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.
摘要：
近年来过敏反应的发病率稳步上升,促使人们对鉴定可以预防或治疗过敏性疾病的有效和安全的天然化合物越来越感兴趣。黄柏。长期以来一直被用作过敏性疾病的治疗方法，其主要成分是黄柏碱。然而,黄柏碱治疗过敏性疾病的疗效尚待评估。肥大细胞是过敏反应的主要效应，它们不仅被IgE依赖性途径激活，而且还通过不依赖IgE的途径通过人MRGPRX2，大鼠对应物MRGPRB3。因此，本研究探讨黄柏碱通过该家族受体在体内外治疗过敏性疾病的作用及机制。这些分析表明，黄柏碱的给药足以防止C48/80引起的小鼠足部肿胀和伊文思蓝渗出，并抑制C48/80诱导的RBL-2H3大鼠嗜碱性白血病细胞脱颗粒，和β-HEX,HIS,IL-4和TNF-α释放。此外，黄柏碱可以通过改变其结构来降低MRGPRB3的mRNA表达和MRGPRX2的反应性。它能够降低Ca2+水平，CaMK的磷酸化水平，PLCβ1,PKC,ERK,JNK,p38和p65，并抑制IκB-α的降解。这些分析表明，小檗碱通过改变MRGPRB3/MRGPRX2蛋白的构象，抑制PLC的激活并下调内质网中Ca2的释放。从而抑制PKC的激活，随后抑制下游MAPK和NF-κB信号，最终抑制过敏反应。因此，专注于开发黄柏碱作为新型抗过敏药物的研究可能有进一步的价值。
