Isothiocyanates(ITCs)are an important class of organic compounds characterized by the functional group R-N=C=S.These functional groups are widely found in multiple natural products and pharmaceutical important drugs.M...Isothiocyanates(ITCs)are an important class of organic compounds characterized by the functional group R-N=C=S.These functional groups are widely found in multiple natural products and pharmaceutical important drugs.Moreover,due to their high and versatile reactivity,they are widely used as an intermediate in organic synthesis.Keeping in view ITCs importance,this review summarizes their synthesis from nitrogen rich raw materials like amines,isocyanides,azides and some other compounds like oximes.Besides their synthesis,their application in organic compound synthesis as an intermediate will also be covered.Future research will likely focus on optimizing the synthesis of multifunctional isothiocyanates,understanding their complex biological mechanisms,exploring new applications,and highlighting the continued importance of isothiocyanates in modern chemistry and biotechnology.展开更多
Obesity has brought great challenges to global human health,and how to effectively prevent and control the occurrence and development of obesity has become an urgent problem.The role and mechanism of 4-[(α-Lrhamnosyl...Obesity has brought great challenges to global human health,and how to effectively prevent and control the occurrence and development of obesity has become an urgent problem.The role and mechanism of 4-[(α-Lrhamnosyloxy)benzyl]isothiocyanate(MITC),an active ingredient of Moringa oleifera Lam.,in the regulation of lipid metabolism have not been comprehensively investigated.In the present study,we investigated the mechanism of MITC in inhibiting lipid accumulation in mice fed with a high-fat diet(HFD)in terms of both lipolysis and central appetite regulation mediated by the gut microbe-gut-brain axis.MITC enhanced the characteristic indices associated with HFD mice and also promoted adipocytolysis and brown fat thermogenesis.Moreover,MITC was observed to improve leptin resistance,modulate the composition of gut microbiota such as Ruminococcaceae,Parasutterella,and Acetatifactor,promote 5-hydroxytryptamine secretion,further enhance the secretion of glucagon-like peptide-1(GLP-1)and peptide tyrosine-tyrosine(PYY)to activate peroxisome proliferator-activated receptor(PPAR)signaling in the hypothalamus,and modulate feeding behavior to inhibit lipid accumulation in HFD mice.These data suggest that MITC supplementation can help to alleviate obesity or obesity-related diseases.展开更多
A novel photocatalytic energy transfer-driven radical relay strategy has been introduced for the chemoand regioselective 1,4-difunctionalization of carbon-sulfur double bonds.This represents the first instance of radi...A novel photocatalytic energy transfer-driven radical relay strategy has been introduced for the chemoand regioselective 1,4-difunctionalization of carbon-sulfur double bonds.This represents the first instance of radical-mediated dual-functionalization of X-Y type unsaturated bonds,enabling the synthesis of complex linear molecules with C–O,C–N,and C-S bonds in a single operation.The method surpasses traditional approaches by avoiding the need for thiourea intermediates and the harsh conditions typically associated with them.The developed strategy exemplifies versatility,being applicable to 1,4-oxyamination,1,4-diamination,and 1,4-sulfonamination reactions,and has demonstrated compatibility with over 60 different substrates.The research also elucidates the role of electronic complementarity between radicals and receptors in achieving high selectivity in 1,4-difunctionalization reactions.This study significantly advances the field of bifunctionalization and remote difunctionalization reactions,with profound implications for the development of pharmaceuticals and materials science.展开更多
Objectives:An allergy is an exaggerated immune response,and mast cells play central roles in allergic pathologies.Allyl isothiocyanate can suppress inflammatory responses;however,whether allyl isothiocyanate has a sup...Objectives:An allergy is an exaggerated immune response,and mast cells play central roles in allergic pathologies.Allyl isothiocyanate can suppress inflammatory responses;however,whether allyl isothiocyanate has a suppressive effect on allergic pathologies remains unclear.Methods:2,4-dinitrofluorobenzen or ovalbumin was used to establish a mouse model of allergic contact dermatitis or food allergy,respectively.The mRNA level of cytokines was determined using real-time polymerase chain reaction.To examine the effects of allyl isothiocyanate on mast cells,degranulation and intracellular calcium measurement,RNA sequencing,real-time polymerase chain reaction,and Western blotting were performed.Results:Allyl isothiocyanate ameliorated allergic contact dermatitis and food allergy.Allyl isothiocyanate decreased the mRNA levels of cytokines and degranulated mast cells in the allergic contact dermatitis model.Furthermore,allyl isothiocyanate decreased the mRNA levels of cytokines and the mast cell marker mMCP-1 in the food allergy model.Moreover,allyl isothiocyanate inhibited immunoglobulin E/antigeninduced β-hexosaminidase release in murine bone marrow-derived mast cells and RBL-2H3 cells.Allyl isothiocyanate also decreased the increase in intracellular calcium levels induced by immunoglobulin E/antigen in mast cells.In addition,allyl isothiocyanate suppressed calcium ionophore A23187-induced mast cell degranulation.Furthermore,allyl isothiocyanate reduced A23187 or compound 48/80-induced human mast cells degranulation.RNA-sequencing data revealed that immunoglobulin E/antigen induced the expression of activating transcription factor 3 in murine bone marrow-derived mast cells;however,allyl isothiocyanate downregulated activating transcription factor 3 levels.Additionally,allyl isothiocyanate inhibited endoplasmic reticulum stress-related proteins.Conclusions:The results of the present study showed that allyl isothiocyanate ameliorated allergic contactdermatitis and foodallergy via inhibition of mast cells.展开更多
Gelatin (Gel) and chitosan (CTS) have several biomedical applications because of their biodegradability and biocompatibility. Crosslinking of Gel and Gel/CTS systems was evaluated using N-acetyl-D-glucosamine (GlcNAc)...Gelatin (Gel) and chitosan (CTS) have several biomedical applications because of their biodegradability and biocompatibility. Crosslinking of Gel and Gel/CTS systems was evaluated using N-acetyl-D-glucosamine (GlcNAc) formed into sponges by lyophilization. The prepared sponges were used to study the adsorption and desorption of fluorescein isothiocyanate (FITC) labeled bovine serum albumin (BSA) as a model instead of a growth factor. The effect of FITC-BSA concentration and temperature on the adsorption behavior of Gel/CTS sponges was investigated. The Langmuir adsorption isotherm model was used on the basis of the assumption that monolayer adsorption occurs on the surface;the results fit with the experiment data. The adsorption constants were 5.77 and 9.68 mL/mg for Gel and Gel/CTS sponges, respectively. The adsorption thermodynamic constants were found;adsorption onto sponges was an exothermic reaction. In particular, Gibbs free energy (ΔG) exhibited negative values in the range of 283 - 343 K for both Gel and Gel/CTS sponges, demonstrating the spontaneous nature of adsorption reaction. In addition, desorption behavior was evaluated for different concentrations and pH values of the FITC-BSA solution. The high adsorbed amounts of FITC-BSA on sponge resulted in high desorbed amounts in sponge, up to 55% from 3.5 mg/mL adsorbed concentration (around 1.5 mg from 3 mg adsorb amount). Desorption decreased following the buffer solution pH decrease, from 7.4 to 4 and 2 in Gel and Gel/CTS sponges, respectively. Based on the results of this preliminary study, these composite sponges could have significant application in biomedical materials.展开更多
As important constitutes in many drugs, piperazine comprised compounds are of great interest for drug design. In this paper, two piperazine-based compounds were synthesized for the first time, with different strategie...As important constitutes in many drugs, piperazine comprised compounds are of great interest for drug design. In this paper, two piperazine-based compounds were synthesized for the first time, with different strategies exploited. For one compound, a highly reactive intermediate of isothiocyanate was constructed to get the desired piperazinecarbothioamide. The synthesis of the other compound was completed sequentially through Friedel-Crafts acylation, coupling reaction and Michael addition. Both synthetic routes have short steps and acceptable yields, and such strategies can be applied to the synthesis of similar oioerazine-containin~ comoounds.展开更多
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 ...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.展开更多
AIM:Hydrogen sulfide (H2S) is a prominent gaseous constituent of the gastrointestinal (GI) tract with known cytotoxic properties. Endogenous concentrations of H2S are reported to range between 0.2-3.4 mmol/L in the GI...AIM:Hydrogen sulfide (H2S) is a prominent gaseous constituent of the gastrointestinal (GI) tract with known cytotoxic properties. Endogenous concentrations of H2S are reported to range between 0.2-3.4 mmol/L in the GI tract of mice and humans. Considering such high levels we speculate that, at non-toxic concentrations, H2S may interact with chemical agents and alter the response of colonic epithelium cells to such compounds. The GI tract is a major site for the absorption of phytochemical constituents such as isothiocyanates, flavonoids, and carotenoids, with each group having a role in the prevention of human diseases such as colon cancer. The chemopreventative properties of the phytochemical agent p-phenyethyl isothiocyanate (PEITC) are well recognized. However, little is currently known about the physiological or biochemical factors present in the GI tract that may influence the biological properties of ITCs. The current study was undertaken to determine the effects of H2S on PEITC mediated apoptosis in colon cancer cells. METHODS: Induction of apoptosis by PEITC in human colon cancer HCT116 cells was assessed using classic apoptotic markers namely SubGl population analysis, caspase-3 like activity and nuclear fragmentation and condensation coupled with the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide) viability assay and LDH leakage. RESULTS: PEITC significantly induced apoptosis in HCT116 cells as assessed by SubGl population formation, nuclear condensation, LDH leakage and caspase-3 activity after 24 h, these data being significant from control groups (P<0.01). In contrast, co-treatment of cells with physiological concentrations of H2S (0.1-1 mmol/L) prevented PEITC mediated apoptosis as assessed using the parameters described. CONCLUSION: PEITC effectively induced cell death in the human adenocarcinoma cell line HCT116 in vitro through classic apoptotic mechanisms. However, in the presence of H2S, apoptosis was abolished. These data suggest that H2S may play a significant role in the response of colonic epithelial cells to beneficial as well as toxic agents present within the GI tract.展开更多
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.
Cancer is one of the leading causes of death worldwide.Commonly used cancer treatments,including chemotherapy and radiation therapy,often have side effects and a complete cure is sometimes impossible.Therefore,prevent...Cancer is one of the leading causes of death worldwide.Commonly used cancer treatments,including chemotherapy and radiation therapy,often have side effects and a complete cure is sometimes impossible.Therefore,prevention,suppression,and/or delaying the onset of the disease are important.The onset of gastroenterological cancers is closely associated with an individual's lifestyle.Thus,changing lifestyle,specifically the consumption of fruits and vegetables,can help to protect against the development of gastroenterological cancers.In particular,naturally occurring bioactive compounds,including curcumin,resveratrol,isothiocyanates,(-)-epigallocatechin gallate and sulforaphane,are regarded as promising chemopreventive agents.Hence,regular consumption of these natural bioactive compounds found in foods can contribute to prevention,suppression,and/or delay of gastroenterological cancer development.In this review,we will summarize natural phytochemicals possessing potential antioxidant and/or anti-inflammatory and anti-carcinogenic activities,which are exerted by regulating or targeting specific molecules against gastroenterological cancers,including esophageal,gastric and colon cancers.展开更多
Tumorigenicity-inhibiting compounds have been identifled in our daily diet.For example,isothiocyanates(ITCs)found in cruciferous vegetables were reported to have potent cancer=prevention activities.The best characteri...Tumorigenicity-inhibiting compounds have been identifled in our daily diet.For example,isothiocyanates(ITCs)found in cruciferous vegetables were reported to have potent cancer=prevention activities.The best characterized ITC is sulforaphane(SF).SF can simultaneously modulate multiple cellular targets involved in carcinogenesis,including(1)modulating carcinogen-metabolizing enzymes and blocking the action of mutagens;(2)inhibition of cell proliferation and induction of apoptosis;and(3)inhibition of neo-angiogenesis and metastasis.SF targets cancer stem cells through modulation of nuclear factor kappa B(NF-κB),Sonic hedgehog(SHH),epithelial-mesenchymal transition,and Wnt/βcatenin pathways.Conventional chemotherapy/SF combination was tested in several studies and resulted in favorable outcomes.With its favorable toxicological profile,SF is a promising agent in cancer prevention and/or therapy.In this article,we discuss the human metabolism of SF and its effects on cancer prevention,treatment,and targeting cancer stem cells,as well as providing a brief review of recent human clinical trials on SF.展开更多
Hydroxypropyl chitosan(HP-chitosan) has been shown to have promising applications in a wide range of areas due to its biocompatibility, biodegradability and various biological activities, especially in the biomedical ...Hydroxypropyl chitosan(HP-chitosan) has been shown to have promising applications in a wide range of areas due to its biocompatibility, biodegradability and various biological activities, especially in the biomedical and pharmaceutical fields. However, it is not yet known about its pharmacokinetics and biodegradation performance, which are crucial for its clinical applications. In order to lay a foundation for its further applications and exploitations, here we carried out fluorescence intensity and GPC analyses to determine the pharmacokinetics mode of fluorescein isothiocyanate-labeled HP-chitosan(FITC-HP-chitosan) and its biodegradability. The results showed that after intraperitoneal administration at a dose of 10 mg per rat, FITC-HP-chitosan could be absorbed rapidly and distributed to liver, kidney and spleen through blood. It was indicated that FITC-HP-chitosan could be utilized effectively, and 88.47% of the FITC-HP-chitosan could be excreted by urine within 11 days with a molecular weight less than 10 k Da. Moreover, our data indicated that there was an obvious degradation process occurred in liver(< 10 k Da at 24 h). In summary, HP-chitosan has excellent bioavailability and biodegradability, suggesting the potential applications of hydroxypropyl-modified chitosan as materials in drug delivery, tissue engineering and biomedical area.展开更多
Free amino acids and short peptides(FAPS)that play an important role in plant nutrition can be extracted from rapeseed meal(RSM)by microbial enzymolysis.The enzymolytic activity of one bacterial strain isolated from R...Free amino acids and short peptides(FAPS)that play an important role in plant nutrition can be extracted from rapeseed meal(RSM)by microbial enzymolysis.The enzymolytic activity of one bacterial strain isolated from RSM for the production of FAPS fertilizer(FAPSF)via solid-state fermentation,as well as its detoxification activity for isothiocyanates and oxazolidinethione,was investigated in this study.The strain NJNPD41 isolated from RSM piled-soil possessed effective proteolytic activity and was identified as Bacillus flexus on the basis of its morphological,physiological,and biochemical properties,as well as 16S rDNA analysis.Compared to the uninoculated control,inoculation with the strain NJNPD41 significantly increased the yield of total free amino acids and short peptides by 115%and decreased the content of isothiocyanates and oxazolidinethione by 53%and 60%,respectively,after solid-state fermentation.The pot and field experiments showed that FAPSF significantly promoted eggplant growth and enhanced the fruit yield and quality of eggplant compared to the control.In conclusion,this study provided a novel method for the high-value utilization of RSM to produce high-quality and low-toxicity FAPSF using the newly isolated strain B.flexus NJNPD41.展开更多
Brassicaceae vegetables are an important traditional daily food in China and around the world, which provide nutrients and phytochemicals that are beneficial for human health. Among them, Brassica and Raphanus are wid...Brassicaceae vegetables are an important traditional daily food in China and around the world, which provide nutrients and phytochemicals that are beneficial for human health. Among them, Brassica and Raphanus are widely cultivated and eaten, have been evolved and/or bred for special characteristics during the long history of cultivation. Epidemiological studies suggest that the health benefits of Brassicaceae vegetables are mainly associated with glucosinolates(GSLs) and their hydrolytic products. In this review, we discuss the diversity of common consumed Brassicaceae vegetables and their GSL composition in edible parts. We also discuss the diversity factors affecting GSL content, and the diversity roles and functions of GSL. The information in this review provides guidance for consumers to select vegetables with a high GSL content,optimum edible stages, suitable edible methods, and provides a theoretical basis for crop molecular breeding and market development of GSL products.展开更多
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·-)...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.展开更多
The aim of this research was to assess the antinociceptive activity of the transient receptor potential （TRP） channel TRPV1, TRPM8, and TRPA1 antagonists in neurogenic, tonic, and neuropathic pain models in mice. Fo...The aim of this research was to assess the antinociceptive activity of the transient receptor potential （TRP） channel TRPV1, TRPM8, and TRPA1 antagonists in neurogenic, tonic, and neuropathic pain models in mice. For this purpose, TRP channel antagonists were administered into the dorsal surface of a hind paw 15 min before capsaicin, allyl isothiocyanate （AITC）, or formalin. Their antiallodynic and antihyperalgesic efficacies after intraperitoneal ad- ministration were also assessed in a paclitaxel-induced neuropathic pain model. Motor coordination of paclitaxel- treated mice that received these TRP channel antagonists was investigated using the rotarod test. TRPV1 antagonists, capsazepine and SB-366791, attenuated capsaicin-induced nociceptive reaction in a concentration-dependent manner. At 8 pg/20 pl, this effect was 51% （P〈0.001） for capsazepine and 37% （P〈0.05） for SB-366791. A TRPA1 antagonist, A-967079, reduced pain reaction by 48% （P〈0.05） in the AITC test and by 54% （P〈0.001） in the early phase of the formalin test. The test compounds had no influence on the late phase of the formalin test. In paclitaxel-treated mice, they did not attenuate heat hyperalgesia but N-（3-aminopropyl）-2-{[（3-methylphenyl）methyl]oxy}-N-（2-thienylmethyl） benzamide hydrochloride salt （AMTB）, a TRPM8 antagonist, reduced cold hyperalgesia and tactile allodynia by 31% （P〈0.05） and 51% （P〈0.01）, respectively. HC-030031, a TRPA1 channel antagonist, attenuated tactile allodynia in the von Frey test （62%; P〈0.001）. In conclusion, distinct members of TRP channel family are involved in different pain models in mice. Antagonists of TRP channels attenuate nocifensive responses of neurogenic, tonic, and neuropathic pain, but their efficacies strongly depend on the pain model used.展开更多
Chitosan, an excellent biomedical material, has received a widespread in vivo application. In contrast, its metabolism and distribution once being implanted were less documented. In this study, the pharmacokinetics an...Chitosan, an excellent biomedical material, has received a widespread in vivo application. In contrast, its metabolism and distribution once being implanted were less documented. In this study, the pharmacokinetics and biodegradation of fluorescein isothiocyanate(FITC) labeled and muscle implantation administrated chitosan in rats were investigated with fluorescence spectrophotometry, histological assay and gel chromatography. After implantation, chitosan was degraded gradually during its distribution to diverse organs. Among the tested organs, liver and kidney were found to be the first two highest in chitosan content, which was followed by heart, brain and spleen. Urinary excretion was believed to be the major pathway of chitosan elimination, yet 80% of chitosan administered to rats was not trackable in their urine. This indicated that the majority of chitosan was degraded in tissues. In average, the molecular weight of the degradation products of chitosan in diverse organs and urine was found to be <65 k Da. This further confirmed the in vivo degradation of chitosan. Our findings provided new evidences for the intensive and safe application of chitosan as a biomedical material.展开更多
Objective: To analyze two isothiocyanates(sulforaphene and sulforaphane) and their antiproliferative effect of 11 indigenous cruciferous vegetables.Methods: Phytoconstituents identification was conducted by high perfo...Objective: To analyze two isothiocyanates(sulforaphene and sulforaphane) and their antiproliferative effect of 11 indigenous cruciferous vegetables.Methods: Phytoconstituents identification was conducted by high performance liquid chromatography and gas chromatography-mass spectrometer techniques. The antiproliferation was evaluated in colon cancer cell line HCT116 by MTT assay.Results: Isothiocyanate identification by high performance liquid chromatography showed that broccoli, cabbage, "Khi-Hood"(Raphanus sativus L. var. caudatus Alef) and Chinese radish contained isothiocyanates sulforaphane. Sulforaphene and sulforaphane in broccoli, cabbage and "Khi-Hood" were characterized by the gas chromatography-mass spectrometer analysis. Antiproliferation screening by MTT assay found that the potent plants which possessed IC_(50) below 50 mg/m L were cabbage and "Khi-Hood", while the others had low antiproliferation with IC_(50) higher than 50 mg/m L. Difference in antiproliferation was probably due to difference existed phytochemical constituents in each plant. "Khi-Hood" possessed the highest antiproliferation against HCT116 with the lowest IC_(50)at(9.42 ± 0.46) mg/m L. The IC_(50) of chemotherapeutic drug(mitomycin C)was(19.12 ± 1.00) mg/m L, while both melphalan and 5-fluorouracil possessed the IC_(50) value higher than 50 mg/m L.Conclusions: Commonly consumed cruciferous vegetables exerted varied antiproliferation and isothiocyanate contents. High isothiocyanate content in "Khi-Hood" was contributed to high antiproliferation. Among 11 plants studied, "Khi-Hood" could be an alternative chemopreventive diet.展开更多
文摘Isothiocyanates(ITCs)are an important class of organic compounds characterized by the functional group R-N=C=S.These functional groups are widely found in multiple natural products and pharmaceutical important drugs.Moreover,due to their high and versatile reactivity,they are widely used as an intermediate in organic synthesis.Keeping in view ITCs importance,this review summarizes their synthesis from nitrogen rich raw materials like amines,isocyanides,azides and some other compounds like oximes.Besides their synthesis,their application in organic compound synthesis as an intermediate will also be covered.Future research will likely focus on optimizing the synthesis of multifunctional isothiocyanates,understanding their complex biological mechanisms,exploring new applications,and highlighting the continued importance of isothiocyanates in modern chemistry and biotechnology.
基金supported by the Basic Research Project of Yunnan Provincial Science and Technology Department(202201AT070262)the Project of Yunnan Province Food and Drug Homologous Resources Functional Food Innovation Team(A3032023057)+1 种基金the Yunnan Province Ten Thousand Plan Industrial Technology Talents Project(YNWR-CYJS-2020-010)the Yunnan Province-City Integration Project(202302 AN360002).
文摘Obesity has brought great challenges to global human health,and how to effectively prevent and control the occurrence and development of obesity has become an urgent problem.The role and mechanism of 4-[(α-Lrhamnosyloxy)benzyl]isothiocyanate(MITC),an active ingredient of Moringa oleifera Lam.,in the regulation of lipid metabolism have not been comprehensively investigated.In the present study,we investigated the mechanism of MITC in inhibiting lipid accumulation in mice fed with a high-fat diet(HFD)in terms of both lipolysis and central appetite regulation mediated by the gut microbe-gut-brain axis.MITC enhanced the characteristic indices associated with HFD mice and also promoted adipocytolysis and brown fat thermogenesis.Moreover,MITC was observed to improve leptin resistance,modulate the composition of gut microbiota such as Ruminococcaceae,Parasutterella,and Acetatifactor,promote 5-hydroxytryptamine secretion,further enhance the secretion of glucagon-like peptide-1(GLP-1)and peptide tyrosine-tyrosine(PYY)to activate peroxisome proliferator-activated receptor(PPAR)signaling in the hypothalamus,and modulate feeding behavior to inhibit lipid accumulation in HFD mice.These data suggest that MITC supplementation can help to alleviate obesity or obesity-related diseases.
基金the National Natural Science Foundation of China(No.22101059)the financial support from Guangxi Science and Technology Program of China(No.2023GXNSFBA026275)Guangxi Normal University。
文摘A novel photocatalytic energy transfer-driven radical relay strategy has been introduced for the chemoand regioselective 1,4-difunctionalization of carbon-sulfur double bonds.This represents the first instance of radical-mediated dual-functionalization of X-Y type unsaturated bonds,enabling the synthesis of complex linear molecules with C–O,C–N,and C-S bonds in a single operation.The method surpasses traditional approaches by avoiding the need for thiourea intermediates and the harsh conditions typically associated with them.The developed strategy exemplifies versatility,being applicable to 1,4-oxyamination,1,4-diamination,and 1,4-sulfonamination reactions,and has demonstrated compatibility with over 60 different substrates.The research also elucidates the role of electronic complementarity between radicals and receptors in achieving high selectivity in 1,4-difunctionalization reactions.This study significantly advances the field of bifunctionalization and remote difunctionalization reactions,with profound implications for the development of pharmaceuticals and materials science.
基金funded by the“Xinlin Young Talent Program”from Shanghai University of Traditional Chinese Medicine,and the Skate Key Laboratory of Drug Research(No.SIMMI1803KF-11).
文摘Objectives:An allergy is an exaggerated immune response,and mast cells play central roles in allergic pathologies.Allyl isothiocyanate can suppress inflammatory responses;however,whether allyl isothiocyanate has a suppressive effect on allergic pathologies remains unclear.Methods:2,4-dinitrofluorobenzen or ovalbumin was used to establish a mouse model of allergic contact dermatitis or food allergy,respectively.The mRNA level of cytokines was determined using real-time polymerase chain reaction.To examine the effects of allyl isothiocyanate on mast cells,degranulation and intracellular calcium measurement,RNA sequencing,real-time polymerase chain reaction,and Western blotting were performed.Results:Allyl isothiocyanate ameliorated allergic contact dermatitis and food allergy.Allyl isothiocyanate decreased the mRNA levels of cytokines and degranulated mast cells in the allergic contact dermatitis model.Furthermore,allyl isothiocyanate decreased the mRNA levels of cytokines and the mast cell marker mMCP-1 in the food allergy model.Moreover,allyl isothiocyanate inhibited immunoglobulin E/antigeninduced β-hexosaminidase release in murine bone marrow-derived mast cells and RBL-2H3 cells.Allyl isothiocyanate also decreased the increase in intracellular calcium levels induced by immunoglobulin E/antigen in mast cells.In addition,allyl isothiocyanate suppressed calcium ionophore A23187-induced mast cell degranulation.Furthermore,allyl isothiocyanate reduced A23187 or compound 48/80-induced human mast cells degranulation.RNA-sequencing data revealed that immunoglobulin E/antigen induced the expression of activating transcription factor 3 in murine bone marrow-derived mast cells;however,allyl isothiocyanate downregulated activating transcription factor 3 levels.Additionally,allyl isothiocyanate inhibited endoplasmic reticulum stress-related proteins.Conclusions:The results of the present study showed that allyl isothiocyanate ameliorated allergic contactdermatitis and foodallergy via inhibition of mast cells.
文摘Gelatin (Gel) and chitosan (CTS) have several biomedical applications because of their biodegradability and biocompatibility. Crosslinking of Gel and Gel/CTS systems was evaluated using N-acetyl-D-glucosamine (GlcNAc) formed into sponges by lyophilization. The prepared sponges were used to study the adsorption and desorption of fluorescein isothiocyanate (FITC) labeled bovine serum albumin (BSA) as a model instead of a growth factor. The effect of FITC-BSA concentration and temperature on the adsorption behavior of Gel/CTS sponges was investigated. The Langmuir adsorption isotherm model was used on the basis of the assumption that monolayer adsorption occurs on the surface;the results fit with the experiment data. The adsorption constants were 5.77 and 9.68 mL/mg for Gel and Gel/CTS sponges, respectively. The adsorption thermodynamic constants were found;adsorption onto sponges was an exothermic reaction. In particular, Gibbs free energy (ΔG) exhibited negative values in the range of 283 - 343 K for both Gel and Gel/CTS sponges, demonstrating the spontaneous nature of adsorption reaction. In addition, desorption behavior was evaluated for different concentrations and pH values of the FITC-BSA solution. The high adsorbed amounts of FITC-BSA on sponge resulted in high desorbed amounts in sponge, up to 55% from 3.5 mg/mL adsorbed concentration (around 1.5 mg from 3 mg adsorb amount). Desorption decreased following the buffer solution pH decrease, from 7.4 to 4 and 2 in Gel and Gel/CTS sponges, respectively. Based on the results of this preliminary study, these composite sponges could have significant application in biomedical materials.
基金National Basic Research Program of China(Grant No.2012CB518000)the National Natural Science Foundation of China(Grant No.21172012)the Specialized Research Fund for the Doctoral Program of Higher Education of China(Grant No.20120001110010)
文摘As important constitutes in many drugs, piperazine comprised compounds are of great interest for drug design. In this paper, two piperazine-based compounds were synthesized for the first time, with different strategies exploited. For one compound, a highly reactive intermediate of isothiocyanate was constructed to get the desired piperazinecarbothioamide. The synthesis of the other compound was completed sequentially through Friedel-Crafts acylation, coupling reaction and Michael addition. Both synthetic routes have short steps and acceptable yields, and such strategies can be applied to the synthesis of similar oioerazine-containin~ comoounds.
基金Supported by Natural Science Foundation of China,No.81700504 and No.81700511Science Foundation of Health Bureau of Zhejiang Province,No.2017183691+1 种基金Natural Science Foundation of Zhejiang Province,No.LY17H030006 and No.LQ15H030002Zhejiang Medical Science and Technology Project,No.2017193668
文摘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.
文摘AIM:Hydrogen sulfide (H2S) is a prominent gaseous constituent of the gastrointestinal (GI) tract with known cytotoxic properties. Endogenous concentrations of H2S are reported to range between 0.2-3.4 mmol/L in the GI tract of mice and humans. Considering such high levels we speculate that, at non-toxic concentrations, H2S may interact with chemical agents and alter the response of colonic epithelium cells to such compounds. The GI tract is a major site for the absorption of phytochemical constituents such as isothiocyanates, flavonoids, and carotenoids, with each group having a role in the prevention of human diseases such as colon cancer. The chemopreventative properties of the phytochemical agent p-phenyethyl isothiocyanate (PEITC) are well recognized. However, little is currently known about the physiological or biochemical factors present in the GI tract that may influence the biological properties of ITCs. The current study was undertaken to determine the effects of H2S on PEITC mediated apoptosis in colon cancer cells. METHODS: Induction of apoptosis by PEITC in human colon cancer HCT116 cells was assessed using classic apoptotic markers namely SubGl population analysis, caspase-3 like activity and nuclear fragmentation and condensation coupled with the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide) viability assay and LDH leakage. RESULTS: PEITC significantly induced apoptosis in HCT116 cells as assessed by SubGl population formation, nuclear condensation, LDH leakage and caspase-3 activity after 24 h, these data being significant from control groups (P<0.01). In contrast, co-treatment of cells with physiological concentrations of H2S (0.1-1 mmol/L) prevented PEITC mediated apoptosis as assessed using the parameters described. CONCLUSION: PEITC effectively induced cell death in the human adenocarcinoma cell line HCT116 in vitro through classic apoptotic mechanisms. However, in the presence of H2S, apoptosis was abolished. These data suggest that H2S may play a significant role in the response of colonic epithelial cells to beneficial as well as toxic agents present within the GI tract.
基金National Natural Science Foundation of China(Grant No.20972005)
文摘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.
基金Supported by Grants from the Next-Generation BioGreen 21 Program (Plant Molecular Breeding Center,No. PJ008187),Rural Development Administrationthe Leap Research Program(2010-0029233)World Class University Program (GrantR31-2008-00-10056-0) through the National Research Foundation of Korea funded by the Ministry of Education,Science and Technology,South Korea
文摘Cancer is one of the leading causes of death worldwide.Commonly used cancer treatments,including chemotherapy and radiation therapy,often have side effects and a complete cure is sometimes impossible.Therefore,prevention,suppression,and/or delaying the onset of the disease are important.The onset of gastroenterological cancers is closely associated with an individual's lifestyle.Thus,changing lifestyle,specifically the consumption of fruits and vegetables,can help to protect against the development of gastroenterological cancers.In particular,naturally occurring bioactive compounds,including curcumin,resveratrol,isothiocyanates,(-)-epigallocatechin gallate and sulforaphane,are regarded as promising chemopreventive agents.Hence,regular consumption of these natural bioactive compounds found in foods can contribute to prevention,suppression,and/or delay of gastroenterological cancer development.In this review,we will summarize natural phytochemicals possessing potential antioxidant and/or anti-inflammatory and anti-carcinogenic activities,which are exerted by regulating or targeting specific molecules against gastroenterological cancers,including esophageal,gastric and colon cancers.
文摘Tumorigenicity-inhibiting compounds have been identifled in our daily diet.For example,isothiocyanates(ITCs)found in cruciferous vegetables were reported to have potent cancer=prevention activities.The best characterized ITC is sulforaphane(SF).SF can simultaneously modulate multiple cellular targets involved in carcinogenesis,including(1)modulating carcinogen-metabolizing enzymes and blocking the action of mutagens;(2)inhibition of cell proliferation and induction of apoptosis;and(3)inhibition of neo-angiogenesis and metastasis.SF targets cancer stem cells through modulation of nuclear factor kappa B(NF-κB),Sonic hedgehog(SHH),epithelial-mesenchymal transition,and Wnt/βcatenin pathways.Conventional chemotherapy/SF combination was tested in several studies and resulted in favorable outcomes.With its favorable toxicological profile,SF is a promising agent in cancer prevention and/or therapy.In this article,we discuss the human metabolism of SF and its effects on cancer prevention,treatment,and targeting cancer stem cells,as well as providing a brief review of recent human clinical trials on SF.
基金financially supported by National High Technology Research and Development Program of China(863 Program,Grant No.2007AA091603)
文摘Hydroxypropyl chitosan(HP-chitosan) has been shown to have promising applications in a wide range of areas due to its biocompatibility, biodegradability and various biological activities, especially in the biomedical and pharmaceutical fields. However, it is not yet known about its pharmacokinetics and biodegradation performance, which are crucial for its clinical applications. In order to lay a foundation for its further applications and exploitations, here we carried out fluorescence intensity and GPC analyses to determine the pharmacokinetics mode of fluorescein isothiocyanate-labeled HP-chitosan(FITC-HP-chitosan) and its biodegradability. The results showed that after intraperitoneal administration at a dose of 10 mg per rat, FITC-HP-chitosan could be absorbed rapidly and distributed to liver, kidney and spleen through blood. It was indicated that FITC-HP-chitosan could be utilized effectively, and 88.47% of the FITC-HP-chitosan could be excreted by urine within 11 days with a molecular weight less than 10 k Da. Moreover, our data indicated that there was an obvious degradation process occurred in liver(< 10 k Da at 24 h). In summary, HP-chitosan has excellent bioavailability and biodegradability, suggesting the potential applications of hydroxypropyl-modified chitosan as materials in drug delivery, tissue engineering and biomedical area.
基金supported by the National Key Research and Development Program of China (Nos. 2016YFE0101100 and 2016YFD0200106)the National Key Basic Research Program of China (No. 2015CB150506)+3 种基金the Fundamental Research Funds for the Central Universities of China (Nos. KYZ201519 and BK20160710)the Jiangsu Science and Technology Program of China (No. BY2016077-05)the Jiangsu Provincial Natural Science Foundation of China (Nos. BK20150059 and BK20160710)the Top-notch Academic Programs Project of Jiangsu Higher Education Institution, China (No. PPZY2015A061)
文摘Free amino acids and short peptides(FAPS)that play an important role in plant nutrition can be extracted from rapeseed meal(RSM)by microbial enzymolysis.The enzymolytic activity of one bacterial strain isolated from RSM for the production of FAPS fertilizer(FAPSF)via solid-state fermentation,as well as its detoxification activity for isothiocyanates and oxazolidinethione,was investigated in this study.The strain NJNPD41 isolated from RSM piled-soil possessed effective proteolytic activity and was identified as Bacillus flexus on the basis of its morphological,physiological,and biochemical properties,as well as 16S rDNA analysis.Compared to the uninoculated control,inoculation with the strain NJNPD41 significantly increased the yield of total free amino acids and short peptides by 115%and decreased the content of isothiocyanates and oxazolidinethione by 53%and 60%,respectively,after solid-state fermentation.The pot and field experiments showed that FAPSF significantly promoted eggplant growth and enhanced the fruit yield and quality of eggplant compared to the control.In conclusion,this study provided a novel method for the high-value utilization of RSM to produce high-quality and low-toxicity FAPSF using the newly isolated strain B.flexus NJNPD41.
基金financially supported by the National Natural Science Foundation of China (Grant Nos. 31972394, 31501748)。
文摘Brassicaceae vegetables are an important traditional daily food in China and around the world, which provide nutrients and phytochemicals that are beneficial for human health. Among them, Brassica and Raphanus are widely cultivated and eaten, have been evolved and/or bred for special characteristics during the long history of cultivation. Epidemiological studies suggest that the health benefits of Brassicaceae vegetables are mainly associated with glucosinolates(GSLs) and their hydrolytic products. In this review, we discuss the diversity of common consumed Brassicaceae vegetables and their GSL composition in edible parts. We also discuss the diversity factors affecting GSL content, and the diversity roles and functions of GSL. The information in this review provides guidance for consumers to select vegetables with a high GSL content,optimum edible stages, suitable edible methods, and provides a theoretical basis for crop molecular breeding and market development of GSL products.
基金Supported by the Natural Science Foundation of Zhejiang Province(Y3090135)
文摘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.
基金supported by the National Science Centre Grant(No.DEC-2012/05/B/NZ7/02705),Poland
文摘The aim of this research was to assess the antinociceptive activity of the transient receptor potential （TRP） channel TRPV1, TRPM8, and TRPA1 antagonists in neurogenic, tonic, and neuropathic pain models in mice. For this purpose, TRP channel antagonists were administered into the dorsal surface of a hind paw 15 min before capsaicin, allyl isothiocyanate （AITC）, or formalin. Their antiallodynic and antihyperalgesic efficacies after intraperitoneal ad- ministration were also assessed in a paclitaxel-induced neuropathic pain model. Motor coordination of paclitaxel- treated mice that received these TRP channel antagonists was investigated using the rotarod test. TRPV1 antagonists, capsazepine and SB-366791, attenuated capsaicin-induced nociceptive reaction in a concentration-dependent manner. At 8 pg/20 pl, this effect was 51% （P〈0.001） for capsazepine and 37% （P〈0.05） for SB-366791. A TRPA1 antagonist, A-967079, reduced pain reaction by 48% （P〈0.05） in the AITC test and by 54% （P〈0.001） in the early phase of the formalin test. The test compounds had no influence on the late phase of the formalin test. In paclitaxel-treated mice, they did not attenuate heat hyperalgesia but N-（3-aminopropyl）-2-{[（3-methylphenyl）methyl]oxy}-N-（2-thienylmethyl） benzamide hydrochloride salt （AMTB）, a TRPM8 antagonist, reduced cold hyperalgesia and tactile allodynia by 31% （P〈0.05） and 51% （P〈0.01）, respectively. HC-030031, a TRPA1 channel antagonist, attenuated tactile allodynia in the von Frey test （62%; P〈0.001）. In conclusion, distinct members of TRP channel family are involved in different pain models in mice. Antagonists of TRP channels attenuate nocifensive responses of neurogenic, tonic, and neuropathic pain, but their efficacies strongly depend on the pain model used.
基金supported funancialy by Qingdao Bio-temed Biomaterial Co.,Ltd.the National ‘Twelfth Five-Year’ Support Plan for Science&Technology of Chinia(2012BAI18B06)
文摘Chitosan, an excellent biomedical material, has received a widespread in vivo application. In contrast, its metabolism and distribution once being implanted were less documented. In this study, the pharmacokinetics and biodegradation of fluorescein isothiocyanate(FITC) labeled and muscle implantation administrated chitosan in rats were investigated with fluorescence spectrophotometry, histological assay and gel chromatography. After implantation, chitosan was degraded gradually during its distribution to diverse organs. Among the tested organs, liver and kidney were found to be the first two highest in chitosan content, which was followed by heart, brain and spleen. Urinary excretion was believed to be the major pathway of chitosan elimination, yet 80% of chitosan administered to rats was not trackable in their urine. This indicated that the majority of chitosan was degraded in tissues. In average, the molecular weight of the degradation products of chitosan in diverse organs and urine was found to be <65 k Da. This further confirmed the in vivo degradation of chitosan. Our findings provided new evidences for the intensive and safe application of chitosan as a biomedical material.
基金Supported by Higher Education Research Promotion and National Research University Project of Thailand,Office of the Higher Education Commission,through the Food and Functional Food Research Cluster and Research and Development of Herbal Nutraceutics Subcluster of Khon Kaen University(F-2553-M-11 and NRU541051)
文摘Objective: To analyze two isothiocyanates(sulforaphene and sulforaphane) and their antiproliferative effect of 11 indigenous cruciferous vegetables.Methods: Phytoconstituents identification was conducted by high performance liquid chromatography and gas chromatography-mass spectrometer techniques. The antiproliferation was evaluated in colon cancer cell line HCT116 by MTT assay.Results: Isothiocyanate identification by high performance liquid chromatography showed that broccoli, cabbage, "Khi-Hood"(Raphanus sativus L. var. caudatus Alef) and Chinese radish contained isothiocyanates sulforaphane. Sulforaphene and sulforaphane in broccoli, cabbage and "Khi-Hood" were characterized by the gas chromatography-mass spectrometer analysis. Antiproliferation screening by MTT assay found that the potent plants which possessed IC_(50) below 50 mg/m L were cabbage and "Khi-Hood", while the others had low antiproliferation with IC_(50) higher than 50 mg/m L. Difference in antiproliferation was probably due to difference existed phytochemical constituents in each plant. "Khi-Hood" possessed the highest antiproliferation against HCT116 with the lowest IC_(50)at(9.42 ± 0.46) mg/m L. The IC_(50) of chemotherapeutic drug(mitomycin C)was(19.12 ± 1.00) mg/m L, while both melphalan and 5-fluorouracil possessed the IC_(50) value higher than 50 mg/m L.Conclusions: Commonly consumed cruciferous vegetables exerted varied antiproliferation and isothiocyanate contents. High isothiocyanate content in "Khi-Hood" was contributed to high antiproliferation. Among 11 plants studied, "Khi-Hood" could be an alternative chemopreventive diet.
