Catalpol attenuates lipopolysaccharide-induced inflammatory responses in BV2 microglia through inhibiting the TLR4-mediated NF-κB pathway.

Abstract

Catalpol, an iridoid glucoside mainly found in the root of Rehmannia glutinosa Libosch, is known to possess various pharmacological effects. Here, we investigated its inhibitory potential against inflammatory responses in lipopolysaccharide (LPS)-stimulated BV2 microglia. Our results showed that catalpol significantly suppressed LPS-induced secretion of pro-inflammatory mediators, including nitric oxide (NO) and prostaglandin E2. Consistent with these results, catalpol downregulated LPS-stimulated expression of their regulatory enzymes, such as inducible NO synthase and cyclooxygenase-2. Catalpol also inhibited LPS-induced production and expression of pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-1β. Additionally, catalpol suppressed the nuclear factor-kappa B (NF-κB) signaling pathway by disrupting the phosphorylation and degradation of inhibitor of κB-α and blocking the nuclear translocation of NF-κB p65. Moreover, catalpol inhibited LPS-induced expression of toll-like receptor 4 (TLR4) and myeloid differentiation factor 88, which was related to suppression of the binding of LPS with TLR4 on the cell surface. Furthermore, catalpol markedly reduced LPS-induced generation of reactive oxygen species (ROS). Collectively, these results suggest that catalpol can repress LPS-mediated inflammatory action in BV2 microglia through inactivating NF-κB signaling by antagonizing TLR4 and eliminating ROS, indicating that catalpol can have potential benefits by inhibiting the onset and/or treatment of inflammatory diseases.