Trigonelline insulates against oxidative stress, proinflammatory cytokines and restores BDNF levels in lipopolysaccharide induced cognitive impairment in adult mice

Metab Brain Dis. 2018 Jun;33(3):681-691. doi: 10.1007/s11011-017-0147-5. Epub 2017 Dec 26.


Neuroinflammation is said to play a pivotal role in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD). Trigonelline (TRG) is a naturally occurring alkaloid, commonly isolated from fenugreek and coffee beans. In the present study, we investigated whether TRG exerts neuroprotective action against LPS mediated cognitive impairment. Mice pretreated with TRG (50 and 100 mg/kg po) were administered with LPS (250 μg/kg ip) for 7 days. Memory was assessed in the Morris water maze (MWM) and Y maze. LPS administration caused poor memory retention in MWM and Y maze paradigms, and resulted in marked oxidative stress as evidenced by decrease in superoxide dismutase (SOD), reduced glutathione (GSH) levels and increased lipid peroxidation in the hippocampus and cortex. Cholinergic involvement during neuroinflammation was evaluated by measuring levels of acetylcholinesterase (AChE) enzyme. TRG treatment at both the doses reversed LPS induced behavioral and memory disturbances, significantly decreased the oxidative stress and AChE levels in both the hippocampus and cortex. LPS administration also elevated the tumour necrosis factor (TNF-α) and interleukin -6 (IL-6) levels, whereas brain derived neurotrophic factor (BDNF) levels were significantly depleted. TRG pretreatment led to decreased TNF-α and IL-6 levels and caused a significant upregulation of BDNF levels. In conclusion, present study highlights the promising neuroprotective role of TRG against LPS mediated cognitive impairment which could be attributed to reduced oxidative stress, inhibition of proinflammatory cytokines and restoration of BDNF levels.

Keywords: Brain derived neurotrophic factor; Lipopolysaccharide; Neuroinflammation; Oxidative stress; Trigonelline.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkaloids / pharmacology*
  • Animals
  • Antioxidants / pharmacology
  • Brain-Derived Neurotrophic Factor / metabolism*
  • Cognitive Dysfunction / chemically induced
  • Cognitive Dysfunction / metabolism*
  • Cytokines / metabolism*
  • Disease Models, Animal
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Lipopolysaccharides / pharmacology
  • Male
  • Memory Disorders / drug therapy
  • Mice
  • Oxidative Stress / drug effects*


  • Alkaloids
  • Antioxidants
  • Brain-Derived Neurotrophic Factor
  • Cytokines
  • Lipopolysaccharides
  • trigonelline