Acorus gramineus inhibits microglia mediated neuroinflammation and prevents neurotoxicity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson's disease

J Ethnopharmacol. 2012 Dec 18;144(3):506-13. doi: 10.1016/j.jep.2012.09.026. Epub 2012 Oct 17.

Abstract

Ethnopharmacological relevance: Acorus gramineus Solander (Acoraceae, AG), is a widely distributed plant in Asian countries. Rhizome part of this plant has long been used as a traditional medicine for treating various symptoms including central nervous system (CNS) disorders.

Aim of study: The anti-neuroinflammatory effect of AG aqueous extract was investigated using in vitro cellular and in vivo Parkinson's disease (PD) mouse model.

Materials and methods: Lipopolysaccharide (LPS) is used to stimulate BV-2 microglial cells in vitro and the changes in neuroinflammatory expressional levels were measured using ELISA, Western blotting, RT-PCR and immunofluorescence techniques. In in vivo experiments, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-intoxicated mouse model of PD was developed followed by immunohistochemical analysis of specific brain tissues.

Results: LPS-stimulation to BV-2 cells increased the production of nitric oxide (NO) and proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β. Pretreatment with AG extract inhibited the increased levels of NO and pro-inflammatory cytokines in LPS-stimulated BV-2 cells. Mechanistic study revealed that AG acts via the regulation of nuclear factor kappa B (NF-κB), mitogen-activated protein kinases (MAPKs) and TRIF-dependent signaling pathways. Further, AG protected MPTP-induced neuronal cell death and inhibited neuroinflammation in vivo.

Conclusion: Our results indicated that AG extract exerted anti-neuroinflammatory effects against activated microglia mediated insults through multiple signaling pathways and prevented in vivo neuronal cell death in mouse model of PD substantiating the traditional claims for its use in CNS disorders.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Acorus*
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Cell Line
  • Cell Survival / drug effects
  • Cytokines / genetics
  • Disease Models, Animal
  • Heme Oxygenase-1 / metabolism
  • Lipopolysaccharides
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Microglia
  • Mitogen-Activated Protein Kinases / metabolism
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / etiology
  • Parkinson Disease / pathology
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Rhizome

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Lipopolysaccharides
  • Membrane Proteins
  • Neuroprotective Agents
  • Plant Extracts
  • Nitric Oxide
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Heme Oxygenase-1
  • Hmox1 protein, mouse
  • Mitogen-Activated Protein Kinases