Investigation of the molecular mechanism underlying the inhibitory activities of ethanol extract of Bombyx mori pupa-incubated Cordyceps militaris fruiting bodies toward allergic rhinitis

Biomed Pharmacother. 2021 Mar:135:111248. doi: 10.1016/j.biopha.2021.111248. Epub 2021 Feb 1.

Abstract

Cordyceps militaris has been widely studied for its various pharmacological activities such as antitumor, anti-inflammation, and immune regulation. The binding of an allergen to IgE-sensitized mast cells in nasal mucosa triggers allergic rhinitis. We found that oral administration of 300 mg/kg of the ethanol extract prepared from silkworm pupa-cultivated Cordyceps militaris fruiting bodies significantly alleviated the symptoms of ovalbumin-induced allergic rhinitis in mice, including sneeze/scratch, mast cell activation, eosinophil infiltration, and Syk activation. The treatment of ethanol extract significantly suppressed the release of β-hexosaminidase (a degranulation marker) and mRNA expression levels of various cytokines, including IL-3, IL-10, and IL-13 in activated RBL2H3 cells. The ethanol extract and β-sitostenone, which was purified from the extract, could respectively reduce the Ca2+ ion mobilization in activated RBL-2H3 cells. Furthermore, results collected from western immunoblotting demonstrated that ethanol extract significantly retarded Ca2+ ion mobilization-initiated signaling cascade, which provoked the expression of various allergic cytokines. Also, the extract incubation interfered with P38 as well as NF-kB activation and Nrf-2 translocation. Our study suggested that ethanol extract possessed some natural constituents which could inhibit immediate degranulation and de novo synthesis of allergic cytokines via inhibition of Ca2+ ion mobilization in mast cells in the nasal mucosa of allergic rhinitis mice.

Keywords: Allergic rhinitis; CM-EE; Ca(2+) ion mobilization; Cordyceps militaris; PKC; Syk.

MeSH terms

  • Animals
  • Anti-Allergic Agents / isolation & purification
  • Anti-Allergic Agents / pharmacology*
  • Bombyx / embryology
  • Bombyx / metabolism*
  • Calcium Signaling
  • Cell Degranulation / drug effects
  • Cell Line, Tumor
  • Cordyceps / physiology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Ethanol / chemistry
  • Fruiting Bodies, Fungal / physiology*
  • Larva / metabolism
  • Male
  • Mast Cells / drug effects
  • Mast Cells / immunology
  • Mast Cells / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Nasal Mucosa / drug effects*
  • Nasal Mucosa / immunology
  • Nasal Mucosa / metabolism
  • Ovalbumin
  • Rats
  • Rhinitis, Allergic / chemically induced
  • Rhinitis, Allergic / immunology
  • Rhinitis, Allergic / metabolism
  • Rhinitis, Allergic / prevention & control*
  • Solvents / chemistry

Substances

  • Anti-Allergic Agents
  • Cytokines
  • Solvents
  • Ethanol
  • Ovalbumin