title: The immunostimulating activity of quercetin 3-O-xyloside in murine macrophages via activation of the ASK1/MAPK/NF-κB signaling pathway.
abstract: Quercetin is a natural plant flavonoid that has been reported to possess a wide range of beneficial health effects, including anti-cancer and anti-inflammatory activities. Glycosylation of natural flavonoids with various sugar moieties can affect their physical, chemical, and biological properties. In this study, quercetin 3-O-xyloside (Quer-xyl) was enzymatically synthesized, and the immunomodulatory activities of quercetin and Quer-xyl were evaluated and compared. The results showed that Quer-xyl more effectively induced the secretion of TNF-α and IL-6 than quercetin by 2.5 and 1.5-fold, respectively. Quer-xyl dose-dependently induced the inducible nitric oxide synthase (iNOS) expression and increased the production of nitric oxide (NO) 1.3-fold more than quercetin. Quer-xyl also increased the phosphorylation of ASK1 and MAPKs (JNK and p38). Treatment with NQDI-1 (an inhibitor of ASK1) significantly attenuated the Quer-xyl-induced up-regulation of TNF-α secretion. The activation and subsequent nuclear translocation of NF-κB were substantially enhanced upon treatment with Quer-xyl (2.5-20 μM), while NQDI-1 treatment blocked the nuclear translocation of NF-κB. These results demonstrated that Quer-xyl can enhance the early innate immunity more effectively than quercetin by activating macrophages to secrete TNF-α and IL-6 through up-regulation of the redox-dependent ASK1/MAPK/NF-κB signaling pathway, suggesting for the first time that Quer-xyl may represent a new immunostimulator.
authors.affiliation: Department of Biotechnology, The Catholic University of Korea, Bucheon, Gyeonggi-do, 420-743, Republic of Korea.
authors.forename: Jisun
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biotechnology, The Catholic University of Korea, Bucheon, Gyeonggi-do, 420-743, Republic of Korea.
authors.forename: Ji Won
authors.initials: JW
authors.lastname: Choi
authors.affiliation: Institute of Biomolecule Reconstruction, Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, Chungnam, 336-708, Republic of Korea.
authors.forename: Jae Kyung
authors.initials: JK
authors.lastname: Sohng
authors.affiliation: Institute of Biomolecule Reconstruction, Department of BT-Convergent Pharmaceutical Engineering, Sun Moon University, Chungnam, 336-708, Republic of Korea.
authors.forename: Ramesh Prasad
authors.initials: RP
authors.lastname: Pandey
authors.affiliation: Department of Biotechnology, The Catholic University of Korea, Bucheon, Gyeonggi-do, 420-743, Republic of Korea. Electronic address: yongil382@catholic.ac.kr.
authors.forename: Yong Il
authors.initials: YI
authors.lastname: Park
mesh_terms: D000818:Animals; D001060:Aporphines / Q000494:pharmacology; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006031:Glycosylation; D007114:Immunization; D048848:MAP Kinase Kinase Kinase 5 / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D029562:Magnoliaceae / Q000276:immunology; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D011794:Quercetin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C000592751:2,7-dioxo-2,7-dihydro-3H-naphtho(1,2,3-de)quinoline-1-carboxylate; D001060:Aporphines; D016207:Cytokines; D016328:NF-kappa B; D011804:Quinolines; D011794:Quercetin; D052247:Nitric Oxide Synthase Type II; D048049:Extracellular Signal-Regulated MAP Kinases; D048848:MAP Kinase Kinase Kinase 5
keywords: Glycosylation; Immunostimulating activity; Quercetin; Quercetin 3-O-xyloside