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Chemical structure of 6-MSITC. 6-MSITC contains methyl sulfoxide group and ITC group linked by alkyl chain.
Source publication
6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a major bioactive compound in wasabi (Wasabia japonica), which is a typical Japanese pungent spice. Recently, in vivo and in vitro studies demonstrated that 6-MSITC has several biological properties, including anti-inflammatory, antimicrobial, antiplatelet, and anticancer effects. We previously re...
Contexts in source publication
Context 1
... differs from other Brassicaceae species in that it contains higher concentration of ITCs, especially long-chain ITCs. The bioactive components of wasabi have been identified as a series of ITC analogues, of which 6-(methylsulfinyl)hexyl isothiocyanate (6-MSITC or 6-MITC) (Figure 1) is a major active compound in wasabi. Several lines of evidence demonstrated the pharmacological potencies of 6-MSITC, such as anti-inflammatory [11][12][13], antimicrobial [14], antiplatelet [15], and anticancer [16][17][18] effects. ...Context 2
... contains much higher levels of all methylsulfinylalkyl ITCs than horseradish [19]. One of the methylsulfinylalkyl ITCs is 6- MSITC, and the chemical structure of 6-MSITC contains methyl sulfoxide group and ITC group linked by alkyl chain (Figure 1). Although the ITCs are generated throughout the entire plant of wasabi, the root is the predominant site of storage. ...Similar publications
Isothiocyanates (ITCs) contained in purees extracted from wasabi (Wasabia japonica (Miq) Matsum) can be used to manufacture a range of interesting spicy foods. In New Zealand, local manufacturers are showing interest in producing various forms of processed wasabi based sauces. However, isothiocyanates have been shown to degrade quickly in some situ...
Citations
... At the same time, 6-MSITC restored the expression of LPSreduced chemokines CCL11 and CCL25, and IL-3, and its receptors IL1ra-12, IL8-ra, TNFRSF23, and TNFRSF4. These data suggest that 6-(methylsulfinyl)hexyl isothiocyanate showed anti-inflammatory activity by acting through multiple mechanisms [84,85]. ...
Sulfur has been used as a medicinal agent by the Greeks since ancient times. Approximately 350 sulfur-containing compounds have been approved as drugs by the Food and Drug Administration (FDA). Generally, sulfur exists as organosulfur in plants and as glucosinolates and isothiocyanates. Metabolic disorders and infectious diseases are becoming worldwide public health problems, directly affecting individuals' quality of life and constitute a robust economic challenge to healthcare systems. Glucosinolates have been reported in several vegetables, bacteria, plants, fungi, and animals. In addition to organosulfur, glucosinolates, and their hydrolyzed products, isothiocyanates have immense therapeutic value. Several studies suggest glucosinolates have a potential role in treating metabolic disorders, including cancer, diabetes, and inflammation. Also, some of the glucosinolates had shown broad-spectrum antimicrobial activity against gram-positive and gram-negative bacteria and antifungal activity against fungal strains. This review discusses recently identified naturally occurring sulfur-containing compounds, including glucosinolates and organosulfur, and their therapeutic potential for treating metabolic disorders and infectious diseases.
... Wasabi (Eutrema japonicum), particularly due to its active ingredient 6-methylsulfinyl hexyl isothiocyanate (6-MSITC), represents a promising example of a natural compound with a wide range of biological activities. It possesses strong anti-inflammatory, antiatherosclerotic, and antioxidant properties, which can support cardiovascular function and are neuroprotective [4][5][6][7][8][9][10][11][12]. Also, it has a minimal toxicity risk compared with synthetic substances, making it an attractive candidate for the prevention and treatment of lifestylerelated diseases. ...
... Structural elements of 6-MSITC, such as the methylsulfinyl group (CH 3 -S(=O)-) and the length of the alkyl chain, are essential for cell membrane permeability, as they influence the substance's ability to penetrate target cells [12]. ...
... The isothiocyanate 6-MSITC belongs to a class of biologically active compounds that share similar pharmacokinetic characteristics [12]. The limited availability of literature focusing on the pharmacokinetics of 6-MSITC necessitates an analogy-based exploration of its pharmacological activity. ...
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.
... 6-(Methylsulfnyl) hexyl isothiocyanate has been found to decrease COX-2 and cytokine levels as well as inhibited inducible nitric oxide synthase (iNOS), all of which are regarded as key mediators of infammatory responses. Tese fndings emphasised the potential of phytochemicals derived of glucosinolates in the management of infammatory reactions in mast cells and allergic diseases [21]. ...
Allergic diseases (ADs) are a major concern when it comes to public well-being. Moringa oleifera Lam is a tropical plant that is used in traditional medicine due to the presence of isothiocyanate. The present study investigated the antiallergic properties of 4-(α-L-rhamnopyranosyloxy)-benzyl isothiocyanate or moringin isolated from Moringa oleifera seeds in the form of alpha-cyclodextrin-moringin (α-CD/MG) complex on rat basophilic leukaemia (RBL-2H3) cell line at both the early and late stages of an allergic reaction. The α-CD/MG complex was initially elucidated using nuclear magnetic resonance (NMR) followed by the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt proliferation assay to evaluate the cytotoxicity and cell viability with respect to ketotifen fumarate (KF) and α-CD/MG. The release of beta-hexosaminidase (β-hexosaminidase) and histamine was used to determine the level of inhibition in the early stage while the suppression of the release of prostaglandin (PGD2), tumour necrosis factor-alpha (TNF-α), and interleukin (IL-4) was considered in the late stage. Higher concentrations of α-CD/MG (5 μM, p<0.001) in mast cell degranulation significantly inhibited the expression of β-hexosaminidase, histamine, TNF-α, PGD2, and IL-4 in both the early and late stages. Thus, α-CD/MG can potentially be developed as an antiallergic drug as it has the ability to inhibit allergic responses in the late and early stages.
... Bioactive isothiocyanate compounds have been found in wasabi, and 6-methylsulfinylhexyl isothiocyanate (6-MSITC) is the major component [1]. Nonclinical studies have reported that 6-MSITC shows antioxidant [2], anti-inflammatory [3], antibacterial, anticancer, antiplatelet aggregation [4][5][6][7][8], antidiabetic [9], and antiallergic activity [10]. Furthermore, intake of 6-MSITC improved cognitive impairment in mouse models of Alzheimer's disease [11]. ...
... Activated Nrf2 translocates into the nucleus, binds to the antioxidant response element, and enhances the transcription of antioxidant proteins and phase II metabolic enzymes, thereby exerting antioxidant and detoxifying metabolic enzyme-inducing effects. 6-MSITC suppresses lipopolysaccharide-stimulated cyclooxygenase-2 expression, which is closely related to inflammation [3]. Furthermore, 6-MSITC has various biochemical effects, including an anticancer effect exerted by acting on the mitochondria of cancer cells and inducing apoptosis [6]. ...
Background:
This study aimed to conduct a preliminary evaluation of the effects of 6-methylsulfinylhexyl isothiocyanate (6-MSITC) contained in wasabi rhizomes on fatigue and sleep and to examine its safety through overdose study.
Methods:
A total of 20 healthy volunteers who were experiencing daily fatigue were given powder containing 6-MSITC (4.8 mg/day of 6-MSITC) extracted from wasabi for 4 weeks. Then, fatigue, sleep, autonomic nervous functioning, stress, and immunity were evaluated. In addition, an overdose safety study of the extract powder (up to 16 mg/day of 6-MSITC for 4 weeks) was performed with 30 healthy volunteers in a double-blind, placebo-controlled method.
Results:
The powder containing 6-MSITC did not improve fatigue after a mental task, but fatigue before the mental task, sleep, and mood were improved significantly after 4 weeks intake. No changes were observed in the autonomic nerve function, stress, or immune markers. In the overdose safety study, no changes in the parameters or side effects were observed, and the results showed that high doses of the extract powder containing 6-MSITC is safe.
Conclusion:
This study confirmed the possibility that this powder extracted from wasabi that contains 6-MSITC might improve fatigue and sleep. However, because the effectiveness evaluation in this study was a single-arm, open-label study and there was no placebo control group, these points must be considered when interpreting the results. Safety was confirmed in an overdose study of more than three times the amount compared to that in the efficacy evaluation study. In the future, further research should be conducted on its effectiveness for treating fatigue and sleep problems.
Trial registration:
UMIN clinical trial registration system, UMIN000049913. Registered 27 December 2022 Retrospectively registered, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000056818.
... This study illustrated that the highest content of long-chain ITCs (6-MHITC and 6-MSITC) are mainly found in Eutrema species in Japan. Wasabi also contains higher concentrations of ITCs, especially long-chain ITCs (Uto et al. 2012). It is likely that the division of precursors to the aliphatic branch of the GLS pathway was generated when or shortly thereafter the ancestral populations of Eutrema species migrated to Japan. ...
Wasabi (Japanese horseradish, Eutrema japonicum) is the only cultivated species in the genus Eutrema with functional components that provide a strong pungent flavor. To evaluate genetic resources for wasabi breeding, we surveyed variations in the two most abundant isothiocyanate (ITC) components in wasabi, allyl isothiocyanate (AITC) and 6-methylsulfinyl (hexyl) isothiocyanate (6-MSITC, hexaraphane). We also examined the phylogenetic relationships among 36 accessions of wild and cultivated wasabi in Japan using chloroplast DNA analysis. Our results showed that (i) the 6-MSITC content in currently cultivated wasabi accessions was significantly higher than in escaped cultivars, whereas the AITC content was not significantly different. (ii) Additionally, the 6-MSITC content in cultivated wasabi was significantly lower in the spring than during other seasons. This result suggested that the 6-MSITC content responds to environmental conditions. (iii) The phylogenetic position and the 6-MSITC content of accessions from Rebun, Hokkaido Prefecture had different profiles compared with those from southern Honshu, Japan, indicating heterogeneity of the Rebun populations from other Japanese wasabi accessions. (iv) The total content of AITC and 6-MSITC in cultivated wasabi was significantly higher than that of wild wasabi. In conclusion, old cultivars or landraces of wasabi, “zairai”, are the most suitable candidates for immediate use as genetic resources.
... Theacrine is an alkaloid found in wild tea plants [8], and it has been demonstrated in pre-clinical and clinical trials to reduce inflammation [9,10], act as an antioxidant [11], Physiologia 2023, 3 234 and favorably alter blood lipid profiles [5,6]. Preclinical data also suggests that long-chain 6, 7, and 8-methylsulfinylhexyl/heptyl/octyl isothiocyanates (ITCs) in wasabi (Wasabia japonica) elicit anti-inflammatory and cytoprotective effects [12][13][14]. Additionally, ITCs can affect histone deacetylase (HDAC) and DNA methyltransferase (DNMT) activities [15], thus implicating their potential role in gene regulation. ...
Herein, we determined if a multi-ingredient supplement (NAD3; 312 mg of combined Wasabia japonica extract, theacrine, and copper (I)niacin chelate) versus a placebo (CTL) affected peripheral blood mononuclear (PMBC) transcriptomic, DNA methylation, and sirtuin activity profiles in middle-aged adults after 12 weeks of supplementation. Several mRNAs demonstrated interactions (n = 148 at ±1.5-fold change, p < 0.01), and more stringent filtering indicated that 25 mRNAs were upregulated and 29 were downregulated in the NAD3 versus CTL group. Bioinformatics on these 64 mRNAs suggested that DNA conformational alterations may have been promoted with NAD3 supplementation, and this was corroborated with more CpG sites being hypermethylated (p < 0.001) in the CTL versus the NAD3 group when examining pre- to post-intervention changes (369 versus 35). PBMC SIRT activity decreased in CTL participants (p < 0.001), but not in NAD3 participants (p = 0.289), and values at 12 weeks trended higher in NAD3 participants (p = 0.057). Interestingly, the pre- to post- changes in SIRT activity values significantly correlated with changes in PBMC NAD+: NADH values obtained from a previous investigation in these participants (r = 0.534, p = 0.015). In conclusion, the current mRNA and DNA methylation data indirectly suggest that NAD3 supplementation may affect PBMC DNA conformation, while other direct assays suggest that NAD3 supplementation maintains SIRT activity through the potential maintenance of NAD+: NADH levels. However, these results are preliminary due to limited n-sizes and the study being performed in middle-aged adults.
... Because our research facility is located in Nagano Prefecture, Japan, which is well-known as an area that produces Wasabi, we focused on 6-MITC, a major chemical compound of Wasabi [8]. 6-MITC has been reported to exhibit various bioactivities such as anti-inflammatory [9], antioxidative [10], and glucose tolerance improvement [11,12], and has been suggested to show anti-tumor effects against melanoma [13], pancreas [14], breast [15], colorectal [16,17], and hematological tumors [18]. However, there is no report on its cytotoxic effects against EMC. ...
Purpose
Wasabi is a traditional plant seasoning with an anti-septic function. Recent studies revealed several functions of Wasabi, such as anti-inflammation; however, the anti-tumor effect against endometrial carcinoma (EMC) cells has not been examined. In the present study, we investigated the anti-tumor effect of 6-(methylsulfinyl) hexyl isothiocyanate (6-MITC), a major chemical compound of Wasabi, against various EMC cell lines in vitro and in vivo.
Methods
The effect of 6-MITC on cell viability was measured by the WST-1 assay in EMC and HUVEC cells. The impact of 6-MITC oral administration in nude mice was measured to assess the growth of the EMC xenograft and natural killer (NK) cell activity in the spleen.
Results
The addition of 6-MITC suppressed the proliferation of EMC cells (Ishikawa, HEC265, HEC108, KLE, and HEC1B) dose-dependently, but not HUVEC cells. 6-MITC (5 µM) enhanced the cisplatin sensitivity of EMC cells. 6-MITC induced apoptosis in a dose-dependent fashion in EMC cells other than HEC1B cells and was associated with increased expression of cleaved-caspase3 and decreased expression of BCL2. Oral administration of 6-MITC (2 and 4 µmol/kg) to Ishikawa and HEC1B xenografting mice resulted in a reduced tumor volume compared with the control (P < 0.05, 4 µmol/kg). Immunohistochemical staining of resected tumors revealed increased expression of Ki-67 and reduced cleaved-caspase3. Furthermore, 6-MITC treatment enhanced NK cell activity, especially when administered before tumor xenografting.
Conclusion
These results indicate that 6-MITC has a marked anti-tumor effect against EMC cells and a novel effect to enhance NK cell activity. These effects suggest the therapeutic potential of 6-MITC.
... In the rhizome of the wasabi plant there is a sulfinyl compound, called 6-methylsulfinylhexyl isothiocyanate . In laboratory animals, 6-MSITC has been demonstrated to have anti-inflammatory [7,8], antiallergenic [9], and antioxidant [10][11][12] effects, as well as to inhibit neuroinflammation [13]. It has also been shown to improve cognitive function [12,14]. ...
... Currently, it is not fully understood how 6-MSITC improves ME/CFS. In vivo and in vitro studies have demonstrated that 6-MSITC has numerous biological effects, such as anti-inflammatory [7,8], antiplatelet [35], antiallergenic [9], antioxidant [10][11][12], and anti-cancer [36,37]. Moreover, peripheral administration of 6-MSITC also has central effects. ...
Background
Wasabi ( Eutrema japonicum ) is a common pungent spice used in Japan. 6-Methylsulfinylhexyl isothiocyanate (6-MSITC) found in the rhizome of wasabi has been shown to have anti-inflammatory and antioxidant effects, as well as improve neuroinflammation and memory. Therefore, we hypothesized that these effects would be beneficial for treating myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The present study was conducted to investigate the effectiveness of wasabi extract containing 6-MSITC on ME/CFS in an open-label trial.
Methods
Fifteen patients (3 males, 12 females, 20–58 years old) were orally administered wasabi extract (9.6 mg of 6-MSITC/day) for 12 weeks. The following parameters and test results were compared pre- and post-treatment: performance status (PS), self-rating questionnaires, pressure pain threshold (PPT) on the occiput, Trail Making test-A (TMT-A), and hemodynamic patterns determined by an active standing test.
Results
After treatment with 6-MSITC, PS improved significantly ( p = 0.001). Although the scores on the 11-item Chalder Fatigue scale (CFS-11) and numerical rating scale (NRS) of fatigue did not show significant changes, subjective symptoms improved significantly, including headache frequency (4.1 to 3.0 times/week, p = 0.001) and myalgia (4.1 to 2.4 times/week, p = 0.019), NRS brain fog scores (5.7 to 4.5, p = 0.011), difficulty finding appropriate words (4.8 to 3.7, p = 0.015), photophobia (4.8 to 3.5, p = 0.008), and the Profile of Mood Status vigor score (46.9 to 50.0, p = 0.045). The PPT of the right occiput (17.3 to 21.3 kPa, p = 0.01) and TMT-A scores (53.0 to 38.1 s, p = 0.007) also changed, suggesting reduced pain sensitivity, and improved cognitive function, respectively. Orthostatic patterns determined by a standing test did not show remarkable changes. There were no serious adverse reactions.
Conclusion
This study suggests that 6-MSITC improves PS as well as subjective symptoms such as pain and cognitive dysfunction, and psychological vitality of patients with ME/CFS. It also improved cognitive performance and increased pain thresholds in these patients. 6-MSITC may be a promising therapeutic option especially for improving cognitive dysfunction associated with ME/CFS.
... The isothiocyanates, which are a major product of the myrosinase-glucosinolate system, have been a focus of research efforts, especially in terms of understanding the health benefits of wasabi and associated biological activities [6,7]. Isothiocyanates are the main constituent of wasabi, particularly allyl isothiocyanate (AITC, Figure 1-(8)) (around 100-150 mg/100 g), along with lesser amounts of 6-(methylthio)hexyl isothiocyanate (6-MTITC, Figure 1-(9)), and 6-(methylsulfinyl)hexyl isothiocyanate (6-MSITC, Figure 1- (10)). The latter being derived from sinigrin ( Figure 1- (11)) and glucohesperin ( Figure 1- (12)), respectively [8,9]. ...
... The latter being derived from sinigrin ( Figure 1- (11)) and glucohesperin ( Figure 1- (12)), respectively [8,9]. 6-MSITC has been shown to suppress the activities of cyclooxygenase-2 and inducible nitric oxide synthase, and lipopolysaccharide-induced cytokine production including the inflammatory cytokines tumour necrosis factor, interferon-γ and the interleukin (IL)-1β and IL-6 [10]. Wasabi extract has previously demonstrated anti-obesogenic effects in high-fat diet-fed mice, and antiplatelet, antibacterial, antimutagenic and anticancer activity in the human carcinogenic cell lines in vitro [11]. ...
... This value was 17% higher than those in fresh Japanese or Korean wasabi leaves, stems or roots [17], though this is probably due to the reduced water content in the dry powder. Another study determined ~550-556 μg/g of 6-MSITC in wet weight of wasabi root [10]. The present study observed a concentration of 120-150 μg/g wet weight of 6-MSITC in stem and rhizome blend. ...
6-(Methylsulfinyl)hexyl isothiocyanate (6-MSITC) has several biological functions. The present study aimed to evaluate the composition of hydroponically grown Tasmanian wasabi (Eutrema japonicum (Miq.) Koidz.) for 6-MSITC in all plant tissues and investigate the influence of wasabi (rhizome and stem blend) in high-carbohydrate, high-fat (H) diet-fed rats. Male Wistar rats were fed either a corn starch (C) or H diet. After the initial 8 weeks, half of the animals on the C and H diets were given 5% (w/w) wasabi powder in their respective diets for an 8-week duration (CW and HW). The control animals received diets without supplementation throughout the 16-week experiment. Our findings demonstrated that wasabi grown under hydroponic conditions contained 6-MSITC in all parts of the plant such as the stem, leaf and flower, as well as the commonly used rhizome, albeit at lower concentrations. Rats treated with wasabi showed reductions in body weight (H, 460.0 ± 9.5; HW, 416.0 ± 3.6 g), fat mass (H, 178 ± 14; HW, 120 ± 23 g), plasma triglycerides (H, 1.7 ± 0.3; HW, 0.9 ± 0.3 mmol/L) and total cholesterol (H, 1.5 ± 0.1; HW, 1.0 ± 0.04 mmol/L), and the plasma activities of aspartate transaminase. Systolic blood pressure and the area under the curve of blood glucose concentration were decreased by wasabi treatment. Thus, wasabi may be a novel alternative treatment to assist in the management of obesity and related metabolic disorders.
... The natural product, 6-(methylsulfinyl)hexyl isothiocyanate (6-MITC), was isolated from Wasabia japonica (wasabi), a popular spice used in Japanese food worldwide. This compound has anti-inflammatory [10], anti-microbial, and anti-cancer [11,12] properties. Furthermore, 6-MITC may prevent the complications of opportunistic infection and de novo malignancy following transplant. ...
We tested the effect of 6-(Methylsulfinyl)hexyl Isothiocyanate (6-MITC) and derivatives (I7447 and I7557) on the differentiation and maturation of human myeloid dendritic cells (DCs) in vitro, and skin transplantation in vivo. Triggering of CD14+ myeloid monocyte development toward myeloid DCs with and without 6-MITC and derivatives to examine the morphology, viability, surface marker expression, and cytokine production. Stimulatory activity on allogeneic naive T cells was measured by proliferation and interferon-g production. The skin allograft survival area model was used to translate the 6-MITC and derivatives’ antirejection effect. All of the compounds had no significant effects on DC viability and reduced the formation of dendrites at concentrations higher than 10 mM. At this concentration, 6-MITC and I7557, but not I7447, inhibited the expression of CD1a and CD83. Both 6-MITC and I7557 exhibited T-cells and interferon-g augmentation at lower concentrations and suppression at higher concentration. The 6-MITC and I7557 prolonged skin graft survival. Both the 6-MITC and I7557 treatment resulted in the accumulation of regulatory T cells in recipient rat spleens. No toxicity was evident in 6-MITC and I7557 treatment. The 6-MITC and I7557 induced human DC differentiation toward a tolerogenic phenotype and prolonged rat skin allograft survival. These compounds may be effective as immunosuppressants against transplant rejection.