Scutellarin alleviates lipopolysaccharide-induced cognitive deficits in the rat: Insights into underlying mechanisms

Int Immunopharmacol. 2018 Jan:54:311-319. doi: 10.1016/j.intimp.2017.11.033. Epub 2017 Nov 27.

Abstract

Inflammation is a common hallmark of neurodegenerative disorders. Systemic inflammation is usually associated with cognitive deficits. Scutellarin is a flavone with established antioxidant, anti-inflammatory, and neuroprotective effects. In this study, the effect of this flavone in prevention of lipopolysaccharide (LPS)-induced cognitive deficit was evaluated. LPS was i.p. injected at a dose of 500μg/kg/day and scutellarin was administered i.p. at doses of 5, 25, or 50mg/kg/day. Treatment of LPS-injected rats with scutellarin dose-dependently ameliorated deficits of spatial recognition memory in Y maze, discrimination index in novel object discrimination task, and retention and recall index in passive avoidance test. Additionally, scutellarin lowered hippocampal malondialdehyde (MDA) and potentiated antioxidant defense elements comprising superoxide dismutase (SOD), catalase, and glutathione (GSH) in addition to reduction of acetylcholinesterase (AChE) activity. Furthermore, scutellarin decreased hippocampal nuclear factor-kappaB (NF-κB), tumor necrosis factor α (TNFα), interleukin 6 (IL-6) and elevated nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Inappropriate alterations of authophagy markers including beclin-1, LC3 II, mTOR, and P62 were also prevented in the presence of scutellarin. Our findings demonstrate that scutellarin alleviates LPS-induced cognitive disturbances, however, the precise mechanism remains still speculative.

Keywords: Autophagy; Inflammation; Learning and memory; Lipopolysaccharide; Oxidative stress; Scutellarin.

MeSH terms

  • Animals
  • Apigenin / therapeutic use*
  • Cognitive Dysfunction / drug therapy*
  • Glucuronates / therapeutic use*
  • Hippocampus / metabolism*
  • Inflammation / drug therapy*
  • Interleukin-6 / metabolism
  • Lipopolysaccharides / immunology
  • Male
  • Malondialdehyde / metabolism
  • NF-kappa B / metabolism
  • Neuroprotective Agents / therapeutic use*
  • Rats
  • Rats, Wistar
  • Superoxide Dismutase / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Glucuronates
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Neuroprotective Agents
  • Tumor Necrosis Factor-alpha
  • scutellarin
  • Malondialdehyde
  • Apigenin
  • Superoxide Dismutase