Japanese encephalitis virus (JEV), known to affect children, is a major cause of severe encephalopathy. Its prevalence has been percolated over wider regions of Southern Asia. JEV is associated with neurodegeneration, severe inflammation, increased oxidative stress and elevated levels of stress linked proteins. Four groups of 15 mice each (4-5 weeks old BALB/c mice of either sex) was used for the study. Mice were intravenously infected with lethal dose of 3 x 10(5) pfu of JEV, followed by mortality after 8 days. On the next day and onwards, the animals were administered intraperitonially with (-)-tetrahydropalmatine (LTHP) solution (0.1 mg/mL in PBS) for the next 7 days. Animals exhibited protection against JEV infection, after being administered with LTHP. Reduction in levels of, viral population, caspase-2 expression, reactive oxygen and nitrogen species, microglial cells and proinflammatory mediators, stress linked protein molecules and neuronal apoptosis was exhibited in JEV infected animals treated with LTHP. The effects produced by the administration of LTHP indicated its possible use to treat JEV in mouse model. Potential to reduce viral count in brain and subsequent neuronal apoptosis, reduction in mediators of inflammation and oxidative stress, strictly advocate the use of LTHP for treatment of JEV. Thus, the present investigation indorses LTHP as a potentially strong drug candidate for the treatment of JEV infection due to its neuroprotective, anti-inflammatory, antiviral and anti-oxidative effect.

This study evaluates the protective effect of corilagin against Parkinsonismin Japanese encephalitis virus (JEV) induced Parkinson's disease. The JaGAr-01 strain of virus was used to induce JE. The virus was injected into the rats (13 days age) at the midpoint between the two ears. Adult rats, 12 week after the inoculation of virus, were used for the further study. Corilagin (20 mg/kg) and levodopa with dopa decarboxylase inhibitor (LEV, 10 mg/kg) were administered intraperitoneally for the duration of one week. Bradykinesia and the levels of dopamine in the brain were estimated at the end of protocol. There was a significant decrease inthe motor function in the corilagin, LEV and LEV + corilagin treated groupscompared to the negative control group. However treatment with corilagin, LEV and LEV + corilagin significantly increases the level of dopamine in the brain compared to the negative control group. This study concludes that corilagin ameliorates the Parkinsonismin JEV induced Parkinsonism. Moreover it shows a synergistic effect when treated with LEV. Data presented in the investigation supports that corilagin can be used clinically.

Background Elevated fibrinogen (Fg) level is a known risk factor for ischemic stroke. There are few clinical trials on oral fibrinogen-depleting therapies for secondary ischemic stroke prevention. We aimed to assess the effects of one-year therapy with oral lumbrokinase enteric-coated capsules on secondary ischemic stroke prevention.Methods This is a multicenter, randomized, parallel group and controlled study that began treatment in hospitalized patients with ischemic stroke and continued for 12 months. Patients were randomized to either the control group that received the standard stroke treatment or the fibrinogen-depleting group that received the standard stroke treatment plus enteric-coated lumbrokinase capsules. The NIH Stroke Scale scores (NIHSSs) and plasma Fg level were recorded. The carotid artery intima-media thickness (IMT) and status of plaques were examined through carotid ultrasound examination. Primary outcomes included all-cause mortality, any event of recurrent ischemic stroke/transient ischemic attack (TIA), hemorrhagic stroke, myocardial infarction and angina, and other noncerebral ischemia or hemorrhage. Kaplan-Meier survival analysis and the Long-rank test were used to compare total vascular end point incidence between the two groups. Comparison of median values between two groups was done by the Student t test, one-way analysis of variance (ANOVA), or non-parametric rank sum test.Results A total of 310 patients were enrolled, 192 patients in the treatment group and 118 patients in the control group. Compared to the control group, the treatment group showed favorable outcomes in the Fg level, carotid IMT, the detection rate of vulnerable plaques, the volume of carotid plaques, NIHSS scores, and incidence of total vascular (6.78% and 2.08%, respectively) and cerebral vascular events (5.93% and 1.04%, respectively) (P <0.05). In the treatment group, the volume of carotid plaques was significantly related to the carotid IMT, the plaque diameter, width and number (P=0.000, 0.000, 0.000, 0.022; F=13.51, 2.52, 11.33, 3.29, but there was a weak correlation with the Fg level (P=0.056). After 1-year therapy, the incidence of overall vascular end points was reduced by 4.7%.Conclusion Long-term oral fibrinogen-depleting therapy may be beneficial for secondary ischemic stroke prevention.