BIOCHEMICAL PHARMACOLOGY
·
2020
·
IF 4.96
Nan Wang,Jue Wang,Yongjing Zhang,Yingnan Zeng,Shiling Hu,Haoyun Bai,Yajing Hou,Cheng Wang,Huaizhen He,Langchong He
Background Allergic asthma is a common inflammatory lung disease associated with complex pathogenesis. Mast cell (MC) is one of the key drivers of allergic asthma, Mas-related G protein-coupled receptor X2 (MRGPRX2) on the MC could mediate MC activation and trigger a pseudo-allergic reaction. Imperatorin (IMP), the main active compound of Radix Angelicae Dahuricae , has been reported to exert various pharmacological effects. In this study, we focused on the therapeutical mechanism of IMP on MRGPRX2-induced pseudo-allergy and allergic asthma. Methods We examined the effect of IMP on MRGPRX2 related mast cell activation in mouse peritoneal MC (MPMC), Human Laboratory of Allergic Disease 2 MCs (LAD2 cells) and Mrgprx2 -expressing HEK293 cells. Molecular docking and Surface plasmon resonance (SPR) were taken to reveal the binding character between IMP and MRPGRX2. MRGPRX2 downstream proteins were also detected by western blotting . IgE-independent responses was evaluated by using passive cutaneous anaphylaxis (PCA) and active systemic anaphylaxis (ASA) models. The therapeutic effect of IMP on asthma was evaluated by a lung inflammation mouse model which was induced by ovalbumin (OVA). Results IMP was found to reduce substance P (SP) induced calcium flux and suppressed degranulation of MC. SP can promote the phosphorylation of ERK and CamKII, which regulates the synthesis of inflammatory factors such as MIP-2 and TNF-α in MC. In vivo assays revealed that IMP can mitigate SP-induced mouse PCA and ASA. IMP could also mitigate lung inflammation in an OVA induced mice model by inhibiting MC activation in the lung tissue. Furthermore, IMP binds well to MRGPRX2 protein. The binding constant ( K D ) is 4.48 ± 0.49 × 10 −7 M. The data suggeste that IMP is a novel inhibitor of MRGPRX2 to treat allergic asthma.
研究领域:
药理学
·
免疫学
·
过敏
·
呼吸系统疾病
✓ 已验证
产品关联
DOI
PubMed
高影响因子
MOLECULES
·
2024
·Vol. 29
·期 16
·3799
·
IF 4.2
Yuying Zhang,Xiaoyu Wang,Dejun Zhou
Allergies are one of the diseases whose incidence rates have increased in recent years due to the greenhouse effect and extreme climate change. Therefore, the development of new antiallergic drugs has attracted the interest of researchers in chemistry and pharmacy fields. Dicoumarin is a coumarin derivative with various biological activities, but its antiallergic activity has not been evaluated. In this study, 14 different dicoumarin derivatives were synthesized by diethylamine-catalyzed condensation reactions of 4-hydroxycoumarin with 14 different aldehydes, and they were identified on the basis of their spectral data. The dicoumarin derivatives were subjected to studies on the degranulation of rat basophilic leukemia cells (RBL-2H3 cells) and mouse bone-marrow-derived mast cells (mBMMCs), and some of them showed good inhibitory effects on the degranulation of the two types of mast cells, demonstrating their good antiallergic activity. This study presents a new method of developing new antiallergic drugs.
研究领域:
药理学
·
有机化学
✓ 已验证
DOI
高影响因子
SENSORS AND ACTUATORS B-CHEMICAL
·
2023
·
IF 8.4
Yiyu Chen,Huiting Lian,Bin Liu,Guangming Liu,Xiaofeng Wei
Food allergy diagnosis requires a highly sensitive detection of allergen-specific immunoglobulin E (sIgE) in the serum. Enzyme-linked immunosorbent assay (ELISA) is a classical method widely used for sIgE detection but had to rely on costly and time-consuming assay procedures, skilled technicians, and bulky equipment. Here, a multiplexed origami paper analytical device (moPAD) that is hexahistidine-tagged and integrated with a nitrilotriacetic acid-functionalized surface with nickel (Ni-NTA) was developed to achieve low-cost and high-efficiency immunosensing of multiple allergen-specific IgEs in serum. The major oyster allergens, Cra a 1, Cra a 2, and Cra a 4, were used to detect sIgE in human serum. The feasibility of the moPAD-based immunosensing strategy was successfully demonstrated by desirable sensitivities for multiple targets. The detection results of moPAD for 72 serum samples were 100% consistent with clinical test results, while 69 of these results showed no significant differences from ELISA results, demonstrating the accuracy and stability of this method. A fully integrated moPAD reduces detection time and achieves highly sensitive quantification using a simple smartphone-based readout. Efficient allergen modification of paper devices has great applicability in allergen component-resolved diagnostics. The implementation of moPAD can make the process of allergy diagnosis simpler for patients, physicians, and healthcare systems alike.
研究领域:
免疫学
·
生物医学工程
·
诊断技术
·
过敏研究
✓ 已验证
产品关联
DOI
高影响因子
Food Bioscience
·
2024
·
IF 4.8
Caiying Yang,Ying Zhang,Xiaoya Zhou,Zhihua Wu,Jinyan Gao,Hongbing Chen,Ping Tong
Allergen modification is a novel strategy for preventing and treating food allergy. Resveratrol (RES) can be used as a modifying ligand for allergens, but the interaction mechanism between RES and allergens is still not detailed, and the ramifications of this interaction on the structure, epitope and allergenicity of allergens are also lacking a clear explanation. In addition, the application of heat can promote protein structure to unfold and expose more binding sites to facilitate interaction. Therefore, in this study, ovalbumin (OVA) was selected as the allergen model and was heated to expose more binding sites. The effects of the interaction between RES and heat-stressed ovalbumin (HOVA) on allergen structure, epitope and allergenicity were investigated by combining routine experimental analysis and computer simulation. Results showed heat stress at 323 K for 15 min could better unfold the molecular structure of OVA. On this basis, the interaction between RES and OVA was strengthened, which showed a static quenching of the ground state complex with binding affinity of 1.25 × 10 6 L/mol. The binding of RES induced the variation of protein microenvironment, and the overall structure tended to disordered direction. Computer simulation had shown RES could directly act on the IgE epitope region (AA251-260) of the OVA. The allergenicity evaluation experiment further indicated the combination of RES alleviated the IgE binding capacity of HOVA. These findings are helpful to further study the mechanism of RES ligand modification to change food allergy.
研究领域:
食品科学
·
过敏反应
·
生物化学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
MOLECULAR NUTRITION & FOOD RESEARCH
·
2023
·
IF 5.2
Xiaoying Tian,Xi Liang,Hong He,Qingyu Cui,Qiqi Liu,Rongbo Fan,Tongjie Liu,Huaxi Yi,Pimin Gong,Qingzhu Wang,Lanwei Zhang
Scope Food allergy has become a world recognized public health problem due to its versatility and lack of efficacious methods for its treatment. Probiotics supplement is a potential way to prevent food allergy. Methods and results In this study, potential strains are screen out by peripheral blood mononuclear cells (PBMCs), and their abilities of alleviating food allergy are examined using a mouse model induced by ovalbumin (OVA). The results show that six strains increase ratio of interferon-γ (IFN-γ)/interleukin (IL)-4 secreted by PBMCs with good abilities in intestinal adhesion and gastrointestinal tolerance. Oral administration of Bifidobacterium animalis KV9 (KV9) and Lactobacillus vaginalis FN3 (FN3) attenuates allergic responses in allergy mice, including allergic symptoms, mast cells aggregation and activity, serum OVA-special-immunoglobulins E (OVA-sIgE) production. KV9 and FN3 upregulate the production of IFN-γ/IL-4 in splenocytes, increase the genes and proteins expression of toll-like receptor 4 (TLR4), myeloid differentiation primary response 88 (Myd88) and interferon regulatory factor (IRF)-1 in allergic mice spleen, and decrease the IRF-4. Conclusion The study demonstrates that KV9 and FN3 possess anti-allergic activities via activation of TLR4 pathway and modulating the expression of IRF-1 and IRF-4 which leads to T helper type 1 (Th1)/T helper type 2 (Th2) cell immunology balance.
研究领域:
免疫学
·
微生物学
·
过敏
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
FOOD CHEMISTRY
·
2023
·
IF 8.8
Enning Zhou,Weiwei Wang,Xiaofeng Xue,Pianpian Wang,Fan Wu,Liming Wu,Qiangqiang Li
Bee pollen is a byproduct of pollination, which is a necessary process to produce foods. However, bee pollen can induce significant food-borne allergies. We previously identified a bee pollen-derived pan-allergen in the profilin family, Bra c p. Herein, we aimed to reduce Bra c p allergenicity via protein oxidation with hydrogen peroxide and explore the changes induced. Ion-mobility mass spectrometry revealed aggregation of the oxidized product; we also found irreversible sulfonation of the free sulfhydryl group of the Bra c p Cys98 residue to a more stable cysteine derivative. A significant proportion of the α-helices in Bra c p were transformed into β-sheets after oxidation, masking the antigenic epitopes. An immunoassay demonstrated that the IgE-binding affinity of Bra c p was decreased in vitro after oxidation. To our knowledge, this is the first report describing the application of protein oxidation to reduce the allergenicity of profilin family member in foods.
研究领域:
过敏反应
·
免疫学
·
蛋白质化学
·
食品科学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Revista Brasileira de Farmacognosia-Brazilian Journal of Pharmacognosy
·
2019
·Vol. 29
·期 1
·46-53
·
IF 1.754
Peng Wei,Han Ping,Yu Luyao,Chen Ying,Ye Bingzhu,Qin Luping,Xin Hailiang,Han Ting
The fruits of Xanthium strumarium L., Asteraceae, have been used for various diseases in Chinese folk medicine, including allergic rhinitis, tympanitis, arthritis, ozena etc. The current study was aimed to investigate the therapeutic effects of caffeoylquinic acids from fruits of X. strumarium on allergic rhinitis in animals. The toxicity test indicated that the caffeoylquinic acids have no obvious toxicity. By using HPLC assays combined with reference standards, ten caffeoylquinic acids were identified as the predominant constituents. Anti-allergic activities of the caffeoylquinic acids were evaluated using passive cutaneous anaphylaxis test and Schultz-Dale test; dimethylbenzene induced ear edema test was performed to evaluate its anti-inflammatory effect. Then, the allergic rhinitis model in rats was established to evaluate the therapeutic effects of the caffeoylquinic acids against allergic rhinitis with the following indexes: allergic rhinitis symptom scores, serum levels of pro-inflammatory cytokines, histopathological examination, and histamine release. Our study revealed that the caffeoylquinic acids showed obvious anti-allergic and anti-inflammatory properties, and its treatments were beneficial for ameliorating the nasal symptoms, decreasing pro-inflammatory cytokines, and inhibiting the releases of histamine. Collectively, the caffeoylquinic acids might be utilized as effective and safe disease therapeutic agents for allergic rhinitis.
研究领域:
药理学
·
免疫学
·
过敏
·
植物化学
✓ 已验证
产品关联
DOI
高影响因子
FOOD CHEMISTRY
·
2022
·
IF 9.231
Xu-mei Wang,Zong-cai Tu,Yun-hua Ye,Guang-xian Liu,Yue-ming Hu,Hui Wang
This study aimed to isolate and evaluate the allergenicity of glycated α-lactalbumin (ALA) digestive products and identify its allergenic peptides. The digestive products of native-, alone glycated- and ultrasound-assisted glycated ALA (ALA-D, ALA-gal-D, 100ALA-gal-D) were isolated into three fractions (F1, F2 and F3). High-resolution mass spectrometry showed that the digestion-resistant peptides of F2 and F3 mainly distributed in amino acid sequence (AA) 25–31, AA32-53, AA40-53, AA54-60, AA80-90, AA94-104. The allergenicity of the three fractions of glycated ALA was lower than that in ALA-D, indicating glycation of ALA could indeed reduce its allergenicity after digestion. Furthermore, most fractions isolated from high glycation-degree ALA had the lowest allergenicity. The IgG/IgE binding abilities of synthesized peptides indicated that AA94-104 firstly identified by us embodied the strongest allergenicity and might be the potential allergenic peptide. This will provide a theory for preparing hypoallergenic products based on the identified allergenic peptides.
研究领域:
食品科学
·
过敏学
·
蛋白质组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
NEUROSCIENCE LETTERS
·
2025
·
IF 2
Xiao Li,Hui Yang,Ming Qian,Hang Liu,Shuang Zuo,Jin-Chun Liu,Wei-Hong Ge,Lin Zhou
Vincristine (VCR) is a commonly used clinical anti-cancer drug, but it can also induce neurotoxicity and cause vincristine-induced neuropathic pain (VINP). The metabotropic glutamate receptor 5 (mGluR5) within spinal dorsal horn neurons regulates the transmission of pain mediated by glutamate. In this study, we investigated for the first time the role of mGluR5 in the transmission of noxious information in VINP. Expression of mGluR5 protein was significantly increased in the spinal cord from days 6 to 14 after VCR injection. Immunofluorescence double staining showed that mGluR5 colocalized with the neuron-specific marker NeuN. The intrathecal administration of MPEP (a specific antagonist of mGluR5) or DHPG (an agonist of mGluR5) influenced the pain threshold and mGluR5 protein expression in VINP mice. The expression of c-Fos protein was also affected by MPEP. Furthermore, simulated blockade of intracellular mGluR5 site by intrathecal injection of small interfering RNA (siRNA) of the excitatory amino acid transporter 3 (EAAT3) reduced mechanical allodynia and thermal hyperalgesia and suppressed the expression of mGluR5 and c-Fos proteins. The results collectively indicate that mGluR5 site in spinal dorsal horn neurons may be involved in the regulation of intracellular nociceptive signal transmission in VINP, and the expression of c-Fos largely depends on the intracellular mGluR5.
研究领域:
神经科学
·
药理学
·
疼痛研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
LWT-FOOD SCIENCE AND TECHNOLOGY
·
2024
·
IF 6
Yiling Zhou,Yaru Liao,Jing Bai,Xinlei Xia,Zhihua Wu,Xin Li,Ping Tong,Hongbing Chen,Anshu Yang
This study aimed to investigate the effects of active soybean isoflavones on the structure and potential allergenicity of glycinin, a major allergen, in soybean. The interaction mechanism between two active soybean isoflavones, namely, genistein (Gen) and daidzein (Dai), and glycinin were investigated using a series of spectral techniques. The structure of the isoflavone-glycinin complexes was characterized by SDS-PAGE and spectral techniques. In addition, the potential allergenicity of the isoflavone-glycinin complexes and their digestion products in vitro was measured via Western blot and enzyme-linked immunosorbent assay. Results showed that Gen and Dai effectively quenched the intrinsic fluorescence of glycinin largely through static quenching. Dai interacted with glycinin through hydrogen bonding and van der Waals forces, while Gen relied on hydrophobic interactions with glycinin. Furthermore, the neutral complex of daidzein-glycinin (Dai-G) exhibited weaker IgE binding ability compared with the glycinin samples. These findings provided new insights into the molecular mechanisms that underlay the immunomodulatory effects of soybean isoflavones and their potential applications in food allergy prevention and management.
CAS / MDL:
研究领域:
食品科学
·
过敏与免疫学
·
分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Food & Function
·
2019
·Vol. 10
·期 7
·3934-3941
·
IF 3.241
Ziye Zhang,Hang Xiao,Xiaofeng Zhang,Peng Zhou
Shrimp tropomyosin (TM) is a glycoprotein allergen with high lysine content, however, there is little data on how deglycosylation and glycation modify the allergenicity of TM. In this work, the effects of deglycosylation (enzymatic and chemical) and glycation of TM by glucose on in vivo allergenicity and mast cell function were investigated using BALB/c mouse and RBL-2H3 mast cells. Compared with TM, after deglycosylation, the deglycosylated TMs (DGTMs) exacerbated the in vivo allergenicity and mast cell allergy response. As for the TM glycated by glucose (TM-G), glycation led to weaker allergy responses on mouse and mast cells, which might be due to glucose destroying the epitopes with glycation sites. Moreover, the glucose residues on TM-G functioned as both a resistance to prevent the accessibility of TM-G to the IgE on mast cell and masking epitopes. Therefore, deglycosylation of TM was not suitable for desensitizing TM-induced food allergy, while glycation of TM might be applied to desensitize TM allergenicity, which could provide new insight into food allergy desensitization for larger cohorts of shrimp-allergic patients.
研究领域:
免疫学
·
食品科学
·
过敏研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
PHYTOTHERAPY RESEARCH
·
2021
·Vol. 35
·期 6
·3181-3193
·
IF 5.882
Rui Liu,Shiling Hu,Yuanyuan Ding,Jue Wang,Yuejin Wang,Jiapan Gao,Langchong He
Anaphylactoid reactions are potentially fatal allergic diseases caused by mast cells (MCs), which release histamine and lipid mediators under certain stimuli. Therefore, there is an urgent need to develop new drug candidates to treat anaphylactoid reactions. The MrgX2 receptor mediates anaphylactoid reactions that cause inflammatory diseases. Cortex dictamni is a Chinese herb used for treating allergy-related diseases; however, its active compound is still unknown and its mechanism of action has not yet been reported. The aim of this study was to screen the anti-anaphylactoid compound from C . dictamni extracts. An MrgX2/CMC-HPLC method was established for screening MrgX2-specific compounds retained from the alcohol extract of C . dictamni . A mouse model of hindpaw extravasation was used to evaluate the anti-anaphylactoid effect of this ingredient. Intracellular Ca 2+ mobilization was assessed using a calcium imaging assay. Enzyme immunoassays were performed to measure cytokine and chemokine release levels. The molecular signaling pathways were explored by western blotting. As a result, dictamnine was identified as an effective compound using the MrgX2/CMC method, which remarkably suppressed MC intracellular Ca 2+ mobilization and the release of de novo degranulated substances, and inhibited PKC-PLCγ-IP3R-associated protein signaling molecules. Hence, dictamnine is a novel therapeutic candidate for anaphylactoid reactions via MrgX2.
研究领域:
药理学
·
免疫学
·
中药学
·
分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）