curcumin and Encephalitis--Japanese

Japanese encephalitis (JE) is prevalent throughout eastern and southern Asia and the Pacific Rim. It is caused by the JE virus (JEV), which belongs to the family Flaviviridae. Despite the importance of JE, little is known about its pathogenesis. The role of oxidative stress in the pathogenesis of viral infections has led to increased interest in its role in JEV infections. This review focuses mainly on the role of oxidative stress in the pathogenesis of JEV infection and the antiviral effect of antioxidant agents in inhibiting JEV production. First, this review summarizes the pathogenesis of JE. The pathological changes include neuronal death, astrocyte activation, and microglial proliferation. Second, the relationship between oxidative stress and JEV infection is explored. JEV infection induces the generation of oxidants and exhausts the supply of antioxidants, which activates specific signaling pathways. Finally, the therapeutic efficacy of a variety of antioxidants as antiviral agents, including minocycline, arctigenin, fenofibrate, and curcumin, was studied. In conclusion, antioxidants are likely to be developed into antiviral agents for the treatment of JE.

Topics: Animals; Antioxidants; Antiviral Agents; Astrocytes; Cell Death; Curcumin; Encephalitis Virus, Japanese; Encephalitis, Japanese; Fenofibrate; Furans; Humans; Lignans; Microglia; Minocycline; Neurons; Oxidative Stress

Japanese encephalitis virus (JEV) is the foremost cause of viral encephalitis in Southeast Asia and Australia leading to approximately 68 000 clinical cases and about 13 600-20 400 deaths annually. Vaccination is not completely sure and safe. Despite this, no specific antiviral has been available or approved for JEV infection yet and treatment is generally symptomatic. Therefore, this study aims to examine the antiviral activity of natural compounds against JEV proteins. The antiviral activity of natural compounds was investigated via molecular docking, cytopathic effect (CPE) inhibition assay, western blotting, and indirect immunofluorescence assay. Physiochemical, pharmacokinetics, and toxicity analysis were evaluated for the safety and efficacy of natural compounds. Network pharmacology-based approaches have been used to study the molecular mechanisms of drug-target interactions. Molecular docking results suggested that the NS5 protein of JEV is the major target for natural compounds. Network pharmacology-based analysis revealed that these drugs majorly target IL6, AKT1, tumor necrosis factor (TNF), and PTGS2 to regulate key immune and inflammatory pathways such as nuclear factor kappa B, PI3K-Akt, and TNF signaling, during JEV infection. Our in vitro results show that among the natural compounds, curcumin provides the highest protection against JEV infection via reducing the JEV-induced CPE (IC

Topics: Antiviral Agents; Curcumin; Cyclooxygenase 2; Encephalitis Virus, Japanese; Encephalitis, Japanese; Humans; Interleukin-6; Molecular Docking Simulation; Phosphatidylinositol 3-Kinases; Signal Transduction; Virus Replication

Japanese encephalitis (JE) is an arboviral disease common in Southeast Asia encompassing a population of 3 billion people. Periodic outbreak of JE takes hundreds of lives. Children are major victims of JE. About one third of JE patients die, and many of the survivors suffer from permanent neuropsychiatric sequel, owing to the lack of specific therapeutic measure. Curcumin is a naturally occurring phenolic compound extracted from Curcuma longa L. Previous studies have reported that curcumin possesses strong antioxidant, anti-inflammatory, antiviral activity. We used Neuro2a cell line and infected them with JE virus. The infected cells were treated with varying doses of curcumin. Cell viability, reactive oxygen species (ROS) production within the cells, and change in cellular membrane integrity were studied. The changes in expression of some signaling and stress-related proteins were also assessed. We also studied the inhibitory role of curcumin on the production of infective viral particles by dysregulation of the ubiquitin-proteasome system. In this study, we found that curcumin imparts neuroprotection in vitro, probably by decreasing cellular reactive oxygen species level, restoration of cellular membrane integrity, decreasing pro-apoptotic signaling molecules, and modulating cellular levels of stress-related proteins. We have also shown that curcumin, by inhibition of ubiquitin-proteasome system causes reduction in infective viral particle production from previously infected neuroblastoma cells.

Topics: Anisotropy; Antioxidants; Cell Death; Cell Line; Cell Survival; Curcumin; Cytopathogenic Effect, Viral; Encephalitis Viruses, Japanese; Encephalitis, Japanese; Gene Expression Regulation; Humans; Immunoblotting; In Situ Nick-End Labeling; Neurons; Neuroprotective Agents; Proteasome Endopeptidase Complex; Reactive Oxygen Species; Ubiquitin; Virion