Jiawei Yanghe Decoction attenuate allergic airway inflammation by suppressing group 2 innate lymphoid cells responses
Jiawei Yanghe Decoction attenuate allergic airway inflammation by suppressing group 2 innate lymphoid cells responses
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DOI：
10.1016/j.jep.2024.117927
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发表时间：
2024-02-29
影响因子：
5.4
通讯作者：
Li，Cui
中科院分区：
文献类型：
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作者：
Wang，Yu;Cui，Jie;Li，Cui
民族药理学相关性加味阳和汤为阳和汤加味。YHD历史上被用作解决慢性炎症状况的有效药物解决方案，在治疗哮喘方面具有很好的治疗潜力。然而，JWYHD对过敏性哮喘的作用机制尚不清楚。本研究的目的是探讨JWYHD对哮喘小鼠的治疗作用及其机制。随后，对支气管肺泡灌洗液（BALF）和肺组织中的炎性细胞进行检测。检测BALF中IL-4、IL-5、IL-13、IL-33、肿瘤坏死因子（TNF）-α、干扰素（IFN）-γ等细胞因子水平及血清总免疫球蛋白E（IgE）含量。肺功能和组织病理学检查，以评估JWYHD的保护作用。采用超高效液相色谱-四极杆飞行时间质谱联用技术（UPLC-Q-TOF/MS）对加味养阴汤及其肺原型化合物（指加味养阴汤中存在的在肺中观察到的化学成分）的化学成分进行了研究。RNA-seq分析揭示了JWYHD治疗哮喘的调节机制。采用流式细胞术和Smart-RNA-seq分析检测加味养阴汤对哮喘小鼠2型先天淋巴细胞（ILC 2）的影响。结果加味养阴活血方能显著减轻哮喘小鼠气道炎症，降低BALF中炎性细胞数量，降低BALF中细胞因子IL-4、IL-5、IL-13、IL-33、TNF-α和血清IgE水平。加味养阴活血汤还能减轻气道高反应性（AHR）和肺组织炎症浸润。RNA-seq分析显示加味养阴汤通过调节免疫功能减轻哮喘小鼠气道炎症。流式细胞术证实JWYHD可以抑制ILC 2的反应。ILC 2 Smart-RNA-seq分析表明，JWYHD损害了ILC 2中炎症反应相关的信号通路，神经毛蛋白-1（Nrp 1）、内皮转录因子3（GATA 3）和白细胞介素1受体样蛋白1（ST 2）可能是关键靶点。分子对接分析研究的主要目标和JWYHD的原型化合物在肺之间的连接表明，甘草苷apioside，淫羊藿苷，甘草酸，和uralsaponin B，通过UPLC-Q-TOF/MS鉴定，表现出显着的亲和力结合到上述关键targets.ConclusionOur结果表明，JWYHD治疗哮喘的机制可能与限制ILC 2反应。本研究结果为加味养阴汤治疗哮喘的临床应用提供了一定的药理学依据。
Ethnopharmacological relevanceJiawei Yanghe Decoction (JWYHD) is modified Yanghe Decoction (YHD). YHD historically utilized as a potent medicinal solution for addressing chronic inflammatory conditions, holds promising therapeutic potential in the treatment of asthma. However, the mechanisms underlying JWYHD's effects on allergic asthma remain unclear.Aim of the studyTo investigate the therapeutic effect as well as the underlying mechanisms of JWYHD on asthmatic mice.Materials and methodsThe ovalbumin (OVA)-induced mouse model was utilized, followed by the administration of JWYHD to allergic asthmatic mice. Subsequently, inflammatory cells in the bronchoalveolar lavage fluid (BALF) and lung tissues were conducted. The levels of various cytokines including interleukin (IL)-4, IL-5, IL-13, IL-33, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ in BALF, as well as the total immunoglobulin E (IgE) content in serum, were assessed. Lung function and tissue pathology examinations were performed to assess the protective impacts of JWYHD. The chemical components of JWYHD and its lung prototype compounds (referred to the chemical components present in JWYHD that were observed in the lung) were explored by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). RNA-seq analysis revealed the regulation mechanisms of JWYHD treating asthma. Furthermore, the effect of JWYHD on type 2 innate lymphoid cells (ILC2s) in asthmatic mice was detected by flow cytometry and Smart-RNA-seq analysis. Then molecular docking analysis was used to show the interaction between identified compounds and key targets.ResultsJWYHD significantly attenuated the airway inflammation of asthmatic mice, reduced the levels of inflammatory cells in BALF, as well the levels of the cytokines IL-4, IL-5, IL-13, IL-33, and TNF-α in BALF and IgE in serum. Airway hyperresponsiveness (AHR) and lung inflammation infiltration were also alleviated by JWYHD. Moreover, RNA-seq analysis revealed that JWYHD attenuated airway inflammation in asthmatic mice via regulating immunity. Flow cytometry confirmed that JWYHD could inhibit ILC2 responses. ILC2 Smart-RNA-seq analysis showed that JWYHD impaired the inflammation reaction-related signaling pathways in ILC2s, and neuropilin-1 (Nrp1), endothelial transcription factor 3 (GATA3) and interleukin 1 receptor like protein 1 (ST2) might be the key targets. The molecular docking analysis investigating the connection between the primary targets and JWYHD's prototype compounds in the lung demonstrated that liquiritin apioside, icariin, glycyrrhizic acid, and uralsaponin B, identified through UPLC-Q-TOF/MS, exhibited significant affinity in binding to the mentioned key targets.ConclusionOur results suggested that the mechanism of JWYHD in treating asthma might be related to limiting ILC2 responses. Our findings provided some pharmacological evidence for the clinical application of JWYHD in the treatment of asthma.