A calcium channel blocker, manoalide exerts an anti-allergic inflammatory effect through attenuating NF-κB activity

Immunopharmacol Immunotoxicol. 2021 Dec;43(6):799-805. doi: 10.1080/08923973.2021.1988101. Epub 2021 Oct 28.

Abstract

Background: Many people are troubled by allergic inflammation including ocular allergic diseases, anaphylaxis, allergic rhinitis, atopic dermatitis, and eczema. Consequently, finding medications for use in allergic inflammation therapy is crucial in human health. Manoalide, a marine natural product isolated as an anti-bacterial metabolite from Luffariella variabilis, is a calcium channel blocker. However, its latent ability as an anti-allergic inflammatory agent has not yet been reported. Our research aimed to elucidate whether manoalide exerts an anti-allergic inflammatory effect in the human mast cell line, HMC-1.

Methods: Herein, we investigated the immunoregulatory effects and molecular mechanisms of manoalide in HMC-1 cells.

Results: Manoalide significantly alleviated secretion of the inflammatory cytokines interleukin (IL)-1β, thymic stromal lymphopoietin, tumor necrosis factor-α, IL-6, and IL-8 via blockage of caspase-1 without cytotoxicity in activated HMC-1 cells. Activation of nuclear factor-κB increased by mast cell stimulation was attenuated by treatment with manoalide. In addition, we demonstrated that manoalide treatment remarkably attenuated the activation of mitogen-activated protein kinases in activated-HMC-1 cells.

Conclusions: Taken together, our findings indicate manoalide has an anti-allergic inflammatory role, and we propose that manoalide might have potential as a novel anti-allergic inflammatory agent.

Keywords: HMC-1 cells; Manoalide; allergic inflammation; caspase-1; nuclear factor-κB.

MeSH terms

  • Anti-Allergic Agents / pharmacology*
  • Calcium Channel Blockers / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Dose-Response Relationship, Drug
  • Humans
  • Inflammation Mediators / antagonists & inhibitors
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Mast Cells / drug effects*
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / immunology
  • NF-kappa B / metabolism
  • Terpenes / pharmacology*

Substances

  • Anti-Allergic Agents
  • Calcium Channel Blockers
  • Inflammation Mediators
  • NF-kappa B
  • Terpenes
  • manoalide