Xiaoqinglong decoction

小青龙汤
  • 文章类型: Journal Article
    过敏性鼻炎(AR)是以免疫应答失调为特征的呼吸免疫系统病症。在AR的背景下,肠道微生物群及其代谢物已被确定为免疫调节的贡献者。这些微生物错综复杂地连接着呼吸道和肠道免疫系统,形成通常所说的肠-肺轴。小青龙汤(XQLD),一种传统的中草药,中医在临床上广泛用于AR的治疗。在这项研究中,据推测,肠-肺轴内共生微生物群平衡的恢复在支持XQLD在AR治疗中的长期疗效方面起着关键作用.因此,本研究的主要目的是研究XQLD对AR小鼠模型中肠道菌群组成和功能的影响.
    使用卵清蛋白致敏小鼠模型来模拟AR,研究了药物治疗后AR症状的改善情况,采用高通量测序技术分析肠道菌群组成。
    XQLD在AR小鼠中表现出实质性的治疗作用,其特点是过敏性炎症反应显著减少,显著缓解鼻部症状,恢复正常的鼻功能.此外,在XQLD治疗之后,AR小鼠肠道微生物群的破坏显示出恢复的趋势,显示与西药(氯雷他定)组相比有显著差异。
    该结果表明,XQLD可能通过调节小鼠肠道菌群失调来增强AR过敏性炎症反应,从而影响肠-肺轴的动力学。该机制的提出为该领域的未来研究提供了基础。
    UNASSIGNED: Allergic rhinitis (AR) is a respiratory immune system disorder characterized by dysregulation of immune responses. Within the context of AR, gut microbiota and its metabolites have been identified as contributors to immune modulation. These microorganisms intricately connect the respiratory and gut immune systems, forming what is commonly referred to as the gut-lung axis. Xiaoqinglong Decoction (XQLD), a traditional Chinese herbal remedy, is widely utilized in traditional Chinese medicine for the clinical treatment of AR. In this study, it is hypothesized that the restoration of symbiotic microbiota balance within the gut-lung axis plays a pivotal role in supporting the superior long-term efficacy of XQLD in AR therapy. Therefore, the primary objective of this research is to investigate the impact of XQLD on the composition and functionality of the gut microbiota in a murine model of AR.
    UNASSIGNED: An ovalbumin-sensitized mouse model to simulate AR was utilized, the improvement of AR symptoms after medication was investigated, and high-throughput sequencing was employed to analyze the gut microbiota composition.
    UNASSIGNED: XQLD exhibited substantial therapeutic effects in AR mice, notably characterized by a significant reduction in allergic inflammatory responses, considerable alleviation of nasal symptoms, and the restoration of normal nasal function. Additionally, following XQLD treatment, the disrupted gut microbiota in AR mice displayed a tendency toward restoration, showing significant differences compared to the Western medicine (loratadine) group.
    UNASSIGNED: This results revealed that XQLD may enhance AR allergic inflammatory responses through the regulation of intestinal microbiota dysbiosis in mice, thus influencing the dynamics of the gut-lung axis. The proposal of this mechanism provides a foundation for future research in this area.
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  • 文章类型: English Abstract
    本研究利用鼻腔灌洗液进行代谢组学研究,探讨其可行性,并应用于小青龙汤治疗变应性鼻炎(AR)的临床代谢组学研究,目的探讨小青龙汤通过局部鼻腔代谢差异变化治疗AR的分子机制。选择AR患者作为研究对象,收集鼻腔灌洗液作为样品。对正常组进行液相色谱-质谱代谢组学分析,AR组,和小青龙汤组。使用主成分分析和偏最小二乘判别分析比较各组间代谢谱的差异,和差异代谢物被鉴定并进行相应的代谢途径分析。成果显示小青龙汤能显著改良AR患者的症状。代谢组学分析显示AR组和小青龙汤组存在20种差异代谢产物。与正常组相比,具有趋势回报的核心代谢物是三甲基己二酸。代谢产物涉及多种途径,包括β-丙氨酸代谢,谷胱甘肽代谢,和苯丙氨酸,酪氨酸,和色氨酸生物合成。初步论证了鼻灌洗液在鼻代谢组学中应用的可行性。鉴定小青龙汤治疗AR患者的差异代谢产物和富集途径,表明它可以通过调节各种代谢物来改善鼻炎症状,包括抗氧化作用和纠正Th1/Th2失衡。
    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 β-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.
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  • 文章类型: Journal Article
    背景:小青龙汤(XQLD),首先记录在《尚汉论》中,是用于治疗过敏性鼻炎(AR)的传统中药。XQLD通过抑制炎症反应的发生来缓解AR的临床症状,但具体的监管机制尚不清楚。
    目的:NLRP3介导的焦亡与AR发病密切相关。因此,本研究旨在探讨NLRP3介导的焦亡通路在XQLD相关AR药理机制中的潜在作用。
    方法:采用卵清蛋白(OVA)和氢氧化铝致敏方法建立BALB/C小鼠AR模型。不同剂量的XQLD灌胃后,观察鼻腔过敏症状。ELISA法检测血清中OVA-sIgE和Th2炎症因子(IL-4、IL-5、IL-13)的表达。观察鼻黏膜组织病理学形态及炎症因子的表达情况。进行分子对接以分析XQLD的代表性化合物与NLRP3的结合。通过免疫荧光和蛋白质印迹检测NLRP3炎性体的激活。
    结果:XQLD显著改善了小鼠的鼻过敏症状,降低杯状细胞增殖的程度,肥大细胞浸润,鼻粘膜胶原纤维增生。同时,它可以下调血清和鼻黏膜中Th2炎症因子(IL-4,IL-5和IL-13)的表达。XQLD显著降低GSDMD和TUNEL双阳性细胞的数量以及IL-1β和IL-18的表达。分子对接证实XQLD的7个代表性化合物与NLRP3具有良好的结合性质,并且能够抑制NLRP3炎性体的活化。
    结论:XQLD的代表化合物可能抑制NLRP3炎性体介导的鼻黏膜细胞焦凋亡,有助于AR的恢复。这为XQLD治疗AR提供了新的现代药理学证据。
    BACKGROUND: Xiaoqinglong decoction (XQLD), first recorded in Shang Han Lun, is a traditional Chinese medicine prescribed for the treatment of allergic rhinitis (AR). XQLD alleviates the clinical symptoms of AR by inhibiting the occurrence of an inflammatory response, but the specific regulatory mechanism remains unclear.
    OBJECTIVE: NLRP3-mediated pyroptosis is closely related to AR pathogenesis. Hence, this study aimed to explore the potential role of NLRP3-mediated pyroptosis pathway in the AR-associated pharmacological mechanism of XQLD.
    METHODS: BALB/C mice models of AR was established by using ovalbumin (OVA) and aluminum hydroxide sensitization. After intragastric administration of different dosages of XQLD, nasal allergic symptoms were observed. The expression of OVA-sIgE and Th2 inflammatory factors (IL-4, IL-5, and IL-13) in serum was detected by ELISA. The histopathological morphology and expression of inflammatory factors in nasal mucosa along with pyroptosis were investigated. Molecular docking was performed to analyze the binding of representative compounds of XQLD with NLRP3. Activation of the NLRP3 inflammasome was detected by immunofluorescence and western blotting.
    RESULTS: XQLD significantly improved the nasal allergic symptoms of mice, reduced the degree of goblet cell proliferation, mast cell infiltration, and collagen fiber hyperplasia in nasal mucosa. Meanwhile, it could downregulate the expression of Th2 inflammatory factors (IL-4, IL-5, and IL-13) in serum and nasal mucosa. XQLD significantly reduced the number of GSDMD and TUNEL double-positive cells and IL-1β and IL-18 expression. Molecular docking confirmed that seven representative compounds of XQLD had good binding properties with NLRP3 and were able to inhibit the activation of the NLRP3 inflammasome.
    CONCLUSIONS: The representative compounds of XQLD might inhibit pyroptosis in nasal mucosa mediated by the NLRP3 inflammasome to helping the recovery of AR, which provides a new modern pharmacological proof for XQLD to treat AR.
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  • 文章类型: Journal Article
    小青龙汤(XQLD)临床上广泛应用于儿童咳嗽变异性哮喘(CVA)的治疗。然而,其潜在机制尚不清楚。在本研究中,作者使用基于网络药理学的分析和实验验证,研究XQLD治疗儿童CVA的生物学网络和信号通路.利用生物信息学分析工具中药分子机制(BATMAN-TCM)数据库,作者证实了XQLD与哮喘之间的相关性,作者筛选了麻黄和桂枝的1338个潜在靶基因,XQLD中最活跃的草药。通过重叠DisGeNet数据库的“儿童哮喘相关基因”,作者鉴定了58个儿童哮喘的交叉基因和1338个麻黄和桂枝的靶基因。相交的基因用于构建蛋白质与蛋白质的相互作用,并进行基因本体论(GO)功能和京都百科全书的基因和基因组途径富集分析。基因本体富集分析显示359个生物过程术语,16细胞组件术语,和26个分子功能项。同时,在富集分析中涉及75项京都基因百科全书和基因组信号传导途径。这些候选物显示与炎症反应和STAT蛋白酪氨酸磷酸化的正调控显著相关。此外,XQLD治疗显著上调血清干扰素-γ表达,并下调CVA小鼠的血清interlukin-6表达。XQLD处理显著抑制支气管肺组织中STAT3的磷酸化。我们的数据表明,XQLD通过调节interlukin-6/STAT3信号通路有效减轻了CVA小鼠的支气管肺组织损伤,并抑制了机体炎症反应。
    Xiaoqinglong decoction (XQLD) is widely used clinically in the treatment of childhood cough variant asthma (CVA). However, its potential mechanism is still unknown. In the present study, the authors investigate the biological network and signalling pathway of XQLD in treatment of childhood CVA using network pharmacology-based analysis and experimental validation. By using the Bioinformatics Analysis Tool Molecular Mechanism of Traditional Chinese Medicine (BATMAN-TCM) database, the authors confirmed the correlation between XQLD and asthma, and the authors screened 1338 potential target genes of Mahuang and Guizhi, the most active herbs in XQLD. By overlapping \"Childhood asthma-related genes\" of DisGeNET database, the authors identified 58 intersecting genes of Childhood asthma and 1338 target genes of Mahuang and Guizhi. The intersecting genes were used to construct the protein-to-protein interaction and performed Gene Ontology (GO) functional and the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Gene Ontology enrichment analysis demonstrated 359 Biological Process terms, 16 Cellular Component terms, and 26 Molecular Function terms. Meantime, 75 terms of Kyoto Encyclopedia of Genes and Genomes signalling pathway were involved in enrichment analysis. These candidates showed a significant correlation with inflammatory response and positive regulation of tyrosine phosphorylation of STAT protein. In addition, XQLD treatment significantly upregulated serum interferon-γ expression, and downregulated serum interlukin-6 expression of CVA mice. XQLD treatment significantly inhibited phosphorylation of STAT3 in bronchial-lung tissues. Our data suggest that XQLD effectively alleviated bronchial-lung tissue damage in CVA mice and inhibited the body inflammatory response by regulating interlukin-6/STAT3 signalling pathway.
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  • 文章类型: Journal Article
    背景:作为最常见的过敏性疾病之一,变应性鼻炎(AR)引起了世界各国的广泛关注。应该彻底探索更合适的AR治疗方法。近年来,中医药在AR治疗中越来越受到重视。作为一个经典的中药处方,小青龙汤(XQLD)已被广泛用于治疗AR。尽管其对AR的治疗效果已得到临床证实,更多的分子机制还有待进一步研究。我们的研究目的是探讨XQLD治疗AR的治疗机制。
    方法:本研究在卵清蛋白致敏小鼠模型中进行评估,并采用液相色谱-质谱法测试XQLD的有效成分的稳定性。
    结果:结果证实了XQLD有效成分的稳定性和安全性。XQLD显著下调AR小鼠HDACs(HDAC1、HDAC3和HDAC4)和Th2炎症因子(IL4、IL5和IL13)的表达。XQLD和HDAC抑制剂JNJ-26481585促进了AR小鼠鼻粘膜中上皮紧密连接蛋白(claudin-1和ZO-1)的表达,并降低了粘蛋白(Muc5ac和Muc5b)的表达。
    结论:结论:我们的发现表明了XQLD对AR和鼻上皮恢复的有益作用。我们还将降低的HDAC确定为用于AR治疗的XQLD的潜在靶标。本研究为阐明XQLD的治疗机制提供了重要的实验依据。
    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.
    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.
    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.
    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.
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  • DOI:
    文章类型: Journal Article
    Allergic asthma is a complex and chronic inflammatory airway disease. The thymic stromal lymphopoietin (TSLP) signaling pathway plays an important role in asthma. Xiaoqinglong Decoction (XQL) is the first choice to treat cold asthma in clinical settings. In this study, the role of the TSLP pathway in the onset of asthma and the protective mechanism of XQL were investigated. A total of 50 female mice were randomly divided into the following groups: the blank group (A), the model group (B), the XQL group (C), the dexamethasone group (D), and the XQL + dexamethasone group (E). Asthma was induced with ovalbumin, and corresponding drug intervention was carried out for 7 days, after which serum and lung tissue end points were analyzed. Serum interleukin 1β (IL-1β), tumor necrosis factor-α (TNF-α), nuclear factor κB (NF-κB), and TSLP levels were higher in group B than in group A (p<0.05). However these levels were lower in group C and D than in group B (p<0.05), and there was no significant difference between groups C and D (p>0.05). Interestingly, these end points were significantly lower in group E than in groups C and D (p<0.05). Regarding pathologic changes, the inflammatory infiltrate in the lungs of groups C, D, and E was lower than that of group B, especially in group E. We conclude that the TSLP pathway plays an important role in the course of asthma, and can be used as an important target for asthma treatment; XQL may play a role in reducing inflammation and relieving asthma by regulating the TSLP signaling pathway.
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