Schizandrin ameliorates behavioral disorders in hepatic injury mice via regulation of oxidative stress and neuroinflammation

Abstract

Aim: The present study was aimed to evaluate the anxiolytic and antidepressant-like effects of schizandrin (from Schisandra chinensis (Turcz.) Baill. which is a functional food) against chronic liver injury in mice.

Methods: Chronic liver injury was induced by the treatment of d-galactose (d-GaIN, 200 mg/kg, s.c.) for 8 weeks.

Results: Administration of schizandrin (30 mg/kg, i.g.) significantly ameliorated d-GaIN-induced anxiety and depression-like behavior as evident from the results of open field test (OFT), sucrose preference test (SPT), tail suspension test (TST), forced swimming test (FST), novelty-suppressed feeding test (NSFT), and elevated plus maze (EPM) test. In addition, schizandrin remarkably reduced the oxidative stress due to its potential to enhance the levels of decreased CAT, GSH/GSSG, SOD, and increased MDA in peripheral and brain, the antioxidant activities might be related with the Nrf2/HO-1 pathway. Furthermore, schizandrin could dramatically inhibit the neuroinflammation in mice by reducing pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) through regulating NF-κB/NLRP3/Iba-1 signaling. Besides, the elevated levels of ammonia, AST, and ALT were significantly reduced by schizandrin.

Conclusion: The present data revealed that hyperammonemia produced due to liver injury-induced oxidative stress and neuroinflammation in the hippocampus and prefrontal cortex resulting in anxiety and depression were improved by schizandrin.

Keywords:

• Hyperammonemia
• schizandrin
• depression
• anxiety
• neuroinflammation

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work is supported by Key Laboratory of Polysaccharide Bioactivity Evaluation of TCM of Liaoning Province and Liaoning Distinguished Professor Project for Ying Jia [2017], Precise Screening Technology of Chinese Traditional Medicine Anti-Depressant Active Ingredients [2017LZD01], and The Doctoral Scientific Research Foundation of Liaoning Province [2019-BS-233]. Project funded by China Postdoctoral Science Foundation [2020M681518].