Intranasal administration of ceramide liposome suppresses allergic rhinitis by targeting CD300f in murine models.

Allergic rhinitis (AR) is caused by type I hypersensitivity reaction in the nasal tissues. The interaction between CD300f and its ligand ceramide suppresses immunoglobulin E (IgE)-mediated mast cell activation. However, whether CD300f inhibits the development of allergic rhinitis (AR) remains elusive. We aimed to investigate the roles of CD300f in the development of AR and the effectiveness of intranasal administration of ceramide liposomes on AR in murine models. We used ragweed pollen-induced AR models in mice. Notably, CD300f deficiency did not significantly influence the ragweed-specific IgE production, but increased the frequency of mast cell-dependent sneezing as well as the numbers of degranulated mast cells and eosinophils in the nasal tissues in our models. Similar results were also obtained for MCPT5-exprssing mast cell-specific loss of CD300f. Importantly, intranasal administration of ceramide liposomes reduced the frequency of sneezing as well as the numbers of degranulated mast cells and eosinophils in the nasal tissues in AR models. Thus, CD300f-ceramide interaction, predominantly in mast cells, alleviates the symptoms and progression of AR. Therefore, intranasal administration of ceramide liposomes may be a promising therapeutic approach against AR by targeting CD300f.

Medicinal plants for allergic rhinitis: A systematic review and meta-analysis.

Herbal medicine is popularly used among patients who suffer from allergic rhinitis. This systematic review and meta-analysis was conducted to evaluate the efficacy and safety of single medicinal plants in the management of allergic rhinitis. We searched MEDLINE, CENTRAL, and Web of Science for randomised controlled trials which evaluated the use of single medicinal plant for allergic rhinitis among adults and children. Twenty-nine randomised controlled trials (n = 1879) were eligible while 27 (n = 1769) contributed data for meta-analyses. Most studies (studies = 20) compared medicinal plants against placebo and Petasites hybridus was most frequently investigated (studies = 5). Very-low-to-low-certainty evidence suggests that compared to placebo, single medicinal plants may improve overall total nasal symptoms (SMD -0.31, 95% CI -0.59 to -0.02; participants = 249; studies = 5; I2 = 21%) especially nasal congestion and sneezing; and rhinoconjunctivitis quality of life (RQLQ) scores (MD -0.46, 95% CI -0.84 to -0.07; participants = 148; studies = 3; I2 = 0%). Moderate-certainty evidence show no clear differences between single medicinal plants and antihistamine in overall symptoms (Total nasal symptoms: SMD -0.14, 95% CI -0.46 to 0.18; participants = 149; studies = 2; I2 = 0%). As adjunctive therapy, moderate-certainty evidence shows that medicinal plants improved SNOT-22 scores when given as intranasal treatment (MD -7.47, 95% CI -10.75 to -4.18; participants = 124; studies = 2; I2 = 21%). Risk of bias domains were low or not clearly reported in most studies while heterogeneity was substantial in most pooled outcomes. Route of administration and age were identified to be plausible source of heterogeneity for certain outcomes. Medicinal plants appear to be well tolerated up to 8 weeks of use. Clear beneficial evidence of medicinal plants for allergic rhinitis is still lacking. There is a need for improved reporting of herbal trials to allow for critical assessment of the effects of each individual medicinal plant preparation in well-designed future clinical studies.

Evaluation of Urtica dioica Phytochemicals against Therapeutic Targets of Allergic Rhinitis Using Computational Studies.

Allergic rhinitis (AR) is a prevalent inflammatory condition affecting millions globally, with current treatments often associated with significant side effects. To seek safer and more effective alternatives, natural sources like Urtica dioica (UD) are being explored. However, UD's mechanism of action remains unknown. Therefore, to elucidate it, we conducted an in silico evaluation of UD phytochemicals' effects on known therapeutic targets of allergic rhinitis: histamine receptor 1 (HR1), neurokinin 1 receptor (NK1R), cysteinyl leukotriene receptor 1 (CLR1), chemoattractant receptor-homologous molecule expressed on type 2 helper T cells (CRTH2), and bradykinin receptor type 2 (BK2R). The docking analysis identified amentoflavone, alpha-tocotrienol, neoxanthin, and isorhamnetin 3-O-rutinoside as possessing a high affinity for all the receptors. Subsequently, molecular dynamics (MD) simulations were used to analyze the key interactions; the free energy of binding was calculated through Generalized Born and Surface Area Solvation (MMGBSA), and the conformational changes were evaluated. Alpha-tocotrienol exhibited a high affinity while also inducing positive conformational changes across all targets. Amentoflavone primarily affected CRTH2, neoxanthin targeted NK1R, CRTH2, and BK2R, and isorhamnetin-3-O-rutinoside acted on NK1R. These findings suggest UD's potential to treat AR symptoms by inhibiting these targets. Notably, alpha-tocotrienol emerges as a promising multi-target inhibitor. Further in vivo and in vitro studies are needed for validation.

[Integrated traditional Chinese and western medicine expert consensus on the diagnosis and treatment of combined allergic rhinitis and asthma syndrome].

Combined allergic rhinitis and asthma syndrome (CARAS) refers to a common respiratory disease that occurs simultaneously with clinical or subclinical allergic symptoms of the upper respiratory tract (allergic rhinitis) and the lower respiratory tract (asthma). The incidence of CARAS is high and the quality of life of the patients is greatly affected. At present, treatment of this comprehensive disease is often carried out separately in the otorhinolaryngology and respiratory departments. One of the reasons is a lack of coordinated treatment consensus on the comprehensive management of this disease. As a common respiratory disease, this syndrome also has a profound clinical basis of traditional Chinese medicine in its diagnosis and treatment. Therefore, the Allergy Committee of Chinese Association of Integrative Medicine organized domestic experts in respiratory medicine, otolaryngology, allergy, pediatrics, traditional Chinese Medicine internal medicine and other related fields to discuss and summarize the etiology and anatomical characteristics, pathophysiology and pathogenesis, laboratory examination, diagnostic evaluation and differential diagnosis as well as treatment of both traditional Chinese medicine and western medicine, in order to provide integrated diagnosis and treatment opinions for this common integrative disease of upper and lower respiratory system in clinical practice.

The effectiveness of pharmacist-led educational model in adult patients with allergic rhinitis: a single-center randomized control trial protocol (AR-PRISE RCT).

BACKGROUND: Allergic rhinitis is a chronic respiratory disorder that significantly impacts patients' quality of life (QoL) and work performance. Pharmacists are recognized as suitable professionals to provide patient education and pharmaceutical care for managing allergic rhinitis patients. However, local clinical practice guidelines, particularly regarding pharmaceutical care in public healthcare institutions, are lacking. This study protocol outlines a randomized controlled trial (RCT) designed to evaluate the effectiveness of a pharmacist-led educational model (AR-PRISE Model) in managing allergic rhinitis in adult patients compared to standard pharmaceutical care. The AR-PRISE model delivers patient educational material and a pharmaceutical care algorithm. METHOD: This is a 6-month, single-center, prospective, randomized, two-arm, and parallel-group controlled trial. The trial recruits patients attending the otorhinolaryngology clinics of a tertiary referral hospital. Participants are randomized into control or intervention groups in a 1:1 ratio using permuted block randomization. The total number of participants estimated is 154, with each group requiring 77 participants. The control group receives standard pharmaceutical care, while the intervention group receives pharmacist-led education according to the AR-PRISE model. Both groups are assessed for middle turbinate endoscopy findings, disease severity, knowledge level, symptom control, medication adherence, and QoL at baseline and the end-of-study follow-up (day 180 ± 7). Depending on feasibility, intermediate follow-ups are conducted on days 60 ± 7 and 120 ± 7, either virtually or face-to-face. During intermediate follow-ups, participants are assessed for symptom control, medication adherence, and QoL. The intention-to-treat analysis includes all participants assigned to each group. An independent T-test compares the mean difference in knowledge level between the two groups. A two-way repeated measures ANOVA analysis is employed to determine between-group differences for scores of symptom control, adherence rate, and QoL. A P-value < 0.05 is considered statistically significant. DISCUSSION: This study protocol will provide a framework for conducting a randomized controlled trial (RCT) to evaluate the effectiveness of pharmacist-led education intervention in managing allergic rhinitis within public healthcare settings. The parameters measured in this trial will quantify outcomes associated with improvements in symptoms and QoL. By systematically assessing these outcomes, we aim to contribute valuable insights into the role of pharmacist-led interventions in enhancing the management of allergic rhinitis in public healthcare settings. TRIAL REGISTRATION: ClinicalTrials.gov NCT06027736 . Registered on 9 July 2023-retrospectively registered.

Hydrangea serrata extract attenuates PM-exacerbated airway inflammation in the CARAS model by modulating the IL-33/ST2/NF-κB signaling pathway.

Particulate matter (PM) significantly contributes to the global health crisis of respiratory diseases. It is known to induce and exacerbate conditions such as asthma and respiratory infections. Long exposure to PM can increase the risk of combined allergic rhinitis and asthma syndrome (CARAS). Although therapeutic drugs can be used to improve symptoms of respiratory diseases caused by PM, their usage is often accompanied by side effects. Therefore, many studies are being conducted to discover functional food materials that can more effectively treat respiratory diseases while minimizing the side effects of these therapeutic drugs. This study was conducted to investigate the efficacy of Hydrangea serrata extract (HSE) in airway inflammation in a mouse model of CARAS exacerbated by PM. In the CARAS mouse model worsened by PM, the airway inflammation improvement effect of HSE was evaluated by analyzing allergic nasal symptoms, changes in inflammatory cells, OVA-specific immunoglobulin (Ig) levels, cytokines, mast cell activation, and histopathological findings of both nasal mucosa and lung tissue. HSE effectively reduced OVA-specific IgE and IgG1 and inhibited the production of T helper type 2 (Th2)-related cytokines such as IL-4 and IL-5. Importantly, HSE reduced IL-33 and ST2 expression and inhibited the activation of the NF-κB signaling pathway. In addition, HSE inhibited airway hypersensitivity, mucus production, and inflammatory cell infiltration. These results suggest that HSE may inhibit airway inflammation in CARAS/PM mice by regulating the IL-33/ST2/NF-κB signaling pathway, opening avenues for considering HSE as a potential material for treating allergic airway inflammation diseases in the future.

Immunomodulation in allergic rhinitis: Insights from Th2 cells and NLRP3/IL-18 pathway.

Allergic rhinitis (AR) is characterized by nasal symptoms such as rubbing and sneezing, often triggered by allergen exposure. The purpose of this study is to dissect the roles of NLRP3-mediated immune modulation and macrophage pyroptosis in modulating T cell differentiation within the context of ovalbumin (OVA)-induced AR in mice. OVA-induced AR was established in mice, evaluating nasal symptoms, macrophage infiltration, cytokine levels, and T cell differentiation. Manipulations using NLRP3-/-, ASC-/- mice, clodronate liposome treatment, and NLRP3 inhibitor MCC950 were performed to assess their impact on AR symptoms and immune responses. Following OVA stimulation, increased nasal symptoms were observed in the OVA group along with augmented GATA3 expression and elevated IL-4 and IL-1b levels, indicative of Th2 polarization and cellular pyroptosis involvement. NLRP3-/- and ASC-/- mice exhibited reduced CD3+ T cells post OVA induction, implicating cellular pyroptosis in AR. Macrophage depletion led to decreased IgE levels, highlighting their involvement in allergic responses. Further investigations revealed enhanced macrophage pyroptosis, influencing Th1/Th2 differentiation in AR models. IL-18 released through NLRP3-mediated pyroptosis induced Th2 differentiation, distinct from IL-1b. Additionally, MCC950 effectively mitigated AR symptoms by modulating Th2 responses and reducing macrophage infiltration. This comprehensive study unravels the pivotal role of NLRP3-mediated immune modulation and macrophage pyroptosis in Th1/Th2 balance regulation in OVA-induced AR. Targeting NLRP3 pathways with MCC950 emerged as a promising strategy to alleviate AR symptoms, providing insights for potential therapeutic interventions in AR management.

Mahuang Fuzi Xixin decoction alleviates allergic rhinitis by inhibiting NLRP3/Caspase-1/GSDMD-N-mediated pyroptosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Allergic rhinitis (AR) is a prevalent nasal inflammatory disorder, and pyroptosis plays a crucial role in aggravating AR. Current medications for AR treatment still have deficiencies, and finding new agents is of great interest. Mahuang Fuzi Xixin decoction (MFXD), an ancient Chinese medicine, is now commonly used to treat AR, which has anti-inflammatory and immunomodulatory effects, but its underlying mechanism is unknown. AIM OF THIS STUDY: This study aims to evaluate the effects of MFXD on AR and explore its potential mechanisms in view of the regulatory effect on pyroptosis. METHODS: MFXD, Mahuang, Fuzi, and Xixin water extracts were analyzed using ultra high performance liquid chromatography-Orbitrap-high-resolution accurate mass spectrometry. In in vivo study, the effects of MFXD on AR treatment were evaluated in an ovalbumin-induced mouse model. Mice were administered saline (control and model groups), MFXD (1.375, 2.75 g/kg), and dexamethasone (2.5 mg/kg) for 13 days. AR symptoms were evaluated by blinded observers. Immunoglobulin E (IgE) and histamine levels were measured using enzyme-linked immunosorbent assays. Expression of pyroptosis-related proteins (NLRP3, ASC, Caspase-1 p10/p20, GSDMD-N and IL-1ß) in AR mouse nasal mucosa were estimated by immunohistochemistry. In in vivtro study, the effects of MFXD on pyroptosis were assessed in human nasal epithelial cells (HNEpCs) stimulated with lipopolysaccharide (LPS) and adenosine triphosphate (ATP), and incubated with MFXD (12.5, 25, and 50 µg/mL). Pyroptosis-related protein expression was measured by western blotting. RESULTS: Thirty-three compounds in MFXD were identified, including ephedrine, pseudoephedrine, higenamine, aconine, aconitine, benzoylmesaconitine, benzoylhypaconine and hypaconitine. In the in vivo study, oral taken of MFXD/dexamethasone significantly ameliorated AR symptoms, reduced swelling of the nasal mucosa, and decreased the levels of IgE and histamine in AR mice serum. MFXD/dexamethasone attenuated histopathological changes and reduced the expression of pyroptosis-related proteins in nasal mucosa, indicating the inhibitory effect on nasal epithelial pyroptosis. In the in vitro study, MFXD (50 µg/mL) significantly alleviated cytotoxicity, protected cells from swelling and rupture, and downregulated the expression of pyroptosis-related proteins in LPS/ATP-induced HNEpCs. CONCLUSION: MFXD suppressed nasal epithelial pyroptosis by inhibiting the NLRP3/Caspase-1/GSDMD-N signaling pathway, which alleviates AR. Our results offer valuable insights into potential AR therapies and provide evidence for the clinical utilization of MFXD to treat AR.

Undaria pinnatifida ameliorates nasal inflammation by inhibiting eosinophil and mast cell activation and modulating the NF-κB/MAPKs signaling pathway.

BACKGROUND: Allergic rhinitis (AR) is the most prevalent form of atopic disease. Undaria pinnatifida has potent antioxidative, antidiabetic, and anti-inflammatory properties. AIMS: We investigated the immunomodulatory effect of Undaria pinnatifida extract (UPE) on allergic inflammation in an AR mouse model. MATERIALS & METHODS: Mice were sensitized and intranasally challenged with ovalbumin (OVA), and the Th1/Th2 and Th17/Treg-related cytokines and histopathology were exanimated after UPE treatments. Enzyme-linked immunosorbent assay was performed using serum samples and NALF to detect OVA-specific immunoglobulins and inflammatory cytokines. Mitogen-activated protein kinases (MAPKs) were measured by western blotting analysis, and an in vitro study measured mast cell activation induced by compound 48/80. RESULTS: After UPE treatment, nasal and lung allergy symptoms, nasal mucosal swelling, and goblet cell hyperplasia were ameliorated. Oral UPE regulated the balance of Th1/Th2 and Th17/Treg cell differentiation in AR mice in a dose-dependent manner. In addition, UPE attenuated the migration of eosinophils and mast cells to the nasal mucosa by suppressing nuclear factor kappa B (NF-κB)/MAPKs. The levels of anti-OVA IgE and IgG1 were also decreased. DISCUSSION: UPE inhibited inflammation by regulating the NF-κB/MAPKs signaling pathway and supressing the activation of critical immune cells such as eosinophils and mast cells. CONCLUSION: UPE may have therapeutic potential for AR.

Identification of diagnostic signature, molecular subtypes, and potential drugs in allergic rhinitis based on an inflammatory response gene set.

Background: Rhinitis is a complex condition characterized by various subtypes, including allergic rhinitis (AR), which involves inflammatory reactions. The objective of this research was to identify crucial genes associated with inflammatory response that are relevant for the treatment and diagnosis of AR. Methods: We acquired the AR-related expression datasets (GSE75011 and GSE50223) from the Gene Expression Omnibus (GEO) database. In GSE75011, we compared the gene expression profiles between the HC and AR groups and identified differentially expressed genes (DEGs). By intersecting these DEGs with inflammatory response-related genes (IRGGs), resulting in the identification of differentially expressed inflammatory response-related genes (DIRRGs). Afterwards, we utilized the protein-protein interaction (PPI) network, machine learning algorithms, namely least absolute shrinkage and selection operator (LASSO) regression and random forest, to identify the signature markers. We employed a nomogram to evaluate the diagnostic effectiveness of the method, which has been confirmed through validation using GSE50223. qRT-PCR was used to confirm the expression of diagnostic genes in clinical samples. In addition, a consensus clustering method was employed to categorize patients with AR. Subsequently, extensive investigation was conducted to explore the discrepancies in gene expression, enriched functions and pathways, as well as potential therapeutic drugs among these distinct subtypes. Results: A total of 22 DIRRGs were acquired, which participated in pathways including chemokine and TNF signaling pathway. Additionally, machine learning algorithms identified NFKBIA, HIF1A, MYC, and CCRL2 as signature genes associated with AR's inflammatory response, indicating their potential as AR biomarkers. The nomogram based on feature genes could offer clinical benefits to AR patients. We discovered two molecular subtypes, C1 and C2, and observed that the C2 subtype exhibited activation of immune- and inflammation-related pathways. Conclusions: NFKBIA, HIF1A, MYC, and CCRL2 are the key genes involved in the inflammatory response and have the strongest association with the advancement of disease in AR. The proposed molecular subgroups could provide fresh insights for personalized treatment of AR.

A Supramolecular Assembly of EGCG for Long-Term Treatment of Allergic Rhinitis.

Allergic rhinitis (AR) is a type-I hypersensitivity disease mediated by immunoglobulin E (IgE). Although antihistamines, glucocorticoids, leukotriene receptor antagonists, and other drugs are widely used to treat AR, the various adverse side effects of long-term use of these drugs should not be ignored. Therefore, more effective and safe natural alternative strategies are urgently needed. To this end, this study designed a nanosupramolecular delivery system composed of ß-cyclodextrin supramolecular polymer (PCD), thiolated chitosan (TCS), and natural polyphenol epigallocatechin gallate (EGCG) for intranasal topical continuous treatment of AR. The TCS/PCD@EGCG nanocarriers exhibited an excellent performance in terms of retention and permeability in the nasal mucosa and released the vast majority of EGCG responsively in the nasal microenvironment, thus resulting in the significantly high antibacterial and antioxidant capacities. According to the in vitro model, compared with free EGCG, TCS/PCD@EGCG inhibited mast cell activity and abnormal histamine secretion in a more long-term and sustained manner. According to the in vivo model, whether in the presence of continuous or intermittent administration, TCS/PCD@EGCG substantially inhibited the secretion of allergenic factors and inflammatory factors, mitigated the pathological changes of nasal mucosa, alleviated the symptoms of rhinitis in mice, and produced a satisfactory therapeutic effect on AR. In particular, the therapeutic effect of TCS/PCD@EGCG systems were even superior to that of budesonide during intermittent treatment. Therefore, the TCS/PCD@EGCG nanocarrier is a potential long-lasting antiallergic medicine for the treatment of AR.

Morita-Baylis-Hillman adduct 2-(3-hydroxy-1-methyl-2-oxoindolin-3-il) acrylonitrile (CISACN) ameliorates the pulmonary allergic inflammation in CARAS model by increasing IFN-γ/IL-4 ratio towards the Th1 immune response.

Combined allergic rhinitis and asthma syndrome (CARAS) is an airway-type 2 immune response with a profuse inflammatory process widely affecting the world population. Due to the compromise of quality of life and the lack of specific pharmacotherapy, the search for new molecules becomes relevant. This study aimed to evaluate the effectiveness of the Morita-Bailys-Hillman adduct (CISACN) treatment in the CARAS experimental model. Female BALB/c mice were ovalbumin (OVA) -sensitized and -challenged and treated with CISACN. The treatment decreased the eosinophil migration to the nasal and lung cavities and tissues and the goblet cell hyperplasia/hypertrophy, attenuated airway hyperactivity by reducing the hyperplasia/hypertrophy of the smooth muscle and the extracellular matrix's thickness. Also, the treatment reduced the clinical signs of rhinitis as nasal rubbing and sneezing in a histamine-induced nasal hyperreactivity assay. The immunomodulatory effect of CISACN was by reducing OVA-specific IgE serum level, and IL-33, IL-4, IL-13, and TGF-ß production, dependent on IFN-γ increase. Furthermore, the effect of CISACN on lung granulocytes was by decreasing the p-p38MAPK/p65NF-κB signaling pathway. Indeed, CISACN reduced the p38MAPK and p65NF-κB activation. These data demonstrated the anti-inflammatory and immunomodulatory effects of the CISACN with scientific support to become a pharmacological tool to treat airway inflammatory diseases.

Evaluation of two different remineralising toothpastes in children with drug-controlled asthma and allergic rhinitis: a randomised clinical trial.

AIM: To compare the efficacy of two remineralising toothpastes in children suffering from asthma and allergic rhinitis after a 6-month study. METHODS: 40 patients aged between 6-14 years with enamel demineralisations were enrolled for the study at the Unit of Dental Hygiene of the University of Pavia (Italy). The following indices were collected: Schiff air index (SAI), plaque index (PI), bleeding on probing (BoP), salivary pH, Basic Erosive Wear Examination (BEWE), susceptibility index (SI) for hard and soft tissues' pathologies, and decayed missing filled teeth (DMFT). After mechanical debridement with piezoelectric instrumentation and glycine powder, patients were equally divided into two groups: Group 1 using a toothpaste with zinc hydroxyapatite, and Group 2 using a toothpaste containing calcium sodium phosphosilicate. The toothpaste had to be used twice a day. The time frames of the study were: baseline (T0), after 1 month (T1), after 3 months (T2), after 6 months (T3). CONCLUSION: The tested toothpastes can be proposed for home use in children with asthma and allergic rhinitis as they significantly reduced dental sensitivity and periodontal indices.

Long-acting anti-inflammatory injectable DEX-Gel with sustained release and self-healing properties regulates TH1/TH2 immune balance for minimally invasive treatment of allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a prevalent immune-related allergic disease, and corticosteroid nasal sprays serve as the primary treatment for this patient population. However, their short duration of efficacy and frequent administration pose challenges, leading to drug wastage and potential adverse effects. To overcome these limitations, we devised a novel approach to formulate DEX-Gel by incorporating dexamethasone (DEX) into a blend of Pluronic F127, stearic acid (SA), and polyethylene glycol 400 (PEG400) to achieve sustained-release treatment for AR. RESULTS: Following endoscopic injection into the nasal mucosa of AR rats, DEX-Gel exhibited sustained release over a 14-day period. In vivo trials employing various assays, such as flow cytometry (FC), demonstrated that DEX-Gel not only effectively managed allergic symptoms but also significantly downregulated helper T-cells (TH) 2 and TH2-type inflammatory cytokines (e.g., interleukins 4, 5, and 13). Additionally, the TH1/TH2 cell ratio was increased. CONCLUSION: This innovative long-acting anti-inflammatory sustained-release therapy addresses the TH1/TH2 immune imbalance, offering a promising and valuable approach for the treatment of AR and other inflammatory nasal diseases.

The airway neuro-immune axis as a therapeutic target in allergic airway diseases.

Recent evidence has increasingly underscored the importance of the neuro-immune axis in mediating allergic airway diseases, such as allergic asthma and allergic rhinitis. The intimate spatial relationship between neurons and immune cells suggests that their interactions play a pivotal role in regulating allergic airway inflammation. Upon direct activation by allergens, neurons and immune cells engage in interactions, during which neurotransmitters and neuropeptides released by neurons modulate immune cell activity. Meanwhile, immune cells release inflammatory mediators such as histamine and cytokines, stimulating neurons and amplifying neuropeptide production, thereby exacerbating allergic inflammation. The dynamic interplay between the nervous and immune systems suggests that targeting the neuro-immune axis in the airway could represent a novel approach to treating allergic airway diseases. This review summarized recent evidence on the nervous system's regulatory mechanisms in immune responses and identified potential therapeutic targets along the peripheral nerve-immune axis for allergic asthma and allergic rhinitis. The findings will provide novel perspectives on the management of allergic airway diseases in the future.

Fructus Xanthii and Magnolia liliiflora Volatile Oils Liposomes-Loaded Thermosensitive in situ Gel for Allergic Rhinitis Management.

Purpose: The aim of the present study was to fabricate a Fructus Xanthii and Magnolia liliiflora volatile oils liposomes-loaded thermosensitive in situ gel (gel/LIP/volatile oil) for effectively treating allergic rhinitis via intranasal administration. Patients and Methods: Particle size, polymer dispersity index (PDI), entrapment effectiveness, and cumulative drug permeation of the developed liposomes were assessed. Then, a thermoreversible in situ gel was created using the liposomes loaded with volatile oils of Fructus Xanthii and Magnolia liliiflora. The effectiveness of this treatment for allergic rhinitis was confirmed by evaluating nasal symptoms, and hematological results, after injecting the formulation into the ovalbumin (OVA)-sensitized mice, we conducted hematoxylin-eosin staining (HE) and immunohistochemistry to evaluate the outcomes. The effects of the gel/LIP/volatile oil formulation for nasal delivery of volatile oil in the treatment of rhinitis were then assessed. Results: The average particle size was 95.1 ± 3.6 nm, and the encapsulation efficiencies of Fructus Xanthii and Magnolia liliiflora volatile oils were 70.42 ± 5.41% and 67.10 ± 6.08%, respectively. Drug loadings of Fructus Xanthii and Magnolia liliiflora volatile oils were 9.10 ± 0.98% and 16.10 ± 1.03%, respectively. The binary formulation produced a gel rapidly in the nasal cavity with a strong mucosal adherence at a temperature of delivering volatile oil to the nasal mucosa steadily and continuously. After nasal administration, the gel/LIP/volatile oil sustained the volatile oil delivery into the mucosa. In comparison to the monolithic formulations, the gel/LIP/volatile oil binary formulation exhibited superior performance in terms of drug delivery capability and pharmacodynamic effects. Conclusion: This binary preparation displayed the ability to deliver drugs to the nasal mucosa and exhibited positive pharmacodynamic effects in treating OVA-induced rhinitis in mice. As a result, it has the potential to serve as a delivery platform for Traditional Chinese medicine in the treatment of allergic rhinitis.

Silencing of forkhead box C1 reduces nasal epithelial barrier damage in mice with allergic rhinitis via epigenetically upregulating secreted frizzled-related protein 5.

Allergic rhinitis (AR) is caused by immunoglobulin E (IgE)-mediated reactions to inhaled allergens, which leads to mucosal inflammation and barrier dysfunction. The transcription factor forkhead box C1 (FOXC1) has been identified to be associated with allergic inflammation. This study sought to uncover the role of FOXC1 in AR. A murine model of AR was induced by repeated intranasal ovalbumin (OVA) challenges. Results revealed that high FOXC1 expression was found in the nasal mucosal epithelium of AR mice. Nasal allergy symptoms, mucosal epithelial swelling, goblet cell hyperplasia and eosinophil infiltration in AR mice were attenuated after silencing of FOXC1. Knockdown of FOXC1 decreased the levels of T-helper 2 cytokines interleukin(IL)-4 and IL-13 in nasal lavage fluid, and serum OVA-specific IgE and histamine. Silencing of FOXC1 restored nasal epithelial integrity in AR mice by enhancing the expression of tight junctions (TJs) and adherence junction. Furthermore, knocking down FOXC1 increased tight junction expression and transepithelial electrical resistance (TEER) in IL-13-treated air-liquid interface (ALI) cultures of human nasal epithelial cells (HNEpCs). Mechanistically, silencing of FOXC1 induced DNA methylation of secreted frizzled-related protein 5 (SFRP5) promoter and increased its expression in the nasal mucosa of AR mice and IL-13-treated ALI cultures. FOXC1 overexpression transcriptionally activated DNA methyltransferase 3B (DNMT3B) in IL-13-treated ALI cultures. Knockdown of SFRP5 reversed the protection of FOXC1 silencing on epithelial barrier damage induced by IL-13. Collectively, silencing of FOXC1 reduced allergic inflammation and nasal epithelial barrier damage in AR mice via upregulating SFRP5, which may be attribute to DNMT3B-driven DNA methylation. Our study indicated that FOXC1 may represent a potential therapeutic target for AR.

Effects of Anatolian Propolis and Hypertonic Saline Combination Nasal Spray on Allergic Rhinitis Symptoms: A Prospective, Multicenter Study.

Objectives: This study aimed to evaluate how Rhinapi nasal spray affects symptoms of allergic rhinitis. Methods: In this prospective, multicenter, observational study, 10,000 patients (comprising 5028 males and 4972 females) exhibiting symptoms of allergic rhinitis (namely, nasal discharge, sneezing, nasal itching, and nasal obstruction) from different centers in different regions of Turkey were enrolled in the study between March 2022 and March 2023. All the patients wanted to participate in the study and were administered Rhinapi one puff to each nostril three times a day, for a period of 3 weeks. Total symptom scores, quality of life (QoL) scores, and otolaryngological examination scores were evaluated before and 3 weeks after treatment. Results: The scores for discharge from the nose, sneezing, nasal pruritus, and blockage of the nose all indicated improvement when compared to pre-medication and post-medication. This difference achieved statistical significance (P < .001). The mean total symptom score fell following treatment (P < .001): whilst the score was 11.09 ± 3.41 before administering Rhinapi; after administration, the average score was 6.23 ± 2.41. The mean QoL scores also altered after medication (P < .001), improving from a mean value of 6.44 ± 1.55 to a mean of 7.31 ± 1.24. Significant improvement was also noted in the scores for conchal color and degree of edema after the treatment had been administered (P < .001). Conclusion: The study demonstrates that Rhinapi nasal spray decreases total symptom scores, and results in improved QoL and otolaryngological examination scores. Propolis spray may be recommended for patients with allergic rhinitis alongside other treatments.