title: Allyl methyl disulfide inhibits IL-8 and IP-10 secretion in intestinal epithelial cells via the NF-кB signaling pathway.
abstract: Garlic and its active constituents have shown versatile medicinal activities in the prevention and treatment of various disorders. Allyl methyl disulfide (AMDS) was identified as one of the major bioactive components in an effective inhalation fork remedy using fresh garlic paste in our previous study. In this work, we investigated the immunological properties of AMDS to elucidate the underlying mechanisms of the fork inhalation treatment using fresh garlic. The inhibition effect of AMDS on TNF-α-induced IL-8 and IP-10 production in intestinal epithelial cell lines HT-29 and Caco-2 was first evaluated. Pretreatment of the cells with AMDS attenuated IL-8 and IP-10 secretion induced by TNF-α in a dose-dependent manner in the non-cytotoxic concentration range of 20 to 150 μM. Mechanistic studies revealed that AMDS suppressed the accumulation of IL-8 mRNA and inhibited IкBα degradation and NF-кB p65 translocation into the nucleus at both the transcriptional and translational levels, suggesting that the attenuation effort of AMDS on cytokine IL-8 secretion might at least be partially related to the NF-κB signaling pathway. These results suggest that AMDS may be a promising phytochemical agent in the treatment of immunological disorders, such as ulcerative colitis, Crohn's disease, intestinal inflammatory diseases and others. In addition, the mechanistic study data indicated that immune modulation could be one of the therapeutic mechanisms of the effective fork treatment containing AMDS as one of the major components.
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China; School of Chemistry and Pharmaceutical Engineering, Qilu University of Technology, Daxue Road, Western University Science Park, Jinan, Shandong 250353, PR China.
authors.forename: Yongchun
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors.forename: Kaiming
authors.initials: K
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors.forename: Guangpu
authors.initials: G
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Luan
authors.affiliation: School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, Jinan, Shandong 250012, PR China; Shandong Provincial Key Laboratory of Mucosal and Transdermal Drug Delivery Technologies, Shandong Academy of Pharmaceutical Sciences, 989 Xinluo Street, Jinan, Shandong 250101, PR China. Electronic address: uszxzhao@gmail.com.
authors.forename: Zhongxi
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Shandong Provincial Key Laboratory of Mucosal and Transdermal Drug Delivery Technologies, Shandong Academy of Pharmaceutical Sciences, 989 Xinluo Street, Jinan, Shandong 250101, PR China.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Shandong Provincial Key Laboratory of Mucosal and Transdermal Drug Delivery Technologies, Shandong Academy of Pharmaceutical Sciences, 989 Xinluo Street, Jinan, Shandong 250101, PR China.
authors.forename: Xinke
authors.initials: X
authors.lastname: Cao
authors.affiliation: Shandong Provincial Key Laboratory of Mucosal and Transdermal Drug Delivery Technologies, Shandong Academy of Pharmaceutical Sciences, 989 Xinluo Street, Jinan, Shandong 250101, PR China.
authors.forename: Daizhou
authors.initials: D
authors.lastname: Zhang
mesh_terms: D018938:Caco-2 Cells; D016207:Cytokines / Q000378:metabolism; D004220:Disulfides / Q000494:pharmacology*; D005737:Garlic / Q000276:immunology; D019073:HT29 Cells; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016207:Cytokines; D004220:Disulfides; D007166:Immunosuppressive Agents; D016328:NF-kappa B; C054528:allyl methyl disulfide
keywords: Allyl methyl disulfide; IL-8; IP-10; NF-кB; TNF-α