The anti-anaphylactoid effects of hydroxysafflor yellow A on the suppression of mast cell Ca²⁺ influx and degranulation

Background: Anaphylaxis is a type of potentially fatal hypersensitivity reaction resulting from the activation of mast cell mediators, especially histamine and lipid mediators. Non-IgE-mediated anaphylaxis can occur because of the direct activation of mast cells. Hydroxysafflor yellow A (HSYA) is the main chemical component of safflower (Carthamus tinctorius) and has been reported to have pharmacological activities. However, the anti-anaphylactoid effect of HSYA has not yet been investigated. Purpose: The aims of this study were to evaluate the anti-anaphylactoid activity of HSYA in vivo and to investigate the underlying mechanism in vitro. Methods: The anti-anaphylactoid activity of HSYA was evaluated in a mouse model of hindpaw extravasation. Calcium imaging was used to assess intracellular Ca²⁺ mobilization. The levels of cytokines and chemokines released by stimulated mast cells were measured using enzyme immunoassay kits. Western blotting was used to explore the related molecular signaling pathways. Results: HSYA markedly inhibited mast cell degranulation by suppressing the activation of intracellular Ca²⁺ mobilization and preventing the release of cytokines and chemokines from mast cells in a dose-dependent manner via the PKC-PLCγ-IP3R signaling pathway. Conclusion: In summary, HSYA has anti-anaphylactoid pharmacological activity, which makes it a potential candidate for the development of a novel agent to suppress drug-induced anaphylactoid reactions.