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

Amentoflavone also known as didemethyl-ginkgetin, 3’,8”-biapigenin, is a plant bioflavonoid found in serval 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 gamma-stimulated BV2 microglial cells. Meanwhile, protein expression of inducible nitric oxide synthase and cyclooxygenase-2 induced by LPS/INF-gamma were inhibited by amentoflavone in the same concentration range. Moreover, amentoflavone not only reduced the phosphorylation of nuclear factor-kappaB but also inhibited the phosphorylation of mitogen-activated protein kinases, including ERK, JNK, 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 NO, expression of inducible nitric oxide synthase and cyclooxygenase-2, and phosphorylation of mitogen-activated protein kinases and nuclear factor-kappaB pathway. These results suggested that amentoflavone possessed the potential to act against lipopolysaccharide/interferon gamma-induced secretion of prostaglandin E2 and NO via downregulation of inducible nitric oxide synthase and cyclooxygenase-2 expressions by blocking the activation of nuclear factor-kappaB pathway via phosphorylation of mitogen-activated protein kinases.