ABSTRACT
This study used nasal lavage fluid for metabolomics to explore its feasibility, and applied it to the clinical metabolomics study of Xiaoqinglong Decoction in the treatment of allergic rhinitis(AR), aiming to investigate the molecular mechanism of Xiaoqing-long Decoction in the treatment of AR through differential changes in local nasal metabolism. AR patients were selected as the research subjects, and nasal lavage fluid was collected as the sample. Metabolomics analysis using liquid chromatography-mass spectrometry was performed on normal group, AR group, and Xiaoqinglong Decoction group. The differences in metabolic profiles among the groups were compared using principal component analysis and partial least squares discriminant analysis, and differential metabolites were identified and subjected to corresponding metabolic pathway analysis. The results showed that Xiaoqinglong Decoction significantly improved the symptoms of AR patients. The metabolomics analysis revealed 20 differential metabolites between AR group and Xiaoqinglong Decoction group. The core metabolite with a trending return in comparison to normal group was trimethyladipic acid. The metabolites were involved in multiple pathways, including ß-alanine metabolism, glutathione metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. The feasibility of applying nasal lavage fluid in nasal metabolomics was preliminarily demonstrated. Differential metabolites and enriched pathways in the treatment of AR patients with Xiaoqinglong Decoction were identified, indicating that it may improve rhinitis symptoms through the regulation of various metabolites, including antioxidant effects and correction of Th1/Th2 imbalance.
Subject(s)
Rhinitis, Allergic , Humans , Nasal Lavage Fluid , Rhinitis, Allergic/drug therapy , Metabolomics/methods , MetabolomeABSTRACT
BACKGROUND: Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa that is mediated by immunoglobulin E (IgE). Xiao-qing-long-tang (XQLT) is a traditional Chinese medicine compound that is widely used to treat respiratory diseases such as AR. However, the underlying mechanism of the effect of XQLT on AR remains unclear. PURPOSE: To elucidate the effect of XQLT on ovalbumin (OVA)-induced AR and the mechanisms of action. METHODS: The therapeutic efficacy of XQLT was evaluated in a well-established OVA-induced AR mouse model. Nasal symptoms were analyzed, type 2 cytokines and OVA-sIgE levels were measured, nasal mucosa tissues were collected for histological analysis, and the changes of Group 2 innate lymphoid cells (ILC2s) and the IL-33/ST2 and JAK/STAT signaling pathways in the nasal mucosa were observed. RESULTS: XQLT significantly alleviated the nasal symptoms and histological damage to the nasal mucosa in AR mice, and reduced the levels of type 2 cytokines and OVA-sIgE. In addition, after XQLT treatment, the numbers of ILC2s in the nasal mucosa of AR mice were reduced, and the mRNA levels of the transcription factors GATA3 and ROR-α were decreased. Moreover, IL-33/ST2 signaling pathway was inhibited. The costimulatory cytokine associated JAK/STAT signaling pathway was also inhibited in ILC2s. CONCLUSION: Our study demonstrated that XQLT regulated ILC2s through the IL-33/ST2 and JAK/STAT pathways to ameliorate type 2 inflammation in OVA-induced AR. These findings suggest that XQLT might be used to treat AR.
Subject(s)
Immunity, Innate , Rhinitis, Allergic , Animals , Mice , Ovalbumin , Interleukin-1 Receptor-Like 1 Protein/metabolism , Janus Kinases/metabolism , Interleukin-33/metabolism , Lymphocytes , Signal Transduction , STAT Transcription Factors/metabolism , Rhinitis, Allergic/chemically induced , Rhinitis, Allergic/drug therapy , Cytokines/metabolism , Disease Models, Animal , Mice, Inbred BALB CABSTRACT
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.