Chrysoeriol ameliorates COX-2 expression through NF-κB, AP-1 and MAPK regulation via the TLR4/MyD88 signaling pathway in LPS-stimulated murine macrophages

Abstract

Chrysoeriol is a flavonoid that has diverse biological properties, including antioxidation, anti-inflammation, chemoprevention and immunomodulation. Despite its reported anti-inflammatory activity, the exact underlying molecular mechanism has not yet been elucidated. In the current study, the anti-inflammatory mechanism of chrysoeriol involving lipopolysaccharide (LPS)-induced cyclooxygenase-2 (COX-2) and its upstream signaling molecules was investigated in RAW 264.7 cells. The mechanism was evaluated via ELISA and western blotting assays. Chrysoeriol significantly inhibited LPS-induced prostaglandin E₂ (PGE₂) production and COX-2 expression without cytotoxicity. Activated transcription factors that further induced the inflammation response, including nuclear factor (NF)-κB and activator protein-1 (AP-1), were significantly attenuated by chrysoeriol treatment. Furthermore, LPS-induced phosphorylation levels of phosphoinositide-3-kinase (PI3K)/Akt and mitogen-activated protein kinase (MAPK) were abolished by chrysoeriol treatment, which was confirmed by selective inhibitors. Additionally, chrysoeriol significantly inhibited the LPS-induced activation of adaptor molecules in RAW 264.7 cells, including toll-like receptor 4 (TLR4) and myeloid differentiation primary response 88. Therefore, the results suggested that chrysoeriol ameliorates TLR4-mediated inflammatory responses by inhibiting NF-κB and AP-1 activation as well as suppressing PI3K/Akt and MAPK phosphorylation in LPS-stimulated RAW 264.7 cells.

Keywords: activator protein-1; chrysoeriol; cyclooxygenase-2; mitogen-activated protein kinase; myeloid differentiation primary response 88; nuclear factor-κB; phosphoinositide 3-kinase; toll like receptor 4.