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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. [ABSTRACT FROM AUTHOR]

Lunaria annua L. (Brassicaceae) is an ornamental plant newly identified in Europe as a promising industrial oilseed crop for its valuable very-long-chain monounsaturated fatty acids (MUFAs), especially erucic acid (EA) and nervonic acid (NA). L. annua seeds were obtained from annual winter-type plants selected and cultivated in Northern France. Using a systematic multiple-method approach, we set out to determine the profile and content of glucosinolates (GSLs), which are the relevant chemical tag of Brassicaceae. Intact GSLs were analyzed through a well-established LC-MS method. Identification and quantification were performed by HPLC-PDA of desulfo-GSLs (dGLs) according to the official EU ISO method. Moreover, GSL structures were confirmed by GC-MS analysis of the related isothiocyanates (ITCs). Seven GSLs were identified, directly or indirectly, as follows: 1-methylethyl GSL, (1S)-1-methylpropyl GSL, (Rs)-5-(methylsulfinyl)pentyl GSL, (Rs)-6-(methylsulfinyl)hexyl GSL, (2S)-2-hydroxy-4-pentenyl GSL, 2-phenylethyl GSL, and 1-methoxyindol-3-ylmethyl GSL. In other respects, the FA composition of the seed oil was determined. Results revealed cultivated L. annua seed to be a source of NA-rich oil, and presscake as a valuable coproduct. This presscake is indeed rich in GSLs (4.3% w/w), precursors of promising bioactive molecules for agricultural and nutraceutical applications. [ABSTRACT FROM AUTHOR]

Oxidative stress is a common feature of neurodegenerative diseases. Different natural compounds mediate neuroprotective effects by activating the Nrf2 antioxidant response. Some isothiocyanates are Nrf2 activators, including Moringin (MOR). In this study, the transcriptional profile of differentiated NSC-34 motor neurons was evaluated after treatment for 48 h and 96 h with concentrations of 0.5, 5, and 10 µM of a new MOR formulation obtained with α-cyclodextrin (α-CD). All the concentrations increased gene expression and cytoplasmic protein levels of Nrf2 at 96 h. However, the highest dose also increased nuclear Nrf2 levels at 96 h. Then, Nrf2 interactors were selected using STRING, and common biological process (BP) terms between the groups were evaluated. α-CD/MOR was able to modulate BP related to responses to oxidative stress, proteostasis, and autophagy. Specifically, the treatment with 10 µM of α-CD/MOR for 96 h induced genes involved in glutathione synthesis and proteasome subunits and reduced the expression of genes related to endoplasmic reticulum stress. Moreover, this group showed the lowest levels of the apoptotic markers Bax, cleaved caspase 9, and cleaved caspase 3. These results indicate the beneficial effects of prolonged α-CD/MOR supplementation that are mediated, at least in part, by Nrf2 activation. Then, α-CD/MOR could be a valuable treatment against neurodegenerative diseases, in particular motor neuron degeneration. [ABSTRACT FROM AUTHOR]

Breast cancer is the most common tumor in women. Chemotherapy is the gold standard for cancer treatment; however, severe side effects and tumor resistance are the major obstacles to chemotherapy success. Numerous dietary components and phytochemicals have been found to inhibit the molecular and signaling pathways associated with different stages of breast cancer development. In particular, this review is focused on the antitumor effects of PUFAs, dietary enzymes, and glucosinolates against breast cancer. The major databases were consulted to search in vitro and preclinical studies; only those with solid scientific evidence and reporting protective effects on breast cancer treatment were included. A consistent number of studies highlighted that dietary components and phytochemicals can have remarkable therapeutic effects as single agents or in combination with other anticancer agents, administered at different concentrations and via different routes of administration. These provide a natural strategy for chemoprevention, reduce the risk of breast cancer recurrence, impair cell proliferation and viability, and induce apoptosis. Some of these bioactive compounds of dietary origin, however, show poor solubility and low bioavailability; hence, encapsulation in nanoformulations are promising tools able to increase clinical efficiency. [ABSTRACT FROM AUTHOR]

The compound 1-(3-chlorophenyl)-3-(6-((1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)amino)hexyl)thiourea was synthesized for the first time from 6-((1,7,7-trimethylbicyclo[2.2.1]heptan-2-ylidene)amino)hexan-1-amine and 3-chlorophenylisothiocyanate in DMF with a 60% yield. It was characterized by 1H, 13C{1H} NMR, FT-IR, MS, and elemental analysis. [ABSTRACT FROM AUTHOR]

This work represents an overview of the current investigations involving organosulfur compounds and colorectal cancer. The molecules discussed in this review have been investigated regarding their impact on colorectal cancer directly, at the in vitro, in vivo, and clinical stages. Organosulfur compounds may have indirect effects on colorectal cancer, such as due to their modulating effects on the intestinal microbiota or their positive effects on intestinal mucosal health. Here, we focus on their direct effects via the repression of multidrug resistance proteins, triggering of apoptosis (via the inhibition of histone deacetylases, increases in reactive oxygen species, p53 activation, β-catenin inhibition, damage in the mitochondrial membrane, etc.), activation of TGF-β, binding to tubulin, inhibition of angiogenesis and metastasis mechanisms, and inhibition of cancer stem cells, among others. In general, the interesting positive effects of these nutraceuticals in in vitro tests must be further analyzed with more in vivo models before conducting clinical trials. [ABSTRACT FROM AUTHOR]

Isothiocyanates are biologically active products resulting from the hydrolysis of glucosinolates predominantly present in cruciferous vegetables belonging to the Brassicaceae family. Numerous studies have demonstrated the diverse bioactivities of various isothiocyanates, encompassing anticarcinogenic, anti-inflammatory, and antioxidative properties. Nature harbors distinct isothiocyanate precursors, glucosinolates such as glucoraphanin and gluconastrin, each characterized by unique structures, physical properties, and pharmacological potentials. This comprehensive review aims to consolidate the current understanding of Moringa isothiocyanates, mainly 4-[(α-L-rhamnosyloxy) benzyl] isothiocyanate), comparing this compound with other well-studied isothiocyanates such as sulforaphane and phenyl ethyl isothiocyanates. The focus is directed toward elucidating differences and similarities in the efficacy of these compounds as agents with anticancer, anti-inflammatory, and antioxidative properties. [ABSTRACT FROM AUTHOR]

Metformin (Met) is the first-line therapy in type 2 diabetes mellitus but, in last few years, it has also been evaluated as anti-cancer agent. Several pathways, such as AMPK or PI3K/Akt/mTOR, are likely to be involved in the anti-cancer Met activity. In addition, hydrogen sulfide (H2S) and H2S donors have been described as anti-cancer agents affecting cell-cycle and inducing apoptosis. Among H2S donors, isothiocyanates are endowed with a further anti-cancer mechanism: the inhibition of the histone deacetylase enzymes. On this basis, a hybrid molecule (Met-ITC) obtained through the addition of an isothiocyanate moiety to the Met molecule was designed and its ability to release Met has been demonstrated. Met-ITC exhibited more efficacy and potency than Met in inhibiting cancer cells (AsPC-1, MIA PaCa-2, MCF-7) viability and it was less effective on non-tumorigenic cells (MCF 10-A). The ability of Met-ITC to release H2S has been recorded both in cell-free and in cancer cells assays. Finally, its ability to affect the cell cycle and to induce both early and late apoptosis has been demonstrated on the most sensitive cell line (MCF-7). These results confirmed that Met-ITC is a new hybrid molecule endowed with potential anti-cancer properties derived both from Met and H2S. [ABSTRACT FROM AUTHOR]

Background: Cognitive functions decline with age. Declined cognitive functions negatively affect daily behaviors. Previous studies showed the positive effect of spices and herbs on cognition. In this study, we investigated the positive impact of wasabi, which is a traditional Japanese spice, on cognitive functions. The main bioactive compound of wasabi is 6-MSITC (6 methylsulfinyl hexyl isothiocyanate), which has anti-oxidant and anti-inflammatory functions. Anti-oxidants and anti-inflammatories have an important role in cognitive health. Therefore, 6-MSITC is expected to have positive effects on cognitive function. Previous studies showed the beneficial effects on cognitive functions in middle-aged adults. However, it is unclear that 6-MSITC has a positive effect on cognitive functions in healthy older adults aged 60 years and over. Here, we investigated whether 12 weeks' 6-MSITC intervention enhances cognitive performance in older adults using a double-blinded randomized controlled trial (RCT). Methods: Seventy-two older adults were randomly assigned to 6-MSITC or placebo groups. Participants were asked to take a supplement (6-MSITC or a placebo) for 12 weeks. We checked a wide range of cognitive performances (e.g., executive function, episodic memory, processing speed, working memory, and attention) at the pre- and post-intervention periods. Results: The 6-MSITC group showed a significant improvement in working and episodic memory performances compared to the placebo group. However, we did not find any significant improvements in other cognitive domains. Discussion: This study firstly demonstrates scientific evidence that 6-MSITC may enhance working memory and episodic memory in older adults. We discuss the potential mechanism for improving cognitive functions after 6-MSITC intake. [ABSTRACT FROM AUTHOR]

To identify the volatile flavor components in mustard paste (MP), the volatile compounds in seven MPs available on the market were isolated and analyzed by headspace solid-phase microextraction combined with gas chromatography–mass spectrometry. A total of 27 volatile constituents were found by mass spectra and retention index compared to the data obtained from reference compounds or the related literature and databases; these compounds included nine esters, three sulfur-containing compounds, two nitriles, three ketones, three alkenes, and seven other compounds. Of the 27 compounds, 6 compounds came from the turmeric added to MPs. Among the components detected, some compounds derived from AITC were allyl thiocyanate, carbon disulfide, allyl mercaptan, diallyl sulfide, and diallyl disulfide. The results obtained provide a better and comprehensive recognition of the volatile flavor compounds in MPs, and have some reference values for developing and applying isothiocyanate compounds. [ABSTRACT FROM AUTHOR]

The glucosinolates of Brassicaceae plants are converted into bioactive isothiocyanates and other volatiles during a challenge by pathogens and other biotic stressors. However, the role of alternative downstream products with weaker potency (e.g., nitriles) is far from being fully understood. This study tested the possible synergistic antifungal interaction between various glucosinolate-derived nitriles and 2-phenylethyl isothiocyanate (PEITC) on 45 fungal strains, including endophytes from horseradish roots (Brassicaceae) and soil fungi, using an airtight system enabling the accurate study of extremely volatile antifungal agents. The median minimal inhibitory concentrations (MICs) were 1.28, 6.10, 27.00 and 49.72 mM for 1H-indole-3-acetonitrile (IAN), 3-phenylpropanenitrile (PPN), 4-(methylsulfanyl)-butanenitrile (MSBN) and 3-butenenitrile (BN, = allyl cyanide), respectively. Thus, nitriles were considerably weaker antifungal agents compared to PEITC with a median MIC of 0.04 mM. For the same nitriles, the median fractional inhibitory concentration indices (FICIs) of the combinations were 0.562, 0.531, 0.562 and 0.625, respectively. Altogether, 47.7%, 56.8%, 50.0% and 27.3% of tested fungal strains showed a synergistic antifungal activity (FICI ≤ 0.5) for the nitrile–isothiocyanate combinations, respectively. Hypocreales strains showed the least sensitivity towards the GSL decomposition products and their combinations. The mean MIC values for PEITC showed 0.0679 ± 0.0358, 0.0400 ± 0.0214, 0.0319 ± 0.0087 and 0.0178 ± 0.0171 mM for Hypocreales, Eurotiales, Glomerellales and Pleosporales, respectively. In addition, nitriles, especially IAN, also showed significant differences. For the same fungi, the median FICI values fell in the ranges of 0.61–0.67, 0.52–0.61, 0.40–0.50 and 0.48–0.67, respectively, depending on the nitrile. Our results suggest that glucosinolate-derived nitriles may enhance isothiocyanate antifungal activity and that they may play an active role in shaping the plant microbiome and contribute to the filtering of microbes by plants. [ABSTRACT FROM AUTHOR]

Sulforaphane (SFN), an isothiocyanate, is one of the major dietary phytochemicals found in cruciferous vegetables. Many studies suggest that SFN can protect against cancer and cardiometabolic diseases. Despite the proposed systemic and local vascular protective mechanisms, SFN's potential to inhibit atherogenesis by targeting macrophages remains unknown. In this study, in high fat diet fed ApoE-deficient (ApoE−/−) mice, oral SFN treatment improved dyslipidemia and inhibited atherosclerotic plaque formation and the unstable phenotype, as demonstrated by reductions in the lesion areas in both the aortic sinus and whole aorta, percentages of necrotic cores, vascular macrophage infiltration and reactive oxygen species (ROS) generation. In THP-1-derived macrophages, preadministration SFN alleviated oxidized low-density lipoprotein (ox-LDL)-induced lipid accumulation, oxidative stress and mitochondrial injury. Moreover, a functional study revealed that peritoneal macrophages isolated from SFN-treated mice exhibited attenuated cholesterol influx and enhanced apolipoprotein A-I (apoA-I)- and high-density lipoprotein (HDL)-mediated cholesterol efflux. Mechanistic analysis revealed that SFN supplementation induced both intralesional and intraperitoneal macrophage phenotypic switching toward high expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and ATP-binding cassette subfamily A/G member 1 (ABCA1/G1) and low expression of peroxisome proliferator-activated receptor γ (PPARγ) and cluster of differentiation 36 (CD36), which was further validated by the aortic protein expression. These results suggest that the regulation of macrophages' cholesterol transport and accumulation may be mainly responsible for SFN's potential atheroprotective properties, and the regulatory mechanisms might involve upregulating ABCA1/G1 and downregulating CD36 via the modulation of PPARγ and Nrf2. [ABSTRACT FROM AUTHOR]

Inhibition of several protein pathways involved in cancer cell regulation is a necessary key in the discovery of cancer chemotherapy. Moringa oleifera Lam is often used in traditional medicine for the treatment of various illnesses. The plant contains glucomoringin isothiocyanate (GMG-ITC) with therapeutic potential against various cancer cells. Therefore, GMG-ITC was evaluated for its cytotoxicity against the PC-3 prostate cancer cell line and its potential to induce apoptosis. GMG-ITC inhibited cell proliferation in the PC-3 cell line with IC50 value 3.5 µg/mL. Morphological changes as a result of GMG-ITC-induced apoptosis showed chromatin condensation, nuclear fragmentation, and membrane blebbing. Additionally, Annexin V assay showed proportion of cells in early and late apoptosis upon exposure to GMG-ITC in a time-dependent manner. Moreover, GMG-ITC induced a time-dependent G2/M phase arrest, with reduction of 39.1% in the PC-3 cell line. GMG-ITC also activates apoptotic genes including caspase, tumor suppressor gene (p53), Akt/MAPK, and Bax of the proapoptotic Bcl family. Early apoptosis proteins (JNK, Bad, Bcl2, and p53) were significantly upregulated upon GMG-ITC treatment. It is concluded that apoptosis induction was observed in PC-3 cells treated with GMG-ITC. These phenomena suggest that GMG-ITC from M. oleifera seeds could be useful as a future cytotoxic agent against prostate cancer. [ABSTRACT FROM AUTHOR]

Chinese kale is a vegetable belonging to the family Brassicaceae in which members of this family produce unique metabolites called glucosinolates and isothiocyanates. These substances have been found to exhibit many benefits to human health. This study aimed to investigate and compare the contents of glucosinolates and isothiocyanates, and the anti-leukemic activity of fresh and steamed Chinese kale juice (CKJ). Cell viability and proliferation activity of U937 cells treated with CKJ were determined. Cell apoptosis and alterations of apoptosis-related protein expression were studied. Results showed that CKJ significantly decreased the viability of leukemic cells and inhibited cell proliferation in a dose- and time-dependent manner. After treatment with 5% v/v fresh and steamed CKJ for 24 h, the percentage of apoptotic cells increased to 53% and 36%, respectively. Increased amounts of cleaved caspase-3 in U937 cells treated with CKJ were observed, indicating that CKJ can trigger apoptotic cell death through a caspase-dependent pathway. Fresh CKJ was found to be more effective than steamed CKJ in suppressing cell survival and inducing cell apoptosis. The results suggest that Chinese kale possesses an anti-leukemic potential and could be further developed for cancer therapy and prevention. However, thermal cooking could reduce its beneficial function. [ABSTRACT FROM AUTHOR]

Broccoli sprouts have high isothiocyanate and selenium accumulation capacity. This study used a combination of methods, including physiological and biochemical, gene transcription and proteomic, to investigate the isothiocyanate and endogenous selenium accumulation mechanisms in broccoli sprouts under exogenous sodium selenite treatment during germination. Compared with the control, the sprouts length of broccoli sprouts under exogenous selenium treatment was significantly lower, and the contents of total phenol and malondialdehyde in 6-day-old broccoli sprouts were substantially higher. The contents of isothiocyanate and sulforaphane in 4-day-old were increased by up-regulating the relative expression of genes of UGT74B1, OX-1, and ST5b. The relative expression of BoSultr1;1, BoSMT, BoHMT1, and BoCOQ5-2 genes regulating selenium metabolism was significantly up-regulated. In addition, 354 proteins in 4-day-old broccoli sprouts showed different relative abundance compared to the control under selenium treatment. These proteins were classified into 14 functional categories. It was discovered that metabolic pathways and biosynthetic pathways of secondary metabolites were significantly enriched. The above results showed that exogenous selenium was beneficial in inducing the accumulation of isothiocyanate and selenium during the growth of broccoli sprouts. [ABSTRACT FROM AUTHOR]

N-arylcyanothioformamides are useful coupling components for building key chemical intermediates and biologically active molecules in an expedited and efficient manner. Similarly, substituted (Z)-2-oxo-N-phenylpropanehydrazonoyl chlorides have been utilized in numerous one-step heteroannulation reactions to assemble the structural core of several different types of heterocyclic compounds. Herein, we demonstrate the effectiveness of the reaction of N-arylcyanothioformamides with various substituted (Z)-2-oxo-N-phenylpropanehydrazonoyl chlorides to produce, stereoselectively and regioselectively, a range of 5-arylimino-1,3,4-thiadiazole derivatives decorated with a multitude of functional groups on both aromatic rings. The synthetic methodology features mild room-temperature conditions, large substrate scope, wide array of functional groups on both reactants, and good to high reaction yields. The products were isolated by gravity filtration in all cases and structures were confirmed by multinuclear NMR spectroscopy and high accuracy mass spectral analysis. Proof of molecular structure of the isolated 5-arylimino-1,3,4-thiadiazole regioisomer was obtained for the first time by single-crystal X-ray diffraction analysis. Crystal-structure determination was carried out on (Z)-1-(5-((3-fluorophenyl)imino)-4-(4-iodophenyl)-4,5-dihydro-1,3,4-thiadiazol-2-yl)ethan-1-one and (Z)-1-(4-phenyl-5-(p-tolylimino)-4,5-dihydro-1,3,4-thiadiazol-2-yl)ethan-1-one. Similarly, the tautomeric structures of the N-arylcyanothioformamides and (Z)-geometries of the 2-oxo-N-phenylpropanehydrazonoyl chloride coupling partners were proven by X-ray diffraction studies. As representative examples, crystal-structure determination was carried out on (4-ethoxyphenyl)carbamothioyl cyanide and (Z)-N-(2,3-difluorophenyl)-2-oxopropanehydrazonoyl chloride. Density functional theory calculations at the B3LYP-D4/def2-TZVP level were carried out to rationalize the observed experimental findings. [ABSTRACT FROM AUTHOR]

Simple Summary: Mutations in the p53 gene frequently occur in human cancers. The mutations are localized to "hotspot" residues and are classified as structural or contact mutants. p53 mutations disable wild-type (WT) p53 activity; they exert a "dominant negative" effect on WT p53 activity or a "gain-of-function" activity rendering the p53 mutants oncogenic. Mutant p53 rescue by small molecules is a promising chemotherapeutic strategy. Previously, we discovered that a dietary-related phenethyl isothiocyanate could reactivate p53R175H structural mutants in HER2 + SK-BR-3 breast cancer (BC) cells. The current study revealed that 2,2-diphenethyl isothiocyanate (DPEITC) is a more potent synthetic analog that can inhibit the growth of different subtypes of BC cells, irrespective of p53 mutant-type, via mutant p53 rescue. DPEITC acts synergistically with the topoisomerase inhibitors doxorubicin and camptothecin. Furthermore, for the first time, we report that DPEITC suppresses multi-drug resistance 1 and ETS1, which have been shown to play a role in chemoresistance. We previously reported that phenethyl isothiocyanate (PEITC), a dietary-related compound, can rescue mutant p53. A structure–activity relationships study showed that the synthetic analog 2,2-diphenylethyl isothiocyanate (DPEITC) is a more potent inducer of apoptosis than natural or synthetic ITCs. Here, we showed that DPEITC inhibited the growth of triple-negative breast cancer cells (MDA-MB-231, MDA-MB-468, and Hs578T) expressing "hotspot" p53 mutants, structural (p53R280K, p53R273H) or contact (p53V157F), at IC50 values significantly lower than PEITC. DPEITC inhibited the growth of HER2+ (p53R175H SK-BR-3, p53R175H AU565) and Luminal A (p53L194F T47D) breast cancer (BC) cells harboring a p53 structural mutant. DPEITC induced apoptosis, irrespective of BC subtypes, by rescuing p53 mutants. Accordingly, the rescued p53 mutants induced apoptosis by activating canonical WT p53 targets and delaying the cell cycle. DPEITC acted synergistically with doxorubicin and camptothecin to inhibit proliferation and induce apoptosis. Under these conditions, DPEITC delayed BC cells in the G1 phase, activated p53 canonical targets, and enhanced pS1981-ATM. DPEITC reduced the expression of MDR1 and ETS1. These findings are the first report of synergism between a synthetic ITC and a chemotherapy drug via mutant p53 rescue. Furthermore, our data demonstrate that ITCs suppress the expression of cellular proteins that play a role in chemoresistance. [ABSTRACT FROM AUTHOR]

The list of known health benefits from inclusion of brassica vegetables in the diet is long and growing. Once limited to cancer prevention, a role for brassica in prevention of oxidative stress and anti-inflammation has aided in our understanding that brassica provide far broader benefits. These include prevention and treatment of chronic diseases of aging such as diabetes, neurological deterioration, and heart disease. Although animal and cell culture studies are consistent, clinical studies often show too great a variation to confirm these benefits in humans. In this review, we discuss causes of variation in clinical studies, focusing on the impact of the wide variation across humans in commensal bacterial composition, which potentially result in variations in microbial metabolism of glucosinolates. In addition, as research into host–microbiome interactions develops, a role for bitter-tasting receptors, termed T2Rs, in the gastrointestinal tract and their role in entero-endocrine hormone regulation is developing. Here, we summarize the growing literature on mechanisms of health benefits by brassica-derived isothiocyanates and the potential for extra-oral T2Rs as a novel mechanism that may in part describe the variability in response to brassica among free-living humans, not seen in research animal and cell culture studies. [ABSTRACT FROM AUTHOR]

Moringin, obtained via enzymatic conversion of the glucosinolate precursor glucomoringin, is an uncommon member of the isothiocyanate class, and has been proven to possess a broad range of biological activities such as antitumor activity, protection against neurodegenerative disorders and bactericidal effects. Since moringin is weakly soluble in water and unstable in aqueous medium, cyclodextrins (CDs) were considered for the development of a new moringin formulation, with a view to improving its solubility and stability in aqueous solution for use as an anti-inflammatory. A combined structural study using proton nuclear magnetic resonance (1H-NMR), diffusion-ordered spectroscopy (DOSY) and ion mobility mass spectrometry (IM-MS) is reported, highlighting the formation of a 1:1 α-CD/moringin inclusion complex. The association constant K was determined (1300 M−1 at 300 K). Completion of the structural characterization was performed by T-ROESY and MS/MS experiments, which evidenced the mode of penetration of moringin into α-CD. Finally, the “chaperone-like” properties of α-CD with respect to the stability of moringin have been highlighted. [ABSTRACT FROM AUTHOR]

This note describes a séquence converting an oxime-substituted pyrrolidine into a trisubstituted pyrrole structure. The synthetic route is based on a double chlorination of the pyrrolidine substrate followed by the base induced formation of both an irnine and a nitrile oxide functionality. The latter reacts with an immobilized thiourea to yield an isothiocyanate which upon élimination générâtes the final pyrrole in an unprecedented cascade of events. [ABSTRACT FROM AUTHOR]

Colorectal cancer is an increasingly significant cause of mortality whose risk is linked to diet and inversely correlated with cruciferous vegetable consumption. This is likely to be partly attributable to the isothiocyanates derived from eating these vegetables, such as sulforaphane, which is extensively characterised for cytoprotective and tumour-suppressing activities. However, its bioactivities are likely to extend in complexity beyond those currently known; further insight into these bioactivities could aid the development of sulforaphane-based chemopreventive or chemotherapeutic strategies. Evidence suggests that sulforaphane modulates the expression of microRNAs, many of which are known to regulate genes involved at various stages of colorectal carcinogenesis. Based upon existing knowledge, there exist many plausible mechanisms by which sulforaphane may regulate microRNAs. Thus, there is a strong case for the further investigation of the roles of microRNAs in the anti-cancer effects of sulforaphane. There are several different types of approach to the wide-scale profiling of microRNA differential expression. Array-based methods may involve the use of RT-qPCR or complementary hybridisation probe chips, and tend to be relatively fast and economical. Cloning and deep sequencing approaches are more expensive and labour-intensive, but are worth considering where viable, for their greater sensitivity and ability to detect novel microRNAs. [ABSTRACT FROM AUTHOR]

In our current work, acetyl chloride-mediated synthesis of phenethyl isothiocyanate (PEITC) derivatives proves to be convenient and provides the expected products at good to excellent yields. Biological evaluation and structure-activity relationship analysis found that the novel compound 7 showed the best anticancer activity against human cancer cell line Panc1 and HGC27 compared with PEITC. Compounds 6 and 7 induced more apoptosis in pancreatic cancer cells but less toxicity in non-cancer cells. Further biological study demonstrated that 7 substantially increased intracellular reactive oxygen species (ROS) and depleted glutathione (GSH), leading to an oxidative stress to kill cancer cell. [ABSTRACT FROM AUTHOR]

Glucosinolates, their hydrolysis products and primary metabolites were analyzed in five pak choi cultivars to determine the effect of methyl jasmonate (MeJA) on metabolite flux from primary metabolites to glucosinolates and their hydrolysis products. Among detected glucosinolates (total 14 glucosinolates; 9 aliphatic, 4 indole and 1 aromatic glucosinolates), indole glucosinolate concentrations (153–229%) and their hydrolysis products increased with MeJA treatment. Changes in the total isothiocyanates by MeJA were associated with epithiospecifier protein activity estimated as nitrile formation. Goitrin, a goitrogenic compound, significantly decreased by MeJA treatment in all cultivars. Changes in glucosinolates, especially aliphatic, significantly differed among cultivars. Primary metabolites including amino acids, organic acids and sugars also changed with MeJA treatment in a cultivar-specific manner. A decreased sugar level suggests that they might be a carbon source for secondary metabolite biosynthesis in MeJA-treated pak choi. The result of the present study suggests that MeJA can be an effective agent to elevate indole glucosinolates and their hydrolysis products and to reduce a goitrogenic compound in pak choi. The total glucosinolate concentration was the highest in “Chinese cabbage” in the control group (32.5 µmol/g DW), but indole glucosinolates increased the greatest in “Asian” when treated with MeJA. [ABSTRACT FROM AUTHOR]

Broccoli consumption brings many health benefits, including reducing the risk of cancer and inflammatory diseases. The objectives of this study were to identify global alterations in the cecal microbiota composition using 16S rRNA sequencing analysis and glucoraphanin (GRP) hydrolysis to isothiocyanates ex vivo by the cecal microbiota, following different broccoli diets. Rats were randomized to consume AIN93G (control) or different broccoli diets; AIN93G plus cooked broccoli, a GRP-rich powder, raw broccoli, or myrosinase-treated cooked broccoli. Feeding raw or cooked broccoli for four days or longer both changed the cecal microbiota composition and caused a greater production of isothiocyanates ex vivo. A more than two-fold increase in NAD(P)H: quinone oxidoreductase 1 activity of the host colon mucosa after feeding cooked broccoli for seven days confirmed the positive health benefits. Further studies revealed that dietary GRP was specifically responsible for the increased microbial GRP hydrolysis ex vivo, whereas changes in the cecal microbial communities were attributed to other broccoli components. Interestingly, a three-day withdrawal from a raw broccoli diet reversed the increased microbial GRP hydrolysis ex vivo. Findings suggest that enhanced conversion of GRP to bioactive isothiocyanates by the cecal microbiota requires four or more days of broccoli consumption and is reversible. [ABSTRACT FROM AUTHOR]

One important strategy to develop effective anticancer agents is based on natural products. Many active phytochemicals are in human clinical trials and have been used for a long time, alone and in association with conventional anticancer drugs, for the treatment of various types of cancers. A great number of in vitro, in vivo and clinical reports document the multi-target anticancer activities of isothiocyanates and of compounds characterized by a naphthalenetetracarboxylic diimide scaffold. In order to search for new anticancer agents with a better pharmaco-toxicological profile, we investigated hybrid compounds obtained by inserting isothiocyanate group(s) on a naphthalenetetracarboxylic diimide scaffold. Moreover, since water-soluble fullerene derivatives can cross cell membranes thus favoring the delivery of anticancer therapeutics, we explored the cytostatic and cytotoxic activity of hybrid compounds conjugated with fullerene. We studied their cytostatic and cytotoxic effects on a human T-lymphoblastoid cell line by using different flow cytometric assays. In order to better understand their pharmaco-toxicological potential, we also analyzed their genotoxicity. Our global results show that the synthesized compounds reduced significantly the viability of leukemia cells. However, the conjugation with a non-toxic vector did not increase their anticancer potential. This opens an interesting research pattern for certain fullerene properties. [ABSTRACT FROM AUTHOR]

Glucosinolates (GLs) are natural compounds present in species of the order Brassicales and precursors of bioactive isothiocyanates (ITCs). In the recent years, they have been studied mainly for their chemopreventive as well as novel chemotherapeutics properties. Among them 4-(α-L-rhamnosyloxy)benzyl glucosinolate (glucomoringin; GMG), purified from seeds of Moringa oleifera Lam., a plant belonging to the Moringaceae family, represents an uncommon member of the GL family with peculiar characteristics. This short communication reports new evidences about the properties of GMG and presents a new innovative utilization of the molecule. The bioactivation of GMG by myrosinase enzyme just before treatment, permits to maximize the power of the final product of the reaction, which is the 4-(α-L-rhamnosyloxy)benzyl isothiocyanate (GMG-ITC). We tested the antibiotic activity of this latter compound on two strains of pathogens affecting the health of patients in hospital, namely Staphylococcus aureus and Enterococcus casseliflavus, and on the yeast Candida albicans. Results show that the sensibility of S. aureus BAA-977 strain and E. casseliflavus to GMG-ITC treatment reveals an important possible application of this molecule in the clinical care of patients, more and more often resistant to traditional therapies. [ABSTRACT FROM AUTHOR]

Liquid crystals, compounds and mixtures with positive dielectric anisotropies are reviewed. The mesogenic properties and physical chemical properties (viscosity, birefringence, refractive indices, dielectric anisotropy and elastic constants) of compounds being cyano, fluoro, isothiocyanato derivatives of biphenyl, terphenyl, quaterphenyl, tolane, phenyl tolane, phenyl ethynyl tolane, and biphenyl tolane are compared. The question of how to obtain liquid crystal with a broad range of nematic phases is discussed in detail. Influence of lateral substituent of different kinds of mesogenic and physicochemical properties is presented (demonstrated). Examples of mixtures with birefringence Δn in the range of 0.2-0.5 are given. [ABSTRACT FROM AUTHOR]

The levels of bioactive compounds in broccoli and their bioavailability following broccoli intake can be affected by the cooking procedures used for vegetable preparation. In the present pilot study, we compared the human plasma bioavailability of antioxidant compounds (β-carotene, lutein and isothiocyanate) and of phylloquinone (vitamin K) on seven volunteers before and after the administration of boiled and steamed broccoli. Moreover, plasma isothiocyanate (ITCs) levels were also evaluated after the administration of a single dose of BroccoMax®, a dietary supplement containing GLSs with active myrosinase. Steam-cooking has been demonstrated to promote higher plasma bioavailability in ITCs than boiling (AUCSTEAMED = 417.4; AUCBOILED = 175.3) and is comparable to that reached following the intake of BroccoMax®, a supplement containing glucoraphanin and active myrosinase (AUC = 450.1). However, the impact of boiling and steaming treatment on plasma bioavailability of lipophilic antioxidants (lutein and β-carotene) and of phylloquinone was comparable. The lutein and β-carotene plasma levels did not change after administration of steamed or boiled broccoli. Conversely, both treatments led to a similar increase of phylloquinone plasma levels. Considering the antioxidant action and the potential chemopreventive activity of ITCs, steaming treatments can be considered the most suitable cooking method to promote the health benefits of broccoli in the diet. [ABSTRACT FROM AUTHOR]

Dietary supplements are widely used as a nutritional strategy to improve and maintain performance and achieve faster recovery in sports and exercise. Exercise-induced muscle damage (EIMD) is caused by mechanical stress and subsequent inflammatory responses including reactive oxygen species and cytokine production. Therefore, dietary supplements with anti-inflammatory and antioxidant properties have the potential to prevent and reduce muscle damage and symptoms characterized by loss of muscle strength and delayed-onset muscle soreness (DOMS). However, only a few supplements are considered to be effective at present. This review focuses on the effects of dietary supplements derived from phytochemicals and listed in the International Olympic Committee consensus statement on muscle damage evaluated by blood myofiber damage markers, muscle soreness, performance, and inflammatory and oxidative stress markers. In this review, the effects of dietary supplements are also discussed in terms of study design (i.e., parallel and crossover studies), exercise model, and such subject characteristics as physical fitness level. Future perspectives and considerations for the use of dietary supplements to alleviate EIMD and DOMS are also discussed. [ABSTRACT FROM AUTHOR]

The microsporidian fungus Nosema ceranae represents one of the primary bee infection threats worldwide and the antibiotic fumagillin is the only registered product for nosemosis disease control, while few alternatives are, at present, available. Natural bioactive compounds deriving from the glucosinolate–myrosinase system (GSL–MYR) in Brassicaceae plants, mainly isothiocyanates (ITCs), are known for their antimicrobial activity against numerous pathogens and for their health-protective effects in humans. This work explored the use of Brassica nigra and Eruca sativa defatted seed meal (DSM) GSL-containing diets against natural Nosema infection in Apis mellifera colonies. DSM patties from each plant species were obtained by adding DSMs to sugar candy at the concentration of 4% (w/w). The feeding was administered in May to mildly N. ceranae-infected honey bee colonies for four weeks at the dose of 250 g/week. In the treated groups, no significant effects on colony development and bee mortality were observed compared to the negative controls. The N. ceranae abundance showed a slight but significant decrease. Furthermore, the GSL metabolism in bees was investigated, and MYR hydrolytic activity was qualitatively searched in isolated bee midgut and hindgut. Interestingly, MYR activity was detected both in the bees fed DSMs and in the control group where the bees did not receive DSMs. In parallel, ITCs were found in gut tissues from the bees treated with DSMs, corroborating the presence of a MYR-like enzyme capable of hydrolyzing ingested GSLs. On the other hand, GSLs and other GSL hydrolysis products other than ITCs, such as nitriles, were found in honey produced by the treated bees, potentially increasing the health value of the final product for human consumption. The results are indicative of a specific effect on the N. ceranae infection in managed honey bee colonies depending on the GSL activation within the target organ. [ABSTRACT FROM AUTHOR]

Isothiocyanates, such as sulforaphane and iberin, derived from glucosinolates (GLS) in cruciferous vegetables, are known to prevent and suppress cancer development. GLS can also be converted by bacteria to biologically inert nitriles, such as sulforaphane-nitrile (SFN-NIT) and iberin-nitrile (IBN-NIT), but the role of the gut microbiome in this process is relatively undescribed and SFN-NIT excretion in humans is unknown. An ex vivo fecal incubation model with in vitro digested broccoli sprouts and 16S sequencing was utilized to explore the role of the gut microbiome in SFN- and IBN-NIT production. SFN-NIT excretion was measured among human subjects following broccoli sprout consumption. The fecal culture model showed high inter-individual variability in nitrile production and identified two sub-populations of microbial communities among the fecal cultures, which coincided with a differing abundance of nitriles. The Clostridiaceae family was associated with high levels, while individuals with a low abundance of nitriles were more enriched with taxa from the Enterobacteriaceae family. High levels of inter-individual variation in urine SFN-NIT levels were also observed, with peak excretion of SFN-NIT at 24 h post broccoli sprout consumption. These results suggest that nitrile production from broccoli, as opposed to isothiocyanates, could be influenced by gut microbiome composition, potentially lowering efficacy of cruciferous vegetable interventions. [ABSTRACT FROM AUTHOR]

The bacterium Xanthomonas campestris pv. campestris (Xcc) causes black rot disease in Brassica crops. Glucosinolates are known to be part of the defence system of Brassica crops against Xcc infection. They are activated upon pathogen attack by myrosinase enzymes. Their hydrolytic products (GHPs) inhibit the growth of Xcc in vitro. However, the mechanisms underlying this inhibition and the way Xcc can overcome it are not well understood. We studied the transcriptomic reprogramming of Xcc after being supplemented with two chemically different GHPs, one aliphatic isothiocyanate (allyl-ITC) and one indole (indol-3-carbinol), by RNA-seq. Based on our results, the arrest in Xcc growth is related to the need to stop cell division to repair damaged DNA and cell envelope components. Otherwise, GHPs modify energy metabolism by inhibiting aerobic respiration and increasing the synthesis of glycogen. Xcc induces detoxification mechanisms such as the antioxidant defence system and the multidrug efflux system to cope with the toxic effects driven by GHPs. This is the first time that the transcriptomic reprogramming of a plant pathogenic bacterium treated with GHPs has been studied. This information will allow a better understanding of the interaction of a plant pathogen mediated by GSLs. [ABSTRACT FROM AUTHOR]

Six pseudohalide zinc(II) containing a variety of N-donor auxiliary amines were structurally characterized. These include two mononuclear trigonal bipyramidal [Zn(NTB)(N3)]ClO4·½H2O (3) and [Zn(TPA)(NCS)]ClO4 (4), two distorted octahedral [Zn(1,8-damnph)2(dca)2] (5) and [Zn(8-amq)2(dca)2] (6a) as well as two 1D polymeric chains catena-[Zn(isq)2(μ1,5-dca)2] (7) and catena-[Zn(N,N-Me2en)2(μ1,5-dca)]dca (8), where NTB = tris(2-benzimidazolylmethyl)amine, TPA = tris(2-pyridylmethyl)amine, 1,8-damnph = 1,8-diaminonaphthalene, 8-amq = 8-amino-quinoline, isq = isoquinoline (isq) and N,N-Me2en = N,N-dimethylethylenediamine. In general, with the exception of 6 and 8, the complexes exhibited luminescence emission in MeOH associated with red shift of the emission maxima, and the strongest visible fluorescence peak was detected at 421 nm (λex = 330 nm) in the case of Complex 5. [ABSTRACT FROM AUTHOR]

Preservation of vascular wall integrity against degenerative processes associated with ageing, fat-rich diet and metabolic diseases is a timely therapeutical challenge. The loss of endothelial function and integrity leads to cardiovascular diseases and multiorgan inflammation. The protective effects of the H2S-donor erucin, an isothiocyanate purified by Eruca sativa Mill. seeds, were evaluated on human endothelial and vascular smooth muscle cells. In particular, erucin actions were evaluated on cell viability, ROS, caspase 3/7, inflammatory markers levels and the endothelial hyperpermeability in an inflammatory model associated with high glucose concentrations (25 mM, HG). Erucin significantly prevented the HG-induced decrease in cell viability as well as the increase in ROS, caspase 3/7 activation, and TNF-α and IL-6 levels. Similarly, erucin suppressed COX-2 and NF-κB upregulation associated with HG exposure. Erucin also caused a significant inhibition of p22phox subunit expression in endothelial cells. In addition, erucin significantly prevented the HG-induced increase in endothelial permeability as also confirmed by the quantification of the specific markers VE-Cadherin and ZO-1. In conclusion, our results assess anti-inflammatory and antioxidant effects by erucin in vascular cells undergoing HG-induced inflammation and this protection parallels the preservation of endothelial barrier properties. [ABSTRACT FROM AUTHOR]

Nosema ceranae is a widespread parasite responsible for nosemosis Type C in Apis mellifera honey bees, reducing colony survival. The antibiotic fumagillin is the only commercial treatment available, but concerns are emerging about its persistence, safety, and pathogen resistance. The use of natural substances from Brassicaceae defatted seed meals (DSMs) with known antimicrobial and antioxidant properties was explored. Artificially infected bees were fed for 8 days with candies enriched with two concentrations, 2% and 4%, of two DSMs from Brassica nigra and Eruca sativa, containing a known amount of different glucosinolates (GSLs). The food palatability, GSL intake, bee survival, and treatment effects on N. ceranae spore counts were evaluated. Food consumption was higher for the two 2% DSM patties, for both B. nigra and E. sativa, but the GSL intake did not increase by increasing DSM to 4%, due to the resulting lower palatability. The 2% B. nigra patty decreased the bee mortality, while the higher concentration had a toxic effect. The N. ceranae control was significant for all formulates with respect to the untreated control (312,192.6 +/− 14,443.4 s.e.), and was higher for 4% B. nigra (120,366.3 +/− 13,307.1 s.e.). GSL hydrolysis products, the isothiocyanates, were detected and quantified in bee gut tissues. Brassicaceae DSMs showed promising results for their nutraceutical and protective effects on bees artificially infected with N. ceranae spores at the laboratory level. Trials in the field should confirm these results. [ABSTRACT FROM AUTHOR]

Decades of research has convinced us that phytochemical compounds contained within the plant products are the real deal, and they provide benefits such as health maintenance an d cure to illnesses. One of the deadliest noncommunicable diseases today is lung cancer, hence its disease management still deserves attention. Wnt/β-catenin pathway activation conferring cancer stem cell (CSC) activities to non-small cell lung carcinomas (NSCLCs) may explain why the disease is still difficult to cure. In the present study, we assessed several representatives of phytochemical categories consisting of alkaloids, chalcones and isothiocyanates for their inhibitory activity to nuclear localization of β-catenin—an important event for Wnt/β-catenin pathway activation, in lung cancer cell lines. Real-time cell analyzer confirmed that evodiamine (EVO), chelidonine (CHE), isoliquiritigenin (ISO), licochalcone-A (LICO), benzyl isothiocyanate (BI) and phenethylisothiocyanate (PI) exhibited anti-proliferative activities and cytotoxicities to adenocarcinoma cell line SK-LU-1 and human lung CSC primary cell line (HLCSC). Immunofluorescence assay identified that CHE, ISO, LICO, BI and PI were capable of reducing the number of cells harboring β-catenin within the nuclei of these cells. We extended the characterizations of BI and PI in Wnt-dependent squamous cell carcinoma cell line NCI-H1703 on several CSC functions and found that BI was better at inhibiting soft agar colony formation as an output of self-renewal ability, whereas PI was more effective in inhibiting the growth of multicellular tumor spheroid model mimicking micrometastases. Both however were not able to inhibit migration and invasion of NCI-H1703. In conclusion, BI could potentially be used as a safer alternative to target undifferentiated CSCs as adjuvant therapy, whereas PI could be used as chemotherapy to remove bulk tumor. [ABSTRACT FROM AUTHOR]