Protective Effect of Isopulegol in Alleviating Neuroinflammation in Lipopolysaccharide-Induced BV-2 Cells and in Parkinson Disease Model Induced with MPTP

J Environ Pathol Toxicol Oncol. 2021;40(3):75-85. doi: 10.1615/JEnvironPatholToxicolOncol.2021038944.

Abstract

Background: Parkinson's disease (PD) is the most prevalent disease linked with age-associated neuronal degeneration. Phytotherapeutic compounds or agents have gained increased importance because of their increased specificity and minimal side effects. Isopulegol, a monoterpene, was utilized in the present study because of its wide range of therapeutic properties. Our aim was to examine the underlying mechanism of anti-neuroinflammatory action and neuroprotective efficacy of isopulegol in cell lines and in an experimental animal model of PD.

Methods: The MTT assay was performed in microglial BV-2 cells subjected to lipopolysaccharides (LPS). The release of NO and synthesis of ROS intracellularly in BV-2 cells were detected. C57BL/6 mice induced with MPTP were examined for motor function and coordination. Expression of proinflammatory mediators was also assessed both in vivo and in vitro. Histopathological sections of brain and expression of iNOS and COX-2 were also analyzed.

Results: BV-2 cells did not exhibit noticeable toxicity at selected concentrations and LPS-incubated cells showed marked elevation of NO levels and increased production of intracellular ROS. Increased expression of proinflammatory cytokines was also observed. Motor function and coordination deficits were observed in mice induced with MPTP. Histopathological abnormalities and increased iNOS and COX-2 expression were noted in MPTP-induced mice. Administration of isopulegol reversed the changes brought about by LPS and MPTP.

Conclusion: The study indicated that isopulegol is a potential therapeutic drug against clinical complications of PD.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / pathology
  • Cell Line
  • Cell Survival / drug effects
  • Cyclohexane Monoterpenes / pharmacology*
  • Cyclooxygenase 2 / genetics
  • Cytokines / metabolism
  • Inflammation Mediators / metabolism
  • Lipopolysaccharides / toxicity
  • MPTP Poisoning / drug therapy
  • MPTP Poisoning / genetics
  • MPTP Poisoning / physiopathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microglia / drug effects
  • Microglia / metabolism
  • Motor Activity / drug effects
  • Neuroprotective Agents / pharmacology*
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / pathology
  • Reactive Oxygen Species / metabolism

Substances

  • Cyclohexane Monoterpenes
  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Nitric Oxide
  • isopulegol
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2