BACKGROUND: Celastrol is one of the active components extracted from the traditional Chinese medicine Celastrus orbiculatus characterized by expelling the wind and promoting blood circulation and relieving swelling and pain.
OBJECTIVE: To investigate the effects of celastrol on tumor necrosis factor-α (TNF-α) induced proliferation and inflammatory responses in RAW264.7 cells.
METHODS: In vitro inflammatory cell models induced by TNF-α (0, 1, 10, 100 μg/L) were treated with celastrol (0.1, 0.5, 1.0, 2.0 μmol/L). Interleukin-1β, -6, -8 and prostaglandin E2 in the models were measured by enzyme-linked immunosorbent assay. Cell survival was determined by cell counting kit-8. The inflammatory mediator nitric oxide secretion was detected by nitrate reductase assay. mRNA expressions of inducible nitric oxide synthase, cyclin D1 and cyclin E1 were detected by real-time polymerase chain reaction technique.
RESULTS AND CONCLUSION: Significantly increased secretion of interleukin-1β, -6, -8, prostaglandin E2 and nitric oxide, cell proliferation, and mRNA expressions of inducible nitric oxide synthase, cyclin D1 and cyclin E1 were observed after the induction of TNF-α (0.1, 10, 100 μg/L) compared with the control group (without the induction of TNF-α) (P < 0.05); especially, 10 μg/L of TNF-α exhibited the strongest effects. 0.4 μmol/L celastrol significantly suppressed TNF-α-induced release of interleukin-1β, -6, -8, prostaglandin E2 and nitric oxide, cell proliferation, and mRNA expressions of inducible nitric oxide synthase, cyclin D1 and cyclin E1 in RAW264.7 cells (P < 0. 05). Our results demonstrate that celastrol can inhibit TNF-α-induced inflammatory response and proliferation in RAW264.7 cells.