Natural isothiocyanates of the genus Capparis as potential agonists of apoptosis and antitumor agents:Mechanisms and implications

In this editorial,we comment on a recent publication,which highlights the important findings from the study,including the antitumor and anti-inflammatory effects of isothiocyanates,their underlying mechanisms,and implications.Additionally,a related perspective is discussed.

Natural isothiocyanates of the genus Capparis as potential agonists of apoptosis and antitumor drugs

BACKGROUND Using gas chromatography-mass spectrometry(GC/MS)analysis,we examined the composition of volatile components present in the yellow and green fruits,seeds,and jam of the scrambling shrub Capparis cartilaginea(C.cartilaginea).These plant samples were collected from Kibbutz Yotvata in Israel.In all the tested samples,isothiocyanates were identified.Utilizing the PASS program,we ascertained the biological activity of these isothiocyanates present in the Capparis genus.The study results highlighted that all isothiocyanates could potentially act as apoptosis agonists,making them strong candidates for antitumor drugs.This information holds significant value for the fields of medicinal chemistry,pharmacology,and practical medicine.AIM To investigate the volatile components present in the yellow and green fruits,seeds,and jam of the C.cartilaginea shrub using GC/MS analysis,to detect isothiocyanates in all the analyzed plant samples,and to assess the biological activity of these isothiocyanates utilizing the PASS program.METHODS We utilized two primary methods to analyze the volatile compounds present in the yellow and green fruits,seeds,and jams of the C.cartilaginea,native to Israel.We identified biologically active isothiocyanates in these samples.Their anticipated biological activities were determined using the PASS program,with the most dominant activities being apoptosis agonist,anticarcinogenic,and antineoplastic specifically for genitourinary cancer.RESULTS Fruits,seeds,and jams containing isothiocyanates,which exhibit antineoplastic and anticarcinogenic activities,could be suggested for cancer prevention and management.Specific isothiocyanates,with therapeutic potential in this realm,could be recommended as potent anticancer agents in practical medicine following clinical trials.CONCLUSION The discovery that isothiocyanates exhibit potent antineoplastic and anticarcinogenic activities was unexpected.Additionally,certain isothiocyanates demonstrated antifungal,antiviral(specifically against arbovirus),and antiparasitic properties.

Allyl isothiocyanate ameliorates lipid accumulation and inflammation in nonalcoholic fatty liver disease via the Sirt1/AMPK and NF-κB signaling pathways

BACKGROUND Allyl isothiocyanate(AITC),a classic anti-inflammatory and antitumorigenic agent,was recently identified as a potential treatment for obesity and insulin resistance.However,little is known about its direct impact on the liver.AIM To investigate the effect and underlying mechanism of AITC in nonalcoholic fatty liver disease(commonly referred to as NAFLD).METHODS To establish a mouse and cellular model of NAFLD,C57BL/6 mice were fed a high fat diet(HFD)for 8 wk,and AML-12 cells were treated with 200μM palmitate acid for 24 h.For AITC treatment,mice were administered AITC(100 mg/kg/d)orally and AML-12 cells were treated with AITC(20μmol/L).RESULTS AITC significantly ameliorated HFD-induced weight gain,hepatic lipid accumulation and inflammation in vivo.Furthermore,serum alanine aminotransferase and aspartate aminotransferase levels were markedly reduced in AITC-treated mice.Mechanistically,AITC significantly downregulated the protein levels of sterol regulatory elementbinding protein 1(SREBP1)and its lipogenesis target genes and upregulated the levels of proteins involved in fatty acidβ-oxidation,as well as the upstream mediators Sirtuin 1(Sirt1)and AMPactivated protein kinaseα(AMPKα),in the livers of HFD-fed mice.AITC also attenuated the nuclear factor kappa B(NF-κB)signaling pathway.Consistently,AITC relieved palmitate acid-induced lipid accumulation and inflammation in AML-12 cells in vitro through the Sirt1/AMPK and NF-κB signaling pathways.Importantly,further studies showed that the curative effect of AITC on lipid accumulation was abolished by siRNA-mediated knockdown of either Sirt1 or AMPKαin AML-12 cells.CONCLUSION AITC significantly ameliorates hepatic steatosis and inflammation by activating the Sirt1/AMPK pathway and inhibiting the NF-κB pathway.Therefore,AITC is a potential therapeutic agent for NAFLD.

Antioxidant Activity of Isothiocyanate Extracts from Broccoli

Isothiocyanates(ITCs) extracts were prepared from fresh broccoli.Their antioxidant properties were evaluated by using the in vitro bioassays,including superoxide anion radical( 2 O·-) ,hydroxyl radical(HO·-) and 2,2-diphenyl-1-picrylhydracyl(DPPH·) radical-scavenging methods,lipid peroxidation assay,and reducing power assay.The ITCs extracts exhibited significant dose-dependent antioxidant activities(P<0.01) .Its antioxidant-stability was affected by temperature and storage condition,although it was more stable than vitamin C(Vc) .GC-MS iden-tified sulforaphane in the ITCs extracts.The antioxidant activity of sulforaphane was approximately one tenth to one fifth of that of Vc.Sulforaphane was experimented to be one of dominating contributors to antioxidant capacity of ITCs extracts.However,there was no direct antioxidant activity found for benzyl isothiocyanate(BITC) in vitro. Therefore,it could be concluded that the general group(-N=C=S) was not the essential part for the antioxidant activity of sulforaphane.It is suggested that the ITCs extracts from broccoli can be developed into a promising food additive for healthy food.

Preparation and Performance of Fluorescein Isothiocyanate⁃Labeled Fluorescent Starch and Polyvinyl Alcohol for Warp Sizing

In order to solve the problems of low accuracy and poor variety adaptability of the current measurement method of the permeability and coating property of sizing paste in textile industry, taking starch and polyvinyl alcohol(PVA) as the representatives of the most commonly used textile sizes, various concentrations of fluorescent molecules fluorescein isothiocyanate(FITC) were used to label starch and PVA to prepare fluorescein(F)-starch and F-PVA fluorescent sizes with different degrees of labeling(DLs) for the first time, respectively. Then the starch and PVA derivatives were employed to size pure cotton warp yarns. After preparing the sections of the sized yarns, the permeability and coating percentage of starch and PVA paste to the yarns were calculated by using a fluorescence microscope and the Photoshop software, respectively. The results demonstrate that F-starch and F-PVA with appropriate DL of 0.791% and 0.161%, respectively, exhibit good fluorescence property and similar sizing performance to the sizing performance of unlabeled starch and PVA. It is considered that fluorescence labeling of sizing agents with fluorescein units can provide an innovative way for the accurate determination of the permeability and coating property of sizing paste to warp yarns.

Electro-optical properties of high birefringence liquid crystal compounds with isothiocyanate and naphthyl group

Liquid crystal（LC） compound with isothiocyanate and naphthyl group is an attractive high birefringence LC material,and can be used in optical devices. In this paper, the electro-optical properties of a series of this type of LC compounds were investigated. The melting points and enthalpy values of these LC compounds were higher than those of corresponding compounds with the phenyl group. These compounds exhibited high birefringence with a maximum value of 0.66. Fluorine substitution in the molecular almost does not affect the birefringence value. When these LC compounds with the naphthyl group were dissolved in a commercial LC mixture, the electro-optical properties depending on temperature were investigated. In the low-temperature region, LC mixtures with the naphthyl-group LC compounds exhibited higher viscosity than pure commercial LCs. In the high-temperature region, viscosity values very closely approached each other. When response performance was investigated, figure-of-merit（FoM） values were measured. The Fo M values of LC mixtures containing LC compounds with naphthyl group were lower than those of reference benzene LCs in the low-temperature region. However, in the high-temperature region, the results were reversed. These isothiocyanate LC compounds with naphthyl group can be applied in special fast-response LC device, particularly the ones used under high-temperature conditions.

Synthesis of ethoxycarbonyl isothiocyanate by orthogonal design

Using Schiff base as a phase transfer catalyst, ethoxycarbonyl isothiocyanate was synthesized by reacting ethyl chloroformate with sodium thiocyanate. In order to get the best synthetic technology, an orthogonal test （L9（34）） was applied. The results show that reaction temperature, reaction time, content of catalyst and molar ratio of sodium thiocyanate to ethyl chloroformate are the main factors influencing the yield. The four factors chosen for the present investigation are based on the results of a single-factor test. The optimum synthetic technology is determined as follows： reaction temperature 35 ℃, reaction time 3 h, the content of catalyst （molar fraction based on ethyl chloroformate） 1.5% and molar ratio of sodium thiocyanate to ethyl chloroformate 1.1. Under the optimized synthetic technology, the experimental yield reaches 96.8%.

Synthesis and Determination of Standard Molar Enthalpies of Formation for Complexes of Rare Earth Isothiocyanates with Glycine

Four solid complexes of rare earth isothiocyanates with glycine were synthesized. They were characterized by chemical analysis, elemental analysis, Infrared spectra, X-ray powder diffraction and TO-DSC analysis. Their chemical formulae were proved to be RE(NCS)2.Gly .H2O, where RE is La, Ce, Pr or Nd. The integral heats of solution of RE(NCS)3.3Gly. H2O in water, of RE(NCS)2. 7H2O in aqueous glycine solution and of glycine in water have been measured calorimetricaliy at 298. 15K. By means of a thermochemical cycle suggested in this paper, the standard molar enthalpies of formation for RE(NCS)2. 3Gly.H2O(c) were obtained and their lattice energies were calculated.

REACTION OF α-(1H-1,2,4-TRIAZOL-1-YL)ACETOPHENONE WITH PHENYL ISOTHIOCYANATE

Reaction of α-(1H-1,2,4-triazol-1-yl)acetophenone with phenyl isothiocyanate in the presence of a base and subse- quent alkylation leads to the ketene S,N-acetal(2),(4),(7), (8);thiazolidone(3),thiazolidine(5)and 1,3-thiazine(6),

Studies on Rare Earth Complexes with Crown Ether (ⅩⅩⅣ)——Synthesis and Characterization of Complexes of Lanthanide Isothiocyanates with Dibenzo-30-crown-10

Introduction The study of metal complexes with the crown ether is a quite interesting research field, but the research has mainly focused on the metal complexes with some crown ethers with a relatively small cavity such as 12-crown-4, 15-crown-5 and 18- crown-6 as well as their derivatives. Crown ethers with a larger cavity contain more oxygen atoms, so they have the ability to form the complexes of a higher co-

Tissue distribution of Lycium barbarum polysaccharides in rat tissue by fluorescein isothiocyanate labeling

To date, in vivo investigations of polysaccharide’s pharmacokinetics are significantly restricted by the difficulty in their detection. This study was conducted to establish the quantitative determination of Lycium barbarum polysaccharides(LBPs) based on fluorescein isothiocyanate(FITC) pre-labeling and to investigate their tissue distribution in rat. We obtained the calibration curves linear over the range of 0.0–25 μg/m L in rat tissue samples with correlation coefficients greater than 0.99. The inter-day and intra-day precisions(RSD, %) were within 15%, and the relative recovery ranged 95.2%–102.4%, with RSD range 1.48%–9.58%, indicating that this experiment was suitable for the determination of LBPs. The fluorescence intensity was measured after 24 h storage at room temperature, 3 times of freeze-cycle and cryopreservation at –20 ℃ for 15 day, these results indicated that the stability of the samples was good. LBP-FITC was mainly absorbed by the small intestine and stomach, and mainly excreted in the urine through the kidney;this distinct difference in the tissue distribution of LBPs could be attributed to the size of these LBPs in relation to the pore sizes of the vascular beds in the kidney and liver. Results showed in this study enable us to comprehensively understand the biological effects of LBPs following its oral ingestion.

Impact of Soil Texture and Organic Matter Content on Methyl Isothiocyanate Volatilization from Soil Columns

Metam sodium （MS; sodium N-methyl dithiocarbamate） has emerged as a promising soil fumigant in the US to replace methyl bromide （MeBr）. Metam potassium （MK; potassium N-methyl dithiocarbamate） and MS break down into the volatile gas methyl isothiocyanate （MITC） to control soil borne pests. Many studies have focused on MS, but MK has not been studied as thoroughly. The objective of this research was to determine the effect of increasing organic matter （OM） treatments and soil texture to minimize the off-gassing of MS and MK. Bench-scale soil column studies were performed to simulate organic matter treatments that may decrease the volatilization loss of MITC. Incorporation depth of OM simulated surface tillage （0-15 cm） practices. Soil was packed in steel columns and MS or MK was applied at a depth of 15 cm and MITC volatilization was measured using gas chromatography/mass spectroscopy. Volatilization of MITC behaved similarly for MS and MK with MITC movement impacted by soil texture. MITC volatilization was lower from a sandy clay loam than a sandy soil. Surface incorporation of OM did not significantly decrease MITC volatilization. These results suggest that soil texture is the dominant factor reducing MITC off-gassing and prolonging the time needed to control soil borne pests.

Nonlinear Intestinal Absorption of Fluorescein Isothiocyanate Dextran 4, 000 Caused by Absorptive and Secretory Transporting System

The mechanism of the nonlinear concentration dependence of the intestinal absorption of fluorescein isothiocyanate dextran 4,000 (FD-4) was studied using in situ rat intestinal loops and the in vitro Ussing-type chamber method. The intestinal absorption rate constant of FD-4, as evaluated by the intestinal loop method, increased significantly in a nonlinear fashion as the FD-4 concentration increased up to 0.2 mM and tended to decrease at concentrations higher than 0.2 mM. The mucosal-to-serosal permeation of FD-4 across rat ileal sheets, as evaluated by the in vitro Ussing-type chamber method, also increased in a nonlinear fashion in the low concentration range (0.01 - 0.02 mM), before decreasing as the concentration increased further, whereas serosal-to-mucosal permeation decreased in a concentration-dependent manner. In addition, mucosal-to-serosal flux and serosal-to-mucosal flux were increased and reduced in the presence of the metabolic inhibitor 2, 4-dinitrophenol, respectively. These results suggest that FD-4 is predominantly secreted into the intestinal lumen by an efflux transport system.

Synthesis of highly functional quinazolins via metal-free,visible-light-enabled radical cascade arylation/cyclization of fluorinated imidoyl isothiocyanates

A metal-free,efficient and easy-to-hand protocol for the synthesis of 2-perfluoroalkylquinazolins has been achieved by Eosin B catalyzed radical cascade arylation/cyclization reaction of fluorinated imidoyl isothiocyanates with aryldiazonium Salts.A variety of highly functionalized quinozaline derivatives bearing pharmaceutically important thiol and fluoroalkyl groups were efficiently assembled with broad substrate scope and good functional group tolerance.A series of mechanism experiments indicate that this reaction undergoes a radical cascade arylation/cyclization pathway.

Efficient synthesis of thiohydantoin derivatives from amino acid esters and isothiocyanates in alkaline Al_2O_3

Various amino acid esters were reacted with different isothiocyanates in alkaline Al2O3 at room temperature for 1 h affording thiohydantoins in moderate to excellent yields.

Perspective on dietary isothiocyanates in the prevention,development and treatment of cancer

Epidemiological evidence has highlighted the association of specific diets and a lower incidence of cancer.Foremost,the Mediterranean diet provides high levels of polyphenolics and a high consumption of healthier fats,e.g.,as from olive oil.In the Mediterranean region the consumption of vegetables is elevated providing a class of compounds,the isothiocyanates(ITCs)as found in the cabbage family.The ITCs have raised great interest for their health benefits over the past few decades.Some of the key ITC compounds,sulforaphane,phenethylisothiocyanate and benzyl isothiocyanate,have been studied in vitro and in vivo and the data support their promise for cancer chemoprevention,as anti-tumor agents,and for chemoprotection of normal tissues and organs.Along with other polyphenolic compounds in the diet,in general,they also possess key anti-inflammatory properties thus satisfying the criteria for compounds that could intervene in cancer initiation and progression.In this review we provide a larger overview of the advantages of including ITCs in the diet as food or as supplements and speculate on what could constitute a valuable therapeutic strategy for improving and sustaining good health and countering cancer disease in humans.

Phenethyl isothiocyanate as an anti-nutritional factor attenuates deoxynivalenol-induced IPEC-J2 cell injury through inhibiting ROSmediated autophagy

Deoxynivalenol(DON)is considered to be the most harmful mycotoxin that affects the intestinal health of animals and humans.Phenethyl isothiocyanate(PEITC)in feedstuff is an anti-nutritional factor and impairs nutrient digestion and absorption in the animal intestinal.In the current study,we aimed to explore the effects of PEITC on DON-induced apoptosis,intestinal tight junction disorder,and its potential molecular mechanism in the porcine jejunum epithelial cell line(IPEC-J2).Our results indicated that PEITC treatment markedly alleviated DON-induced cytotoxicity,decreasing the apoptotic cell percentage and pro-apoptotic mRNA/protein levels,and increasing zonula occludens-1(ZO-1),occludin and claudin-1 mRNA/protein expression.Meanwhile,PEITC treatment ameliorated DON-induced an increase of the inducible nitric oxide synthase(iNOS)and cyclooxygenase 2(COX-2)mRNA levels and intracellular reactive oxygen species(ROS)level,and a decrease of glutathione peroxidase 1(GPx1),superoxide dismutase 2(SOD2),catalase(CAT)and heme oxygenase 1(HO-1)mRNA levels.Additionally,PEITC treatment significantly down-regulated autophagy-related protein 5(ATG5),beclin-1 and microtubuleassociated protein 1 light chain 3B(LC3-II)mRNA/protein levels,decreased the number of green fluorescent protein-microtubule-associated protein 1 light-chain 3(GFP-LC3)puncta and phosphatidylinositol 3 kinase(PI3K)protein expression,and up-regulated phospho-protein kinase B(p-Akt)and phospho-mammalian target of rapamycin(p-mTOR)protein expression against DON.However,the activation of autophagy by rapamycin,an autophagy agonist,abolished the protective effects of PEITC against DON-induced cytotoxicity,apoptosis and intestinal tight junction disorder.Collectively,PEITC could confer protection against DON-induced porcine intestinal epithelial cell injury by suppressing ROSmediated autophagy.

Postharvest quality and reactive oxygen species metabolism improvement of Coprinus comatus mushroom using allyl isothiocyanate fumigation

The aim of this study was to evaluate the effect of allyl isothiocyanate(AITC)on the reactive oxygen species(ROS)metabolism and quality of postharvest Coprinus comatus(C.comatus).Fresh mushrooms were stored at 4℃with AITC at 5,10,and 20μL/L for 18 d,respectively.Sampling was performed every 3 d,and physicochemical parameters and ROS metabolism related enzymes activities were analyzed.Compared with the control,the application of AITC at 10μL/L significantly(P<0.05)decreased xanthine oxidase activity after 9 d of storage,while it significantly(P<0.05)improved the activities of succinic dehydrogenase,glutathione reductase,peroxidase,catalase,and ascorbate peroxidase in the middle and later stages of storage.Furthermore,the Ca^(2+)-ATPase and superoxide dismutase activities in sample treated by 10μL/L were all significantly(P<0.05)higher than those in the control.Therefore,the accumulation trends of malondialdehyde and ROS were retarded and membrane integrity was maintained.However,high-concentration AITC(20μL/L)treatment accelerated the ROS generation and increased electrolyte leakage rate.All AITC treatments significantly(P<0.05)inhibited the respiration rate during the first 9 d of storage and retarded browning of C.comatus during the storage of 18 d.These findings suggested that AITC treatment would be a promising method to maintain C.comatus quality,but the concentrations need to be optimized.

Quantification of Total Glucosinolates and Isothiocyanates for Common Brassicaceous Vegetables Consumed in the US Market Using Cyclocondensation and Thiocyanate Ion Measurement Methods

Glucosinolates are a group of important sulfur and nitrogen containing plant secondary metabolites found in Brassicaceous vegetables that are associated with many health benefits.There is a growing interest in assessing dietary glucosinolates and their degradation products’isothiocyanates exposure to humans.Determination of glucosinolates in plants is a very challenging task.In this study,the total glucosinolates from 22 commonly consumed Brassicaceous vegetables in the US market were determined by employing 1,2-benzenedithiol cyclocondensation for the determination of isothiocyanates(ITCs)from non-indole glucosinolates and a colorimetric method for the determination of thiocyanate ion(SCN^(−))from indole glucosi-nolates.The total glucosinolates were determined from the sum of these two methods.In the 22 investigated vegetables,the highest level of total ITCs was found in horse radish(5189.0±544.8 nmol/g dry weight)and the highest level of total SCN^(−)level was found in brussel sprouts(1294.0±141.6 nmol/g dry weight).The total glucosinolates ranged from 18.6±3.2 to 2271.2±215.3 nmol/g dry weight.The total glucosinolate and ITC data are necessary for the USDA glucosinolates database and important for establishing the relationship of glucosinolates to human nutrition.

A Phelipanche ramosa KAI2 protein perceives strigolactones and isothiocyanates enzymatically

Phelipanche ramosa is an obligate root-parasitic weed that threatens major crops in central Europe.In order to germinate,it must perceive various structurally divergent host-exuded signals,including isothiocyanates(ITCs)and strigolactones(SLs).However,the receptors involved are still uncharacterized.Here,we identify five putative SL receptors in P.ramosa and show that PrKAI2d3 is involved in the stimulation of seed germination.We demonstrate the high plasticity of PrKAI2d3,which allows it to interact with different chemicals,including ITCs.The SL perception mechanism of PrKAI2d3 is similar to that of endogenous SLs in non-parasitic plants.We provide evidence that PrKAI2d3 enzymatic activity confers hypersensitivity to SLs.Additionally,we demonstrate that methylbutenolide-OH binds PrKAI2d3 and stimulates P.ramosa germination with bioactivity comparable to that of ITCs.This study demonstrates that P.ramosa has extended its signal perception system during evolution,a fact that should be considered for the development of specific and efficient biocontrol methods.