Sea buckthorn leaves and gallic acid inhibit C48/80-induced pseudo-allergic reaction via the PLC/IP3 signaling pathway both in vitro and in vivo

Abstract

A pseudo-allergic reaction is an abrupt, IgE-independent reaction that is similar to an allergic reaction. Sea Buckthorn leaves (SBL) have been extensively researched for their pharmacological benefits, including immunological modulation, anti-inflammatory and anti-tumor properties. However, at present, its anti-pseudo-allergic effect are remains to be assessed. In this work, the therapeutic impact and mechanism of SBL extract and its active monomer gallic acid (GA) on pseudo-allergic reaction were studied. A total of 61 SBL extract components were identified using UPLC-Q-Exactive-Orbitrap-MS and HPLC, of which the main component GA was 16.73 ± 0.30 mg/g. GA was identified as the primary active ingredient in SBL extract through hyaluronidase inhibition experiments and molecular docking techniques. It was found that SBL extract and GA reduced capillary dilatation and the rate of paw swelling and Evans blue exudation in C48/80-induced passive cutaneous anaphylaxis (PCA). In C48/80-induced mice systemic allergy model, SBL extract and GA were observed to reverse the reduction in body temperature and block the release of allergic mediators histamine and inflammatory factors TNF-α, CCL2, and IL-6. Using the C48/80-induced RBL-2H3 cells model, it was further demonstrated that SBL extract and GA prevented RBL-2H3 cells activation in vitro, which lowered the release of allergy mediators histamine and β-hexosaminidase as well as inflammatory factors TNF-α, CCL2, and IL-6. SBL extract and GA also reduced intracellular Ca²⁺ concentration. Furthermore, the phosphorylation levels of PLC γ1 and IP3 could be downregulated by SBL extract and GA. To sum up, SBL extract and GA reduced pseudo-allergic reactions brought on by C48/80 and are anticipated to be created as novel medications to treat pseudo-allergic reactions.