Vinpocetine alleviates lung inflammation via macrophage inflammatory protein-1β inhibition in an ovalbumin-induced allergic asthma model

PLoS One. 2021 Apr 29;16(4):e0251012. doi: 10.1371/journal.pone.0251012. eCollection 2021.

Abstract

Asthma is a well-known bronchial disease that causes bronchial inflammation, narrowing of the bronchial tubes, and bronchial mucus secretion, leading to bronchial blockade. In this study, we investigated the association between phosphodiesterase (PDE), specifically PDE1, and asthma using 3-isobutyl-1-methylxanthine (IBMX; a non-specific PDE inhibitor) and vinpocetine (Vinp; a PDE1 inhibitor). Balb/c mice were randomized to five treatment groups: control, ovalbumin (OVA), OVA + IBMX, OVA + Vinp, and OVA + dexamethasone (Dex). All mice were sensitized and challenged with OVA, except for the control group. IBMX, Vinp, or Dex was intraperitoneally administered 1 h before the challenge. Vinp treatment significantly inhibited the increase in airway hyper-responsiveness (P<0.001) and reduced the number of inflammatory cells, particularly eosinophils, in the lungs (P<0.01). It also ameliorated the damage to the bronchi and alveoli and decreased the OVA-specific IgE levels in serum, an indicator of allergic inflammation increased by OVA (P<0.05). Furthermore, the increase in interleukin-13, a known Th2 cytokine, was significantly decreased by Vinp (P<0.05), and Vinp regulated the release and mRNA expression of macrophage inflammatory protein-1β (MIP-1β) increased by OVA (P<0.05). Taken together, these results suggest that PDE1 is associated with allergic lung inflammation induced by OVA. Thus, PDE1 inhibitors can be a promising therapeutic target for the treatment of asthma.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-3-isobutylxanthine / administration & dosage
  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Animals
  • Anti-Inflammatory Agents / administration & dosage*
  • Anti-Inflammatory Agents / pharmacology
  • Asthma / chemically induced
  • Asthma / drug therapy*
  • Asthma / genetics
  • Chemokine CCL4 / genetics*
  • Dexamethasone / administration & dosage
  • Dexamethasone / pharmacology
  • Disease Models, Animal
  • Down-Regulation*
  • Gene Expression Regulation / drug effects
  • Lung / drug effects
  • Lung / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Ovalbumin / adverse effects*
  • Random Allocation
  • Vinca Alkaloids / administration & dosage*
  • Vinca Alkaloids / pharmacology

Substances

  • Anti-Inflammatory Agents
  • Ccl4 protein, mouse
  • Chemokine CCL4
  • Vinca Alkaloids
  • vinpocetine
  • Dexamethasone
  • Ovalbumin
  • 1-Methyl-3-isobutylxanthine

Grants and funding

This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science & ICT) (grant number NRF-2018R1C1B6008326).