Repeated social defeat stress exacerbates lipopolysaccharide-induced behavioural deficits in mice: ameliorative role of Chrysophyllum albidum fruit extract through anti-neuroinflammation, antioxidant and neurochemical balance

Metab Brain Dis. 2022 Oct;37(7):2467-2481. doi: 10.1007/s11011-022-01053-x. Epub 2022 Jul 22.

Abstract

Development of neuropsychiatric disorder is associated with stress-related increase in pro-inflammatory cytokines. Chrysophyllum albidum fruit is an edible tropical fruit containing vitamins and phenolic compounds, well known for their anti-inflammatory and antioxidant activities. This study was designed to investigate the neuroprotective effect of C. albidum fruit extract (CAFE) on stress and lipopolysaccharide (LPS)-induced behavioral and neurochemical impairments in mice. Male Swiss mice were divided into 6 groups (n = 6). Groups 1-3 were orally treated daily for 14 days with normal saline (0.1 mL/10 g), CAFE (100 mg/kg) and Ferulic acid (FA, 10 mg/kg), and left in home cage as controls. Groups 4-6 were treated similarly but subjected to repeated social defeat (RSD) stress using the resident-intruder model from days 1-14. The RSD-animals were injected with LPS (125 µg/kg, i.p) 60 min after each RSD session from days 8-14. Neurobehavioral functions: locomotor, cognitive and anxiety-like behaviors were assessed 24 h after the last treatment. Pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α), dopamine, acetylcholinesterase, glutamic acid decarboxylase (GAD), malondialdehyde, nitrites, and reduced glutathione (GSH) were determined in brain tissue. CAFE significantly attenuated RSD and LPS-induced hypolocomotion, cognitive impairment and anxiety-like behavior when compared to the control. Treatment with CAFE also significantly reversed the negative effects of RSD and LPS on pro-inflammatory cytokines, dopamine, acetylcholinesterase, GAD, and oxidative-nitrosative stress levels. The findings clearly indicated that Chrysophyllum albidum fruit demonstrated neuroprotective effects and can play a key role in mitigating against chronic stress and inflammation linked to neuropsychiatric disorders.

Keywords: Chronic stress; Chrysophyllum albidum; Inflammation; Memory.

MeSH terms

  • Acetylcholinesterase
  • Animals
  • Antioxidants / pharmacology
  • Antioxidants / therapeutic use
  • Cytokines
  • Dopamine
  • Fruit / chemistry
  • Fruit / metabolism
  • Glutamate Decarboxylase / analysis
  • Glutamate Decarboxylase / pharmacology
  • Glutathione / pharmacology
  • Interleukin-6
  • Lipopolysaccharides / pharmacology
  • Male
  • Malondialdehyde / pharmacology
  • Mice
  • Neuroprotective Agents* / pharmacology
  • Neuroprotective Agents* / therapeutic use
  • Nitrites / analysis
  • Nitrites / pharmacology
  • Oxidative Stress
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Saline Solution / pharmacology
  • Sapotaceae* / chemistry
  • Sapotaceae* / metabolism
  • Social Defeat
  • Tumor Necrosis Factor-alpha / metabolism
  • Vitamins

Substances

  • Antioxidants
  • Lipopolysaccharides
  • Acetylcholinesterase
  • Neuroprotective Agents
  • Tumor Necrosis Factor-alpha
  • Interleukin-6
  • Nitrites
  • Dopamine
  • Glutamate Decarboxylase
  • Saline Solution
  • Plant Extracts
  • Glutathione
  • Cytokines
  • Malondialdehyde
  • Vitamins