PMID: 

J Sci Food Agric. 2018 Jan ;98(2):792-798. Epub 2017 Aug 12. PMID: 28675475

Abstract Title: 

Fumigation of Brazil nuts with allyl isothiocyanate to inhibit the growth of Aspergillus parasiticus and aflatoxin production.

Abstract: 

BACKGROUND: Brazil produces approximately 40 000 tons of Brazil nuts annually, which is commonly contaminated with fungi and mycotoxins. Gaseous allyl isothiocyanate (AITC) was used to inhibit the growth of Aspergillus parasiticus and its production of aflatoxins (AFs) in Brazil nuts.RESULTS: Nuts were inoculated with 10spores gof A. parasiticus and placed in airtight glass jars with controlled relative humidity (RH = 95 or 85%). Samples were treated with 0, 0.5, 1.0 or 2.5µL Lof gaseous AITC and analyzed after 30 days to determine the fungal population and AFs content. Samples were also submitted to sensory evaluation. AITC at 2.5µL Lcould completely inhibit the fungal growth and AFs production in both the RH tested. AITC at 0.5 and 1µL Ldid not affect the microbial growth at RH = 95%, but 1µL Lreduced the production of AFs by∼50%. All AITC treatments reduced the fungal population and AFs to undetectable levels at RH = 85%. None of the concentrations altered sensory characteristics of Brazil nuts.CONCLUSION: Gaseous AITC could be used as an alternative to inhibit the growth of A. parasiticus during storage and transport of Brazil nuts.© 2017 Society of Chemical Industry.

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PMID: 

Mol Nutr Food Res. 2018 03 ;62(6):e1700616. Epub 2018 Mar 12. PMID: 29345776

Abstract Title: 

Allyl Isothiocyanate Ameliorates Obesity by Inhibiting Galectin-12.

Abstract: 

SCOPE: The aim of this study is to investigate the signaling pathways by which allyl isothiocyanate (AITC) reduces adipocyte differentiation and the efficacy of AITC in suppressing galectin-12 levels as a therapeutic for high fat diet (HFD)-induced obesity.METHODS AND RESULTS: AITC presents anti-adipogenic effects on 3T3-L1 cells by decreasing lipid droplet accumulation in a dose-dependent manner. AITC suppresses 3T3-L1 differentiation into adipocytes by decreasing galectin-12 expression and by downregulating key adipogenic transcription factors. AITC influences the expression of 3T3-L1 pre-adipocytes by modulating adipokine expression (leptin and resistin) and by regulating the protein kinase B (PKB/Akt)/cAMP response element-binding protein (CREB) pathway. In HFD-fed mice, oral administration of AITC reduces the body weight, accumulation of lipid droplets in the liver, and white adipocyte size.CONCLUSION: In summary, the results indicate that AITC inhibits adipocyte differentiation by suppressing galectin-12 levels in 3T3L1 cells and has antiobesity effects in HFD-fed mice.

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PMID: 

J Vet Med Sci. 2018 Jun 6 ;80(6):893-897. Epub 2018 Apr 17. PMID: 29669958

Abstract Title: 

Allyl isothiocyanate reduces liver fibrosis by regulating Kupffer cell activation in rats.

Abstract: 

Allyl isothiocyanate (AITC), a metabolite of the glucosinolate sinigrin, protects the liver of rats injured by carbon tetrachloride (CCl). This study evaluated whether AITC reduces hepatic fibrosis in rats repetitively exposed to CCl. Serum chemistry showed that AITC (doses of 5 and 50 mg) administered to rats exposed to CClsignificantly reduced the levels of alanine aminotransferase and aspartate aminotransferase activity that were elevated in CCl-intoxicated rats. The connective tissue in AITC-treated rats was significantly reduced based on Sirius staining. In addition, Kupffer cell activation was significantly reduced in the AITC and CClco-treated groups. Collectively, this study suggests that AITC mitigates hepatic fibrosis in rats repetitively exposed to CClwith concurrent regulation of Kupffer cell and monocyte activation.

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PMID: 

Oncol Lett. 2018 Jun ;15(6):8756-8760. Epub 2018 Apr 4. PMID: 29805614

Abstract Title: 

Effect of allyl isothiocyanate on the viability and apoptosis of the human cervical cancer HeLa cell line.

Abstract: 

The present study aimed to investigate the effect of allyl isothiocyanate (AITC) on the viability and apoptosis of the human cervical cancer HeLa cell line, and to explore the potential underlying mechanisms of this. HeLa cells were treated with varying concentrations of AITC for different durations. The cell viability was then measured using a Cell Counting kit-8 assay and the apoptosis rate of the cells was detected using flow cytometry. Additionally, the B cell lymphoma-2 (Bcl-2) and Bcl-2-associated X protein (Bax) mRNA expression levels were determined by reverse transcription-quantitative polymerase chain reaction, while the Bax and Bcl-2 protein expression levels in cells were detected by western blot analysis. AITC was revealed to inhibit the viability of HeLa cells. AITC was revealed to induce the apoptosis of HeLa cells, as the apoptosis rate increased gradually with an increase in the dose. As the concentration of AITC increased, the Bax mRNA expression level increased, whilst the Bcl-2 mRNA expression level decreased. Furthermore, the Bax protein expression intensity increased whilst Bcl-2 protein expression intensity decreased, thereby resulting in a decrease in the ratio of Bcl-2/Bax proteins. AITC may inhibit cell viability by inducing the apoptosis of HeLa cells and this may be accounted for by the imbalance in the Bcl-2/Bax expression ratio.

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PMID: 

Int J Mol Sci. 2018 Jul 12 ;19(7). Epub 2018 Jul 12. PMID: 30002285

Abstract Title: 

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

Abstract: 

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. 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.

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PMID: 

Am J Chin Med. 2018 Oct 4:1-19. Epub 2018 Oct 4. PMID: 30284468

Abstract Title: 

Allyl Isothiocyanate Induces Autophagy through the Up-Regulation of Beclin-1 in Human Prostate Cancer Cells.

Abstract: 

Allyl isothiocyanate (AITC), one of the most widely studied phytochemicals, inhibits the survival of human prostate cancer cells while minimally affecting normal prostate epithelial cells. Our study demonstrates the mechanism of AITC-induced cell death in prostate cancer cells. AITC induces autophagy in RV1 and PC3 cells, judging from the increased level of LC3-II protein in a dose- and time-dependent manner, but not in the normal prostate epithelial cell (PrEC). Inhibition of autophagy in AITC-treated cells decreased cell viability and enhanced apoptosis, suggesting that the autophagy played a protective role. There are several pathways activated in ATIC-treated cells. We detected the phosphorylation forms of mTOR, ERK, AMPK, JNK and p38, and ERK AMPK and JNK activation were also detected. However, inhibition of AITC-activated ERK, AMPK and JNK by pre-treatment of specific inhibitors did not alter autophagy induction. Finally, increased beclin-1 expression was detected in AITC-treated cells, and inhibition of AITC-induced beclin-1 attanuated autophagy induction, indicating that AITC-induced autophagy occurs through upregulating beclin-1. Overall, our data show for the first time that AITC induces protective autophagy in Rv1 and PC3 cells through upregulation of beclin-1. Our results could potentially contribute to a therapeutic application of AITC in prostate cancer patients.

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PMID: 

Mol Biol Rep. 2019 Feb ;46(1):241-250. Epub 2018 Nov 8. PMID: 30406889

Abstract Title: 

Allyl isothiocyanate attenuates oxidative stress and inflammation by modulating Nrf2/HO-1 and NF-κB pathways in traumatic brain injury in mice.

Abstract: 

Traumatic brain injury (TBI) is the leading cause of mortality and morbidity in young adults and children in the industrialized countries; however, there are presently no FDA approved therapies. TBI results in oxidative stress due to the overproduction of reactive oxygen species and overwhelming of the endogenous antioxidant mechanisms. Recently, it has been reported that antioxidants including phytochemicals have a protective role against oxidative damage and inflammation after TBI. To analyze the effects of a naturally occurring antioxidant molecule, allyl isothiocyanate (AITC), on the nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa B (NF-κB) signaling pathways in TBI, a cryogenic injury model was induced in mice. Here, we showed that AITC administered immediately after the injury significantly decreased infarct volume and blood-brain barrier (BBB) permeability. Protein levels of proinflammatory cytokines interleukin-1β (IL1β) andinterleukin-6 (IL6), glial fibrillary acidic protein (GFAP) and NF-κB were decreased, while Nrf2, growth-associated protein 43 (GAP43) and neural cell adhesion molecule levels were increased with AITC when compared with vehicle control. Our results demonstrated that the antioxidant molecule AITC,when applied immediately after TBI, provided beneficial effects on inflammatory processes while improving infarct volume and BBB permeability. Increased levels of plasticity markers, as well as an antioxidant gene regulator, Nrf2, by AITC, suggest that future studies are warranted to assess the protective activities of dietary or medicinal AITC in clinical studies.

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PMID: 

J Sci Food Agric. 2019 Apr ;99(6):3106-3116. Epub 2019 Jan 25. PMID: 30516283

Abstract Title: 

Preparation of allyl isothiocyanate nanoparticles, their anti-inflammatory activity towards RAW 264.7 macrophage cells and anti-proliferative effect on HT1376 bladder cancer cells.

Abstract: 

BACKGROUND: Allyl isothiocyanate (AITC), a volatile and water-insoluble compound present in several cruciferous vegetables, has been shown to possess several biological qualities such as anti-bacterial, anti-fungal, and anti-cancer activity. In this study, water-soluble allyl isothiocyanate nanoparticles (AITC-NPs) were prepared by oil dispersed in water (O/W) microemulsion and complex coacervation techniques and evaluated for their anti-inflammatory activity towards macrophage cell RAW 264.7 and anti-cancer effect on human bladder cancer cell HT1376.RESULTS: The AITC-NPs with a particle size of 9.4 nm were stable during heating up to 110 °C or three freeze-thawing cycles. No significant cytotoxicity was shown on Caco-2 and intestine epithelial IEC-6 cells at AITC-NP doses ranging from 0.25 to 2 g L(8.75-70 mg LAITC). However, at 2 g Ldosage, AITC-NPs could inhibit the growth of human bladder cancer cells HT1376 by 90%, while their low dosage at 0.25 g Lcould inhibit migration ability by 83.7, 71.3, 58.4 and 31.4% after 4, 8, 12, and 24 h of incubation, respectively. Compared to AITC and NPs, AITC-NPs showed a better inhibition on lipopolysaccharide (LPS)-induced TNF-α, IL-6, NO and iNOS production in RAW 264.7 macrophage cells.CONCLUSION: The results demonstrate the potential of AITC-NPs as therapeutic agents for the treatment of bladder cancer and the enhancement of immune function.© 2018 Society of Chemical Industry.

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PMID: 

Pathol Oncol Res. 2019 Mar 20. Epub 2019 Mar 20. PMID: 30895454

Abstract Title: 

Anti-Estrogenic and Anti-Cell Proliferative Effect of Allyl Isothiocyanate in Chemoprevention of Chemically Induced Mammary Carcinogenesis in Rats.

Abstract: 

The anti-estrogenic and anti-cell proliferative effect of allyl isothiocyanate (AITC) was carried out by analyzing the status of sex hormones and its receptors and cell proliferative markers in chemically induced mammary carcinogenesis in rats. Mammary tumor was induced by a single dose of DMBA (25 mg/rat) and MNU (50 mg/kg bw) injected subcutaneously near mammary gland. RT-PCR, western blotting and immunohistochemical analysis of mammary tissues show an upregulation of ER-α, PR, aromatase, PCNA, cyclin D1 and AgNORs staining and down regulation of p53 expression as well as plasma estradiol, prolactin and testosterone levels increased in DMBA and MNU-induced tumor bearing rats. Oral administration of AITC at a dose of 20 mg/kg bw restored the levels of sex hormones and its receptors, aromatase, cell proliferative markers and AgNORs staining near to normal levels. Molecular docking studies also supported these findings. The results suggest that anti-estrogenic and anti-proliferative effect of AITC prevent the development of DMBA and MNU-induced mammary carcinogenesis in rat.

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PMID: 

J Biochem Mol Toxicol. 2019 Jul ;33(7):e22328. Epub 2019 Mar 30. PMID: 30927557

Abstract Title: 

Effects of allyl isothiocyanate on insulin resistance, oxidative stress status, and transcription factors in high-fat diet/streptozotocin-induced type 2 diabetes mellitus in rats.

Abstract: 

Allyl isothiocyanate (AITC), a dietary phytochemical found in some cruciferous vegetables, is commonly used as an antimicrobial, anticancer, and antioxidant agent. In the present study, we investigated the effects of AITC on insulin resistance and transcription factors in a diabetic rat model. A total of 42 Wistar rats were divided into six groups and orally treated for 12 weeks as follows: (i) control; (ii)AITC (100 mg/kg body weight [BW]); (iii) high fat diet (HFD); (iv) HFD + AITC (100 mg/kg BW); (v) HFD + streptozotocin (STZ, 40 mg/kg BW); and (vi) HFD + STZ + AITC. Administration of AITC reduced blood glucose, total cholesterol, triglycerides, and creatinine levels, but increased (P 

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