| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2541319 | International Immunopharmacology | 2012 | 7 Pages |
Extracts from the leaves of Stewartia koreana are known to exhibit strong anti-inflammatory activity. Investigation of bioactive compounds from S. koreana has led to the isolation of 3-O-β-d‐glucopyanosylspinasterol (spinasterol-Glc), a spinasterol glycoside. In the present study, we examined the effects of spinasterol-Glc on production of nitric oxide (NO) and proinflammatory cytokines in LPS-treated RAW264.7 macrophage cells and in mouse models. Our results showed that spinasterol-Glc inhibited the production of NO and proinflammatory cytokines such as TNF-α, IL-6 and IL-1β in dose-dependent manners in LPS-treated RAW264.7 cells. Spinasterol-Glc inhibited the expression of iNOS and the proinflammatory cytokine genes. Spinasterol-Glc also inhibited phosphorylation of IκB-α and IKKα/β as well as translocation of NF-κB to the nucleus. We demonstrated that spinasterol-Glc reduced transcription of the NF-κB minimal promoter and NF-κB DNA binding activity. Administration of the spinasterol-Glc significantly decreased the plasma levels of these inflammatory mediators including TNF-α, IL-6 and IL-1β in LPS-injected mice and improved survival of septic mice with lethal endotoxemia. These results suggest that spinasterol-Glc has effective inhibitory effects on production of inflammatory mediators via inhibition of MAP kinases/NF-κB activities, and can be used as a potential anti-inflammatory agent for the prevention and treatment of inflammatory diseases.
► Spinasterol-glucoside exhibited potent anti-inflammatory activities in vitro and in vivo. ► It decreased LPS-induced expression of iNOS, TNF-α, IL-1β and IL-6 via inhibition of MAPKs/NF-κB activation. ► It attenuated LPS-induced IKK activity and IκB‐α phosphorylation/degradation. ► Spinasterol-glucoside decreased the plasma levels of TNF-α, IL-1β and IL-6 in LPS-administered mice.
