Oleanolic acid protects against mast cell-mediated allergic responses by suppressing Akt/NF-κB and STAT1 activation

Phytomedicine. 2021 Jan:80:153340. doi: 10.1016/j.phymed.2020.153340. Epub 2020 Oct 15.

Abstract

Background: Oleanolic acid (OA) is an active compound found in a variety of medicinal herbs and plants. Though OA has been widely attributed with a variety of biological activities, studies focused on its anti-allergic inflammation properties are insufficient.

Purpose: Given the rapid increase in allergic diseases and the lack of fundamental treatment options, this study aimed to find a safe and effective therapy for allergic disorders.

Methods: We evaluated the inhibitory effect of OA on allergic inflammatory response and the possible mechanisms underlying the effect using phorbol-12-myristate 13-acetate plus calcium ionophore A23187 (PMACI)-stimulated human mast cell (HMC)-1, and a mouse model of compound 48/80-induced anaphylactic shock.

Results: OA suppressed pro-inflammatory cytokine expressions in PMACI-induced HMC-1 cells by inhibiting activation of the Akt, p38 mitogen-activated protein kinase (MAPK), nuclear factor-κB (NF-κB), and signal transducer and activator of transcription (STAT) 1 signaling pathways. Moreover, OA showed a protective effect against compound 48/80-induced anaphylactic shock through inhibition of histamine release and immunoglobulin E level via regulation of NF-κB and STAT1 activation.

Conclusion: The results showed that OA suppressed mast cell-mediated allergic response by transcriptional regulation. We suggest that OA has potential effect against allergic inflammatory disorders, including anaphylaxis, and might be a useful therapeutic agent for allergic disease.

Keywords: Allergic responses; Anaphylaxis; Mast cell; NF-κB; Oleanolic acid; STAT1.

MeSH terms

  • Anaphylaxis / chemically induced
  • Anaphylaxis / prevention & control*
  • Animals
  • Anti-Allergic Agents / pharmacology*
  • Calcimycin / toxicity
  • Cell Line
  • Cytokines / metabolism
  • Histamine Release / drug effects
  • Humans
  • Inflammation / drug therapy
  • Inflammation Mediators / metabolism
  • Male
  • Mast Cells / drug effects*
  • Mast Cells / metabolism
  • Mice
  • Mice, Inbred ICR
  • NF-kappa B / metabolism
  • Oleanolic Acid / pharmacology*
  • Phorbol Esters / toxicity
  • Proto-Oncogene Proteins c-akt / metabolism
  • STAT1 Transcription Factor / metabolism
  • p-Methoxy-N-methylphenethylamine / toxicity
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anti-Allergic Agents
  • Cytokines
  • Inflammation Mediators
  • NF-kappa B
  • Phorbol Esters
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • phorbol-12-myristate
  • Calcimycin
  • p-Methoxy-N-methylphenethylamine
  • Oleanolic Acid
  • Proto-Oncogene Proteins c-akt
  • p38 Mitogen-Activated Protein Kinases