Acute or chronic liver injury is associated with
hyperammonemia which induced
neuroinflammation and oxidative stress in the brain.
Neuroinflammation, oxidative stress, reduced neurogenesis, and apoptosis are critical factors for the development of anxiety and depression. The present study was aimed to evaluate the
anxiolytic and
antidepressant properties of
matrine against acute liver injury in the rodent model. Acute liver injury in mice was induced by administration of the acute hepatotoxic dose of
carbon tetrachloride (CCl4) (1 ml/kg, i.p.). Pretreatment of mice with
matrine (50 mg/kg i.p.) remarkably ameliorated CCl4-induced anxiety and depression-like behavior as evident from the results of open field test (OFT), elevated plus maze test (EPM), light-dark box test (LDB), forced swimming test (FST), and tail suspension test (TST). Moreover,
matrine significantly inhibited CCl4-induced
neuroinflammation in mice by reducing pro-inflammatory
cytokines such as
interleukins (IL-1β, IL-6) and
tumor necrosis factor-α (TNF-α) levels in the hippocampus (HC) and prefrontal cortex (PFC). CCl4-induced oxidative stress was reduced by
matrine due to its potential to enhance the levels of
reduced glutathione (GSH),
catalase (CAT),
glutathione-S-transferase (GST), and decreased the
malondialdehyde (MDA), and
nitrite level in the PFC and HC of mice brain.
Matrine remarkably reduced the levels of
corticosterone,
ammonia, AST, ALT, and
creatinine.
Matrine pretreatment remarkably ameliorated CCl4-induced morphological liver injury. Acute pretreatment of
matrine enhanced neurogenesis by increasing the number of GFAF (
glial fibrillary acidic protein) positive astrocyte,
BDNF (
brain-derived neurotrophic factor), and
VEGF (
vascular endothelial growth factor) in the hippocampus of CCl4-treated mice. Pretreatment of
matrine inhibited apoptosis and DNA damage in the hippocampus. The present data revealed that
hyperammonemia produced due to liver injury induced oxidative stress,
neuroinflammation, reduced neurogenesis and apoptosis in the hippocampus, thus, resulting in anxiety and depression. Taken together, the present results suggested that
matrine has a significant
antidepressant and
anxiolytic effects through modulation of
neuroinflammation, oxidative stress, reduced neurogenesis and apoptosis induced by CCl4 administration.