Crocin, a natural product attenuates lipopolysaccharide-induced anxiety and depressive-like behaviors through suppressing NF-kB and NLRP3 signaling pathway

Brain Res Bull. 2018 Sep:142:352-359. doi: 10.1016/j.brainresbull.2018.08.021. Epub 2018 Sep 1.

Abstract

Depression is one of the foremost psychological illness which is closely leagued with inflammation. Crocin is a natural product that exhibits both anti-inflammatory and anti-oxidant activities. However, little is known about anti-inflammatory mechanisms of crocin on LPS-induced anxiety and depressive-like behaviors. The objective of this study is emphasized on neuroprotective role of crocin against LPS-induced anxiety and depressive-like behaviors in mice. It is observed that crocin inhibited LPS-induced production of NO, TNF-α, IL-1β and ROS in BV-2 microglial cells. Moreover, crocin significantly declined the expression of iNOS, NF-κB p65 and CD16/32 (M1 marker), as well as elevated the expression of CD206 (M2 marker) in BV-2 cell line with decreased LPS-induced anxiety and depressive-like behaviors by improved locomotor activity, reduced sucrose intake, and decreased immobility time in forced swim and tail suspension test in Kunming mice. Expression of NLRP3, ASC and caspase-1 by i.p administration of LPS found to be neutralized with reduction in level of IL-1β, IL-18 and TNF-α in mouse hippocampus. In conclusion, these results suggested that crocin as a potential therapeutic candidate for neuro-inflammation and depressive-like behaviors induced by LPS. The effect was found to be due to inhibition of NLRP3 inflammasome and NF-κB and its promoted M1 to M2 phenotypic conversion of microglia.

Keywords: Crocin; Depression; Lipopolysaccharide; Microglial cells; NF-κB; NLRP3/caspase-1/IL-1β; Neuroinflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Outbred Strains
  • Anxiety Disorders / drug therapy*
  • Anxiety Disorders / immunology
  • Carotenoids / pharmacology*
  • Cell Line
  • Depressive Disorder / drug therapy*
  • Depressive Disorder / immunology
  • Inflammasomes / drug effects
  • Inflammasomes / metabolism
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Inflammation / psychology
  • Lipopolysaccharides
  • Mice
  • Microglia / drug effects
  • Microglia / immunology
  • NF-kappa B / metabolism*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism*
  • Neuroprotective Agents / pharmacology
  • Psychotropic Drugs / pharmacology*
  • Signal Transduction / drug effects

Substances

  • Inflammasomes
  • Lipopolysaccharides
  • NF-kappa B
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Neuroprotective Agents
  • Nlrp3 protein, mouse
  • Psychotropic Drugs
  • Carotenoids
  • crocin