title: Sinigrin inhibits production of inflammatory mediators by suppressing NF-κB/MAPK pathways or NLRP3 inflammasome activation in macrophages.
abstract: Sinigrin (2-propenyl glucosinolate) is found mainly in broccoli, brussels sprouts, and black mustard seeds. Recently, sinigrin has received attention for its role in disease prevention and health. This study investigated the effect of sinigrin on macrophage function, including the activity of Nod-like receptor protein 3 (NLRP3) inflammasome. In a concentration-dependent manner, sinigrin inhibited lipopolysaccharide (LPS)-induced nitric oxide (NO) production and the expression of COX-2 and prostaglandin E2 (PGE2) in RAW 264.7 cells. In addition, sinigrin significantly suppressed the production of tumor necrosis factor (TNF)-α and interleukin (IL)-6 via suppression of MAPK phosphorylation and nuclear factor-kappa B (NF-κB) activity. Treatment with sinigrin decreased IL-1β and IL-18 production and concurrently suppressed NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1 expression in LPS/ATP-stimulated cells, suggesting that the blocking of NLRP3 inflammasome activation prevented the production of both cytokines. Collectively, these results suggest that sinigrin has immunomodulatory effects by suppressing the production of inflammatory mediators, possibly by inhibiting the NF-κB/MAPK pathways or NLRP3 inflammasome activation. Our findings also provide evidence that the pharmacological modulation of sinigrin could have an anti-inflammatory effect.
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyunggi-do 16419, Republic of Korea.
authors.forename: Hee-Weon
authors.initials: HW
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyunggi-do 16419, Republic of Korea.
authors.forename: Chung Gi
authors.initials: CG
authors.lastname: Lee
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyunggi-do 16419, Republic of Korea.
authors.forename: Dong-Kwon
authors.initials: DK
authors.lastname: Rhee
authors.affiliation: Department of Molecular Cell Biology, Samsung Biomedical Research Institute, School of Medicine, Sungkyunkwan University, Suwon, Gyunggi-do 16419, Republic of Korea.
authors.forename: Sung Hee
authors.initials: SH
authors.lastname: Um
authors.affiliation: School of Pharmacy, Sungkyunkwan University, Suwon, Gyunggi-do 16419, Republic of Korea. Electronic address: snpyo@skku.edu.
authors.forename: Sukneung
authors.initials: S
authors.lastname: Pyo
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005961:Glucosinolates / Q000494:pharmacology*; D058847:Inflammasomes / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy*; D018836:Inflammation Mediators / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005961:Glucosinolates; D058847:Inflammasomes; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D009569:Nitric Oxide; C010330:sinigrin; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: 2-Propenyl glucosinolate; Inflammation; Macrophage; NF-κB/MAPK; NLRP3 inflammasome