6-Gingerol attenuates LPS-induced neuroinflammation and cognitive impairment partially via suppressing astrocyte overactivation

Biomed Pharmacother. 2018 Nov:107:1523-1529. doi: 10.1016/j.biopha.2018.08.136. Epub 2018 Sep 5.

Abstract

6-Gingerol, the major component of gingerols extracted from Zingiber officinale, has been shown to exhibit anti-inflammatory and antioxidant bioactivities. Since neuroinflammation plays an important role in neurodegenerative diseases, such as Alzheimer's disease (AD), and astrocytes have been considered important in the process of neurodegeneration, it was of interest to know whether 6-gingerol reduced astrocytes activation or even attenuated cognitive impairment. Here we examined the neuroprotective effects of 6-gingerol in lipopolysaccharide (LPS)-induced disorder models both in vitro and in vivo. C6 astroglioma cells treated with LPS were found to release excessive pro-inflammatory cytokines, including TNF-α and IL-6, and also increase intercellular ROS, NO, and iNOS (i.e. NOS2). All these were blocked by 6-gingerol in a concentration-dependent manner. The spatial learning and memory of rats challenged with LPS (10 μg, i.c.v.) in the absence or presence of 6-gingerol were evaluated using the Morris water-maze (MWM) test. 6-Gingerol attenuated LPS-induced imapirement of MWM learning and memory in a dose-dependent manner. Besides, 6-gingerol inhibited LPS-induced increases in levels of GFAP and TNF-α in the rat brain. The results suggest that 6-gingerol suppresses astrocyte overactivation, through which it contributes to improvement of cognitive ability.

Keywords: 6-Gingerol; Astrocyte; Learning and memory; Neuroinflammation; Oxidative stress.

MeSH terms

  • Animals
  • Astrocytes / drug effects*
  • Astrocytes / pathology
  • Catechols / administration & dosage
  • Catechols / pharmacology*
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / physiopathology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Fatty Alcohols / administration & dosage
  • Fatty Alcohols / pharmacology*
  • Glial Fibrillary Acidic Protein / metabolism
  • Inflammation / drug therapy
  • Inflammation / pathology
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / toxicity
  • Male
  • Maze Learning / drug effects
  • Memory / drug effects
  • Memory Disorders / drug therapy
  • Memory Disorders / physiopathology
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / physiopathology
  • Neuroprotective Agents / administration & dosage
  • Neuroprotective Agents / pharmacology*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Catechols
  • Cytokines
  • Fatty Alcohols
  • GFAP protein, rat
  • Glial Fibrillary Acidic Protein
  • Inflammation Mediators
  • Lipopolysaccharides
  • Neuroprotective Agents
  • gingerol