Molecular basis of regulatory effect of medicinal plant components on the innate immune response through TLR4 signaling (89.1)

Abstract

Abstract The mammalian immune system consists of two branches: innate and acquired immunity. The innate immune system recognizes microorganisms via germline-encoded pathogen-associated pattern recognition receptors (PARRs) and plays a role in the first line of host defense against pathogens. Toll-like receptors (TLRs) belong to PARRs play indispensable roles for both innate and acquired immunity. One-third of the current top 20 drugs on the market are plant derived. Interestingly, anticancer drug Paclitaxel from Pacific yew tree interacts with human MD-2 and activates dendritic cells through TLR4. We examined effects of components from Glycyrrhizae Radix on the TLR-mediated innate immune response and NF-κB activation. Results: We found that Glycyrrhizic acid (GL, saponin) and Isoliquiritigenin (IQG, chalcone) from Glycyrrhizae Radix suppressed TLR4-mediated TNF-α and IL-6 production by lipid A-stimulated macrophage cells line. GL and IQG also inhibited NF-κB activation induced by lipid A. Western blot analyses revealed that both GL and IQG suppress lipid A-induced IκB-α degradation and ERK1/2 phosphorylation. Intriguingly, GL, but not IQG could inhibit the LPS binding to TLR4-MD2 detected by using anti-TLR4-MD2 mAb. Conclusion: Both GL (saponin) and IQG (chalcone) suppress TLR4-mediated inflammatory cytokine production and NF-κB activation. GL, but not IQG can inhibit TLR4 ligand binding to TLR4-MD-2, indicating that GL and IQG differentially regulate TLR-4-mediated signaling pathway.