High-quality Chromosomal-Level Genome Assembly of the Wasabi (Eutrema japonicum) 'Magic'.

Wasabi (Eutrema japonicum) is a plant belonging to the Brassicaceae family that produces its distinctive pungent taste through allyl isothiocyanate. This study achieved a high-quality chromosome-level genome assembly of the E. japonicum 'Magic' bred in Korea for its rapid growth cycle. The assembly was accomplished using a combination of Illumina, PacBio HIFI, Nanopore MinION, and Pore-C scaffolding technologies. The final assembled genome size is 794.6 Mb, anchored to 14 chromosomes. The genome comprises 67.56% repetitive elements and has a BUSCO score of 99.3%, indicating a high level of completeness. Compared to previously published assemblies with a different cultivar, the total length increased by approximately 48.08 Mb, while the number of Ns decreased from 89,000 to 49,000, and the assembly gaps (500 N padding) reduced from 178 to 98, resulting in a higher quality assembly. This genome will be a valuable resource for genetic and biological research on E. japonicum, aiding in its breeding and genetic improvement.

Immunomodulatory Effects and Regulatory Mechanisms of (R)-6-HITC, an Isothiocyanate from Wasabi (Eutrema japonicum), in an Ex Vivo Mouse Model of LPS-Induced Inflammation.

The present study aimed to investigate the effects of (R)-(-)-1-isothiocyanato-6-(methylsulfinyl)-hexane [(R)-6-HITC], the major isothiocyanate present in wasabi, in an ex vivo model of inflammation using lipopolysaccharide-stimulated murine peritoneal macrophages. (R)-6-HITC improved the immune response and mitigated oxidative stress, which involved suppression of reactive oxygen species, nitric oxide, and pro-inflammatory cytokines (IL-1ß, IL-6, IL-17, IL-18, and TNF-α) production and downregulation of pro-inflammatory enzymes such as inducible nitric oxide synthase, COX-2, and mPGES-1. In addition, (R)-6-HITC was able to activate the Nrf2/HO-1 axis while simultaneously inhibiting key signaling pathways, including JAK2/STAT3, mitogen-activated protein kinases, and canonical and noncanonical inflammasome pathways, orchestrating its potent immunomodulatory effects. Collectively, these findings demonstrate the potential of (R)-6-HITC as a promising nutraceutical for the management of immuno-inflammatory diseases and justify the need for further in vivo validation studies.

Methylsulfinyl Hexyl Isothiocyanate (6-MSITC) from Wasabi Is a Promising Candidate for the Treatment of Cancer, Alzheimer's Disease, and Obesity.

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.

Chemical composition of extracts from leaves, stems and roots of wasabi (Eutrema japonicum) and their anti-cancer, anti-inflammatory and anti-microbial activities.

The purpose of our study was to evaluate the composition of the extracts obtained from the roots and leaves of Eutrema japonicum cultivated in Poland. For this purpose, LC-DAD-IT-MS and LC-Q-TOF-MS analyses were used. The results revealed the presence of forty-two constituents comprising glycosinolates, phenylpropanoid glycosides, flavone glycosides, hydroxycinnamic acids, and other compounds. Then, the resultant extracts were subjected to an assessment of the potential cytotoxic effect on human colon adenocarcinoma cells, the effect on the growth of probiotic and intestinal pathogenic strains, as well as their anti-inflammatory activity. It was demonstrated that 60% ethanol extract from the biennial roots (WR2) had the strongest anti-inflammatory, antibacterial, and cytotoxic activities compared to the other samples. Our results suggest that extracts from E. japonicum may be considered as a promising compound for the production of health-promoting supplements.

Flavonoid and Phenolic Acids Content and In Vitro Study of the Potential Anti-Aging Properties of Eutrema japonicum (Miq.) Koidz Cultivated in Wasabi Farm Poland.

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.

Production of flavonol and flavone 6-C-glucosides by bioconversion in Escherichia coli expressing a C-glucosyltransferase from wasabi (Eutrema japonicum).

OBJECTIVES: To produce flavonol and flavone 6-C-glucosides by bioconversion using recombinant Escherichia coli expressing a C-glucosyltransferase from wasabi (WjGT1). RESULTS: Escherichia coli expressing WjGT1 (Ec-WjGT1) converted flavones (apigenin and luteolin) and flavonols (quercetin and kaempferol) into their 6-C-glucosides in M9 minimal media supplemented with glucose, and released these products into the culture media. Ec-WjGT1 system also converts a flavanone (naringenin) into its C-glucoside at a conversion rate of 60% in 6 h. For scale-up production, apigenin, kaempferol, and quercetin were sequentially fed into the Ec-WjGT1 system at concentrations of 20-50 µM every 15-60 min, and the system was then able to produce isovitexin, kaempferol 6-C-glucoside, and quercetin 6-C-glucoside at an 89-99% conversion rate. CONCLUSIONS: The Ec-WjGT1 system quickly and easily produces flavone and flavonol 6-C-glucosides at high conversion rates when using sequential administration to avoid precipitation of substrates.

6-(methylsulfinyl)hexyl isothiocyanate (6-MITC) from Wasabia japonica alleviates inflammatory bowel disease (IBD) by potential inhibition of glycogen synthase kinase 3 beta (GSK-3ß).

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.

The rodent model of impaired gastric motility induced by allyl isothiocyanate, a pungent ingredient of wasabi, to evaluate therapeutic agents for functional dyspepsia.

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.

Anti-Diabetic Obesity Effects of Wasabia Japonica Matsum Leaf Extract on 45% Kcal High-Fat Diet-Fed Mice.

The present study examined the effects of Wasabi leaf (WL) on 45% Kcal high-fat diet (HFD)-fed mild diabetic obese mice. In particular, the hepatoprotective (i.e., liver weight, histopathology of liver, serum aspartate aminotransferase, alanine aminotransferase, and gamma-glutamyltransferase) effects of 12 weeks of continuous oral administration of 250 mg/kg metformin, and 200, 100, or 50 mg/kg WL were investigated. In addition, the hypolipidemic (i.e., serum triglyceride, total cholesterol, high-density lipoprotein-cholesterol, and low-density lipoprotein levels), hypoglycemic (i.e., glycated hemoglobin, blood glucose and insulin levels, pancreatic weight, and immunohistochemical-histopathological analysis of the pancreas), and anti-obesity effects (i.e., body weight, mean food consumption, total and abdominal body fat mass, periovarian fat weight, and histopathology of the periovarian and abdominal wall adipocytes) were monitored. The liver and general antioxidant defense systems were also assessed by lipid metabolism-related gene expression. All diabetes manifestations and related complications, including obesity and non-alcoholic fatty liver disease (NAFLD), were dose-dependently reduced after 84 days of oral treatment with metformin or each of the three dosages of WL. In particular, 50 mg/kg WL showed effective suppression effects against HFD-induced diabetes and related complications of obesity, NAFLD, and hyperlipidemia, comparable to the effects of metformin.

16S rRNA-based amplicon analysis of changes in the bacterial population in the lesions of papillomatous digital dermatitis in dairy cattle after topical treatment with allyl isothiocyanate.

Papillomatous digital dermatitis (PDD) is a foot disease causing lameness in dairy cattle. It is regarded as a polymicrobial infection, although its etiology is not fully understood. PDD is treated by the topical or systemic administration of antibiotics such as lincomycin (LCM); however, the milk of the cows cannot be marketed during the treatment and withdrawal period due to the residual antibiotics in milk. Allyl isothiocyanate (AITC), an extract of Wasabia japonica (known as wasabi or Japanese horseradish) widely employed as a food additive, can be used as an alternative antimicrobial agent that overcomes this problem. We previously showed that AITC is as effective as LCM in PDD treatment. Here, using the samples obtained in the previous clinical study, we analyzed changes in the bacterial population in the PDD-associated microbiota after AITC treatment and compared those with that following LCM treatment by 16S ribosomal RNA (rRNA)-based amplicon analysis. Both treatments induced major changes in the bacterial population, and Treponema species, which have been regarded as the major causative agents of PDD, were efficiently eliminated by both agents. However, the AITC-treated samples exhibited higher diversity compared with pretreatment samples, but this trend was not observed for LCM treatment, probably reflecting different antibacterial activities of the two agents. Importantly, this analysis detected population changes before morphological changes in PDD lesions (clinical signs of healing) became evident, indicating that 16S rRNA-based amplicon analysis represents an efficient strategy for analyzing and monitoring the treatment efficiency of PDD as well as other polymicrobial diseases.

Individual differences in the perception of orthonasal irritation induced by food.

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.

Wasabi Compound 6-(Methylsulfinyl) Hexyl Isothiocyanate Induces Cell Death with Coexisting Mitotic Arrest and Autophagy in Human Chronic Myelogenous Leukemia K562 Cells.

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.

Complete chloroplast genome sequence and phylogenetic analysis of wasabi (Eutrema japonicum) and its relatives.

In Japan, two Eutrema species, wasabi (Eutrema japonicum, the important traditional Japanese condiment) and yuriwasabi (E. tenue), have been recognized as endemic species. We sequenced complete chloroplast (cp) genomes of seven wasabi and yuriwasabi accessions from Japan to study their phylogeny and evolution, using molecular dating of species divergence. Phylogenetic analyses of the complete cp DNA of these two Japanese species and five other Eurasian Eutrema species revealed that wasabi and yuriwasabi did not form a monophyletic group. One yuriwasabi accession (Gifu) formed a clade with E. yunnanense from China, indicating that this accession should be considered as a different species from the other yuriwasabi accessions. We reveal that Japanese Eutrema species diverged from the 'E. yunnanense-yuriwasabi (Gifu)' clade approximately 1.3 million years ago (Mya), suggesting that the connection between Japan and the Eurasian continent has existed more recently than the Quaternary period. The abundance of cp sequence data in this study also allowed the detection of genetic differentiation among wasabi cultivars. The two polymorphic sites detected between 'Fujidaruma' and 'Shimane No.3' were used to develop genotyping markers. The cp genome information provided here will thus inform the evolutionary histories of Japanese Eutrema species and help in genotyping wasabi cultivars.

Takotsubo cardiomyopathy triggered by wasabi consumption: can sushi break your heart?

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.

Identification and Characterization of Apigenin 6-C-Glucosyltransferase Involved in Biosynthesis of Isosaponarin in Wasabi (Eutrema japonicum).

Wasabi (Eutrema japonicum) is a perennial plant native to Japan that is used as a spice because it contains isothiocyanates. It also contains an isosaponarin, 4'-O-glucosyl-6-C-glucosyl apigenin, in its leaves, which has received increasing attention in recent years for its bioactivity, such as its promotion of type-I collagen production. However, its biosynthetic enzymes have not been clarified. In this study, we partially purified a C-glucosyltransferase (CGT) involved in isosaponarin biosynthesis from wasabi leaves and identified the gene coding for it (WjGT1). The encoded protein was similar to UGT84 enzymes and was named UGT84A57. The recombinant enzyme of WjGT1 expressed in Escherichia coli showed C-glucosylation activity toward the 6-position of flavones such as apigenin and luteolin. The enzyme also showed significant activity toward flavonols, but trace or no activity toward flavone 4'-O-glucosides, suggesting that isosaponarin biosynthesis in wasabi plants would proceed by 6-C-glucosylation of apigenin, followed by its 4'-O-glucosylation. Interestingly, the enzyme showed no activity against sinapic acid or p-coumaric acid, which are usually the main substrates of UGT84 enzymes. The accumulation of WjGT1 transcripts was observed mainly in the leaves and flowers of wasabi, in which C-glucosylflavones were accumulated. Molecular phylogenetic analysis suggested that WjGT1 acquired C-glycosylation activity independently from other reported CGTs after the differentiation of the family Brassicaceae.

Wasabia koreana Nakai: A Preliminary Study on Nutrients and Chemical Compounds That May Impact Sensory Properties.

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.

Differential Pharmacological Activities of Oxygen Numbers on the Sulfoxide Moiety of Wasabi Compound 6-(Methylsulfinyl) Hexyl Isothiocyanate in Human Oral Cancer Cells.

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.

Subchronic toxicity evaluation of 5-hexenyl isothiocyanate, a nature identical flavoring substance from Wasabia japonica, in F344/DuCrj rats.

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 48 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 48 mg/kg BW group. Decreased triglycerides were observed in the male over 12 mg/kg BW and female 48 mg/kg BW groups. Decreased total cholesterol was observed in the male 48 mg/kg BW group. Increases in relative liver weights were observed in the male 48 mg/kg BW and female over 12 mg/kg BW groups. Increases in absolute and relative heart weights were observed in the female over 12 mg/kg BW groups. Simple hyperplasia in the urinary bladder was found in the male and female 12 mg/kg BW groups, and nodular hyperplasia was found in the female 48 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 3 mg/kg BW.

Rare Thioglycosides from the Roots of Wasabia japonica.

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).

Allyl Isothiocyanate Ameliorates Dextran Sodium Sulfate-Induced Colitis in Mouse by Enhancing Tight Junction and Mucin Expression.

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.