Abstract. Inhibition of interleukin-6 (IL-6) has been postulated to be an effective therapy in the pathogenesis of several inflammatory diseases. The current study was performed to examine potential effects of manassantin A and B isolated from Saururus chinensis on the IL-6-induced response to human hepatoma cells. We found that manassantin A and B inhibit signal transducer and activator of transcription 3 (Stat3) activity stimulated by IL-6. We also found that both compounds decreased IL-6-induced Stat3 phosphorylation and nuclear translocation. Both compounds blocked suppressor of cytokine signaling 3 (SOCS-3)-mRNA expression induced by IL-6. In addition, we found that Stat3 inhibitory effects of these compounds could be related to protein tyrosine phosphatase. These findings suggest that manassantin A and B could be useful remedies for treatment of inflammatory diseases by inhibiting IL-6 action.Keywords: manassantin A and B, interleukin-6, signal transducer and activator of transcription 3 (Stat3)Short Communication
Abstract. This study examined the effect of norkurarinol on the toll-like receptor 3 (TLR3)-mediated signaling pathways and rotavirus replication. Norkurarinol, a lavandulylated flavanone, was isolated from the roots of Sophora flavescens, which has been shown to have anti-inflammatory activity. Norkurarinol suppressed the NF-κB and AP-1 inducible secreted embryonic alkaline phosphatase (SEAP) activity induced by poly(I:C), TLR3 ligand, in THP1-Blue-CD14 cells with IC 50 values of 20.9 μM. Norkurarinol also significantly suppressed the mRNA expression of proinflammatory and adhesive molecules induced by poly(I:C) and rotavirus infection. Pretreatment of norkurarinol blocked the NF-κB and AP-1 signaling pathway and the phosphorylation of MAPKs induced by poly(I:C). On the other hand, norkurarinol increased the level of IRF3 phosphorylation and IFNβ expression in a dose-dependent manner. Moreover, norkurarinol inhibited the rotavirus-induced cytopathic effects. These results suggest that norkurarinol can modulate the TLR3-mediated inflammatory responses and rotavirus replication.
The current study was performed to examine the mechanisms underlying the potential effects of E. KANSUI on IL-6-induced cellular signaling in human hepatoma cells. We found that two diterpenoids, kansuinine A and B, from E. KANSUI have an inhibitory effect on IL-6-induced Stat3 activation by activating ERK1/2. Inhibition of MEK significantly blocked the effects of kansuinine A and B on IL-6-induced Stat3 activation and tyrosine phosphorylation. These results suggest that blocking of IL-6-induced signal transduction is partially due to the sustained activation of ERK1/2 by kansuinine A and B, which in turn results in an increase of Stat3 serine phosphorylation and SOCS-3 expression. Treatment with kansuinine A and B represents a novel method to block these IL-6-induced effects.
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