Gomisin M2 Inhibits Mast Cell-Mediated Allergic Inflammation via Attenuation of FcεRI-Mediated Lyn and Fyn Activation and Intracellular Calcium Levels

Abstract

Mast cells are effector cells that induce allergic inflammation by secreting inflammatory mediators. Gomisin M2 (G.M2) is a lignan isolated from Schisandra chinensis (Turcz). Baill. exhibiting anti-cancer activities. We aimed to investigate the anti-allergic effects and the underlying mechanism of G.M2 in mast cell–mediated allergic inflammation. For the in vitro study, we used mouse bone marrow–derived mast cells, RBL-2H3, and rat peritoneal mast cells. G.M2 inhibited mast cell degranulation upon immunoglobulin E (IgE) stimulation by suppressing the intracellular calcium. In addition, G.M2 inhibited the secretion of pro-inflammatory cytokines. These inhibitory effects were dependent on the suppression of FcεRI-mediated activation of signaling molecules. To confirm the anti-allergic effects of G.M2 in vivo , IgE-mediated passive cutaneous anaphylaxis (PCA) and ovalbumin-induced active systemic anaphylaxis (ASA) models were utilized. Oral administration of G.M2 suppressed the PCA reactions in a dose-dependent manner. In addition, G.M2 reduced the ASA reactions, including hypothermia, histamine, interleukin-4, and IgE production. In conclusion, G.M2 exhibits anti-allergic effects through suppression of the Lyn and Fyn pathways in mast cells. According to these findings, we suggest that G.M2 has potential as a therapeutic agent for the treatment of allergic inflammatory diseases via suppression of mast cell activation.

Glaucocalyxin A Attenuates Allergic Responses by Inhibiting Mast Cell Degranulation through p38MAPK/NrF2/HO-1 and HMGB1/TLR4/NF-κB Signaling Pathways

“…Fc ε RI-mediated mast cell activation involves calcium influx [ 25 ]. The release of intracellular calcium leads to the degranulation of mast cells.…”

Gomisin M2 Ameliorates Atopic Dermatitis-like Skin Lesions via Inhibition of STAT1 and NF-κB Activation in 2,4-Dinitrochlorobenzene/Dermatophagoides farinae Extract-Induced BALB/c Mice

“…To date, it has been reported that GM2 was isolated from the fruit of S. rubriflora had an anti-HIV replication effect on H9 lymphocytes in vitro [ 26 ]. In addition, we have previously reported that GM2 isolated from S. chinensis fruit inhibited acute inflammation caused by mast cell-mediated allergic inflammation [ 16 ]. In this study, we have defined the role of GM2 in the chronic inflammatory skin disease, in particular, AD.…”

“…The extracts of S. chinensis have active lignans, such as deoxyschisandrin, γ-schisandrin, and gomisin [ 14 , 15 ]. Among the lignans, gomisin M2 (GM2) has slightly greater antiallergic properties through the suppression of mast cell activation compared to the other lignans [ 16 ]. Although whole S. chinesis extracts have been reported to suppress AD [ 17 , 18 ], the biological and pharmacological activities of GM2 within S. chinesis extracts are not well characterized as chronic relapsing inflammatory skin disease, particularly AD.…”

Gomisin M2 alleviates psoriasis‑like skin inflammation by inhibiting inflammatory signaling pathways

“…In particular, lignans, which function as antioxidants and play a role in plant defenses, and exhibit anti-inflammatory and antioxidant activities that can be utilized to treat skin diseases (16). Among the lignans, gomisin M2 (GM2) has shown antiallergic effects by inhibiting mast cell activation and the human immunodeficiency virus (17)(18)(19).…”

“…1A and S2A). Recently, GM2 has been demonstrated to have anti-allergic effects (17). Therefore, to investigate whether GM2 reduced the number of mast cells in IMQ-induced skin, toluidine blue-stained tissues were microscopically examined.…”