DYES AND PIGMENTS
·
2025
·
IF 4.2
Xiaoxue Mo,Yuexin Lv,Jiayu Lu,Yajing Hou,Hua Qian,Cheng Wang,Huaizhen He
MAS-related G protein-coupled receptor X2 (MRGPRX2) is a key target receptor and an important drug target for triggering pseudo-allergic reactions. Studying its ligands will help to understand the mechanism of pseudo-allergic reactions and discover anti-allergic drugs. Small-molecule fluorescent probes are widely used to study the localization of G protein-coupled receptors (GPCRs) on the cell membrane, the transport and internalization of GPCRs, and the interaction between receptors and ligands due to their high selectivity, sensitivity and safety. MRGPRX2 is one of GPCRs with an active hydrophobic ligand binding domain, so designing small-molecule fluorescent probes with environmental sensitivity is very important for the study of MRGPRX2 ligands and the visualization of this receptor. In this study, we selected the agonist of MRGPRX2 ( R )-ZINC-3573 as the recognition group and used different fluorophore skeleton structures as the luminescent group to synthesize a series of small-molecule fluorescent probes targeting MRGPRX2. Among them, PoX2-B with BODIPY FL as the fluorescent group had good photostability and environmentally sensitive properties to the hydrophobic ligand binding domain of MRGPRX2, and could be used for living cell imaging. Furthermore, PoX2-B could specifically recognize MRGPRX2, and it was expected to be used to screen effective ligands of MRGPRX2 in the future, so as to play a role in the development of anti-allergy drugs and the pathogenesis of allergic diseases.
研究领域:
药理学
·
生物化学
·
分子生物学
✓ 已验证
DOI
高影响因子
American Journal of Translational Research
·
2025
·Vol. 17
·期 3
·2178
·
IF 1.6
Yu Zhang,Fang-Mei Liu,Cun-Yu Li,Xue-Jiao Leng,Yun-Feng Zheng,Guo-Ping Peng
Objective: Qingkailing Injection (QKLI) is a traditional Chinese medicine injection mainly used for sedation, heat clearing, and other treatments. However, recent clinical studies have shown a risk of pseudo-allergic reactions. The purpose of this study is to elucidate the underlying mechanism of QKLI-induced mast cell degranulation in Laboratory of Allergic Diseases 2 (LAD2) and to validate QKLI-induced activation of guinea pig IgE-independent allergic responses. Methods: Levels of β-hexosaminidase (β-Hex), histamine (His), and complement pathway-related indicators in guinea pigs and LAD2 cells were assayed using the Enzyme-linked Immunosorbent Assay (ELISA). The release rates of β-Hex and His from LAD2 cells were measured using the o-phthalaldehyde (OPA) fluorimetric method. The antagonist for complement component 3a (C3a) receptors, SB290157 and siRNAs were used to inhibit the C3a pathway and the Mas-related G-protein-coupled receptor X2 (MRGPRX2) pathway. The MRGPRX2 pathway and its downstream proteins were detected by Western Blot (WB). Results: The results show that QKLI significantly increased levels of β-Hex, His, C3a, complement component 5a (C5a), and terminal complement complex C5b-9 (SC5b-9) in guinea pigs, while levels of interleukin 4 (IL-4), interleukin 13 (IL-13), and interleukin 6 (IL-6) were unaffected. The C3a receptor inhibitor SB290157 significantly reduced levels of β-Hex and His. In LAD2 cells, QKLI increased the release rates of β-Hex and His in a time-dependent manner and decreased the phosphorylation of Extracellular Signal-regulated Kinase 1/2 (ERK1/2) proteins downstream of the MRGPRX2 pathway. The effective components of QKL, baicalin (BA) and geniposide (GE), individually enhance the allergic responses of LAD2 cells to some extent. However, the use of QKL is significantly superior to the individual use of its components. Conclusions: We found that QKLI induced pseudoanaphylaxis via an IgE-independent response in guinea pigs and through the MRGPRX2 pathway in human LAD2 cells. Among these, the main ingredients causing pseudoallergic reactions in QKLI were BA and GE. Our research contributes to a better understanding of the mechanisms underlying drug hypersensitivity reactions (DHRs).
研究领域:
药理学
·
免疫学
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产品关联
DOI
PubMed
高影响因子
International Journal of Nanomedicine
·
2023
·
IF 8
Chang Li,Chunmeng Sun,Shasha Li,Peng Han,Huimin Sun,Ammar Ouahab,Yan Shen,Yourui Xu,Yerong Xiong,Jiasheng Tu
In order to limit the adverse reactions caused by polysorbate 80 in Taxotere®, a widely used formulation of docetaxel, a safe and effective nanocarrier for this drug has been developed based on micelles formed by a new class of well-defined polyoxyethylene sorbitol oleate (PSO) with sorbitol as the matrix in aqueous solution. The physicochemical properties of the amphiphilic surfactant and the resulting micelles can be easily fine-tuned by the homogeneous sorbitol matrix and pure oleic acid. Composition, critical micelle concentration, and entrapment efficiency were investigated by ultraviolet visible spectroscopy, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, fluorospectrophotometry, and high-performance liquid chromatography. In vitro and in vivo evaluation revealed that PSO had exceptionally low hemolysis and histamine release rates compared with commercial polysorbate 80. Moreover, the tumor targeting delivery of PSO was investigated by in vivo imaging in S180 tumor-bearing mice. The results suggest that this novel delivery system, PSO, provides an acceptable alternative to polysorbate 80 for delivery of docetaxel. Further, due to the hypoallergenic nature of PSO, the mechanism of pseudoallergy caused by the polyoxyethylene nonionic surfactant was investigated. Based on in vitro cell analysis, it was assumed that the initial contact of polyoxyethylene nonionic surfactant with mast cells provoked pseudoallergy via polyamine receptor-mediated endocytosis.
研究领域:
药剂学
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生物医学工程
·
肿瘤学
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DOI
PubMed
高影响因子
JOURNAL OF SEPARATION SCIENCE
·
2024
·Vol. 47
·期 1
·2300545
·
IF 2.8
Chen Yang,Jing-Wen Zhang,Jin Qi,Bo-Yang Yu
Pseudoallergy is a typical and common adverse drug reaction to injections, especially in traditional Chinese medicine injections (TCMIs). At present, the evaluation methods for pseudoallergy include cell methods in vitro and animal methods in vivo. The mast cell evaluation method based on the β-hexosaminidase (β-Hex)-catalyzed substrate, 4-nitrophenyl-β-N-acetyl-D-glucosaminide (4-NPG), is an important method for the evaluation of drug-induced pseudoallergy, but it is prone to false positive results and has insufficient sensitivity. In this study, a novel β-Hex evaluation system with rat basophilic leukemia-2H3 cells based on high-performance liquid chromatography-fluorescence detection (HPLC-FLD) was established, which effectively increased the sensitivity and avoided false positive results. Cell viabilities were measured by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide assay. In addition, a method for the determination of histamine, which is another indicator in the development of pseudoallergy, was established to validate the above method. The results of this novel method indicated that two TCMIs (Shuxuening injection and Shenqi Fuzheng injection), which were considered to be pseudoallergenic using 4-NPG, were not pseudoallergenic. Overall, the novel β-Hex/HPLC-FLD evaluation system using Rat basophilic leukemia-2H3 cells established was effective and precise. It could be used for the evaluation of pseudoallergic reactions caused by TCMIs and other injections.
研究领域:
药理学
·
免疫学
·
分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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