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A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease
Published on: April 28, 2019
Neuroprotective effect of (-)-tetrahydropalmatine in Japanese encephalitis virus strain GP-78 infected mouse model
Huang Lixia1, Chen Jun2, Hu Song1
1School of Medicine, Jianghan University, WuHan, 430056, China.
Insights
(-)-tetrahydropalmatine (LTHP) shows neuroprotective effects against Japanese encephalitis virus (JEV) infection in mice. LTHP reduced viral load, inflammation, oxidative stress, and neuronal apoptosis, suggesting its potential as a JEV therapeutic agent.
Area of Science:
- Neuroscience
- Virology
- Pharmacology
Background:
- Japanese encephalitis virus (JEV) causes severe encephalopathy, particularly in children, with increasing prevalence in Southern Asia.
- JEV infection is linked to neurodegeneration, inflammation, oxidative stress, and stress-related proteins.
Purpose of the Study:
- To investigate the therapeutic potential of (-)-tetrahydropalmatine (LTHP) against JEV infection in a mouse model.
- To evaluate LTHP's effects on viral load, neuroinflammation, oxidative stress, and neuronal apoptosis.
Main Methods:
- BALB/c mice were infected with a lethal dose of JEV.
- Mice received intraperitoneal injections of LTHP solution for 7 days post-infection.
- Key indicators of viral load, inflammation, oxidative stress, and apoptosis were assessed.
Main Results:
- LTHP administration protected mice against JEV infection.
- Treated mice showed reduced viral population, caspase-2 expression, reactive oxygen/nitrogen species, microglial cells, and pro-inflammatory mediators.
- Neuronal apoptosis and stress-linked proteins were significantly decreased in LTHP-treated JEV-infected mice.
Conclusions:
- (-)-tetrahydropalmatine (LTHP) demonstrates significant neuroprotective, anti-inflammatory, antiviral, and anti-oxidative effects against JEV.
- LTHP effectively reduces viral count in the brain, mitigating subsequent neuronal apoptosis and oxidative stress.
- These findings support LTHP as a promising drug candidate for treating Japanese encephalitis virus infection.
Abstract:
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 × 105 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.
