Tanshinone IIA improves degranulation of mast cells and allergic rhinitis induced by ovalbumin by inhibiting the PLCγ1/PKC/IP3R pathway

Hum Exp Toxicol. 2021 Dec;40(12_suppl):S702-S710. doi: 10.1177/09603271211058884. Epub 2021 Nov 18.

Abstract

Allergic rhinitis (AR) is a common allergic inflammatory and chronic reactive disease caused by allergen-induced immunoglobulin E (IgE). Tanshinone IIA (Tan IIA) is one of the active ingredients in Salvia miltiorrhiza Bunge (Danshen) and plays a vital role in inhibiting inflammation. Thus, we hypothesized that Tan IIA has anti-allergic effects and studied the function of Tan IIA in mast cells and an AR animal model. We induced RBL-2H3 cell sensitization with monoclonal anti-2,4,6-dinitrophenyl-immunoglobulin (Ig) E/human serum albumin (DNP-IgE/HSA) and constructed an ovalbumin (OVA)-induced AR model in mice. The role of Tan IIA in AR progression was studied using the MTT assay, ELISA, western blot, toluidine blue staining, HE staining, and Alcian blue and safranin O (A&S) staining. Tan IIA treatment significantly increased IgE/HSA-induced cell viability. However, Tan IIA treatment markedly downregulated the expression levels of β-hexosaminidase, histamine, tumor necrosis factor (TNF-α), interleukin 1β (IL-1β), IL-4, and IL-5 in IgE/HSA-induced cells. Furthermore, Tan IIA improved typical symptoms in the OVA-induced AR model mice by inhibiting the phospholipase Cγ1 (PLCγ1)/protein kinase C (PKC)/IP3R pathway. Additionally, Tan IIA effectively improved the degranulation of RBL-2H3 cells and OVA-induced AR in mice. Together, these results suggest that Tan IIA may be a potential drug for the treatment of AR in the future.

Keywords: Tanshinone IIA; allergic rhinitis; degranulation; mast cell; ovalbumin.

MeSH terms

  • Abietanes / pharmacology*
  • Abietanes / therapeutic use
  • Animals
  • Cell Degranulation / drug effects*
  • Cell Line
  • Disease Models, Animal
  • Mast Cells / drug effects*
  • Mice
  • Ovalbumin / adverse effects
  • Phospholipase C gamma / metabolism*
  • Protein Kinase C / metabolism*
  • Rhinitis, Allergic / drug therapy*
  • Rhinitis, Allergic / metabolism

Substances

  • Abietanes
  • tanshinone
  • Ovalbumin
  • Protein Kinase C
  • PLCG1 protein, human
  • Phospholipase C gamma