MrgX2-targeted ligand screening from Artemisia capillaris Thunb. extract and receptor-ligand interaction analysis based on MrgX2-HALO-tag/CMC

• Published in: Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2024-08, Vol.1244, p.124252, Article 124252
• Main Authors: Jiang, Yuhan, Guo, Na, Zhang, Quan, Xu, Xiaochan, Qiang, Mengyang, Lv, Yanni
• Format: Article
• Language: English
• Subjects: Artemisia capillaris Thunb; MrgX2-HALO-tag/CMC; Pseudo‑allergic components; Receptor-ligand interaction
• ISSN: 1570-0232; 1873-376X; 1873-376X
• DOI: 10.1016/j.jchromb.2024.124252

•MrgX2-HALO-tag/CMC-HPLC-MS system was used to screen MrgX2-targeted ligands from A. capillaris extract.•Interactions between ligands and MrgX2 were studied by CMC model and molecular docking.•Seven chlorogenic acid analogs in A. capillaris extract were screened out as potential pseudo‑allergic compounds. Artemisia capillaris Thunb. (A. capillaris) is a well-known traditional Chinese herbal medicine with a wide range of pharmacological effects, such as soothing the liver and gallbladder, heat clearance, and detoxifying. Hence, its extract is commonly added to various traditional Chinese medicine formulas. Traditional Chinese medicine injection (TCMI) is a mature pharmaceutical dosage form developed using TCM theory combined with modern science and technology. Notably, allergic reactions, especially pseudo‑allergic reactions (PARs), greatly limited the use of these injections. Therefore, screening pseudo‑allergic components in A. capillaris extract is clinically significant. In the present study, we proposed a two-dimensional screening and identification system based on mas-related G protein-coupled receptor X2-HALO-tag/cell membrane chromatography (MrgX2-HALO-tag/CMC) high performance liquid chromatography mass spectrometry (HPLC-MS); seven potential active components were screened from 75 % ethanol extract of A. capillaris: NCA, CA, CCA, 1,3-diCQA, ICA-B, ICA-A, and ICA-C. The receptor-ligand interactions between these seven compounds and MrgX2 protein were analyzed using frontal analysis and molecular docking technology. Furthermore, a mast cell degranulation-related assay was used to assess the pseudo‑allergic activity of these compounds. The screened compounds can serve as ligands of MrgX2, and this study provides a research basis for pseudo‑allergic reactions caused by TCMIs containing A. capillaris.