Abstract

Inhibitory effects on Lipopolysaccharide-induced cytokine production in mouse macrophage by Lithospermum erythrorhizon extracts A variety of plant extracts have been shown to exert anti-inflammatory and chemopreventive acitivity via modulation of cytokine production. Lithospermum erythrorhizon (LE) has long been used in traditional oriental medicine for treatment of inflammation and other maladies. In the present study, we demonstrated the inhibitory effects of methanolic extracts from roots of LE on LPS-stimulated production of various inflammatory cytokines including IL-6, TNF-α, INF-γ and IL-1β. As an underlying mechanism of the inhibition, LE extracts reduced LPS-induced transactivation of transcription factors AP-1 as well as NF-κB in mouse macrophage cells. Electrophoretic mobility shift assay analysis indicated that LE extracts inhibited DNA binding activities of AP-1 and NF-κB. In addition, phosphorylation of IκB-α protein, subunit of NF-κB inhibitor was suppressed by LE extracts. Degradation of IκB-α proteins was decreased and translocation of p65 into nucleus was inhibited by LE extracts. Moreover, LE extracts inhibited c-jun N-terminal kinase and extracellular signal regulated signaling pathways. Our results suggest that the anti-inflammatory activity of LE may be mediated by signal transduction pathways leading to activation of AP-1 and NF-κB, which may be useful for chemoprevention of cancer or other inflammatory chromic diseases.

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