Rotundine/L-THP Revealed an Anti-Allergic Asthma Effect Through MRGPRX2

Background: Allergic Asthma is a chronic inflammatory disorder that can be characterized by airway hyperresponsiveness, inflammation, and remodeling. Despite many modern advancements in treatment, still there remains a need for more effective and targeted therapies. Recent studies have identified MRGPRX2 (Mas-Related G Protein-Coupled Receptor X2) as a key factor in mast cell-mediated allergic disease, this makes it a promising therapeutic target. Rotundine, a natural compound with known anti-inflammatory properties, has shown potential in modulating MRGPRX2 activity in mast cells. This review aims to investigate the anti-allergic effects of Rotundine (L-THP, Levo-tetrahydropalmatine) and how it can benefit allergic-asthma patients through its interaction with MRGPRX2, addressing the unknown in current knowledge regarding MRGPRX2-mediated pathways and their therapeutic potential ability. By collecting knowledge from existing literature, this review study will explore the mechanisms underlying Rotundine’s effects, its efficacy in relieving asthma symptoms, and its potential ability as a novel therapeutic treatment for allergic asthma. Objectives: The objective of this systematic review is to demonstrate an overview knowledge of the role of MRGPRX2 in allergic asthma pathogenesis, synthesize and critically evaluate the available evidence regarding the mechanisms by which Rotundine/L-THP modulates MRGPRX2 signaling in mast cells, and its efficacy in alleviating allergic asthma symptoms. Design and Methods: This review synthesizes findings from preclinical and clinical studies, focusing on the mechanisms by which Rotundine/L-THP modulates MRGPRX2 activity and allergic asthma symptoms. A comprehensive search of relevant databases such as PubMed, Web of Science, Google Scholar, and Frontiers. Studies focusing on MRGPRX2, mast cell activation, allergic asthma pathophysiology, and the pharmacological properties of Rotundine/L-THP were analyzed. Emphasis was placed on experimental and clinical studies that investigate the interaction between Rotundine and MRGPRX2, as well as its potential therapeutic applications. Results: This review summarizes results on how Rotundine/L-THP reduces the release of histamine, tryptase, and pro-inflammatory cytokines, hence preventing MRGPRX2-mediated mast cell activation, which in turn has anti-allergic asthma benefits. It minimizes airway inflammation by suppressing Th2 immune responses by lowering IL-4, IL-5, and IL-13 levels as well as by downregulating NF-κB and MAPK pathways. Preclinical research reveals that it successfully lowers immune cell infiltration and airway hyperresponsiveness in animal models. While these outcomes suggest that Rotundine/L-THP is a promising therapeutic target to treat allergic asthma. Moreover, further research is needed to confirm its direct interaction with MRGPRX2 and validate its clinical potential.