title: Anti-Inflammatory and Immunomodulatory Activities of Stevioside and Its Metabolite Steviol on THP-1 Cells.
abstract: Stevioside, a natural noncaloric sweetener isolated from Stevia rebaudiana Bertoni, possesses anti-inflammatory and antitumor promoting properties; however, no information is available to explain its activity. The aim of this study was to elucidate the anti-inflammatory and immunomodulatory activities of stevioside and its metabolite, steviol. Stevioside at 1 mM significantly suppressed lipopolysaccharide (LPS)-induced release of TNF-alpha and IL-1beta and slightly suppressed nitric oxide release in THP-1 cells without exerting any direct toxic effect, whereas steviol at 100 microM did not. Activation of IKKbeta and transcription factor NF-kappaB were suppressed by stevioside, as demonstrated by Western blotting. Furthermore, only stevioside induced TNF-alpha, IL-1beta, and nitric oxide release in unstimulated THP-1 cells. Release of TNF-alpha could be partially neutralized by anti-TLR4 antibody. This study suggested that stevioside attenuates synthesis of inflammatory mediators in LPS-stimulated THP-1 cells by interfering with the IKKbeta and NF-kappaB signaling pathway, and stevioside-induced TNF-alpha secretion is partially mediated through TLR4.
authors.affiliation: Departments of Physiology and Microbiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Chaiwat
authors.initials: C
authors.lastname: Boonkaewwan
authors.forename: Chaivat
authors.initials: C
authors.lastname: Toskulkao
authors.forename: Molvibha
authors.initials: M
authors.lastname: Vongsakul
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002460:Cell Line; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism; D007109:Immunity / Q000187:drug effects*; D007375:Interleukin-1 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013549:Sweetening Agents / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D045786:Diterpenes, Kaurane; D005960:Glucosides; D007375:Interleukin-1; D016328:NF-kappa B; D013549:Sweetening Agents; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C012043:stevioside; D009569:Nitric Oxide; C012042:steviol; D051550:I-kappa B Kinase