Anti-inflammatory effect of austroinulin and 6-O-acetyl-austroinulin from Stevia rebaudiana in lipopolysaccharide-stimulated RAW264.7 macrophages.
Austroinulin (AI) and 6-O-acetyl-austroinulin (6-OAAI) are natural diterpenoids isolated from Stevia rebaudiana with anti-inflammatory activity. However, the mechanisms underlying their anti-inflammatory effects are not well understood. The purpose of this study was to investigate the effect of AI and 6-OAAI on nitric oxide (NO) production and their molecular mechanism in LPS-stimulated RAW264.7 macrophages. We found that AI and 6-OAAI inhibit the production of NO, iNOS, and pro-inflammatory cytokines (TNF-α, IL-6, IL-1β, and MCP-1) in LPS-stimulated RAW264.7 macrophages. In these same cells, AI and 6-OAAI also suppressed the phosphorylation of STAT1 and the production of interferon-beta (IFN-β). Moreover, treatment with AI and 6-OAAI inhibited the activation of interferon regulatory factor-3 (IRF3) and NF-κB. Taken together, our results suggest that AI and 6-OAAI inhibit NO production and iNOS expression by blocking the activation of STAT1, IRF3, and NF-κB in LPS-stimulated RAW264.7 macrophages.
Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Jeonbuk 580-185, Republic of Korea.
Byoung Ok
BO
Cho
Hyung Won
HW
Ryu
Yangkang
Y
So
Jung Keun
JK
Cho
Hyun Sim
HS
Woo
Chang Hyun
CH
Jin
Kwon Il
KI
Seo
Jong Chun
JC
Park
Il Yun
IY
Jeong
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002460:Cell Line / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D050794:STAT1 Transcription Factor / Q000378:metabolism; D036625:Stevia / Q000737:chemistry*
C000590668:6-O-acetyl-austroinulin; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D004224:Diterpenes; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D008070:Lipopolysaccharides; D016328:NF-kappa B; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C498208:austroinulin
6-O-acetyl-austroinulin; Austroinulin; IRF3; NO; Pro-inflammatory cytokine; STAT1