Viridicatol Isolated from Deep-Sea Penicillium Griseofulvum Alleviates Anaphylaxis and Repairs the Intestinal Barrier in Mice by Suppressing Mast Cell Activation

Mar Drugs. 2020 Oct 16;18(10):517. doi: 10.3390/md18100517.

Abstract

Viridicatol is a quinoline alkaloid isolated from the deep-sea-derived fungus Penicillium griseofulvum. The structure of viridicatol was unambiguously established by X-ray diffraction analysis. In this study, a mouse model of ovalbumin-induced food allergy and the rat basophil leukemia (RBL)-2H3 cell model were established to explore the anti-allergic properties of viridicatol. On the basis of the mouse model, we found viridicatol to alleviate the allergy symptoms; decrease the levels of specific immunoglobulin E, mast cell protease-1, histamine, and tumor necrosis factor-α; and promote the production of interleukin-10 in the serum. The treatment of viridicatol also downregulated the population of B cells and mast cells (MCs), as well as upregulated the population of regulatory T cells in the spleen. Moreover, viridicatol alleviated intestinal villi injury and inhibited the degranulation of intestinal MCs to promote intestinal barrier repair in mice. Furthermore, the accumulation of Ca2+ in RBL-2H3 cells was significantly suppressed by viridicatol, which could block the activation of MCs. Taken together, these data indicated that deep-sea viridicatol may represent a novel therapeutic for allergic diseases.

Keywords: X-ray single crystal; calcium influx; deep-sea-derived viridicatol; food allergy; intestinal barrier; mast cell.

MeSH terms

  • Anaphylaxis / drug therapy
  • Animals
  • Anti-Allergic Agents / isolation & purification
  • Anti-Allergic Agents / pharmacology*
  • Aquatic Organisms / chemistry
  • Aquatic Organisms / metabolism
  • B-Lymphocytes / drug effects
  • Calcium / metabolism
  • Cell Line, Tumor
  • Disease Models, Animal
  • Food Hypersensitivity / drug therapy
  • Food Hypersensitivity / etiology
  • Histamine / blood
  • Hydroxyquinolines / chemistry
  • Hydroxyquinolines / isolation & purification
  • Hydroxyquinolines / pharmacology*
  • Immunoglobulin E / blood
  • Interleukin-10 / blood
  • Intestines / drug effects
  • Intestines / pathology
  • Mast Cells / drug effects
  • Mice
  • Ovalbumin / toxicity
  • Penicillium / chemistry*
  • Penicillium / metabolism*
  • Peptide Hydrolases / blood
  • Quinolones / chemistry
  • Quinolones / isolation & purification
  • Quinolones / pharmacology*
  • Rats
  • T-Lymphocytes, Regulatory / metabolism
  • Tumor Necrosis Factor-alpha / blood
  • beta-N-Acetylhexosaminidases / metabolism

Substances

  • Anti-Allergic Agents
  • Hydroxyquinolines
  • IL10 protein, mouse
  • Quinolones
  • Tnf protein, mouse
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Immunoglobulin E
  • viridicatol
  • Histamine
  • Ovalbumin
  • beta-N-Acetylhexosaminidases
  • Peptide Hydrolases
  • Calcium

Supplementary concepts

  • Penicillium griseofulvum