Saikosaponin A inhibits compound 48/80-induced pseudo-allergy via the Mrgprx2 pathway in vitro and in vivo.

Abstract

Pseudo-allergic reactions-adverse, non-immunologic, anaphylaxis-like sudden onset reactions mediated through an IgE-independent pathway-are activated by various basic compounds and occur at least as frequently as IgE-mediated reactions to drugs. A large family of G protein coupled receptors (Mas-related genes; Mrgprs) is closely related to pseudo-allergies. However, few therapies can directly target pseudo-allergies and related Mrgprs. Saikosaponin A (SSA) is effective in the treatment of passive cutaneous anaphylaxis (PCA), adjuvant arthritis, and delayed hypersensitiveness. In this study, we investigated the anti-pseudo-allergy effect of SSA and its underlying mechanism. We examined the effect of SSA on both IgE-independent and IgE-dependent responses using PCA and active systemic anaphylaxis models, as well as in vitro-cultured mast cells. We also evaluated whether the anti-allergy effect is related to Mrgprs by using in vitro Mrgprx2-expressing HEK293 cells. SSA dose dependently suppressed compound 48/80 (C48/80)-induced PCA and mast cell degranulation in mice. When SSA and C48/80 were administered together through the vein, C48/80-induced systemic anaphylaxis did not occur, and C48/80-induced shock ratio decreased dose-dependently upon SSA treatment. However, SSA did not affect IgE-dependent allergy. When administered topically 24 h before antigen challenge, Evans blue leakage and paw swelling were induced in the SSA-treated group and the vehicle group. Our in vitro studies revealed that SSA reduced C48/80-induced calcium flux and suppressed degranulation in LAD2 cells. SSA could also dose-dependently inhibit C48/80-induced Mrgprx2-expressing HEK293 cell activation. As a conclusion, SSA could inhibits IgE-independent allergy, but not IgE-dependent allergy, and this effect involves the Mrgprx2 pathway. This study provided a new sight on pseudo-allergy and its therapy.

• Authors: Nan Wang, Delu Che, Tao Zhang, Rui Liu, Jiao Cao, Jue Wang, Tingting Zhao, Pengyu Ma, Xinzhong Dong, Langchong He
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 148 Pg. 147-154 (02 2018) ISSN: 1873-2968 [Electronic] England
• PMID: 29274317 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Mrgprx2 protein, mouse
• Receptors, G-Protein-Coupled
• Saponins
• Immunoglobulin E
• p-Methoxy-N-methylphenethylamine
• Oleanolic Acid
• saikosaponin D

Topics

• Animals
• Edema (chemically induced, prevention & control)
• Immunoglobulin E
• Male
• Mast Cells
• Mice
• Oleanolic Acid (analogs & derivatives, pharmacology)
• Passive Cutaneous Anaphylaxis
• Receptors, G-Protein-Coupled (metabolism)
• Saponins (pharmacology)
• p-Methoxy-N-methylphenethylamine (toxicity)