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Matrine alleviates neurobehavioral alterations via modulation of JNK-mediated caspase-3 and BDNF/VEGF signaling in a mouse model of burn injury
- Source :
- Psychopharmacology. 237(8)
- Publication Year :
- 2020
-
Abstract
- The c-Jun N-terminal kinase (JNK) pathway and neurotrophic factor dysregulation play a critical role in the pathogenesis of neurobehavioral disorders (anxiety and depression). Targeting the JNK pathway and BDNF/VEGF signaling may signify a new avenue for the treatment of neurobehavioral disorders. The present study investigated the effect of matrine (Mat) against anxiety- and depressive-like emotional status in an acute mouse model of burn injury and explores its underlying mechanism. In the mouse model of thermal injury, anxiety- and depression-related behaviors were evaluated using the elevated plus-maze test, the light-dark box test, the open-field test, the forced swimming test, and the tail suspension test. The JNK/caspase-3 and BDNF/VEGF proteins were determined by immunohistochemistry. Additionally, proinflammatory cytokine, antioxidant, nitric oxide, and corticosterone levels were also measured. The results showed that treatment with Mat significantly improves anxiety- and depressive-like behaviors. It remarkably reduced the levels of proinflammatory cytokines, malondialdehyde, and nitric oxide in the hippocampus and prefrontal cortex of a mouse brain. It considerably improved burn-induced alteration in the antioxidant status, corticosterone, and BDNF/VEGF. It also inhibited burn-induced apoptotic signaling by downregulating the expression of JNK/caspase-3. Similarly, it prevented DNA damage and histopathological changes in the dentate gyrus of the hippocampus. Furthermore, molecular docking results showed that Mat possess better binding affinity for JNK/caspase-3 and BDNF/VEGF proteins. These findings provide convincing evidence that Mat improves anxiety- and depressive-like emotional status through modulation of JNK-mediated inflammatory, oxidative stress, apoptotic, and BDNF/VEGF signaling in an acute mouse model of burn injury.
- Subjects :
- Male
Vascular Endothelial Growth Factor A
medicine.medical_specialty
MAP Kinase Signaling System
Caspase 3
Anxiety
medicine.disease_cause
Proinflammatory cytokine
Nitric oxide
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Alkaloids
Neurotrophic factors
Internal medicine
Medicine
Animals
Maze Learning
Matrines
Pharmacology
Dose-Response Relationship, Drug
business.industry
Dentate gyrus
Brain-Derived Neurotrophic Factor
Tail suspension test
030227 psychiatry
Molecular Docking Simulation
Disease Models, Animal
Oxidative Stress
Endocrinology
chemistry
Anti-Anxiety Agents
business
Burns
030217 neurology & neurosurgery
Oxidative stress
Quinolizines
Behavioural despair test
Subjects
Details
- ISSN :
- 14322072
- Volume :
- 237
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Psychopharmacology
- Accession number :
- edsair.doi.dedup.....ac6e4b4d30461860bd78b14c1b7242a4