Inhibitory effects of 3 alpha-hydroxy-lup-20(29)-en-23, 28-dioic acid on lipopolysaccharide-induced TNF-alpha, IL-1 beta, and the high mobility group box 1 release in macrophages

초록

We investigated the anti-inflammatory effects of 3-hydroxy-lup-20(29)-en-23, 28-dioic acid (HLEDA)a lupane-type triterpene isolated from leaves of Acanthopanax gracilistylus W. W.Smith (AGS), as well as the underlying molecular mechanisms in lipopolysaccharide (LPS)-induced RAW264.7 cells. Our results demonstrated that HLEDA concentration-dependently reduced the production of nitric oxide (NO), significantly suppressed LPS-induced expression of TNF- and IL-1 at the mRNA and protein levels in RAW264.7 cells. Further analysis revealed that HLEDA could reduce the secretion of High Mobility Group Box 1 (HMGB1). Additionally, the results showed that HLEDA efficiently decreased nuclear factor-kappaB (NF-B) activation by inhibiting the degradation and phosphorylation of IB. These results suggest that HLEDA exerts anti-inflammatory properties in LPS-induced macrophages, possibly through inhibition of the NF-B signaling pathway, which mediates the expression of pro-inflammatory cytokines. These results warrant further studies that would concern candidate therapy for diseases, such as fulminant hepatitis and rheumatology of triterpenoids in AGS.

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