Cudraflavanone B Isolated from the Root Bark of Cudrania tricuspidata Alleviates Lipopolysaccharide-Induced Inflammatory Responses by Downregulating NF-κB and ERK MAPK Signaling Pathways in RAW264.7 Macrophages and BV2 Microglia

Abstract

A prenylated flavonoid, cudraflavanone B, is isolated from Cudrania tricuspidata. In this study, we investigated its anti-inflammatory and anti-neuroinflammatory effects in lipopolysaccharide (LPS)-induced RAW264.7 and BV2 cells. In our initial study of the anti-inflammatory effects of cudraflavanone B the production of nitric oxide and prostaglandin E2 was attenuated in LPS-stimulated RAW264.7 and BV2 cells. These inhibitory effects were related to the downregulation of inducible nitric oxide synthase and cyclooxygenase-2. In addition, cudraflavanone B suppressed the production of pro-inflammatory cytokines such as interleukin-6 and tumor necrosis factor-α in LPS-induced RAW264.7 and BV2 cells. Moreover, the evaluation of the molecular mechanisms underlying the anti-inflammatory effects of cudraflavanone B revealed that the compound attenuated the nuclear factor-kappa B signaling pathway in LPS-induced RAW264.7 and BV2 cells. In addition, cudraflavanone B inhibited the phosphorylation of extracellular signal-regulated kinase mitogen-activated protein kinase signaling pathways in these LPS-stimulated cells. Thus, cudraflavanone B suppressed nuclear factor-κB, and extracellular signal-regulated kinase mitogen-activated protein kinase mediated inflammatory pathways, demonstrating its potential in the treatment of neuroinflammatory conditions.