title: Diallyl trisulfide exerts anti-inflammatory effects in lipopolysaccharide-stimulated RAW 264.7 macrophages by suppressing the Toll-like receptor 4/nuclear factor-κB pathway.
abstract: Diallyl trisulfide (DATS; di‑2‑propen‑1‑yl trisulfide) is an organic polysulfide compound found in garlic and other allium vegetables. Although certain studies have demonstrated that DATS possesses strong anti‑inflammatory activity, the underlying molecular mechanisms remain largely unresolved. In the present study, the anti‑inflammatory potential of DATS was investigated using the murine macrophage RAW 264.7 cell model. At non‑toxic concentrations, DATS inhibited the production of nitric oxide (NO) and prostaglandin E2 by inhibiting inducible NO synthase and cyclooxygenase‑2 expression at the transcriptional level in lipopolysaccharide (LPS)‑activated RAW 264.7 macrophages. DATS attenuated the release of the pro‑inflammatory cytokines, tumor necrosis factor‑α and interleukin‑1β, by inhibiting mRNA expression, respectively. DATS also suppressed LPS‑induced DNA‑binding activity of nuclear factor‑κB (NF‑κB), as well as the nuclear translocation of the NF‑κB p65, which correlated with the inhibitory effects of DATS on inhibitor κB (IκB) degradation. In addition, DATS was observed to significantly suppress LPS‑induced Toll‑like receptor 4 (TLR4) and myeloid differentiation factor 88 expression and the binding of LPS to macrophages, indicating the antagonistic effect of DATS against TLR4. Furthermore, blocking TLR4 signaling with the specific TLR4 signaling inhibitor, CLI‑095, increased the anti‑inflammatory potential of DATS in LPS‑stimulated RAW 264.7 macrophages. These data demonstrate that DATS may attenuate the initiation of LPS‑mediated intracellular signaling cascades by suppressing activation of NF‑κB and by inhibiting binding of LPS to TLR4 on macrophages.
authors.affiliation: Daegu Gyeongbuk Institute of Science and Technology, Daegu 711‑873, Republic of Korea.
authors.forename: Hye Hyeon
authors.initials: HH
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614‑052, Republic of Korea.
authors.forename: Min Ho
authors.initials: MH
authors.lastname: Han
authors.affiliation: Anti‑Aging Research Center and Blue‑Bio Industry RIC, Dongeui University, Busan 614‑714, Republic of Korea.
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Hwang
authors.affiliation: Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National University, Jeju 690‑756, Republic of Korea.
authors.forename: Gi-Young
authors.initials: GY
authors.lastname: Kim
authors.affiliation: School of Food Science and Technology, Chung‑Ang University, Ansung 456‑756, Republic of Korea.
authors.forename: Sung-Kwon
authors.initials: SK
authors.lastname: Moon
authors.affiliation: School of Medicine and Institute for Nuclear Science and Technology, Jeju National University, Jeju 690‑756, Republic of Korea.
authors.forename: Jin-Won
authors.initials: JW
authors.lastname: Hyun
authors.affiliation: Department of Urology, Chungbuk National University College of Medicine, Cheongju 361‑763, Republic of Korea.
authors.forename: Wun-Jae
authors.initials: WJ
authors.lastname: Kim
authors.affiliation: Department of Biochemistry, Dongeui University College of Korean Medicine, Busan 614‑052, Republic of Korea.
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
mesh_terms: D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013440:Sulfides / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000498:Allyl Compounds; D000975:Antioxidants; C587672:IL1B protein, mouse; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C498144:Rela protein, mouse; D013440:Sulfides; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; C042577:diallyl trisulfide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2