Fallopia japonica Root Extract Ameliorates Ovalbumin-Induced Airway Inflammation in a CARAS Mouse Model by Modulating the IL-33/TSLP/NF-κB Signaling Pathway.

Fallopia japonica (Asian knotweed) is a medicinal herb traditionally used to treat inflammation, among other conditions. However, the effects of F. japonica root extract (FJE) on airway inflammation associated with combined allergic rhinitis and asthma (CARAS) and the related mechanisms have not been investigated. This study examined the effect of FJE against CARAS in an ovalbumin (OVA)-induced CARAS mouse model. Six-week-old male BALB/c mice were randomly segregated into six groups. Mice were sensitized intraperitoneally with OVA on days 1, 8, and 15, and administered saline, Dexamethasone (1.5 mg/kg), or FJE (50, 100, or 200 mg/kg) once a day for 16 days. Nasal symptoms, inflammatory cells, OVA-specific immunoglobulins, cytokine production, mast cell activation, and nasal histopathology were assessed. Administration of FJE down-regulated OVA-specific IgE and up-regulated OVA-specific IgG2a in serum. FJE reduced the production of T helper (Th) type 2 cytokines, and the Th1 cytokine levels were enhanced in nasal and bronchoalveolar lavage fluid. Moreover, FJE positively regulated allergic responses by reducing the accumulation of inflammatory cells, improving nasal and lung histopathological characteristics, and inhibiting inflammation-associated cytokines. FJE positively modulated the IL-33/TSLP/NF-B signaling pathway, which is involved in regulating inflammatory cells, immunoglobulin levels, and pro-inflammatory cytokines at the molecular level.

Integration of transcriptomics and metabolomics to reveal the effect of ginsenoside Rg3 on allergic rhinitis in mice.

Increasing studies have demonstrated that ginsenoside Rg3 (Rg3) plays an important role in the prevention and treatment of various diseases, including allergic lower airway inflammation such as asthma. To investigate the role of Rg3 in allergic upper airway disease, the effect and therapeutic mechanism of Rg3 in allergic rhinitis (AR) were studied. Ovalbumin-induced AR model mice were intragastrically administered with Rg3. Nasal symptoms, levels of IgE, IL-4, IL-5, IL-13, SOD and MDA in serum, and histopathological analysis of nasal mucosa were used to evaluate the effect of Rg3 on ameliorating AR in mice. Moreover, nasal mucosa samples from the normal control group, AR model group and high dosage of Rg3 were collected to perform omics analysis. The differentially expressed genes and significantly changed metabolites were screened based on transcriptomics and metabolomics analyses, respectively. Integrative analysis was further performed to confirm the hub genes, metabolites and pathways. After Rg3 intervention, the nasal symptoms and inflammatory infiltration were effectively improved, the levels of IgE, IL-4, IL-5, IL-13 and MDA were significantly reduced, and the level of SOD was obviously increased. The results of the qRT-PCR assay complemented the transcriptomic findings. Integrated analysis showed that Rg3 played an anti-AR role mainly by regulating the interaction network, which was constructed by 12 genes, 8 metabolites and 4 pathways. Our findings suggested that Rg3 had a therapeutic effect on ovalbumin-induced AR in mice by inhibiting inflammation development and reducing oxidative stress. The present study could provide a potential natural agent for the treatment of AR.

HDAC Downregulation of Xiaoqinglong Decoction in the Treatment of Allergic Rhinitis.

INTRODUCTION: As one of the most common allergic diseases, allergic rhinitis (AR) has attracted wide attention all over the world. More appropriate treatment of AR should be explored thoroughly. In recent years, traditional Chinese medicine has attracted more attention in AR treatment. As a classical Chinese medicine prescription, Xiaoqinglong decoction (XQLD) has been commonly used in treating AR. Even though its therapeutic effect on AR has been clinically confirmed, more molecular mechanism remains to be further investigated. Our research aimed to investigate the therapeutic mechanism of XQLD for AR management. METHODS: The study was evaluated in an ovalbumin sensitized mouse model and liquid chromatography-mass spectrometry was adopted to test the stability of XQLD's effective components. RESULTS: The results confirmed the stability and safety of the effective components of XQLD. XQLD significantly downregulated the expression of HDACs (HDAC1, HDAC3, and HDAC4) and Th2 inflammatory factors (IL4, IL5, and IL13) in AR mice. XQLD and the HDAC inhibitor JNJ-26481585 promoted the expression of epithelial tight junction proteins (claudin-1 and ZO-1) and decreased the expression of mucins (Muc5ac and Muc5b) in the nasal mucosa of AR mice. CONCLUSIONS: In conclusion, our findings present the beneficial effects of XQLD on AR and recovery of the nasal epithelium. We also identify the decreased HDAC as a potential target of XQLD for AR treatment. This study provides an important experimental proof for elucidating the therapeutic mechanism of XQLD.

SymMap database and TMNP algorithm reveal Huanggui Tongqiao granules for Allergic rhinitis through IFN-mediated neuroimmuno-modulation.

Allergic rhinitis (AR) is a series of reactions to allergen mediated by immunoglobulin E (IgE) and is one of the most common allergic diseases that affects children. Traditional Chinese Medicine, due to its diverse regulatory functions, may offer new strategies for AR therapy. Huanggui Tongqiao Granules (HTG) is a Chinese formula consisting of twelve herbs and has long been prescribed for patients with AR. The aim of this study is to determine the possible targets and action mechanisms of HTG for the AR treatment. SymMap database and TMNP algorithm were employed to show that interferon-gamma (IFN-gamma), acting as a molecular link between immunity and neural circuits, is the involved key target. The enrichment of immune and virus-related signaling pathways indicated the neuroimmunomodulatory potential of HTG. Then, AR mouse model was established by ovalbumin (OVA) challenge and was used to verify the therapeutic effects of HTG in vivo. HTG significantly relieved AR symptoms and nasal mucosal inflammation, reduced OVA-specific IgE levels and balanced IFN-gamma/IL-4 ratio. Moreover, transcriptional profile based on clinical data presented that blood cell-specific IFN-gamma co-expressed gene module (BIM) was underexpressed in AR patients, further validating the potential of IFN-gamma as target for AR. Collectively, these findings suggest that HTG could be a promising candidate drug for AR.

α-Linolenic Acid Screened by Molecular Docking Attenuates Inflammation by Regulating Th1/Th2 Imbalance in Ovalbumin-Induced Mice of Allergic Rhinitis.

α-Linolenic acid (ALA) is a natural essential fatty acid widely found in plant seed oils and beans, which shows positive anti-inflammatory and antiallergic effects. In our previous study, ALA was proven to bind tightly to the seven protein targets closely associated with allergic rhinitis (AR) by molecular docking, which indicates that ALA may have a potential role in the treatment of AR. A mouse model of AR induced by ovalbumin (OVA) was adopted in this study to explore the therapeutical effect and potential mechanism of ALA in treating AR. Results demonstrated that ALA remarkably relieved the nasal symptoms, reduced the OVA-sIgE level in the serum, relieved the histopathological injuries, and downregulated the mRNA expression levels of IL-6 and IL-1ß in the nasal mucosa. ALA also remarkably moderated the imbalance of Th1/Th2 cells, increased the mRNA expression levels of T-bet and STAT1, and reduced GATA3 and STAT6. ALA was proven to have a substantial therapeutic effect on mice with AR, and the underlying mechanism was likely to be the regulation of Th1/Th2 imbalance through the JAK/T-bet/STAT1 and JAK/GATA3/STAT6 pathways. This study provides a specific experimental basis for the clinical use and drug development of ALA in the treatment of AR.

Investigation of the Immunoprotective Effect of Zinc on Ovalbumin Induced BALB/C Male Mice Based on NF-KB Signaling Pathway.

Allergic rhinitis is one of the common chronic inflammatory diseases of the nasal mucosa. In order to investigate the effect of zinc on ovalbumin induced allergic rhinitis in BALB/C male mice based on NF-KB signaling pathway, thirty BALB/C male mice are randomly divided into three groups: control group, ovalbumin induced allergic rhinitis asthma group and zinc intervention group. The experimental results show that Zinc supplementation in allergic asthma mice with allergic rhinitis correct the immune response of TH2 cells by inhibiting THE NF-KB signaling pathway, reduce the infiltration of inflammatory cells into lung nasal tissue, and reduce airway co-hyperreactivity to improve the clinical symptoms of asthma and play an immune protective role.

Dendrobium nobile protects against ovalbumin-induced allergic rhinitis by regulating intestinal flora and suppressing lung inflammation.

Antibiotic exposure-induced dysbiosis of the intestinal flora increases the risk of developing allergic rhinitis. Hence, regulating the balance of intestinal flora may be useful for preventing and treating allergic rhinitis. However, the underlying mechanism is unclear. Dendrobium nobile (Shihu) exhibits anti-inflammatory and immune activities. Hence, in this study, we investigated the mechanism via which Shihu may improve allergic rhinitis. Mouse models of allergic rhinitis with intestinal flora dysbiosis (Model-D, antibiotics induce intestinal flora dysbiosis with ovalbumin-induced allergy) and normal intestinal flora with allergic rhinitis (Model-N, ovalbumin-induced allergy) were established. The effect of Shihu on intestinal flora and inflammation caused during allergic rhinitis were analyzed. Allergic symptoms, infiltration of hematoxylin and eosin in the lungs and nose, and the release of various factors [interleukin (IL)-2, IL-4, IFN-γ, IL-6, IL-10, and IL-17] in the lungs were evaluated. The results indicate that intestinal flora dysbiosis exacerbated lung and nose inflammation in allergic rhinitis. However, treatment with the Shihu extract effectively reversed these symptoms. Besides, the Shihu extract inhibited the PI3K/AKT/mTOR pathway and increased the level of Forkhead box protein in the lungs. Additionally, the Shihu extract reversed intestinal flora dysbiosis at the phylum and genus levels and improved regulator T cell differentiation. Furthermore, in the Model-D group, the Shihu extract inhibited the decrease in the diversity and abundance of the intestinal flora. Screening was performed to determine which intestinal flora was positively correlated with Treg differentiation using Spearman's correlation analysis. In conclusion, we showed that Shihu extract restored the balance in intestinal flora and ameliorated inflammation in the lungs of allergic rhinitis mice and predicted a therapeutic new approach using Traditional Chinese Medicine to improve allergic rhinitis.

[Bioinformatics analysis of nasal epithelial cell gene expression in seasonal and perennial allergic rhinitis].

Objective: Transcriptome sequencing and bioinformatics analysis were performed on the gene expression of nasal epithelial cells in patients with seasonal allergic rhinitis (AR) and perennial AR, so as to obtain the differences in the gene expression of nasal epithelial cells between seasonal AR and perennial AR. Methods: The human nasal epithelial cell line(HNEpC) was cultured in vitro, treated with 100 µg/ml mugwort or house dust mite (HDM) extracts for 24 hours. Total cell RNA was extracted, and quantitative real-time polymerase chain reaction (qPCR) was used to detect the expression of cytokines, including IL-6, IL-8, IL-33 and thymic stromal lymphopoietin (TSLP). From November 2019 to November 2020, 3 seasonal AR patients, 3 perennial AR patients, and 3 healthy controls who attended the Department of Otolaryngology Head and Neck Surgery, China-Japan Union Hospital of Jilin University were analyzed. The patients' primary nasal epithelial cells were cultured in vitro, treated with corresponding allergens for 24 hours. Total RNA was extracted for transcriptome sequencing, and the sequencing results were analyzed by bioinformatics. Results: The qPCR results showed that the cytokines IL-6, IL-8, IL-33 and TSLP of HNEpC treated with mugworts extracts and HDM extracts had the same trend of change. After the nasal epithelial cells from patients with seasonal AR and perennial AR were treated with corresponding allergens, there were differences in biological processes and signal pathways between those and control. Gene ontology (GO) enrichment analysis showed that the differentially expressed genes (DEG) in AR patients allergic to mugwort were mainly enriched in the oxidation-reduction process, the negative regulation of apoptosis process, and the cell adhesion; the DEG in AR patients allergic to HDM were mainly enriched in cell adhesion, the negative regulation of cell proliferation and the response to drug. Enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway showed that the DEG of AR patients allergic to mugwort were significantly enriched in arachidonic acid metabolism, p53 signaling pathway and transforming growth factor ß (TGF-ß) signaling pathway, while the DEG of AR patients allergic to HDM were mainly enriched in cells cycle, Fanconi anemia pathway and DNA replication. Gene Set Enrichment Analysis (GSEA) showed that the inflammatory response, TNF-α/NF-κB signaling pathway and IL-2/STAT5 signaling pathway were significantly up-regulated in AR patients allergic to mugwort, indicating the promotion of inflammatory response; and AR patients allergic to HDM had significant down-regulation of G2M, E2F, and MYC, indicating the inhibition of cell proliferation. The protein-protein interaction network showed that TNF and CDK1 were the most interacting proteins in mugwort and HDM allergic AR patients, respectively. Conclusion: Seasonal AR and perennial AR may affect the different biological processes and signal pathways of nasal epithelial cells, leading to differences in the occurrence and development of AR.

Total glucosides of paeony ameliorates oxidative stress, apoptosis and inflammatory response by regulating the Smad7­TGF­ß pathway in allergic rhinitis.

Total glucosides of paeony (TGP), an active ingredient extracted from the root of Paeonia alba, has been reported to display an anti­inflammatory effect. However, the effect of TGP on allergic rhinitis (AR) is still unknown. The present study aimed to assess the role of TGP in an AR mouse model. An AR mouse model was established using the ovalbumin method. The expression levels of Smad7/TGF­ß pathway­related prtoeins in nasal mucosa tissues were determined by immunofluorescence, immunohistochemistry and western blotting. The severity of nasal allergic symptoms was detected by recording the frequency of sneezing and nose rubbing motions in all mice for 20 min. The levels of IgE and inflammatory cytokines, including IL­4, IL­5, IL­17 and IFN­Î³, in the serum were measured by conducting ELISAs. H&E staining, periodic acid­Schiff staining and Masson staining were used to detected histopathological changes in mice. The concentrations of malondialdehyde and glutathione, and the activities of superoxide dismutase and catalase in tissue supernatant and serum were quantified using commercial assay kits. Apoptosis of nasal tissue cells was detected by performing TUNEL assays and western blotting. The expression of Smad7 was upregulated and that of TGF­ß was downregulated in the nasal tissue of AR mice. Additionally, TGP regulated the Smad7/TGF­ß pathway in the nasal tissue of AR mice. TGP alleviated serum IgE, nasal symptoms and histopathological changes in AR mice. Moreover, TGP ameliorated oxidative stress, cell apoptosis and inflammatory response. Smad7 small interfering RNA intervention aggravated the symptoms of AR mice via activation of the TGF­ß pathway and reversed the protective effect of TGP in AR mice. TGP ameliorated oxidative stress, apoptosis and inflammatory response via the Smad7/TGF­ß pathway in AR.

Bioinformatics analysis of nasal epithelial cell gene expression in seasonal and perennial allergic rhinitis / 中华耳鼻咽喉头颈外科杂志

Objective: Transcriptome sequencing and bioinformatics analysis were performed on the gene expression of nasal epithelial cells in patients with seasonal allergic rhinitis (AR) and perennial AR, so as to obtain the differences in the gene expression of nasal epithelial cells between seasonal AR and perennial AR. Methods: The human nasal epithelial cell line(HNEpC) was cultured in vitro, treated with 100 μg/ml mugwort or house dust mite (HDM) extracts for 24 hours. Total cell RNA was extracted, and quantitative real-time polymerase chain reaction (qPCR) was used to detect the expression of cytokines, including IL-6, IL-8, IL-33 and thymic stromal lymphopoietin (TSLP). From November 2019 to November 2020, 3 seasonal AR patients, 3 perennial AR patients, and 3 healthy controls who attended the Department of Otolaryngology Head and Neck Surgery, China-Japan Union Hospital of Jilin University were analyzed. The patients' primary nasal epithelial cells were cultured in vitro, treated with corresponding allergens for 24 hours. Total RNA was extracted for transcriptome sequencing, and the sequencing results were analyzed by bioinformatics. Results: The qPCR results showed that the cytokines IL-6, IL-8, IL-33 and TSLP of HNEpC treated with mugworts extracts and HDM extracts had the same trend of change. After the nasal epithelial cells from patients with seasonal AR and perennial AR were treated with corresponding allergens, there were differences in biological processes and signal pathways between those and control. Gene ontology (GO) enrichment analysis showed that the differentially expressed genes (DEG) in AR patients allergic to mugwort were mainly enriched in the oxidation-reduction process, the negative regulation of apoptosis process, and the cell adhesion; the DEG in AR patients allergic to HDM were mainly enriched in cell adhesion, the negative regulation of cell proliferation and the response to drug. Enrichment analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway showed that the DEG of AR patients allergic to mugwort were significantly enriched in arachidonic acid metabolism, p53 signaling pathway and transforming growth factor β (TGF-β) signaling pathway, while the DEG of AR patients allergic to HDM were mainly enriched in cells cycle, Fanconi anemia pathway and DNA replication. Gene Set Enrichment Analysis (GSEA) showed that the inflammatory response, TNF-α/NF-κB signaling pathway and IL-2/STAT5 signaling pathway were significantly up-regulated in AR patients allergic to mugwort, indicating the promotion of inflammatory response; and AR patients allergic to HDM had significant down-regulation of G2M, E2F, and MYC, indicating the inhibition of cell proliferation. The protein-protein interaction network showed that TNF and CDK1 were the most interacting proteins in mugwort and HDM allergic AR patients, respectively. Conclusion: Seasonal AR and perennial AR may affect the different biological processes and signal pathways of nasal epithelial cells, leading to differences in the occurrence and development of AR.

Dendrobium nobile protects against ovalbumin-induced allergic rhinitis by regulating intestinal flora and suppressing lung inflammation / 中国天然药物

Antibiotic exposure-induced dysbiosis of the intestinal flora increases the risk of developing allergic rhinitis. Hence, regulating the balance of intestinal flora may be useful for preventing and treating allergic rhinitis. However, the underlying mechanism is unclear. Dendrobium nobile (Shihu) exhibits anti-inflammatory and immune activities. Hence, in this study, we investigated the mechanism via which Shihu may improve allergic rhinitis. Mouse models of allergic rhinitis with intestinal flora dysbiosis (Model-D, antibiotics induce intestinal flora dysbiosis with ovalbumin-induced allergy) and normal intestinal flora with allergic rhinitis (Model-N, ovalbumin-induced allergy) were established. The effect of Shihu on intestinal flora and inflammation caused during allergic rhinitis were analyzed. Allergic symptoms, infiltration of hematoxylin and eosin in the lungs and nose, and the release of various factors [interleukin (IL)-2, IL-4, IFN-γ, IL-6, IL-10, and IL-17] in the lungs were evaluated. The results indicate that intestinal flora dysbiosis exacerbated lung and nose inflammation in allergic rhinitis. However, treatment with the Shihu extract effectively reversed these symptoms. Besides, the Shihu extract inhibited the PI3K/AKT/mTOR pathway and increased the level of Forkhead box protein in the lungs. Additionally, the Shihu extract reversed intestinal flora dysbiosis at the phylum and genus levels and improved regulator T cell differentiation. Furthermore, in the Model-D group, the Shihu extract inhibited the decrease in the diversity and abundance of the intestinal flora. Screening was performed to determine which intestinal flora was positively correlated with Treg differentiation using Spearman's correlation analysis. In conclusion, we showed that Shihu extract restored the balance in intestinal flora and ameliorated inflammation in the lungs of allergic rhinitis mice and predicted a therapeutic new approach using Traditional Chinese Medicine to improve allergic rhinitis.

Studying the Effects of Vitamin A on the Severity of Allergic Rhinitis and Asthma.

Allergic asthma is a complex lung disease characterized by breathlessness, airway inflammation, and obstruction. Allergy and allergic rhinitis (AR) are the main triggers of asthma. Vitamin A is an important supplementary factor for the physiological activation of the immune system. In the present study, we investigated the effects of vitamin A on the exacerbation of allergic asthma symptoms. BALB/c mice were allocated to four groups. Asthma was created in two groups, and in the other two groups, rhinitis was induced. One of the asthma groups and one of the rhinitis groups orally received vitamin A (20 IU/g for 15 days). The levels of Immunoglobulin (Ig) E, histamine, leukotriene B4 (LTB4), Cysteinyl leukotriene receptor (Cys-LT), interleukin (IL)-4, IL-5, IL-13, and IL-35 as well as eosinophil peroxidase activity, were measured. Also, the histopathology of mice lungs was evaluated. The levels of total IgE, LTB4, Cys-LT, IL-4, IL-5, IL-17, and IL-33, eosinophil peroxidase activity, perivascular and peribronchial inflammation significantly decreased in vitamin A-treated asthma and rhinitis groups compared to non-treated groups. Also, IL-13 and histamine levels, hyperplasia of the goblet cell, and hyper-secretion of the mucus insignificantly decreased in vitamin A-treated asthma and rhinitis groups. Asthma and AR are common diseases that are generally developed due to the dysregulation of the immune system. Vitamin A plays an important role in controlling the immunopathologic mechanisms of allergic diseases. Vitamin A could be a useful supplement in managing AR and asthma by decreasing the severity of inflammatory responses. Therefore, control of vitamin A deficiency is recommended in Allergy.

Effects of Yupingfeng nasal drops on serum cytokines, histopathology and eosinophil cationic protein in nasal mucosa of rats with allergic rhinitis.

Allergic rhinitis (AR) is one of the most common atopic disorders, which seriously affects patients' quality of life. Yupingfeng (YPF) Power is a traditional Chinese herb formula, and its oral dosage form has been widely used for the treatment of AR in Asian countries. In this study, we investigated the effects of YPF nasal drops on ovalbumin (OVA) sensitized/stimulated allergic rhinitis in rats. A Sprague-Dawley (SD) rat model of OVA-induced AR was established and then treated with three doses of YPF nasal drops. Besides, histopathological features, eosinophil cationic protein (ECP) in the nasal mucosa, and expression of type 1 helper T (Th1)/type 2 helper T (Th2)-related cytokines in serum were analyzed. The results showed that YPF nasal drops alleviated the injury of nasal mucosal epithelial structure, promoted the recovery of ciliary morphology and function and reduced interstitial edema and inflammatory cell infiltration to some extent. Moreover, YPF nasal drops regulated imbalance in Th1/Th2 cells caused by AR via regulating downward the expression of interleukin 4 (IL-4) and adjusting upward the expression of interferon-γ (INF-γ), and interleukin 12 (IL-12). Furthermore, it inhibited the expression of ECP in nasal epithelial eosinophil-specific granules. The findings of this study provided a new perspective for the treatment of AR with YPF nasal drops based on Traditional Chinese Medicine.

Erythromycin reduces nasal inflammation by inhibiting immunoglobulin production, attenuating mucus secretion, and modulating cytokine expression.

Allergic rhinitis (AR) and chronic rhinosinusitis (CRS) share some similar pathological mechanisms. In current study, we intend to investigate the impact of AR on CRS. In addition, we explored the efficacy of erythromycin (EM) treatment on CRS mice with or without AR (CRSwoAR, CRSwAR). Study subjects were divided into control, CRSwoAR, and CRSwAR groups. Experimental mice were divided similarly into control, CRSwoAR, and CRSwAR groups. In addition, CRS mice were treated with EM at 0.75, 7.5, or 75 mg/kg or with dexamethasone (Dex) at 1 mg/kg. In our results, allergy exacerbates inflammation that was evident in nasal histology and cytokine expression both in patients and in mice with CRS. Dex 1 mg/kg, EM 7.5 or 75 mg/kg treatments significantly inhibited serum IgE and IgG2a in CRS mice. EM-treated CRS mice had significantly elevated IL-10 levels and had a reversal of Th-1/Th-2 cytokine expression in nasal-associated lymphoid tissue. MUC5AC expressions were significantly reduced in the 7.5 or 75 mg/kg EM-treated mice compared with untreated mice. EM showed inhibitions on immunoglobulin production and mucus secretion stronger than Dex. We concluded that comorbid AR enhanced inflammation of CRS. EM and Dex treatments showed similar anti-inflammatory effects on CRS but through partly different mechanisms.

A novel nasal co-loaded loratadine and sulpiride nanoemulsion with improved downregulation of TNF-α, TGF-ß and IL-1 in rabbit models of ovalbumin-induced allergic rhinitis.

PURPOSE: The work aimed to develop a co-loaded loratadine and sulpiride nasal nanoemulsion for allergic rhinitis management. METHODS: Compatibility studies were conducted adopting differential scanning calorimetry and Fourier transform infrared spectroscopy. Nanoemulsion formulations were prepared using soybean lecithin, olive oil and tween 80. Sodium cholate and glycerol were employed as co-surfactants. Nanoemulsions were assessed for viscosity, pH, droplet size, polydispersity index, zeta potential, electrical conductivity, entrapment, In vitro drug release and corresponding kinetics. Stability of the selected formulation was investigated. The biological effectiveness was evaluated in rabbit models of ovalbumin-induced allergic rhinitis by measuring TNF-α, TGF-ß and IL-1. RESULTS: Compatibility studies revealed absence of drug/drug interactions. Nanoemulsions exhibited > 90% entrapment efficiency. The selected nanoemulsion demonstrated small droplet size (85.2 ± 0.2 nm), low PDI (0.35 ± 0.0) and appropriate Zeta Potential (-23.3 ± 0.2) and stability. It also displayed enhanced in vitro drug release following the Higuashi Diffusion and Baker-Lonsdale models. The mean relative mRNA expression of TNF-α, IL-1 and TGF-ß significantly decreased from 9.59 ± 1.06, 4.15 ± 0.02 and 4.15 ± 0.02 to 1.28 ± 0.02, 1.93 ± 0.06 and 1.56 ± 0.02 respectively after treatment with the selected nanoemulsion formulation. CONCLUSION: The results reflected a promising potent effect of the combined loratadine and sulpiride nasal nanoemulsion in managing the symptoms of allergic rhinitis.

Piper Nigrum extract improves OVA-induced nasal epithelial barrier dysfunction via activating Nrf2/HO-1 signaling.

BACKGROUND: Piper nigrum L. (Piperaceae) is commonly used as a spice and traditional medicine in many countries. It has been reported to have anti-oxidant, anti-bacterial, anti-tumor, anti-mutagenic, anti-diabetic, and anti-inflammatory properties. However, the protective role of P. nigrum on epithelial function of upper respiratory tract injury in an allergic rhinitis (AR) mouse model has been unclear. This study aims to investigate the effects of P. nigrum fruit extract (PNE) on the nasal epithelial barrier function of the upper respiratory tract in an ovalbumin (OVA)-induced AR model. METHODS: AR mouse model was established by intraperitoneal injection with 200 µL saline containing 50 µg OVA adsorbed to 1 mg aluminum hydroxide, and intranasal challenge with 20 µL per nostril of 1 mg/ml OVA. Besides, mice were orally administrated once daily with PNE and dexamethasone (Dex) in 13 days. The nasal symptoms, inflammatory cells, OVA-specific immunoglobulins, cytokines, nasal histopathology, and immunohistochemistry were evaluated. RESULTS: The PNE oral administrations inhibited allergic responses via reduction of OVA-specific antibodies levels and mast cells histamine release, accordingly, the nasal symptoms in the early-phase reaction were also clearly ameliorated. In both nasal lavage fluid and nasal tissue, PNE suppressed the inflammatory cells accumulation, specifically with eosinophils. The intravenous Evans blue injection illustrated the epithelial permeability reduction of nasal mucosa layer in PNE-treated mice. Also; PNE treatments protected the epithelium integrity by preventing the epithelial shedding from nasal mucosa; as a result of enhancing the strong expression of the E-cadherin tight junction protein in cell-to-cell junctions, as well as inhibiting the degraded levels of zonula occludens-1 (ZO-1) and occludin into the nasal cavity. Additionally, PNE protected against nasal epithelial barrier dysfunction via enhancing the expression of Nrf2 activated form which led to increasing synthesis of the anti-inflammation enzyme HO-1. CONCLUSIONS: These obtained results suggest that PNE has a promising strategy for epithelial barrier stabilization in allergic rhinitis treatment.

Pattern recognition receptors as potential drug targets in inflammatory disorders.

Pattern recognition receptors (PRRs) are a key part of the innate immune system, the body's first line of defense against infection and tissue damage. This superfamily of receptors including Toll-like receptors (TLRs), NOD-like receptors (NLRs), C-type lectin-like receptors (CLRs) and RIG-like receptors (RLRs) are responsible for initiation of the inflammatory response by their recognition of molecular patterns present in invading microorganisms (such as bacteria, viruses or fungi) during infection or in molecules released following tissue damage during acute or chronic disease states (such as sepsis or arthritis). These receptors are widely expressed and located on the cell surface, in intracellular compartments or in the cytoplasm can detect a single or subset of molecules including lipoproteins, carbohydrates or nucleic acids. In response, they initiate an intracellular signaling cascade that culminates in the synthesis and release of cytokines, chemokines and vasoactive molecules. These steps are necessary to maintain tissue homeostasis and remove potentially dangerous pathogens. However, during extreme or acute responses or during chronic disease, this can be damaging and even lead to death. Therefore, it is thought that targeting such receptors may offer a therapeutic approach in chronic inflammatory diseases or in cases of acute infection leading to sepsis. Herein, the current knowledge on the molecular biology of PRRs is reviewed along with their association with inflammatory and infectious diseases. Finally, the testing of therapeutic compounds and their future merit as targets is discussed.

Effects of Low-Level Laser Irradiation in a Mouse Model of Allergic Rhinitis.

BACKGROUND AND OBJECTIVES: To evaluate the antiallergic effect of low-level laser irradiation (LLLI) at 650 nm in a mouse model of allergic rhinitis (AR), and to examine the underlying mechanisms. STUDY DESIGN/MATERIALS AND METHODS: BALB/c mice were sensitized with ovalbumin (OVA) and alum and challenged intranasally with OVA. Straight- and diffusion-type LLLI were applied directly into the intranasal cavity of the mice once daily for 10 days (650 nm, 5 mW, 15 min/day) and multiple allergic parameters were evaluated. RESULTS: LLLI reduced allergic symptoms, such as rubbing and sneezing, and suppressed the serum total immunoglobulin E (IgE), OVA-specific IgE, and OVA-specific IgG1 levels. Diffusion-type LLLI significantly reduced eosinophil infiltration of nasal mucosa and lymph nodes (LNs). LLLI reduced the expression of interleukin-4 (IL-4) and IL-17 in cervical LN and splenocyte culture supernatant, as well as their messenger RNA levels in nasal mucosa. However, the expression of interferonγ (IFN-γ) and IL-6 was unaffected by LLLI. The levels of reactive oxygen species (ROS) and nitric oxide (NO) in LN cells and the nasal mucosa, which were increased in the AR group, were reduced by LLLI, suggesting involvement of ROS and NO within their mechanism. CONCLUSIONS: LLLI exerted an antiallergic effect by decreasing local and systemic IL-4, IL-17, and IgE levels, as well as eosinophilic infiltration into the nasal mucosa, in a mouse model of AR by modulating ROS and NO levels. Diffusion-type LLLI exhibited greater efficacy against AR than straight-type LLLI. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc.

Potential anti-inflammatory effect of Madi-Ryuk and its active ingredient tannic acid on allergic rhinitis.

Madi-Ryuk (MDR) is a traditional Korean medicine and it has been widely used in Korea to treat arthritis and we previously reported the anti-allergic inflammatory effect of MDR in vitro model. However, therapeutic evidence of MDR on in vivo model of allergic inflammatory reaction has not yet been demonstrated. The research purpose was to investigate the efficacy of MDR and its active ingredient tannic acid (TA) in ovalbumin (OVA)-induced AR mice model. OVA-challenged AR mice orally medicated MDR or its active ingredient TA daily for ten days. In mice having a AR, MDR and TA prominently diminished number of rubs and levels of histamine, IgE, thymic stromal lymphopoietin, interleukin (IL)-1ß, IL-4, IL-5, IL-13, IL-33, and tumor necrosis factor-α. In addition, protein expression levels and activities of caspase-1 were declined by oral medication of MDR and TA. Decline in levels of macrophage inflammatory protein-2 and intercellular adhesion molecules-1 and reduction in penetrations of inflammatory cells into inflamed tissue were also noted in MDR and TA groups. Taken together, identification of MDR effect in preclinical models suggests that MDR may be a therapeutic drug for the treatment and prevention of AR.

The unpredictability of seasonal variations in serum vitamin D levels in children with asthma and/or rhinitis.

BACKGROUND: Some studies have showed that seasonality is an important determinant of vitamin D (vitD) status. OBJECTIVE: We evaluated whether there are differences in individual trends of serum vitD level over one year in asthmatic and rhinitic children. MATERIALS AND METHODS: Ninety-two asthmatic and rhinitic paediatric patients were followed up for one year and their serum vitD level was detected at three-month intervals, once in each season. RESULTS: We observed higher vitD levels at the end of summer and lower at the end of winter. However, the individual seasonal trend was very variable and unpredictable. If it is true that in a given season the majority of patients followed one direction (increase or decrease of serum vitD levels), nevertheless a substantial percentage behaved differently and unpredictably. For example, at the end of spring, 70% of patients showed an increase in serum vitD levels, but 30% showed a decrease. In addition, five individuals had a value ≥50ng/ml in September and showed serum vitD levels ≥30ng/ml throughout the year; 16 patients presented vitD value ≥40ng/ml in September and always had ≥20ng/ml in the other months. CONCLUSIONS: The wide and unpredictable variability of the individual trend of serum vitD levels should be taken into account before deciding whether or not a drug supplementation is appropriate.