RESUMO
Methylsulfinyl hexyl isothiocyanate (6-MSITC) isolated from Eutrema japonicum is a promising candidate for the treatment of breast cancer, colorectal and stomach cancer, metabolic syndrome, heart diseases, diabetes, and obesity due to its anti-inflammatory and antioxidant properties. Also, its neuroprotective properties, improving cognitive function and protecting dopaminergic neurons, make it an excellent candidate for treating neurodegenerative diseases like dementia, Alzheimer's, and Parkinson's disease. 6-MSITC acts on many signaling pathways, such as PPAR, AMPK, PI3K/AKT/mTOR, Nrf2/Keap1-ARE, ERK1/2-ELK1/CHOP/DR5, and MAPK. However, despite the very promising results of in vitro and in vivo animal studies and a few human studies, the molecule has not yet been thoroughly tested in the human population. Nonetheless, wasabi should be classified as a "superfood" for the primary and secondary prevention of human diseases. This article reviews the current state-of-the-art research on 6-MSITC and its potential clinical uses, discussing in detail the signaling pathways activated by the molecule and their interactions.
Assuntos
Doença de Alzheimer , Isotiocianatos , Neoplasias , Obesidade , Wasabia , Humanos , Doença de Alzheimer/tratamento farmacológico , Neoplasias/tratamento farmacológico , Isotiocianatos/farmacologia , Isotiocianatos/uso terapêutico , Obesidade/tratamento farmacológico , Animais , Wasabia/química , Transdução de Sinais/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Antioxidantes/farmacologia , Anti-Inflamatórios/farmacologiaRESUMO
Skin aging is a natural, unavoidable, and complex process caused by oxidative stress. As a consequence, it leads to an increase in the activation of extracellular matrix disruption enzymes and DNA damage. The search for natural sources that inhibit these mechanisms can be a good approach to prevent skin aging. The purpose of our study was to evaluate the composition of flavonoids and phenolic acids in the extracts obtained from the flowers, roots, and leaves of Eutrema japonicum cultivated in Poland. Then, the resultant extracts were subjected to an assessment of antioxidant, anti-collagenase, anti-elastase, anti-hyaluronidase, antibacterial, and cytotoxic properties. It was demonstrated that the extract from the flowers had the highest content of flavonoid glycosides (17.15 mg/g DE). This extract showed the greatest antioxidant, anti-collagenase, anti-elastase, and anti-hyaluronidase activities compared to the other samples. Importantly, the collagenase inhibitory activity of this extract (93.34% ± 0.77%) was better than that of positive control epigallocatechin gallate (88.49% ± 0.45%). An undeniable advantage of this extract was also to possess moderate antibacterial properties and no cytotoxicity towards normal human skin fibroblasts. Our results suggest that extracts from E. japonicum flowers may be considered as a promising antiaging compound for applications in cosmetic formulations.
Assuntos
Envelhecimento/efeitos dos fármacos , Flavonoides , Hidroxibenzoatos , Wasabia/química , Células A549 , Flavonoides/química , Flavonoides/farmacologia , Humanos , Hidroxibenzoatos/química , Hidroxibenzoatos/farmacologia , Polônia , Wasabia/crescimento & desenvolvimentoRESUMO
Inflammatory bowel disease (IBD) describes a set of disorders involving alterations to gastrointestinal physiology and mucosal immunity. Unravelling its complex pathophysiology is important since many IBD patients are refractory to or suffer adverse side effects from current treatments. Isothiocyanates (ITCs), such as 6-(methylsulfinyl)hexyl ITC (6-MITC) in Wasabia japonica, have potential anti-inflammatory activity. We aimed to elucidate the pathways through which 6-MITC alleviates inflammation by examining its role in the nuclear factor-kappa B (NF-κB) pathway through inhibition of glycogen synthase kinase 3 beta (GSK-3ß) using a chemically induced murine model of IBD, cell-based and in silico techniques. The effects of 6-MITC and two NF-κB inhibitors, sulfasalazine (SS), pyrrolidine dithiolcarbamate (PDTC) were investigated on a dextran sulfate sodium (DSS)-induced murine mouse model of acute and chronic colitis using macroscopic measurements and pro-inflammatory markers. The effect of 6-MITC on NF-κB induction was assessed using a murine macrophage cell line. Complexes of GSK-3ß-6-MITC and GSK-3ß-ATP were generated in silico to elucidate the mechanism of 6-MITC's direct inhibition of GSK-3ß. Changes in pro-inflammatory markers, inducible nitric oxide synthase (iNOS) (increased) and interleukin-6 (IL-6) (decreased) demonstrated that iNOS regulation occurred at the translational level. Intraperitoneal (ip) injection of 6-MITC to the colitis-induced mice ameliorated weight loss whereas oral administration had negligible effect. Fecal blood and colon weight/length ratio parameters improved on treatment with 6-MITC and the other NF-κB inhibitors. Levels of NF-κB decreased upon addition of 6-MITC in vitro while structural studies showed 6-MITC acts competitively to inhibit GSK-3ß at the ATP binding site. In this study we demonstrated that 6-MITC inhibits NF-κB signaling via GSK-3ß inhibition ameliorating fecal blood, colonic alterations and DSS-induced weight loss indirectly indicating reduced intestinal stress. Taken together these results suggest a role for 6-MITC in the treatment of IBD acting to alleviate inflammation through the GSK-3ß/NF-κB pathway. Furthermore, the GSK-3ß-6-MITC model can be utilized as a basis for development of novel therapeutics targeting GSK-3ß for use in other disorders including cancer.
Assuntos
Anti-Inflamatórios/química , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Isotiocianatos/química , Wasabia/química , Animais , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Linhagem Celular , Sulfato de Dextrana/toxicidade , Regulação para Baixo/efeitos dos fármacos , Feminino , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Interleucina-6/metabolismo , Isotiocianatos/metabolismo , Isotiocianatos/farmacologia , Isotiocianatos/uso terapêutico , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Wasabia/metabolismoRESUMO
Functional dyspepsia (FD) is thought to be mainly based on gastric motility dysfunction and chronic hypersensitivity, yet FD animal models has been reported a few. We studied to establish the mouse model of impaired gastric motility induced by a pungent ingredient of wasabi allyl isothiocyanate (AITC), which is reliable to evaluate prokinetic agents. Male ddY mice were used. Gastric motility was measured by 13C-acetic acid breath test in conscious mice. AITC (80 mM) was given 60 min before the measurement of motility. Prokinetic agents including itopride (30, 100 mg/kg), mosapride (0.1-1 mg/kg), neostigmine (30 µg/kg), acotiamide (10-100 mg/kg), and daikenchuto (100-1000 mg/kg) were given 40 min before the measurement. AITC impaired gastric motility without mucosal damages, which reverted 24 h after AITC treatment. The decreased motility induced by AITC was restored by prokinetic agents such as itopride, mosapride, neostigmine, and acotiamide. In separate experiment, daikenchuto recovered the decreased motility induced by AITC, although daikenchuto had no effect on motility in normal condition. In conclusion, it is considered that the AITC-induced impaired gastric motility mouse model is useful to develop new prokinetic agents for treatment of FD, and to re-evaluate traditional Japanese herbal medicines.
Assuntos
Benzamidas/administração & dosagem , Compostos de Benzil/administração & dosagem , Dispepsia/tratamento farmacológico , Motilidade Gastrointestinal , Isotiocianatos/efeitos adversos , Morfolinas/administração & dosagem , Neostigmina/administração & dosagem , Fitoterapia , Extratos Vegetais/administração & dosagem , Tiazóis/administração & dosagem , Wasabia/química , Animais , Benzamidas/farmacologia , Compostos de Benzil/farmacologia , Modelos Animais de Doenças , Dispepsia/fisiopatologia , Motilidade Gastrointestinal/efeitos dos fármacos , Isotiocianatos/isolamento & purificação , Masculino , Camundongos Endogâmicos , Morfolinas/farmacologia , Neostigmina/farmacologia , Panax , Extratos Vegetais/farmacologia , Tiazóis/farmacologia , Zanthoxylum , ZingiberaceaeRESUMO
Oral responsiveness to the burning/spicy sensation affects food behaviors and diet; therefore, it is reasonable to hypothesize that the variation in nasal responsiveness to irritant foods may play a role in modulating food behaviors. This study explored the variation among individuals in orthonasal irritation induced by smelling food ingredients containing irritant compounds: mustard oil (2.0, 10.0, and 100.0% v/v mustard oil in corn oil; irritant compound: allyl isothiocyanate); vinegar (3.5, 42.3, and 98.6% v/v vinegar in water; irritant compound: acetic acid); and wasabi (0.1, 0.2, and 0.4% w/w wasabi powder in water; irritant compound: allyl isothiocyanate). Sixty-eight subjects (40% males; 19-87 years) smelled the nine samples and rated their perceived intensity of odor, irritation and liking. Wide individual variation in the perception of irritation and odor intensity was found, especially at the highest concentrations. Young individuals were the most sensitive to all stimuli. No significant differences were found between males and females. Fifty-seven percent of subjects were "HYPO" and 43 percent "HYPER" responsive to irritation, respectively. Perceived irritation was positively correlated with odor intensity and tended to be negatively correlated with liking, especially in familiar stimuli. The results suggest that the variation in nasal responsiveness to irritant foods may contribute to influencing food acceptance and therefore, to modulating food behaviors.
Assuntos
Preferências Alimentares/efeitos dos fármacos , Individualidade , Irritantes/administração & dosagem , Odorantes/análise , Percepção Olfatória/efeitos dos fármacos , Ácido Acético/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Isotiocianatos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Mostardeira , Estimulação Física , Óleos de Plantas/administração & dosagem , Pós/administração & dosagem , Limiar Sensorial/efeitos dos fármacos , Olfato/efeitos dos fármacos , Wasabia/química , Adulto JovemRESUMO
A natural compound from Wasabia japonica, 6-(methylsulfinyl) hexyl isothiocyanate (6-MITC) was investigated for its anti-leukemia activity and mechanism of action. It was found that 6-MITC inhibited the viability of human chronic myelogenous leukemia K562 cells along with extensive mitotic arrest, spindle multipolarity, and cytoplasmic vacuole accumulation. The evidence of autophagy included the validation of autophagosomes with double-layered membranes under transmission electron microscopy, LC3I/II conversion, and the induction of G2/M phase arrest observed with acridine orange staining of treated cells, as well as the elevation of phosphorylated-histone H3 expression at the M phase. With regard to the expression of proteins related to mitosis, the downregulation of p-CHK1, p-CHK2, p-cdc25c, and p-cdc2, as well as the upregulation of cyclin B1, p-cdc20, cdc23, BubR1, Mad2, and p-plk-1 was observed. The knockdown of cdc20 was unable to block the effect of 6-MITC. The differentiation of k562 cells into monocytes, granulocytes, and megakaryocytes was not affected by 6-MITC. The 6-MITC-induced unique mode of cell death through the concurrent induction of mitosis and autophagy may have therapeutic potential. Further studies are required to elucidate the pathways associated with the counteracting occurrence of mitosis and autophagy.
Assuntos
Isotiocianatos/farmacologia , Leucemia/fisiopatologia , Mitose/efeitos dos fármacos , Extratos Vegetais/farmacologia , Wasabia/química , Autofagia/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Histonas/metabolismo , Humanos , Células K562 , Leucemia/tratamento farmacológico , Leucemia/metabolismoRESUMO
Takotsubo cardiomyopathy is a left ventricular dysfunction that typically occurs after sudden intense emotional or physical stress and mimics myocardial infarction. We describe a case of a 60-year-old woman that presented to the emergency department with chest pain after she attended a wedding and ate a large amount of wasabi, assuming it to be an avocado. To the best of our knowledge, this is the first report of takotsubo cardiomyopathy triggered by wasabi consumption.
Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Dor no Peito/induzido quimicamente , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Cardiomiopatia de Takotsubo/induzido quimicamente , Wasabia/efeitos adversos , Dor no Peito/diagnóstico por imagem , Angiografia Coronária , Ecocardiografia , Feminino , Humanos , Pessoa de Meia-Idade , Fatores Desencadeantes , Cardiomiopatia de Takotsubo/diagnóstico por imagem , Cardiomiopatia de Takotsubo/tratamento farmacológico , Cardiomiopatia de Takotsubo/fisiopatologia , Resultado do Tratamento , Wasabia/químicaRESUMO
In this study, the nutritional, functional, and chemical measurements of sensory attributes of different parts of wasabi, namely, leaf, petiole, and rhizome, were investigated. Proximate composition analysis showed the presence of high amounts of carbohydrates in the rhizome and amino acid composition analysis confirmed high proportions of glutamic acid and aspartic acid in all three parts. While proximate composition showed low lipid content in wasabi, ω-3 fatty acids accounted for a high proportion (>44%) of the total lipids. Wasabi leaves had high vitamin C and total phenolic contents, and thus demonstrated antioxidant capacity. Allyl isothiocyanate, which gives wasabi its characteristic pungent taste, was identified by gas chromatography/mass spectrometry and an electronic nose. On an electronic tongue, wasabi leaves showed compounds associated with sourness and saltiness while the petiole had high content of compounds associated with sweetness and bitterness. This study provides basic data for the utilization of wasabi parts as food materials based on their nutritional, functional, and chemical measure of sensory attributes.
Assuntos
Compostos Alílicos/metabolismo , Ácido Ascórbico/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Isocianatos/metabolismo , Componentes Aéreos da Planta/metabolismo , Rizoma/metabolismo , Wasabia/metabolismo , Compostos Alílicos/análise , Ácido Ascórbico/análise , Ácidos Graxos Ômega-3/análise , Isocianatos/análise , Componentes Aéreos da Planta/química , Rizoma/química , Wasabia/químicaRESUMO
6-(methylsulfinyl) hexyl isothiocyanate (6-MITC) is a naturally occurring compound isolated from Wasabia japonica (wasabi). The synthetic derivatives, 6-(methylsulfenyl) hexyl isothiocyanate (I7447) and 6-(methylsulfonyl) hexyl isothiocyanate (I7557), were derived from 6-MITC with the deletion and addition of oxygen, respectively. We aimed to evaluate the effect of these synthetic compounds on human oral cancer cells, SAS and OECM-1. All three compounds (I7447, 6-MITC, and I7557) inhibited the viability of SAS and OECM-1 cells using MTT assay. Morphological observations showed various proportions of mitotic arrest and apoptosis in cells treated with these compounds. Cell cycle analysis revealed relatively abundant G2/M arrest in 6-MITC and I7557-treated cells, whereas sub-G1 accumulation was found in I7447-treated cells. In using phosphorylated histone H3 as a marker for mitosis, the addition of 6-MITC and I7557 (excluding I7447) could be shown to arrest cells during mitosis. In contrast, I7447 induced more prominent apoptosis than the 6-MITC or I7557 compounds. The down-regulated expression of the phosphorylated form of CHK1 and Cdc25c was noted in 6-MITC and I7557-treated cells. I7557 could sensitize SAS cells to death by radiation. The wasabi compound, 6-MITC, and its chemical derivatives with different numbers of oxygen may have differential pharmacological effects on human oral cancer cells.
Assuntos
Antineoplásicos/síntese química , Quinase 1 do Ponto de Checagem/metabolismo , Isotiocianatos/síntese química , Neoplasias Bucais/metabolismo , Wasabia/química , Fosfatases cdc25/metabolismo , Antineoplásicos/química , Antineoplásicos/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Histonas/metabolismo , Humanos , Isotiocianatos/química , Isotiocianatos/farmacologia , Neoplasias Bucais/tratamento farmacológico , Oxigênio/química , Fosforilação , Extratos Vegetais/químicaRESUMO
5-Hexenyl isothiocyanate (5-HeITC) is a naturally derived flavoring substance from Wasabia japonica. To clarify the toxicological profile of 5-HeITC, we performed a subchronic toxicity study of 5-HeITC with intragastric administration at daily doses of 0, 3, 12, or 48â¯mg/kg body weight (BW) to 6-week-old male and female F344/DuCrj rats for 13 weeks. Body weight gain was decreased in the male 48â¯mg/kg BW group. Decreased triglycerides were observed in the male over 12â¯mg/kg BW and female 48â¯mg/kg BW groups. Decreased total cholesterol was observed in the male 48â¯mg/kg BW group. Increases in relative liver weights were observed in the male 48â¯mg/kg BW and female over 12â¯mg/kg BW groups. Increases in absolute and relative heart weights were observed in the female over 12â¯mg/kg BW groups. Simple hyperplasia in the urinary bladder was found in the male and female 12â¯mg/kg BW groups, and nodular hyperplasia was found in the female 48â¯mg/kg BW group. Based on these findings, the target organs of 5-HeITC were determined to be the urinary bladder, heart, and liver. The no-observed-adverse-effect level of 5-HeITC for both sexes was estimated to be 3â¯mg/kg BW.
Assuntos
Aromatizantes/toxicidade , Isotiocianatos/toxicidade , Wasabia/química , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Testes de Química Clínica , Relação Dose-Resposta a Droga , Feminino , Aromatizantes/administração & dosagem , Coração/efeitos dos fármacos , Testes Hematológicos , Hiperplasia/induzido quimicamente , Isotiocianatos/administração & dosagem , Fígado/efeitos dos fármacos , Masculino , Nível de Efeito Adverso não Observado , Tamanho do Órgão/efeitos dos fármacos , Ratos Endogâmicos F344 , Testes de Toxicidade Subcrônica , Bexiga Urinária/patologiaRESUMO
Six new thioglycosides (1-6) were characterized from the roots of Wasabia japonica along with a known analogue (7). Of these compounds, 1-3 possess a disulfide bridge connecting the carbohydrate motif and the aglycone, which is extremely rare in Nature. In particular, compound 1 forms an unusual 1,4,5-oxadithiocane ring system. The structures of the isolated compounds were determined through conventional NMR and HRMS data analysis procedure, and computational methods with advanced statistics were used for the configurational assignments of 1 and two pairs of inseparable epimers, 2/3 and 4/5. All compounds were evaluated for their anti-inflammatory, neuroprotective, and cytotoxic activities, with 1 showing weak anti-inflammatory activity (IC50 41.2 µM).
Assuntos
Tioglicosídeos/isolamento & purificação , Wasabia/química , Anti-Inflamatórios/farmacologia , Espectroscopia de Ressonância Magnética , Raízes de Plantas/química , Tioglicosídeos/química , Tioglicosídeos/farmacologiaRESUMO
Inflammatory bowel disease (IBD) is characterized by chronic or recurrent inflammation of the gastrointestinal tract. Even though the current strategies to treat IBD include anti-inflammatory drugs and immune modulators, these treatments have side-effects. New strategies are, therefore, required to overcome the limitations of the therapies. In this study, we investigated the anti-colitic effects of allyl isothiocyanate (AITC), which is an active ingredient present in Wasabia japonica. The DSS-induced colitis model in the mouse was used to mimic human IBD and we observed that AITC treatment ameliorated the severity of colitis. We further studied the mechanism involved to ameliorate the colitis. To investigate the involvement of AITC on the intestinal barrier function, the effect on the intercellular tight junction was evaluated in the Caco-2 cell line while mucin expression was assessed in the LS174T cell line. AITC positively regulated tight junction proteins and mucin 2 (MUC2) against DSS-induced damage or depletion. Our data of in vivo studies were also consistent with the in vitro results. Furthermore, we observed that MUC2 increased by AITC is dependent on ERK signaling. In conclusion, we propose that AITC can be considered as a new strategy for treating IBD by modulating tight junction proteins and mucin.
Assuntos
Sulfato de Dextrana/toxicidade , Regulação da Expressão Gênica/efeitos dos fármacos , Doenças Inflamatórias Intestinais , Isotiocianatos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Mucina-2/biossíntese , Junções Íntimas/metabolismo , Animais , Células CACO-2 , Feminino , Humanos , Doenças Inflamatórias Intestinais/induzido quimicamente , Doenças Inflamatórias Intestinais/metabolismo , Doenças Inflamatórias Intestinais/patologia , Doenças Inflamatórias Intestinais/prevenção & controle , Isotiocianatos/química , Lipopolissacarídeos/toxicidade , Camundongos , Células RAW 264.7 , Junções Íntimas/patologia , Wasabia/químicaRESUMO
SCOPE: DNA repair inhibitors have broad clinical applications in tumor types with DNA repair defects, including colorectal cancer (CRC). Structural analogs of the anticancer agent sulforaphane (SFN) were investigated as modifiers of histone deacetylase (HDAC) and histone acetyltransferase (HAT) activity, and for effects on DNA damage/repair pertinent to human CRC. METHODS AND RESULTS: In the polyposis in rat colon (Pirc) model, single oral administration of SFN and structurally related long-chain isothiocyanates (ITCs) decreased histone deacetylase 3 (HDAC3) expression and increased pH2AX levels markedly in adenomatous colon polyps, extending prior observations on HDAC3 inhibition/turnover in cell-based assays. Colon cancer cells at a high initial plating density had diminished cytotoxicity from SFN, whereas novel tetrazole-containing heterocyclic analogs of SFN retained their efficacy. The potent SFN analogs triggered DNA damage, cell cycle arrest, apoptosis, and loss of a key DNA repair regulator, C-terminal binding protein (CtBP) interacting protein (CtIP). These SFN analogs also altered HAT/HDAC activities and histone acetylation status, lowered the expression of HDAC3, P300/CBP-associated factor (PCAF) and lysine acetyltransferase 2A (KAT2A/GCN5), and attenuated homologous recombination (HR)/non-homologous end joining (NHEJ) repair activities in colon cancer cells. CONCLUSION: Novel tetrazole-containing heterocyclic analogs of SFN provide a new avenue for chemosensitization in colon cancer cells via modulation of HAT/HDAC activities and associated DNA damage/repair signaling pathways.
Assuntos
Dano ao DNA/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Isotiocianatos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Brassica/química , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Neoplasias do Colo/tratamento farmacológico , Feminino , Regulação da Expressão Gênica , Células HCT116 , Células HEK293 , Histona Acetiltransferases/genética , Histona Acetiltransferases/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Humanos , Masculino , Mostardeira/química , Ratos , Ratos Endogâmicos F344 , Sulfóxidos , Tetrazóis/farmacologia , Verduras/química , Wasabia/química , Fatores de Transcrição de p300-CBP/genética , Fatores de Transcrição de p300-CBP/metabolismoRESUMO
To investigate the compounds present in wasabi leaves (Wasabia japonica Matsumura) that inhibit the adipocyte differentiation, activity-guided fractionation was performed on these leaves. 5-Hydroxyferulic acid methyl ester (1: 5-HFA ester), one of the phenylpropanoids, was isolated from wasabi leaves as a compound that inhibits the adipocyte differentiation. Compound 1 suppressed the intracellular lipid accumulation of 3T3-L1 cells without significant cytotoxicity. Gene expression analysis revealed that 1 suppressed the mRNA expression of 2 master regulators of adipocyte differentiation, PPARγ and C/EBPα. Furthermore, 1 downregulated the expression of adipogenesis-related genes, GLUT4, LPL, SREBP-1c, ACC, and FAS. Protein expression analysis revealed that 1 suppressed PPARγ protein expression. Moreover, to investigate the relationship between the structure and activity of inhibiting the adipocyte differentiation, we synthesized 12 kinds of phenylpropanoid analog. Comparison of the activity among 1 and its analogs suggested that the compound containing the substructure that possess a common functional group at the ortho position such as a catechol group exhibits the activity of inhibiting the adipocyte differentiation. Taken together, our findings suggest that 1 from wasabi leaves inhibits adipocyte differentiation via the downregulation of PPARγ.
Assuntos
Adipócitos/efeitos dos fármacos , Adipogenia/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Ácidos Cumáricos/isolamento & purificação , Ácidos Cumáricos/farmacologia , Ésteres/farmacologia , Folhas de Planta/química , Wasabia/química , Células 3T3-L1 , Adipócitos/fisiologia , Adipogenia/genética , Animais , Proteína alfa Estimuladora de Ligação a CCAAT/genética , Proteína alfa Estimuladora de Ligação a CCAAT/metabolismo , Diferenciação Celular/genética , Ácidos Cumáricos/química , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Ésteres/química , Ésteres/isolamento & purificação , Camundongos , PPAR gama/genética , PPAR gama/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismoRESUMO
Inflammatory bowel diseases (IBDs), including Crohn's disease (CD) and ulcerative colitis (UC), are prevalent and debilitating health problems worldwide. Many types of drugs are used to treat IBDs, but they exhibit adverse effects such as vomiting, nausea, abdominal pain, diarrhea, etc. In order to overcome the limitations of current therapeutic drugs, scientists have searched for functional foods from natural resources. In this study, we investigated the anti-colitic effects of Wasabia japonica extract in a DSS-induced colitis model. Wasabi japonica is a plant of the Brassicaceae family that has recently been reported to exhibit properties of detoxification, anti-inflammation, and induction of apoptosis in cancer cells. In this study, we generated wasabi ethanol extract (WK) and assessed its anti-colitic effect. In addition, in order to improve delivery of the extract to the colon, WK was coated with 5% Eudragit S100 (WKE), after which the anti-colitic effects of WKE were assessed. In conclusion, WK prevented development of colitis through inhibition of the NF-kB signaling pathway and recovery of epithelial tight junctions. In addition, the anti-colitic effect of WK was enhanced by improving its delivery to the colon by coating the WK with Eudragit S100. Therefore, we suggest that wasabi can be used as a new functional food to prevent IBDs due to its anti-colitic effect.
Assuntos
Colite/prevenção & controle , Alimento Funcional/análise , NF-kappa B/imunologia , Extratos Vegetais/administração & dosagem , Wasabia/química , Animais , Colite/genética , Colite/imunologia , Feminino , Humanos , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , Transdução de Sinais/efeitos dos fármacos , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/imunologiaRESUMO
Irritable bowel syndrome (IBS) is a functional gastrointestinal disease with complex pathophysiology involving the brain-gut axis. To assess the effects of Wasabia koreana (WK) on IBS, we employed a mouse model of colonic zymosan injection presenting with diarrhea-predominant IBS-like symptoms. Oral WK administration significantly diminished stool score, suppressed colon length and weight change, and minimized body weight loss without affecting food intake. In WK-treated mice, the submucosal thickening and epithelial lining of the colon were inhibited and were similar to those of naïve mice. Infiltration of mast cells into the colon and serum tumor necrosis factor-α levels were markedly suppressed. These effects were comparable to those of sulfasalazine, an anti-inflammatory drug. Furthermore, the number of visceral pain-related behaviors was significantly decreased, and locomotion activities measured in the elevated plus maze and open field tests were significantly increased by WK in a dose-dependent manner compared with amitriptyline, an antidepressant. These changes were accompanied by reduced FosB2 expression in the brain. Taken together, these data suggest that WK may have potential as a medicinal food for IBS by acting on inflammatory diarrhea and neural activity.
Assuntos
Síndrome do Intestino Irritável/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Wasabia/química , Zimosan/efeitos adversos , Animais , Colo/efeitos dos fármacos , Colo/imunologia , Modelos Animais de Doenças , Humanos , Síndrome do Intestino Irritável/induzido quimicamente , Síndrome do Intestino Irritável/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/análise , Fator de Necrose Tumoral alfa/imunologiaRESUMO
6-MSITC and 6-MTITC are sulforaphane (SFN) analogs found in Japanese Wasabi. As we reported previously, Wasabi isothiocyanates (ITCs) are activators of Nrf2-antioxidant response element pathway, and also inhibitors of pro-inflammatory cyclooxygenase-2. This study is the first to assess the global changes in transcript levels by Wasabi ITCs, comparing with SFN, in HepG2 cells. We performed comparative gene expression profiling by treating HepG2 cells with ITCs, followed by DNA microarray analyses using HG-U133 plus 2.0 oligonucleotide array. Partial array data on selected gene products were confirmed by RT-PCR and Western blotting. Ingenuity Pathway Analysis (IPA) was used to identify functional subsets of genes and biologically significant network pathways. 6-MTITC showed the highest number of differentially altered (≥2 folds) gene expression, of which 114 genes were upregulated and 75 were downregulated. IPA revealed that Nrf2-mediated pathway, together with glutamate metabolism, is the common significantly modulated pathway across treatments. Interestingly, 6-MSITC exhibited the most potent effect toward Nrf2-mediated pathway. Our data suggest that 6-MSITC could exert chemopreventive role against cancer through its underlying antioxidant activity via the activation of Nrf2-mediated subsequent induction of cytoprotective genes.
Assuntos
Anticarcinógenos/farmacologia , Isotiocianatos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Transcriptoma/efeitos dos fármacos , Wasabia/química , Células Hep G2 , Humanos , Fator 2 Relacionado a NF-E2/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , SulfóxidosRESUMO
The relationship between Helicobacter pylori infection and gastric cancer associated with stomach lesions has been reported. Improvement of the adverse effects induced by H. pylori is required for human health. It has been reported that wasabi (Wasabiajaponica Matsum) leaves have various effects on bacteria and mammals. In this study, the effect was examined of wasabi leaf extract and allyl isothiocyanate (AIT), which is a main functional component of wasabi, on stomach lesions in Mongolian gerbils infected with H. pylori. After the gerbils infected with H. pylori were orally administrated with wasabi leaf extract and AIT for two weeks, colony forming units (CFU) of H. pylori, the degree of gastric mucosal erosion, and petechial hemorrhage in the stomachs of the gerbils were evaluated. Wasabi leaf extract and AIT exhibited a decreasing tendency of CFU in the stomachs. The degree of gastric mucosal erosion and petechial hemorrhage were significantly decreased by the intake of wasabi leaf extract and AIT. Wasabi leaf extract and AIT did not affect body weight, dietary intake, water intake, and the pH of the stomach. From these results, wasabi leaves and AIT may provide a natural remedy for stomach lesions induced by H. pylori.
Assuntos
Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Isotiocianatos/administração & dosagem , Extratos Vegetais/administração & dosagem , Wasabia/química , Animais , Gerbillinae , Infecções por Helicobacter/microbiologia , Helicobacter pylori/fisiologia , Humanos , Masculino , Folhas de Planta/química , Úlcera Gástrica/tratamento farmacológico , Úlcera Gástrica/microbiologiaRESUMO
Five new lignan glycosides, wasabisides A-E (1-5), and four known phenolic compounds (6-9), were isolated from the roots of Wasabia japonica. The chemical structures of the new compounds (1-5) were determined through spectroscopic analysis and chemical methods. All isolated compounds (1-9) were evaluated for their potential neuroprotective effects through induction of nerve growth factor in C6 glioma cells, for their effects on nitric oxide levels in lipopolysaccharide-stimulated murine microglia BV2 cells, and for their cytotoxicity against four human tumor cell lines (A549, SK-OV-3, SK-MEL-2, and BT549).
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Glicosídeos/isolamento & purificação , Lignanas/isolamento & purificação , Raízes de Plantas/química , Wasabia/química , Animais , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Glicosídeos/química , Glicosídeos/farmacologia , Humanos , Lignanas/química , Lignanas/farmacologia , Lipopolissacarídeos/farmacologia , Microglia/efeitos dos fármacos , Estrutura Molecular , Óxido Nítrico/biossíntese , República da CoreiaRESUMO
Bone homeostasis is maintained through a balance between osteoblastic bone formation and osteoclastic bone resorption. Bone loss with aging is induced by decreasing in osteoblastic bone formation and increasing in osteoclastic bone resorption, thereby leading to osteoporosis. Osteoporosis with its accompanying decrease in bone mass is widely recognized as a major public heath problem. Pharmacologic and nutritional factors may play a role in the prevention and treatment of bone loss with aging. p-Hydroxycinnamic acid (HCA), which stimulates bone mineralization in mouse bone tissues in vitro, has been found to be present in the leafstalk of wasabi (Wasabi japonica MATSUM) among various food and plants. Other phenolic acids including cinnamic acid, ferulic acid, caffeic acid and 3,4-dimethoxycinnamic acid did not have osteogenic effects. HCA was demonstrated to stimulate osteoblastic bone formation and suppresses osteoclastic bone resorption in vitro by antagonizing activation of the nuclear factor kappa B. Oral administration of HCA was found to exhibit restorative effects on bone loss induced by ovariectomy and diabetic states, supporting a role in the treatment of osteoporosis. Moreover, HCA was demonstrated to prevent the suppressed osteoblastic mineralization and the enhanced osteoclastogenesis in mouse bone marrow cells cocultured with bone metastatic MDA-MB-231 human breast cancer cells in vitro. The botanical molecule HCA, as a new osteogenic agent, is suggested to play a role in the treatment of cancer bone metastases. This review will discuss an advanced recent finding that HCA may be a useful agent to treat bone metabolic disorder.