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.