Pinoresinol diglucoside alleviates ischemia/reperfusion-induced brain injury by modulating neuroinflammation and oxidative stress

Chem Biol Drug Des. 2021 Dec;98(6):986-996. doi: 10.1111/cbdd.13956. Epub 2021 Oct 3.

Abstract

Brain ischemia/reperfusion (I/R) injury is a common pathological process after ischemic stroke. Pinoresinol diglucoside (PDG) has antioxidation and anti-inflammation activities. However, whether PDG ameliorates brain I/R injury is still unclear. In this study, middle cerebral artery occlusion (MCAO) model was established with male C57BL/6 mice, and the mice were treated with 5 and 10 mg/kg PDG via intravenous injection, respectively. The neurological deficit, infarct volume, and brain water content were then evaluated. HE staining and Nissl staining were used to analyze neuron injury. Besides, enzyme-linked immunosorbent assay and colorimetry assay were used to examine the level of inflammatory markers and oxidative stress markers, and Western blot was used to detect the expressions of p-p65, Nrf2, and HO-1. It was revealed that PDG could significantly alleviate the MCAO-induced neurological dysfunction of the mice and reduce the infarct volume, brain water content, and neuron injury. PDG treatment decreased the levels of TNF-α, IL-1β, IL-6, NO, ROS, and MDA, and significantly increased the activities of SOD, GSH, and GSH-Px in the brain tissue of the mice. Additionally, PDG could repress the activation of p65 and promote Nrf2 and HO-1 expressions. In conclusion, PDG exerts anti-inflammatory and antioxidation effects via regulating the NF-κB pathway and Nrf2/HO-1 pathway, thereby reducing the I/R-induced brain injury of mice.

Keywords: brain injury; ischemia; neuroinflammation; oxidative stress; pinoresinol diglucoside; reperfusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Brain Ischemia / drug therapy
  • Brain Ischemia / pathology
  • Cytokines / metabolism
  • Disease Models, Animal
  • Heme Oxygenase-1 / metabolism
  • Lignans / pharmacology*
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Middle Cerebral Artery
  • NF-E2-Related Factor 2 / metabolism
  • Neuroinflammatory Diseases / drug therapy*
  • Neuroinflammatory Diseases / etiology
  • Neurons / drug effects
  • Neurons / pathology
  • Oxidative Stress / drug effects*
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / physiopathology

Substances

  • Cytokines
  • Lignans
  • Membrane Proteins
  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • pinoresinol diglucoside
  • Heme Oxygenase-1
  • Hmox1 protein, mouse