RBL-2H3 Cells Research Articles

Effect of Trichosanthis Radix Extract on Anti-allergy and Skin Inflammation

This study was conducted to study the effects of TR-W and TR-E on anti-allergy and skin inflammation inhibition. In order to check the concentration used in the experiment and its toxicity to cells, RBL-2H3 cells and HMC-1 cells were treated with TR-W and TR-E at different concentrations and tested at a concentration of 100 mg/ml or less, which does not affect the survival rate. proceeded. In order to determine the effect on the inflammatory response to mast cells, the inflammatory cytokines TNF-α, IL-8, and IL-6 were measured. As a result, TR-W and TR were found in TNF-α and IL-8, which promote the early inflammatory response. -E showed a significant effect at 100 mg/ml, and TR-E showed a significant effect at 50 mg/ml, showing the effect even at a lower concentration than TR-W. IL-6, which is involved in causing allergic dermatitis, showed a significant effect at 100 and 50 mg/ml in TR-W and TRE, indicating that it is effective in suppressing inflammation in TR-W and TR-E. In addition, histamine and β-hexosaminidase, which are inflammatory mediators involved in the initial allergic reaction, were significantly suppressed at 100 and 50 mg/ml in TR-W and TR-E, demonstrating anti-allergy effect. These research results are believed to have the highest utility value as a functional cosmetic material in the future, and additional research is considered necessary.

First naturally occurring homoacridone-flavanone dimers from Glycosmis parviflora

The structures of flavacitropones A (1)-B (2), which are new homoacridone-flavanone dimers from Glycosmis parviflora (Sims) Kurz. (Rutaceae), were elucidated by spectroscopic studies. Flavacitropone A (1) was evaluated for its biological effects on cytotoxicity and release of histamine and TNF-α in 2,4-dinitrophenyl-human serum albumin-stimulated RBL-2H3 cells (rat basophilic cell line). The compound downregulated TNF-α release, but not histamine release.

The Effect of In Vitro Digestion on the Anti-allergic, Anti-Inflammatory and Antioxidant Properties of Purple Rice and Purple Barley Phenolic Extracts in Caco-2 and RBL-2H3 Cells

Gastrointestinal diseases are associated with increased oxidative stress and inflammation. Pigmented cereal polyphenols are believed to have therapeutic potential. However, the impact of digestion on their bioactivity has not been fully elucidated. This study investigated the impact of digestion on the ability of purple rice extract (PRx) and purple barley (PBx) to alleviate oxidative stress-induced intestinal epithelial cell death and allergic inflammation. The study used a human colon adenocarcinoma (Caco-2) cell line to simulate intestinal oxidative stress for 4 h using 1 mM hydrogen peroxide. To evaluate the protective effects of digested and undigested cereal extracts, cells were first pre-treated with varying concentrations (50, 100, 200, and 500 μg/ml) of both purple rice (PRx) and purple barley (PBx) extracts. A rat basophilic leukemia (RBL-2H3) cell line was used to investigate the ability of the extracts to prevent calcium ionophore-induced histamine and cytokine release. The results demonstrated that both digested and undigested phenolic extracts prevented oxidative stress-induced cell death in Caco-2 cells and reduced Interleukin (IL)-8 secretion. PRx showed greater cytoprotective effects than PBx. Both digested and undigested extracts showed a time-dependent antihistamine effect, with the greatest inhibitory effects observed after 2 h and 4 h of treatment with PRx. Additionally, the extracts significantly attenuated the release of several cytokines including IL-2, IL-4, IL-13, monocyte chemoattractant protein-1, interferon-gamma, and tumour necrosis factor-alpha. Overall, the study demonstrates that both digested and undigested pigmented rice and barley extracts are potential sources of polyphenols which may promote intestinal health and alleviate allergic inflammation.

Prevention and alleviation of allergic rhinitis by oral administration of Lacticaseibacillus paracasei GOLDGUT-Lpc969.

Allergic rhinitis (AR) is a widespread upper airway disorder characterized by inflammation of the nasal passages. It is immunologically mediated via the hypersensitivity type I mechanism, which is primarily elicited by the immunoglobulin E (IgE)-linking allergen-induced imbalance of the Th2/Th1 immune response. Owing to the limited efficacy of current medications, probiotics have received attention for their potential in preventing and ameliorating AR. In this study, a Lacticaseibacillus paracasei strain, GOLDGUTLpc969 (Lpc969), isolated from the feces of healthy adults, was proven to be effective in preventing AR by LPA-induced RBL-2H3 in-vitro and OVA-induced AR mice in-vivo evaluation. The strain significantly attenuated the release of histamine and degranulation in LPS-induced RBL-2H3 cells. In the OVA-induced AR mice, L. paracasei GOLDGUT-Lpc969 also exhibited a significant decrease in disease indicators such as the disease activity index (DAI score), serum IgE, and serum histamine. Treatment with L. paracasei GOLDGUT-Lpc969 led to significant suppression of the Th2-related cytokines IL-4, IL-5, IL-6, IL-13, and TNF-α in the serum of mice. Furthermore, a comparison of the genomes of three previously reported AR-effective L. paracasei strains (including GOLDGUTLpc969) and one non-effective L. paracasei strain revealed that the gene K03671 may play a key role in alleviating AR symptoms. In conclusion, this study highlights the efficacy of L. paracasei GOLDGUT-Lpc969 in AR prevention by suppressing the Th2 immune response and proposes the potential involvement of the functional gene K03671 in ameliorating AR symptoms. Therefore, L. paracasei GOLDGUT-Lpc969 shows promise as a probiotic for preventing AR.

4-hydroxyderricin from Angelica keiskei: Analysis, Preparation, and Multiple Skin Care Effects

Introduction: The content of the bioactive component 4-hydroxyderricin (4-HD) in the roots, stems, and leaves of Angelica keiskei (Umbelliferae), a well-known medicinal and edible plant, was analyzed by HPLC. The dry root contained the highest level (2. 69 ± 0.09 mg/g) of 4-HD, which was then prepared and spectroscopically identified by column chromatography. Method: The multiple skin care activities of 4-HD, including skin whitening, anti-allergy, and anti-inflammation, were evaluated on enzymatic and cellular models. 4-HD showed a significant inhibitory effect on mushroom tyrosinase, and it could also strongly suppress the activity of tyrosinase in B16F10 cells. A molecular docking study revealed that 4-HD could closely bind to tyrosinase through hydrogen bonding and hydrophobic interactions. Results: In the anti-allergic assay, 4-HD could effectively reduce the degranulation rate in the neutral red staining test and largely down-regulate the release level of β-HEX in RBL-2H3 cells at the concentration of 5 μM. 4-HD decreased the production of NO in RAW264.7 cells induced by Lipopolysaccharide (LPS), showing its anti-inflammatory effect. Conclusion: The skin whitening, anti-allergic, and anti-inflammatory effects of 4-HD have clearly demonstrated its potential usage in the pharmaceutical and cosmetic industries.

Identification of Potential Tryptase Inhibitors from FDA-Approved Drugs Using Machine Learning, Molecular Docking, and Experimental Validation.

This study explores the innovative use of machine learning (ML) to identify novel tryptase inhibitors from a library of FDA-approved drugs, with subsequent confirmation via molecular docking and experimental validation. Tryptase, a significant mediator in inflammatory and allergic responses, presents a therapeutic target for various inflammatory diseases. However, the development of effective tryptase inhibitors has been challenging due to the enzyme's complex activation and regulation mechanisms. Utilizing a machine learning model, we screened an extensive FDA-approved drug library to identify potential tryptase inhibitors. The predicted compounds were then subjected to molecular docking to assess their binding affinity and conformation within the tryptase active site. Experimental validation was performed using RBL-2H3 cells, a rat basophilic leukemia cell line, where the efficacy of these compounds was evaluated based on their ability to inhibit tryptase activity and suppress β-hexosaminidase activity and histamine release. Our results demonstrated that several FDA-approved drugs, including landiolol, laninamivir, and cidofovir, significantly inhibited tryptase activity. Their efficacy was comparable to that of the FDA-approved mast cell stabilizer nedocromil and the investigational agent APC-366. These findings not only underscore the potential of ML in accelerating drug repurposing but also highlight the feasibility of this approach in identifying effective tryptase inhibitors. This research contributes to the field of drug discovery, offering a novel pathway to expedite the development of therapeutics for tryptase-related pathologies.

A biomimetic skin microtissue biosensor for the detection of fish parvalbumin

In this paper, a biomimetic skin microtissue biosensor was developed based on three-dimensional (3D) bioprinting to precisely and accurately determine fish parvalbumin (FV). Based on the principle that allergens stimulate cells to produce ONOO− (peroxynitrite anion), a screen-printed electrode for the detection nanomolar level ONOO− was innovatively prepared to indirectly detect FV based on the level of ONOO− release. Gelatin methacryloyl (GelMA), RBL-2H3 cells, and MS1 cells were used as bio-ink for 3D bioprinting. The high-throughput and standardized preparation of skin microtissue was achieved using stereolithography 3D bioprinting technology. The printed skin microtissues were put into the self-designed 3D platform that integrated cell culture and electrochemical detection. The experimental results showed that the sensor could effectively detect FV when the optimized ratio of RBL-2H3 to MS1 cells and allergen stimulation time were 2:8 and 2 h, respectively. The linear detection range was 0.125–3.0 μg/mL, and the calculated lowest detection limit was 0.122 μg/mL. In addition, the sensor had excellent selectivity, specificity, stability, and reliability. Thus, this study successfully constructed a biomimetic skin microtissue electrochemical sensor for PV detection.

Anti-Allergic and Anti-Inflammatory Signaling Mechanisms of Natural Compounds/Extracts in In Vitro System of RBL-2H3 Cell: A Systematic Review.

Various extracts are tested for anti-allergic or anti-inflammatory properties on in vitro models. RBL-2H3 cells are widely used in allergic or immunological studies. FCεRI and its downstream signaling cascades, such as MAPK, NF-κB, and JAK/STAT signaling pathways, are important allergic or inflammatory signaling mechanisms in mast and basophil cells. This systematic review aims to study common signaling pathways of the anti-allergic or anti-inflammatory compounds on RBL-2H3 cells. We selected the relevant research articles published after 2015 from the PubMed, Scopus, Science Direct and Web of Science databases. The risk of bias of the studies was assessed based on the modified CONSORT checklist for in vitro studies. The cell lines, treatments, assay, primary findings, and signaling pathways on RBL-2H3 cells were extracted to synthesize the results. Thirty-eight articles were included, and FCεRI and its downstream pathways, such as Lyn, Sky, PLCγ, and MAPK, were commonly studied. Moreover, the JAK/STAT pathway was a potential signaling mechanism in RBL-2H3 cells. However, the findings based on RBL-2H3 cells needed to be tested along with human mast cells to confirm its relevance to human health. In conclusion, a single plant extract may act as an anti-inflammatory reagent in RBL-2H3 cells via multiple signaling pathways besides the MAPK signaling pathway.

Inhibitory Effect of Dipeptides Containing Acidic Amino Acid Residue on Degranulation of RBL-2H3 Cells

Inhibitory Effect of Dipeptides Containing Acidic Amino Acid Residue on Degranulation of RBL-2H3 Cells

Synthesis and Antiallergic Activity of Dicoumarin Derivatives.

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.

AYA22A Aptamers Mitigate Peanut Allergenicity: Insights from Degranulation Assays and Modulating Immune Responses

Food allergy, particularly peanut allergy (PA), is a growing health concern affecting millions globally. PA can lead to severe reactions, including fatal anaphylaxis. Despite the availability of FDA-approved therapies like Palforzia, a cure remains elusive. Current immunotherapies show promise but lack a definitive cure. This study applies an established computational biology tool to design aptamers targeting Ara h1 and Ara h2. The in silico design aims to streamline the selection process, enabling cost-effective and rapid identification of aptamer candidates. The developed aptamers (AYA22A, including AYA22AR321, AYA22AR211, and AYA22AR524), demonstrated efficacy in inhibiting degranulation of RBL-2H3 cells (rat basophilic leukemia cell line) in vitro. They showed promise in neutralizing peanut allergen-induced immune responses. The selected aptamers inhibited degranulation in RBL-2H3 cells, addressing concerns in raw peanuts. Moreover, these aptamers demonstrated stability and effectiveness in peanut plant seeds and commercial products. Our aptamers exhibited potential in modulating immune responses associated with peanut allergy. They influenced Th1/Th2 balance, indicating a role in cytokine regulation. In vitro studies also showed the aptamers’ impact on immune cell expression and cytokine production, resembling responses observed with established immunotherapies. The findings suggest AYA22A aptamers as a potential therapeutic option for peanut allergy, providing a basis for further in vivo investigations.

The peels of sacred Lotus (Nelumbo nucifera) rhizomes suppress allergic reactions by inhibiting the A23187-induced degranulation in rat basophilic leukemia (RBL[sbnd]2H3) cells

We isolated ten compounds from methanolic extract of the peels of sacred lotus (Nelumbo nucifera) rhizomes which were identified as β-sitosterol linoleate 1, β-sitosterol 2, lupeol 3, stigmasterol 3-O-β-D-glucoside 4, oleanolic acid 5, betulinic acid 6, pinoresinol 7, 4-hydroxybenzoic acid 8, catechin 9 and gallocatechin 10. All of the isolated compounds from the peels of sacred lotus rhizomes are reported for the first time, and were investigated for their anti-allergic activity. We found that three of them, stigmasterol 3-O-β-D-glucoside 4, oleanolic acid 5 and pinoresinol 7, were capable of inhibiting A23187-induced degranulation in RBL-2H3 cells with IC50 values 0.18 ± 0.01 mM, 0.28 ± 0.06 mM, and 0.27 ± 0.01 mM, respectively. With an exception to 4, compounds 5 and 7 achieved the anti-allergic effect without affecting the cells viability even at higher concentrations with their selectivity indices (SI) being >5. By reducing A23187-induced degranulation, it is suggestive of a mechanism attenuation of Ca2+ elevation. Our findings suggest that, the peels of sacred lotus rhizomes would be beneficial for providing an inexpensive source for the production of bioactive compounds with anti-allergic effect.

Allergenicity assessment of β-lactoglobulin ferulic acid–glucose conjugates

We prepared the β-lactoglobulin (BLG)–ferulic acid (FA)–glucose (Glu) conjugates by alkaline method and Maillard reaction to assess the allergenicity. FA and Glu can form a ternary covalent conjugate with BLG, as evidenced by the shortening of SEC retention time, upward migration of SDS-PAGE protein bands, considerable decrease in free amino and sulfhydryl content, and changes in multistructure. BLG–Glu–FA conjugates weakly bound to immunoglobulin E in allergic sera was weak, reduced interleukin 4 and tumor necrosis factor α levels in RBL-2H3 cells and histamin and interleukin 6 secretion levels in KU812 cells, and inhibited the nuclear factor-κB signaling pathway. In vivo experiments showed that the conjugates regulated T-cell homeostasis in mouse splenic and mesenteric lymphocytes and attenuated splenic and duodenal immune injury. Therefore, the conjugates of BLG with FA combined with Glu altered the epitope structure and exhibited low allergenicity.

Mechanism analysis of essential oil from Radix Bupleuri for the treatment of asthma through regulation of ectopic olfactory receptor

Ethnopharmacological relevanceRadix Bupleuri is the root of Bupleurum chinense DC. (BC) and a classic aromatic traditional Chinese medicine. The traditional pharmacological effects of Radix Bupleuri are alleviating bronchial spasms, dilating airways, and promoting the resolution of respiratory inflammation, thereby reducing asthma symptoms. Aim of the studyStudies have demonstrated the efficacy of water extracts from BC in asthma treatment. However, the potential role of volatile oil, another active constituent in BC, remains unexplored with asthma. Notably, volatile oil is renowned for its ease of absorption and direct targeting of affected areas, offering distinct advantages in alleviating airway inflammation. This study aims to explain the anti-asthmatic mechanism of BC-oil through in vivo and in vitro pharmacological experiments. Materials and methodsFirstly, the OVA-induced SD rat asthma model was utilized to evaluate the pharmacological effect of BC-oil by lung function monitoring, HE staining, flow cytometry, ELISA, and RT-qPCR. The anti-asthmatic mechanism was further analyzed by combining transcriptomic analysis of lung tissue from rat model and airway smooth muscle tissue from public database. Initially, GC-MS was used to analyze the components of BC-oil. The anti-asthmatic activity was evaluated in 16-HBE, RBL-2H3, and ASMC cells using CAMKII inhibitors to explore of the critical signal transduction regulated by BC-oil. Furthermore, molecular docking and calcium flow assay were utilized to screen and identify the active components from BC-oil. ResultsOral administration of BC-oil significantly enhanced pulmonary function in asthmatic SD rats by reducing airway resistance and elastic resistance. Additionally, BC-oil inhibited inflammatory cytokines, including serum IL-2, pulmonary Il1b, Tnf, and Cxcl13, demonstrating potent anti-inflammatory and immunomodulatory effects. In this study, we analyzed the significant role of OR2W3 in asthma using public transcriptomic data. Furthermore, we indicated that BC-oil regulated the expression of Olr1433 and GNAL in rat lung tissue. BC-oil reduced degranulation and inhibited gene expression of Il3 and Tnf in RBL-2H3 cells and suppressed gene expression of IL8 and TNF in 16-HBE cells. BC-oil also attenuated airway smooth muscle cell proliferation and expression of Acta2 and Ccnd1. Furthermore, BC-oil regulates asthma-related cellular processes by activating CAMKII. GC-MS analysis identified 11 components of BC-oil, and n-hexadecanoic acid, linoleic acid and oleic acid from BC-oil were identified to interact with OR2W3 by molecular docking. The calcium flow assay revealed linoleic acid as a significant activator of OR2W3 and indicated that BC-oil alleviated asthma through the ectopic olfactory signaling pathway. ConclusionsThe mechanism of BC-oil in treating asthma through signal transduction of OR2W3 is revealed at the molecular and cellular levels.

SGLT2 Inhibitors Empagliflozin and Canagliflozin Ameliorate Allergic Asthma Responses in Mice.

Inhibitors of sodium/glucose cotransporter 2 (SGLT2), such as empagliflozin and canagliflozin, have been widely used to block glucose reabsorption in the proximal tubules of kidneys in patients with diabetes. A meta-analysis suggested that SGLT2 inhibitors are associated with a decreased risk of asthma development. Therefore, we investigated whether SGLT2 inhibitors could suppress allergic asthma. Empagliflozin and canagliflozin suppressed the in vitro degranulation reaction induced by antigens in a concentration-dependent manner in RBL-2H3 mast cells. Empagliflozin and canagliflozin were administered to BALB/c mice sensitized to ovalbumin (OVA). The administration of empagliflozin or canagliflozin significantly suppressed OVA-induced airway hyper-responsiveness and increased the number of immune cells and pro-inflammatory cytokine mRNA expression levels in bronchoalveolar lavage fluid. The administration of empagliflozin and canagliflozin also suppressed OVA-induced histopathological changes in the lungs. Empagliflozin and canagliflozin also suppressed serum IgE levels. These results suggested that empagliflozin and canagliflozin may be applicable for the treatment of allergic asthma by suppressing immune responses.

Nematode Galectin Inhibits Basophilic Leukaemia RBL-2H3 Cells Apoptosis in IgE-Mediated Activation.

Mast cells are essential immune cells involved in the host's defence against gastrointestinal nematodes. To evade the immune response, parasitic nematodes produce a variety of molecules. Galectin 1, produced by Teladorsagia circumcincta (Tci-gal-1), reduces mast cell degranulation and selectively regulates mediator production and release in an IgE-dependent manner. To uncover the activity of Tci-gal-1, we have examined the effect of the protein on gene expression, protein production, and apoptosis in activated basophilic leukaemia RBL-2H3 cells. Rat RBL-2H3 cells were activated with anti-DNP IgE and DNP-HSA, and then treated with Tci-gal-1. Microarray analysis was used to examine gene expression. The levels of several apoptosis-related molecules and cytokines were determined using antibody arrays and ELISA. Early and late apoptosis was evaluated cytometrically. Degranulation of cells was determined by a β-hexosaminidase release assay. Treatment of activated RBL-2H3 cells with Tci-gal-1 resulted in inhibited apoptosis and decreased degranulation, although we did not detect significant changes in gene expression. The production of pro-apoptotic molecules, receptor for advanced glycation end products (RAGE) and Fas ligand (FasL), and the cytokines IL-9, IL-10, IL-13, TNF-α, and IL-2 was strongly inhibited. Tci-gal-1 modulates apoptosis, degranulation, and production of cytokines by activated RBL-2H3 cells without detectable influence on gene transcription. This parasite protein is crucial for modulation of the protective immune response and the inhibition of chronic inflammation driven by mast cell activity.

Degranulation and expression of cytokines were modulated by diazinon in activated mast cells

Diazinon is an organophosphorus (OP) insecticides used in agriculture, home gardening and indoor pest control in Japan. It can activate macrophages and induce pro-inflammatory responses and has been reported to cause airway hyper-reactivity, suggesting the possibility of asthma exacerbation from exposure to OP insecticides. Despite the correlation between insecticide use and the pathogenesis of allergic diseases, there have been no reports on the effects of diazinon on mast cell function. Therefore, in this study, we investigated the effects of diazinon on mast cell function in rat basophilic leukemia (RBL)-2H3 cells. Surprisingly, we found that diazinon inhibited mast cell activation, although the degree of inhibition varied with concentration. Diazinon induced reactive oxygen species (ROS) generation and HO-1 expression at a concentration of 150 µM without affecting cell viability. Diazinon inhibited A23187-mediated degranulation and Tnf and Il4 expression in RBL-2H3 cells but did not affect calcium influx. Suppression of degranulation by diazinon was reversed when the culture supernatant was removed. As a signaling event downstream of calcium influx, diazinon inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) induced by A23187, whereas the phosphorylation of p38 had little effect. IgE cross-linking-mediated degranulation as well as the induction of Tnf and IL4 expression was significantly inhibited by diazinon, while diazinon had little effect on calcium influx. In conclusion, diazinon inhibited mast cell activation, including degranulation and cytokine expression. When evaluating the in vivo effects of diazinon, its potential to inhibit mast cell activation should be considered in the pathophysiology and development of allergic diseases in terms of basic and clinical aspects, respectively, although the effect of diazinon varies depending on the cell type.

Shiikuwasha leaf and peel extracts inhibit allergic reactions by suppressing degranulation in RBL-2H3 rat basophilic leukemia cells and immunoglobulin production in mouse spleen lymphocytes.

This study aims to investigate the antiallergic effects of Shiikuwasha (Citrus depressa Hayata) leaf and peel extracts by examining the regulation of degranulation and inflammatory cytokine production from rat basophilic leukemia (RBL-2H3) cells and antigen-specific antibody production in sensitized mouse spleen lymphocytes. In vivo antiallergic activity was evaluated using the passive cutaneous anaphylaxis (PCA) reaction model. Extracts of Shiikuwasha leaves and peel were prepared using 80% methanol and dissolved in dimethylsulfoxide. The dinitrophenyl-human serum albumin-induced β-hexosaminidase levels in immunoglobulin (Ig) E-sensitized RBL-2H3 cells were assessed using enzymatic assays. Cytokine production was measured by enzyme-linked immunosorbent assay. Antibody production capacity was evaluated using lymphocytes isolated from spleens of type I allergy model mice. Lymphocytes were cultured for 72 h with Shiikuwasha extracts, and ovalbumin-specific IgE, IgG1, and IgG2a levels were measured. Shiikuwasha leaf and peel extract significantly reduced β-hexosaminidase release and suppressed interleukin-4 and tumor necrosis factor-α production from RBL-2H3 cells. Ovalbumin-specific IgE and IgG1 production decreased in Shiikuwasha extract-treated lymphocytes. These extracts also significantly suppressed the PCA reaction. Shiikuwasha leaf and peel extract reduce degranulation in RBL-2H3 cells and antibody production in spleen-derived lymphocytes and therefore exhibit antiallergic effects.

RhoGDI in RBL-2H3 cells acts as a negative regulator of Rho GTPase signaling to inhibit granule exocytosis

RhoGDI in RBL-2H3 cells acts as a negative regulator of Rho GTPase signaling to inhibit granule exocytosis

Isothiocyanate-Corticosteroid Conjugates against asthma: Unity makes strength

Asthma is a major noncommunicable disease, affecting both children and adults, and represents one of the major causes leading to high health care costs due to the need for chronic pharmacological treatments. The standard gold therapy of inflammation in asthmatic patients involves the use of glucocorticoids even if their chronic use is often related to serious adverse effects. Growing evidence suggests the biological relevance of hydrogen sulfide (H2S) in the pathogenesis of airway diseases. Hence, aiming to associate the beneficial effects of steroidal anti-inflammatory drugs (SAIDs) to H2S biological activity, we designed and synthesized novel multi-target molecules by chemically combining a group of glucocorticoids, usually employed in asthma treatment, with an isothiocyanate moiety, well-known for its H2S releasing properties. Firstly, the synthesized compounds have been screened for their H2S-releasing profile using an amperometric approach and for their in vitro effects on the degranulation process, using RBL-2H3 cell line. The physicochemical profile, in terms of solubility, chemical and enzymatic stability of the newly hybrid molecules, has been assessed at different physiological pH values and in esterase-rich medium (bovine serum albumin, BSA). The selected compound 5c, through both its corticosteroid and H2S releasing component, has been evaluated in vivo in experimental model of asthma. The compound 5c inhibited in vivo all asthma features with a significative effect on the restoration of pulmonary structure and reduction of lung inflammation.