Inhibitory effect of Zingiber cassumunar Roxb. (Phlai) on nasal cytokine productions and eosinophilic recruitment in patients with allergic rhinitis.

BACKGROUND: Zingiber cassumunar Roxb. (Phlai) has been used for the treatment of allergies including allergic rhinitis (AR). Although the anti-histamine effects have been reported, assessment of nasal cytokine and eosinophil production had not been investigated. OBJECTIVE: This study aimed to examine the effect of Phlai on alterations in nasal pro-inflammatory cytokine levels and eosinophil counts in nasal mucosa. METHODS: This was a randomized, double-blind, three-way crossover study. Nasal concentrations of cytokines, namely interleukin (IL)-4, IL-5, IL-13 and interferron-gamma (IFN-γ), nasal smear eosinophilia as well as total nasal symptom score (TNSS) were evaluated before and after a 4 weeks treatment with 200 mg Phlai capsules or placebo in 30 AR patients. RESULTS: We observed significant (p < 0.05) reduction in IL-5, IL-13 as well as the number of eosinophils in subjects given Phlai. The degree of improvement of TNSS after Phlai treatment was initially manifested in week 2 with the greatest effect in week 4. In contrast, there were no significant differences in all nasal cytokines, eosinophil counts or TNSS between before and after receiving placebo. CONCLUSIONS: These findings provided the first evidence for the anti-allergic effect of Phlai which possibly involved inhibition of nasal pro-inflammatory cytokines production and eosinophilic recruitment. Phlai thus represents a promising herbal medicine for alleviating inflammation and AR symptoms.

Effects of a six-month yoga intervention on the immune-inflammatory pathway in antipsychotic-stabilized schizophrenia patients: A randomized controlled trial.

BACKGROUND: Schizophrenia is a complex neuropsychiatric disorder for which several etiopathological theories have been proposed, one of the prominent ones being immune dysfunction. Recent studies on yoga as an add-on therapy have shown improvement in negative symptoms, cognition, and quality of life in schizophrenia patients. However, the biological mechanism/s of action of yoga in schizophrenia are not clear. The current study was aimed at exploring the effects of long-term (6 months) add-on yoga therapy on the immune inflammatory pathway in schizophrenia patients. METHODS: Sixty schizophrenia patients were randomized to add-on yoga therapy (YT=30) and treatment-as-usual (TAU=30) groups of which 21 patients in YT and 20 in TAU group completed the study. Blood samples and clinical assessments were obtained at baseline and at the end of 6 months. The plasma levels of nine cytokines (IL-2, IL-4, IL-5, IL-10, IL-12(p70), IL-13, GM-CSF, IFN-γ, and TNF-α) were quantified using multiplex suspension array. The clinical assessments included SAPS, SANS, BPRS, PSS, CGI, SOFS and WHOQUOL-BREF. RESULTS: Patients in the yoga group showed significant reductions in plasma TNF-α (Z = 2.99, p = 0.003) and IL-5 levels (Z = 2.20, p = 0.03) and greater clinical improvements in SAPS, SANS, PSS, and SOFS scores as compared to TAU group. Further, plasma TNF-α levels exhibited a positive correlation with negative symptoms (rs =0.45, p = 0.02) and socio-occupational functioning (rs =0.61, p = 0.002) in the YT group. CONCLUSIONS: The findings of the study suggest that improvements in schizophrenia psychopathology with yoga interventions are associated with immuno-modulatory effects.

Efficacy of vitamin D supplementation on COPD and asthma control: A systematic review and meta-analysis.

Background: The role of vitamin D (VD) in the management of chronic obstructive pulmonary disease (COPD) and asthma remains largely undetermined. In the present meta-analysis, we aimed to comprehensively investigate the efficacy of VD in the treatment of COPD and asthma according to the latest update. Methods: The PubMed, Embase, and Cochrane Library databases were searched from their inception to June 2, 2022. Randomized controlled trials (RCTs) comparing the efficacy of VD with placebo against COPD or asthma were included. Results: A total of 11 RCTs consisting of 1183 COPD patients and 19 RCTs consisting of 2025 asthmatic patients were finally included. As for pulmonary function, FEV1/FVC was not changed significantly, while FEV1% was improved in the VD group. In the asthma subgroup, FEV1% was not changed significantly, while FEV1/FVC was improved in the VD group. For the questionnaire and rating scale, the mMRC (modified Medical Research Council) dyspnoea scale score for COPD and ACT (Asthma Control Test) score for asthma were not significantly changed, while the SGRQ (St. George's Respiratory Questionnaire) score for COPD was improved in the VD group. For inflammation indicators, IL-6 and IL-10 were statistically equivalent between the VD and placebo groups, while IgE, IL-5, and IL-10 (baseline VD deficiency subgroup) were improved in the VD group. The exacerbation, length of hospital stays, and mortality were statistically equivalent between the two groups. Conclusions: VD supplementation improved the indicators of asthma and COPD, especially in pulmonary function, SGRQ scores, IL-5, and IgE. Registration: The protocol could be found at PROSPERO with the registration number of CRD42020218058.

Ameliorative Effect of Imperatorin on Dermatophagoides pteronyssinus-Induced Allergic Asthma by Suppressing the Th2 Response in Mice.

Imperatorin is a furanocoumarin derivative and an effective ingredient in several Chinese medicinal herbs. It has favorable expectorant, analgesic, and anti-inflammatory effects. In this study, we investigated whether imperatorin has protective effects against Dermatophagoides pteronyssinus (Der p)-induced asthma in mice. Lung and bronchial tissues were histopathologically examined through hematoxylin-eosin staining. The concentrations of immunoglobin E (IgE), IgG1, IgG2a in serum and those of T helper 1 (Th1) and two cytokines and eosinophil-activated chemokines in bronchoalveolar lavage fluid (BALF) were detected using an enzyme immunoassay. Histological examination revealed that imperatorin reduced inflammatory cell infiltration, mucus hypersecretion, and endothelial cell hyperplasia. The examination also indicated that imperatorin could reduce the inflammatory cell count in BALF as well as IgE and IgG1 expression in serum, but IgG2a expression was significantly increased. Imperatorin reduced the production of interleukin (IL)-4, IL-5, and IL-13 by Th2, promoted the production of interferon-γ and IL-12 by Th1, and increased the production of IL-10 in bronchoalveolar lavage fluid. These findings suggest that imperatorin has a considerable anti-inflammatory effect on Der p-induced allergic asthma in mice.

Oxysophocarpine inhibits airway inflammation and mucus hypersecretion through JNK/AP-1 pathway in vivo and in vitro.

Asthma is a high-incidence disease in the world. Oxysophocarpine (OSC), a quinolizidine alkaloid displays various pharmacological functions including anti-inflammation, neuroprotective, anti-virus and antioxidant. Here, we established mice and cell asthmatic model to explore the effects of OSC for asthma treatment. Mice were sensitized and challenged with ovalbumin (OVA) and treated with OSC before challenge. Enzyme-linked immuno sorbent assay (ELISA), hematoxylin and eosin (H&E), periodic acid-schiff (PAS), tolonium chloride staining and immunohistochemical assay were performed. OSC treatment inhibited inflammatory cell infiltration and mucus secretion in the airway, reduced IgE level in mouse serum and decreased IL-4, IL-5 production in bronchoalveolar lavage fluid (BALF). OSC also reduced the spleen index to regulate immune function. Meanwhile, NCI-H292 cells were induced by lipopolysaccharide (LPS) to simulate airway epithelial injury. OSC pretreatment decreased the IL-6 and IL-8 cytokine levels, mucin 5 AC expression, and mucin 5 AC mRNA level in the cell model. Further, OSC suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), and activator protein 1 (AP-1, Fos and Jun). These findings revealed that OSC alleviated bronchial asthma associated with JNK/AP-1 signaling pathway.

Study Effect of Azithromycin and Doxycycline in Mucus Producing and Inflammatory Signaling Pathways of Allergic Asthma.

Asthma is a respiratory disease; involving millions of people worldwide. The main cause of asthma is allergy and immune response dysregulation. The effects of azithromycin and doxycycline as asthma-controlling drugs were evaluated in this study. Mice asthma model was produced and asthmatic mice were treated with azithromycin (75 mg/kg, orally) and doxycycline (20 mg/kg, orally). Eosinophils and neutrophils count, interleukin (IL)-4, IL-5, IL-12, IL-13, and total immunoglobulin E (IgE) levels were measured. Histological study and evaluating the genes expression of Muc5ac, Muc5b, IL-33, COX2, MYD88, and TRAF6 were performed. Azithromycin and doxycycline did not affect eosinophil and neutrophil percentage, IL-4, IL-5, IL-12, and total IgE levels, peribronchial and perivascular inflammation, goblet cell hyperplasia, and gene expression of MYD88, TRAF6, and COX2. Treatment with azithromycin significantly decreased IL-13 level, mucus secretion, and gene expression of IL-33, Muc5ac, and Muc5b; compared to the non-treated asthma group. Azithromycin administration controls mucus secretion and inflammation. Azithromycin therapy and not doxycycline might be an effective adjuvant option in asthma with reducing mucus in the airway.

Sequential Biotherapy Targeting IL-5 and IL-4/13 in Patients with Eosinophilic Asthma with Sinusitis and Otitis Media.

Type 2 (T2) inflammation plays an important role in the pathogenesis of allergic diseases such as asthma, eosinophilic chronic rhinosinusitis (ECRS), or eosinophilic otitis media (EOM). Currently, in severe asthma with the T2 phenotype, biologics targeting mediators of T2 inflammation dramatically improve the management of severe asthma. While treatment with a single biologic is common, little is known about cases of the sequential use of two biologics. Here, we report a case of severe asthma with refractory ECRS and EOM in which total control of these allergic diseases could not be achieved with a single biologic but could be achieved via the sequential use of the anti-IL-5 receptor antibody and human anti-IL-4/13 receptor monoclonal antibody. It is suggested that it is necessary to control multiple T2 inflammatory pathways to achieve total control of severe allergic diseases. Sequential biotherapy may help solve the clinical challenges associated with single-agent molecular-targeted therapies.

Time-dependent dual beneficial modulation of interferon-γ, interleukin 5, and Treg cytokines in asthma patient peripheral blood mononuclear cells by ganoderic acid B.

Th2 cytokines play a dominant role in the pathogenesis of allergic asthma. Interferon gamma (IFN-γ), a Th1 cytokine, links to therapeutic mechanisms of allergic asthma. Interleukin (IL)-10, a regulatory cytokine, is involved in the induction of immune tolerance. We previously demonstrated that Anti-Asthma Simplified Herbal Medicine Intervention (ASHMI) suppressed Th2 and increased IFN-γ in patients with asthma and in animal models, but its bioactive compound is unknown. Ganoderic acid beta (GAB) was isolated from Ganoderma lucidum (one herb in ASHMI). Human peripheral blood mononuclear cells (PBMCs) from adult patients with asthma were cultured with GAB or dexamethasone (Dex) in the presence of environmental allergens. The cytokine levels of IL-10, IFN-γ, IL-5, transcription factors T-bet, Foxp-3, and GATA3 were measured. Following 3-day culture, GAB, but not Dex, significantly increased IL-10 and IFN-γ levels by allergic patients' PBMCs. Following 6-day treatment, GAB inhibited IL-5 production, but IL-10 and IFN-γ remained high. Dex suppressed production of all three cytokines. GAB suppressed GATA3 and maintained Foxp-3 and T-bet gene expression, while Dex significantly suppressed GATA3 and T-bet expression. GAB simultaneously increased IL-10, IFN-γ associated with induction of T-bet and Foxp3, while suppressing IL-5, which was associated with suppression of GATA3, demonstrating unique beneficial cytokine modulatory effect, which distinguishes from Dex's overall suppression.

Water-soluble chitosan-based antisense oligodeoxynucleotide of interleukin-5 for treatment of allergic rhinitis.

Interleukin (IL)-5 produced by allergen specific T cells is a major cytokine in the allergic inflammation such as allergic rhinitis (AR). To inhibit the production of IL-5, water-soluble chitosan (WSC)-based IL-5 antisense oligodeoxynucleotide (AS-ODN) complex was generated. WSC, a biocompatible cationic polymer, was used as a non-viral vector for the improvement of stability and transfection efficiency. After condensation IL-5 AS-ODN with WSC, the size, morphology and zeta potential analysis of IL-5 AS-ODN/WSC complexes were performed. The protective effect of complex was also observed against the enzymatic degradation. In vitro transfection efficiency into H1299 epithelial cells was investigated by flow cytometer and inhibition effect of IL-5 levels was also evaluated in D10.G4.1 cells. In the murine model with AR, the IL-5 and IgE levels closely related to the allergic inflammation were significantly reduced after the intranasal administration of IL-5 AS-ODN/WSC complexes. Based on these results, the condensation with WSC improved the physicochemical stability and transfection efficiency of IL-5 AS-ODN/WSC complex. Our results suggest that AS therapy using IL-5 AS-ODN/WSC complex can be an effective strategy in regulating IL-5 and may be applied to the treatment of allergic disorder related to IL-5.