P-99. Novel Strategy for treatment of Japanese encephalitis using Arctigenin, a plant lignan

Japanese encephalitis virus (JEV), a neurotropic flavivirus, commonly affects children and is a major cause of acute encephalopathy. JEV is active over a vast geographic area that includes India, China, Japan and virtually all of South-East Asia. Approximately 3 billion people live in the JEV endemic area covering much of Asia with nearly 50,000 cases of JE reported each year. There is no specific treatment for Japanese Encephalitis (JE) and no effective anti-viral drugs have been discovered so far. Arctigenin is a naturally occurring phenylpropanoid dibenzylbutyrolactone lignan with antioxidant, anti-inflammatory, neuroprotective and anti-viral efficacies. The goal of the study presented here was to determine the therapeutic effects of arctigenin on a murine model of experimental JE. Here we showed that treatment with arctigenin confers complete protection to animal from JE virus infection. JEV induced neuronal apoptosis, microglial activation, active caspase activity and proinflammatory mediators were markedly decreased in the brains of arctigenin-treated mice. Treatment with arctigenin also reduced the viral replication. Infection with JEV upregulate the level of several stress associated signal-transducing molecules like phospho-p38, phospho-c-Jun, Hsp70, and ERK1/2. Treatment with arctigenin significantly reduces the level of those molecules. Arctigenin may act directly on brain cells, because neuronal cell line Neuro2a were also salvaged from JEV induced cell death. Both the anti-viral, neuroprotective, anti-inflammatory anti-oxidative effects of arctigenin are essential for reducing the severity of diseases induced by Japanese Encephalitis Virus. Thus, arctigenin seemed to have the potential to be used as a new therapeutic agent for JE patients.