Abstract
MAPKs-NF-kappaB Pathway Plays a Crucial Role in the Antiinflammatory Effects of Amentoflavone in Lipopolysaccharide-treated BV2 Microglia
Department of Pediatrics, Kaohsiung Veterans General Hospital, Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, Department of Internal Medicine, Chung Shan Medical University Hospital, Department of Internal Medicine, School of Medicine, School of Medical Applied Chemistry, School of Public Health, Chung Shan Medical University, Taichung, Department of Ophthalmology, Zuoying Branch of Kaohsiung Armed Forced General Hospital, Kaohsiung, Department of Anatomy, School of Medicine, Department of Pharmacology, School of Medicine, Chung Shan Medical University, Department of Pharmacy, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC
Correspondence Address:
Department of Pharmacology, School of Medicine, Chung Shan Medical University, Department of Pharmacy, Chung Shan Medical University Hospital, Taichung, Taiwan, ROC, E-mail: kuanyh@csmu.edu.tw
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.
