings reveal that administering a dose of 100 mg/kg of broccoli sprout aqueous extract and 0.1 mg/kg of SFN to animals for 30 days before introducing 1 × 104 cells effectively halts tumor growth and progression. This study underscores the significance of exploring foods abundant in bioactive compounds, such as derivatives of broccoli, for potential preventive integration into daily diets. Using broccoli sprouts as a natural defense against cancer development might seem idealistic, yet this investigation establishes that administering this extract proves to be a valuable approach in designing strategies for glioma prevention. Although the findings stem from a rat glioma model, they offer promising insights for subsequent preclinical and clinical research endeavors.

Broccoli sprouts have great health and commercial value because they are rich in sulforaphane, a special bioactive compound that helps to prevent chronic diseases, such as cancer and cardiovascular disease.

The aim of this study was to increase the levels of active substances in broccoli sprouts and understand their metabolic mechanisms.

Metabolomics based on liquid chromatography-tandem mass spectrometry and transcriptome analysis were combined to analyse the enrichment of metabolites in broccoli sprouts treated with cold plasma.

After 2 min of cold plasma treatment, the contents of sulforaphane, glucosinolates, total phenols, and flavonoids, as well as myrosinase activity, were greatly improved. Transcriptomics revealed 7460 differentially expressed genes in the untreated and treated sprouts. Metabolomics detected 6739 differential metabolites, including most amino acids, their derivatives, and organic acids. Enrichment analyses of metabolomics and transcriptomics identified the 20 most significantly differentially expressed metabolic pathways.

Overall, cold plasma treatment can induce changes in the expression and regulation of certain metabolites and genes encoding active substances in broccoli sprouts.

To improve resolution to small genomic regions and sensitivity to small-effect loci in the identification of genetic factors conferring the enlarged inflorescence and other traits of cauliflower while also expediting further genetic dissection, 104 near-isogenic introgression lines (NIILs) covering 78.56% of the cauliflower genome, were selected from an advanced backcross population using cauliflower [Brassica oleracea var. botrytis L., mutant for Orange gene (ORG)] as the donor parent and a rapid cycling line (TO1434) as recurrent parent. Subsets of the advanced backcross population and NIILs were planted in the field for 8 seasons, finding 141 marker-trait associations for 15 leaf-, stem-, and flower-traits. Exemplifying the usefulness of these lines, we delineated the previously known flower color gene to a 4.5 MB interval on C3; a gene for small plant size to a 3.4 MB region on C8; and a gene for large plant size and flowering time to a 6.1 MB region on C9. This approach unmasked closely linked QTL alleles with opposing effects (on chr. 8) and revealed both alleles with expected phenotypic effects and effects opposite the parental phenotypes. Selected B. oleracea NIILs with short generation time add new value to widely used research and teaching materials.

Oxidative stress plays a vital role for the adaptive responses to physical training. However, excessive oxidative stress can precipitate cellular damage, necessitating protective mechanisms to mitigate this effect. Glucosinolates, found predominantly in cruciferous vegetables, can be converted into isothiocyanates, known for their antioxidative properties. These compounds activate crucial antioxidant defence pathways and support mitochondrial function and protein integrity under oxidative stress, in both Nrf2-dependent and independent manners. We here administered glucosinolate-rich broccoli sprouts (GRS), in a randomized double-blinded cross-over fashion to 9 healthy subjects in combination with daily intense exercise training for 7 days. We found that exercise in combination with GRS significantly decreased the levels of carbonylated proteins in skeletal muscle and the release of myeloperoxidase into blood. Moreover, it lowered lactate accumulation during submaximal exercise, and attenuated the severe nocturnal hypoglycaemic episodes seen during the placebo condition. Furthermore, GRS in combination with exercise improved physical performance, which was unchanged in the placebo condition.

Higher consumption of broccoli (Brassica oleracea var. italica) is associated with a reduced risk of cardiometabolic diseases, neurological disorders, diabetes, and cancer. Broccoli is rich in various phytochemicals, including glucosinolates, and isothiocyanates. Moreover, it has recently reported the endogenous production of polysulfides, such as cysteine hydropersulfide (CysS2H) and glutathione hydropersulfide (GS2H), in mammals including humans, and that these bioactive substances function as potent antioxidants and important regulators of redox signaling in vivo. However, few studies have focused on the endogenous polysulfide content of broccoli and the impact of germination on the polysulfide content and composition in broccoli. In this study, we investigated the alternations in polysulfide biosynthesis in broccoli during germination by performing untargeted polysulfide omics analysis and quantitative targeted polysulfide metabolomics through liquid chromatography-electrospray ionization-tandem mass spectrometry. We also performed 2,2-diphenyl-1-picrylhydrazyl radical-scavenging assay to determine the antioxidant properties of the polysulfides. The results revealed that the total polysulfide content of broccoli sprouts significantly increased during germination and growth; CysS2H and cysteine hydrotrisulfide were the predominant organic polysulfide metabolites. Furthermore, we determined that novel sulforaphane (SFN) derivatives conjugated with CysS2H and GS2H were endogenously produced in the broccoli sprouts, and the novel SFN conjugated with CysS2H exhibited a greater radical scavenging capacity than SFN and cysteine. These results suggest that the abundance of polysulfides in broccoli sprouts contribute to their health-promoting properties. Our findings have important biological implications for the development of novel pharmacological targets for the health-promoting effects of broccoli sprouts in humans.

Selenoprotein P (SeP) is a major selenoprotein in serum predominantly produced in the liver. Excess SeP impairs insulin secretion from the pancreas and insulin sensitivity in skeletal muscle, thus inhibition of SeP could be a therapeutic strategy for type 2 diabetes. In this study, we examine the effect of sulforaphane (SFN), a phytochemical of broccoli sprouts and an Nrf2 activator, on SeP expression in vitro and in vivo. Treatment of HepG2 cells with SFN decreases inter- and intra-cellular SeP levels. SFN enhances lysosomal acidification and expression of V-ATPase, and inhibition of this process cancels the decrease of SeP by SFN. SFN activates Nrf2 in the cells, while Nrf2 siRNA does not affect the decrease of SeP by SFN or lysosomal acidification. These results indicate that SFN decreases SeP by enhancing lysosomal degradation, independent of Nrf2. Injection of SFN to mice results in induction of cathepsin and a decrease of SeP in serum. The findings from this study are expected to contribute to developing SeP inhibitors in the future, thereby contributing to treating and preventing diseases related to increased SeP.

Cruciferous vegetable consumption is associated with numerous health benefits attributed to the phytochemical sulforaphane (SFN) that exerts antioxidant and chemopreventive properties, among other bioactive compounds. Broccoli sprouts, rich in SFN precursor glucoraphanin (GRN), have been investigated in numerous clinical trials. Broccoli microgreens are similarly rich in GRN but have remained largely unexplored. The goal of this study was to examine SFN bioavailability and the microbiome profile in subjects fed a single serving of fresh broccoli microgreens. Eleven subjects participated in a broccoli microgreens feeding study. Broccoli microgreens GRN and SFN contents and stability were measured. Urine and stool SFN metabolite profiles and microbiome composition were examined. Broccoli microgreens had similar GRN content to values previously reported for broccoli sprouts, which was stable over time. Urine SFN metabolite profiles in broccoli microgreens-fed subjects were similar to those reported previously in broccoli sprouts-fed subjects, including the detection of SFN-nitriles. We also reported the detection of SFN metabolites in stool samples for the first time. A single serving of broccoli microgreens did not significantly alter microbiome composition. We showed in this study that broccoli microgreens are a significant source of SFN. Our work provides the foundation for future studies to establish the health benefits of broccoli microgreens consumption.

Glucosinolates (GSLs), a class of secondary metabolites found in Brassicaceae plants, play important roles in plant defense and contribute distinct flavors and aromas when used as food ingredients. Following tissue damage, GSLs undergo enzymatic hydrolysis to release bioactive volatile compounds. Understanding GSL biosynthesis and enzyme involvement is crucial for improving crop quality and advancing agriculture. Plant sulfotransferases (SOTs) play a key role in the final step of GSL biosynthesis by transferring sulfate groups to the precursor molecules. In the present study, we investigated the enzymatic reaction mechanism and broad substrate specificity of Arabidopsis thaliana sulfotransferase AtSOT16, which is involved in GSL biosynthesis, using crystal structure analysis. Our analysis revealed the specific catalytic residues involved in the sulfate transfer reaction and supported the hypothesis of a concerted acid-base catalytic mechanism. Furthermore, the docking models showed a strong correlation between the substrates with high predicted binding affinities and those experimentally reported to exhibit high activity. These findings provide valuable insights into the enzymatic reaction mechanisms and substrate specificity of GSL biosynthesis. The information obtained in this study may contribute to the development of novel strategies for manipulating GSL synthesis pathways in Brassica plants and has potential agricultural applications.

Parkinson's disease (PD) is characterized by the formation of Lewy bodies (LBs) in the brain. These LBs are primarily composed of α-Synuclein (α-Syn), which has aggregated. A recent report proposes that CCAAT/enhancer-binding proteins β (C/EBPβ) may act as an age-dependent transcription factor for α-Syn, thereby initiating PD pathologies by regulating its transcription. Potential therapeutic approaches to address PD could involve targeting the regulation of α-Syn by C/EBPβ. This study has revealed that Nrf2, also known as nuclear factor (erythroid-derived 2)-like 2 (NFE2L2), suppresses the transcription of C/EBPβ in SH-SY5Y cells when treated with MPP+ . To activate Nrf2, sulforaphane, an Nrf2 activator, was administered. Additionally, C/EBPβ was silenced using C/EBPβ-DNA/RNA heteroduplex oligonucleotide (HDO). Both approaches successfully reduced abnormal α-Syn expression in primary neurons treated with MPP+ . Furthermore, sustained activation of Nrf2 via its activator or inhibition of C/EBPβ using C/EBPβ-HDO resulted in a reduction of aberrant α-Syn expression, thus leading to an improvement in the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) in mouse models induced by 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) and those treated with preformed fibrils (PFFs). The data presented in this study illustrate that the activation of Nrf2 may provide a potential therapeutic strategy for PD by inhibiting the abnormal C/EBPβ/α-Syn signaling pathway.

Dysregulation of innate immune responses can result in chronic inflammatory conditions. Glucocorticoids, the current frontline therapy, are effective immunosuppressive drugs but come with a trade-off of cumulative and serious side effects. Therefore, alternative drug options with improved safety profiles are urgently needed. Sulforaphane, a phytochemical derived from plants of the brassica family, is a potent inducer of phase II detoxification enzymes via nuclear factor-erythroid factor 2-related factor 2 (NRF2) signaling. Moreover, a growing body of evidence suggests additional diverse anti-inflammatory properties of sulforaphane through interactions with mediators of key signaling pathways and inflammatory cytokines. Multiple studies support a role for sulforaphane as a negative regulator of nuclear factor kappa-light chain enhancer of activated B cells (NF-κB) activation and subsequent cytokine release, inflammasome activation and direct regulation of the activity of macrophage migration inhibitory factor. Significantly, studies have also highlighted potential steroid-sparing activity for sulforaphane, suggesting that it may have potential as an adjunctive therapy for some inflammatory conditions. This review discusses published research on sulforaphane, including proposed mechanisms of action, and poses questions for future studies that might help progress our understanding of the potential clinical applications of this intriguing molecule.

Vision loss causes a significant burden on individuals and communities on a financial, emotional and social level. Common causes include age-related macular degeneration (AMD), diabetic retinopathy (DR), glaucoma and retinitis pigmentosa (RP; also known as 'rod-cone dystrophy'). As the population continues to grow and age globally, an increasing number of people will experience vision loss. Hence, there is an urgent need to develop therapies that can curb early pathological events. The broccoli-derived compound, sulforaphane (SFN), is reported to have multiple health benefits and modes of action. In this review, we outline the preclinical findings on SFN in ocular diseases and discuss the future clinical testing of this compound.