MAPKs-NF-kappaB Pathway Plays a Crucial Role in the Antiinflammatory Effects of Amentoflavone in Lipopolysaccharide-treated BV2 Microglia

Abstract

Houng, et al.: Amentoflavone reduced LPS-stimulated BV2 microglia via MAPKs-NFκBAmentoflavone also known as didemethyl-ginkgetin, 3',8"-biapigenin, is a plant bioflavonoid found in several plants, with a number of pharmacological effects including antiinflammatory, antioxidant, antiviral, neuroprotective, and anticancer. The present study revealed that secretion of prostaglandin E2 and nitric oxide were inhibited by amentoflavone in a concentration-dependent manner in the lipopolysaccharide/ interferon γ-stimulated BV2 microglial cells. Meanwhile, protein expression of inducible nitric oxide synthase and cyclooxygenase-2 induced by lipopolysaccharide/gamma interferon were inhibited by amentoflavone in the same concentration range. Moreover, amentoflavone not only reduced the phosphorylation of nuclear factor-κB but also inhibited the phosphorylation of mitogen-activated protein kinases, including extracellular-signal-regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinases induced by lipopolysaccharide. In addition, a parallel concentration-dependent manner was observed in the inhibition of secretion of prostaglandin E2 and nitric oxide, expression of inducible nitric oxide synthase and cyclooxygenase-2, and phosphorylation of mitogen-activated protein kinases and nuclear factor-κB pathway. These results suggested that amentoflavone possessed the potential to act against lipopolysaccharide/ interferon γ-induced secretion of prostaglandin E2 and nitric oxide via downregulation of inducible nitric oxide synthase and cyclooxygenase-2 expressions by blocking the activation of nuclear factor-κB pathway via phosphorylation of mitogen-activated protein kinases.

Neuroinflammation: The Role of Anthocyanins as Neuroprotectants

“…In addition, NF-κB, signal transducer, and activator of transcription (STAT)-1/2/3, c-Jun, and CREB are activated in the process, contributing to the inflammatory response (Fig. 2 ) [ 82 ]. MAP kinases enhance the formation of pro-inflammatory cytokines by working in consonance with IκB kinases (inhibitor of NF-κB protein).…”