Inhibitory effect of phellodendrine on C48/80-induced allergic reaction in vitro and in vivo

https://www.sciencedirect.com/science/article/abs/pii/S1567576924007756

International Immunopharmacology, Volume 134, 15 June 2024, 112256

Jing Wang, Jianzeng Liu, Yang Yang, Guang Sun, Dan Yang, Shuhe Yin, Shuai Zhang, Wenqi Jin, Daqing Zhao, Liwei Sun, Rui Jiang

Highlights

• Phellodendrine prevents allergic reactions in vitro and in vivo.

• Phellodendrine can target MRGPRB3/MRGPRX2 channel to inhibit allergic reaction.

• Phellodendrine inhibits cell degranulation through PLC/PKC/Ca2+ signaling pathways.

• Phellodendrine by MAPK and NF-κB pathway reduce the release of inflammatory factors.

Abstract

The incidence of allergic reactions has risen steadily in recent years, prompting growing interest in the identification of efficacious and safe natural compounds that can prevent or treat allergic diseases. Phellodendron amurense Rupr. has long been applied as a treatment for allergic diseases, whose primary component is phellodendrine. However, the efficacy of phellodendrine as a treatment for allergic diseases remains to be assessed. Mast cells are the primary effectors of allergic reactions, which are not only activated by IgE-dependent pathway, but also by IgE-independent pathways via human MRGPRX2, rat counterpart MRGPRB3. As such, this study explored the effect and mechanism of phellodendrine through this family receptors in treating allergic diseases in vitro and in vivo. These analyses revealed that phellodendrine administration was sufficient to protect against C48/80-induced foot swelling and Evans blue exudation in mice, and suppressed C48/80-induced RBL-2H3 rat basophilic leukemia cells degranulation, and β-HEX, HIS, IL-4, and TNF-α release. Moreover, phellodendrine could reduce the mRNA expression of MRGPRB3 and responsiveness of MRGPRX2 by altering its structure. It was able to decrease Ca2+ levels, phosphorylation levels of CaMK, PLCβ1, PKC, ERK, JNK, p38, and p65, and inhibit the degradation of IκB-α. These analyses indicate that berberine inhibits the activation of PLC and downregulates the release of Ca2+ in the endoplasmic reticulum by altering the conformation of MRGPRB3/MRGPRX2 protein, thereby inhibiting the activation of PKC and subsequently inhibiting downstream MAPK and NF-κB signaling, ultimately suppressing allergic reactions. There may thus be further value in studies focused on developing phellodendrine as a novel anti-allergic drug.

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