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-α and IL-1β and slightly suppressed nitric oxide release in THP-1 cells without exerting any direct toxic effect, whereas steviol at 100 μM did not. Activation of IKKβ and transcription factor NF-κB were suppressed by stevioside, as demonstrated by Western blotting. Furthermore, only stevioside induced TNF-α, IL-1β, and nitric oxide release in unstimulated THP-1 cells. Release of TNF-α 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 IKKβ and NF-κB signaling pathway, and stevioside-induced TNF-α secretion is partially mediated through TLR4. © 2006 American Chemical Society.