Dehydroandrographolide inhibits IgE-mediated anaphylactic reactions via calcium signaling pathway

Zhang

et al. 2019

Phytotherapy Research

Self Cite

Mas-related G protein-coupled receptor-X2 (MRGPRX2) expressed on mast cells (MCs) has been shown to be a pivotal target for pseudo-allergic diseases. Therefore, MRGPRX2 might be a therapeutic target for allergic contact dermatitis, atopic dermatitis, and red man syndrome. Paeoniflorin (PF) was reported to have an antiinflammatory effect in neuroinflammation, enteritis, and so forth. In this study, we investigated the anti-pseudo-allergic effect of PF and the underlying molecular mechanisms. Our results showed that PF can suppress compound 48/80 (C48/80)-induced PCA and MCs degranulation in vivo, in a dose-dependent manner. Moreover, PF can reduce C48/80-induced calcium influx and suppress MC degranulation and chemokines release in vitro. PF can downregulate the phosphorylation levels of key kinases in PLCγ-regulated calcium influx and subsequent cytokine synthesis pathways. Our study revealed that PF could inhibit C48/80-induced allergic responses both in vivo and in vitro. As such, it may be regarded as a novel inhibitor for preventing MRGPRX2mediated allergic diseases.

Section: Discussionmentioning

confidence: 99%

Paeoniflorin inhibits MRGPRX2‐mediated pseudo‐allergic reaction via calcium signaling pathway

Zhang

et al. 2019

Phytotherapy Research

Self Cite

“…HIS secreted by mast cells induces vasodilation, edema, pruritus, and hypothermia [ 21 ]. IL-8 is a chemoattractant substance for the recruitment of eosinophils and neutrophils [ 22 ]. TNF-α and MCP-1 are also strongly associated with the progression of inflammatory cytokines because they promote the pathogenesis of acute and chronic inflammatory diseases [ 23 , 24 ].…”

Section: Discussionmentioning

confidence: 99%

Allantoin Inhibits Compound 48/80-Induced Pseudoallergic Reactions In Vitro and In Vivo

et al. 2022

Pseudoallergic reactions are hypersensitivity reactions mediated by an IgE-independent mechanism. Since allantoin (AT)-mediated pseudoallergy has not been studied, in this study, our objective is to investigate the anti-pseudoallergy effect of AT and its underlying mechanism. In vitro, β-hexosaminidase (β-Hex) and histamine (HIS) release assays, inflammatory cytokine assays, toluidine blue staining, and F-actin microfilament staining were used to evaluate the inhibitory effect of AT in RBL-2H3 cells stimulated with Compound 48/80 (C48/80). Western blot analysis is further performed to investigate intracellular calcium fluctuation-related signaling pathways. In vivo, Evans Blue extraction, paw swelling, and the diameter of Evans Blue extravasation were evaluated, and skin tissues are examined for histopathological examination in mice with passive cutaneous anaphylaxis (PCA) induced by C48/80. Body temperature is measured, and the levels of cytokines are further determined by ELISA kits in mice with active systemic anaphylaxis (ASA) induced by C48/80. The results show that AT dose-dependently inhibited degranulation in C48/80-stimulated RBL-2H3 cells by inhibiting β-Hex and HIS release, reducing the levels of TNF-α, IL-8, and MCP-1, inhibiting shape changes due to degranulation and disassembling the F-actin cytoskeleton. Furthermore, AT dose-dependently inhibits the phosphorylation of PLCγ and IP3R. In vivo, AT decreased Evans Blue extravasation, paw swelling, and the diameter of Evans Blue extravasation and significantly ameliorate pathological changes and mast cell degranulation in C48/80-induced PCA. Furthermore, AT help the mice recover from the C48/80-induced decrease in body temperature and decreased the levels of cytokines in C48/80-treated ASA mice. Our results indicate that allantoin inhibits compound 48/80-induced pseudoallergic reactions. AT has the potential to be used in IgE-independent anti-allergic and anti-inflammatory therapies.

“…After 24 hr, 10 μl of Cell Counting Kit solution was added to each well followed by incubation for 2 hr in 37°C. The relative cell viability was assessed by detection of absorbance at 450 nm using a microplate reader (Bio‐Rad, Carlsbad, CA, USA) (Che et al, 2019).…”

Section: Methodsmentioning

confidence: 99%

“…LAD2 cells (5 × 10 3 cells/well) were seeded into 96-well plate and treated with 90 μl of ISO at different concentrations (0,25,50,100,200, 400, and 800 μM). After 24 hr, 10 μl of Cell Counting Kit solution was added to each well followed by incubation for 2 hr in 37 C. The relative cell viability was assessed by detection of absorbance at 450 nm using a microplate reader (Bio-Rad, Carlsbad, CA, USA) (Che et al, 2019).…”

Section: Cytotoxicity Assaysmentioning

confidence: 99%

Isoimperatorin reduces the effective dose of dexamethasone in a murine model of asthma by inhibiting mast cell activation

Zhang

Zeng

et al. 2020

Phytotherapy Research

Self Cite

Adverse effects that result from dexamethasone (DEX) use are common and serious in patients with asthma. Therefore, alternative anti-inflammatory treatments are being investigated. Isoimperatorin (ISO), an active natural furocoumarin, possesses multiple pharmacological properties, including an anti-inflammation effect. In this study, investigations were conducted on the effect of ISO on mast cell (MC) activation in vitro and whether ISO could reduce the effective dose of DEX in a mast cell-dependent murine model of asthma in vivo. Calcium imaging was used to assess intracellular Ca 2+ mobilization. Enzyme-linked immunosorbent assay was used to measure the chemokines release. Western blot analysis was conducted to investigate the underlying pathway. Airway inflammation and hyperresponsiveness (AHR) were examined in an asthma model. ISO inhibited Ca 2+ flux and MC degranulation via Lyn/PLCγ1/PKC, ERK, and P38 MAPK pathways. In the asthma model, ISO, in combination with DEX, showed an additive inhibitory effect on AHR, inflammation, and the number of activated MCs in the lungs and decreased the levels of interleukin (IL)-4, IL-5, IL-6, IL-13, tumor necrosis factor (TNF)-a, and CC motif chemokine ligand (CCL)-2 in bronchoalveolar lavage fluid. A combination of DEX and ISO may be appropriate if a decrease in the steroid dose is desired owing to dose-dependent adverse effects.