加味阳和汤通过抑制2组固有淋巴细胞反应减轻过敏性气道炎症
2024/05/28
摘要
背景：加味阳和汤为改良阳和汤。阳和汤历来被用作慢性炎症的有效药物治疗方案，在哮喘方面具有良好的治疗潜力。然而，加味阳和汤对过敏性哮喘的作用机制尚不清楚。
目的：本研究旨在探讨加味阳和汤对哮喘小鼠的治疗作用及其可能机制。
方法：本研究采用卵清蛋白（OVA）诱导的过敏性哮喘小鼠模型，予之加味阳和汤；随后，检测支气管肺泡灌洗液（BALF）和肺组织中的炎症细胞，并测定BALF中白介素（IL）-4、IL-5、IL-13、IL-33、肿瘤坏死因子（TNF）-α和干扰素（IFN）-γ等多种细胞因子的水平，以及血清中总免疫球蛋白E（IgE）的含量。之后通过肺功能和组织病理学检查，评估加味阳和汤的保护作用。本研究采用超高效液相色谱-四极飞行时间质谱联用技术（UPLC-Q-TOF/MS）对加味阳和汤及其肺部原型化合物（指在肺部观察到的加味阳和汤中存在的化学成分）的化学成分进行探讨。RNA-seq分析揭示了加味阳和汤治疗哮喘的调控机制。此外，通过流式细胞术和Smart RNA-seq分析检测加味阳和汤对哮喘小鼠2型固有淋巴细胞（ILC2）的影响。最后通过分子对接分析来显示已鉴定化合物与关键靶标之间的相互作用。
结果：本研究发现，加味阳和汤可显著减轻哮喘小鼠的气道炎症，降低BALF中炎症细胞数量，并降低BALF中细胞因子IL-4、IL-5、IL-13、IL-33和TNF-α水平和血清总IgE水平。加味阳和汤还可减轻气道高反应性（AHR）和肺部炎症浸润。此外，RNA-seq分析显示加味阳和汤通过调节免疫减轻哮喘小鼠的气道炎症。流式细胞术证实加味阳和汤可抑制ILC2反应。ILC2 Smart RNA-seq分析表明，加味阳和汤破坏了ILC2中炎症反应相关的信号通路，神经纤毛蛋白1（Nrp1）、内皮转录因子3（GATA3）和白细胞介素1受体样蛋白1（ST2）可能是关键靶点。分子对接分析探索了主要靶标与加味阳和汤肺部原型化合物之间的联系，结果表明，通过UPLC-Q-TOF/MS鉴定的甘草苷、淫羊藿苷、甘草酸和甘草皂苷B在与上述关键靶标的结合中表现出显著的亲和力。
结论：加味阳和汤治疗哮喘的机制可能与限制ILC2反应有关。本研究结果为加味阳和汤在哮喘治疗中的临床应用提供了一些药理学证据。
Jiawei Yanghe Decoction attenuate allergic airway inflammation by suppressing group 2 innate lymphoid cells responses.
Wang Y, Cui J, Jiang Y, Zhang S, Chen L, Ma Z, Yang D, Zhang Z, Huang X, Yang Y, Guo J, Lu Z, Li C.
Abstract
BACKGROUND:Jiawei 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.
OBJECTIVE：To investigate the therapeutic effect as well as the underlying mechanisms of JWYHD on asthmatic mice.
METHODS:The 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.
RESULTS:JWYHD 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.
CONCLUSION:Our 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.
背景：加味阳和汤为改良阳和汤。阳和汤历来被用作慢性炎症的有效药物治疗方案，在哮喘方面具有良好的治疗潜力。然而，加味阳和汤对过敏性哮喘的作用机制尚不清楚。
目的：本研究旨在探讨加味阳和汤对哮喘小鼠的治疗作用及其可能机制。
方法：本研究采用卵清蛋白（OVA）诱导的过敏性哮喘小鼠模型，予之加味阳和汤；随后，检测支气管肺泡灌洗液（BALF）和肺组织中的炎症细胞，并测定BALF中白介素（IL）-4、IL-5、IL-13、IL-33、肿瘤坏死因子（TNF）-α和干扰素（IFN）-γ等多种细胞因子的水平，以及血清中总免疫球蛋白E（IgE）的含量。之后通过肺功能和组织病理学检查，评估加味阳和汤的保护作用。本研究采用超高效液相色谱-四极飞行时间质谱联用技术（UPLC-Q-TOF/MS）对加味阳和汤及其肺部原型化合物（指在肺部观察到的加味阳和汤中存在的化学成分）的化学成分进行探讨。RNA-seq分析揭示了加味阳和汤治疗哮喘的调控机制。此外，通过流式细胞术和Smart RNA-seq分析检测加味阳和汤对哮喘小鼠2型固有淋巴细胞（ILC2）的影响。最后通过分子对接分析来显示已鉴定化合物与关键靶标之间的相互作用。
结果：本研究发现，加味阳和汤可显著减轻哮喘小鼠的气道炎症，降低BALF中炎症细胞数量，并降低BALF中细胞因子IL-4、IL-5、IL-13、IL-33和TNF-α水平和血清总IgE水平。加味阳和汤还可减轻气道高反应性（AHR）和肺部炎症浸润。此外，RNA-seq分析显示加味阳和汤通过调节免疫减轻哮喘小鼠的气道炎症。流式细胞术证实加味阳和汤可抑制ILC2反应。ILC2 Smart RNA-seq分析表明，加味阳和汤破坏了ILC2中炎症反应相关的信号通路，神经纤毛蛋白1（Nrp1）、内皮转录因子3（GATA3）和白细胞介素1受体样蛋白1（ST2）可能是关键靶点。分子对接分析探索了主要靶标与加味阳和汤肺部原型化合物之间的联系，结果表明，通过UPLC-Q-TOF/MS鉴定的甘草苷、淫羊藿苷、甘草酸和甘草皂苷B在与上述关键靶标的结合中表现出显著的亲和力。
结论：加味阳和汤治疗哮喘的机制可能与限制ILC2反应有关。本研究结果为加味阳和汤在哮喘治疗中的临床应用提供了一些药理学证据。
(中日友好医院呼吸与危重症医学科 张婧媛 摘译 林江涛 审校)
(J Ethnopharmacol. 2024 May 23;326:117927. doi: 10.1016/j.jep.2024.117927. Epub 2024 Feb 17.)
(J Ethnopharmacol. 2024 May 23;326:117927. doi: 10.1016/j.jep.2024.117927. Epub 2024 Feb 17.)
Jiawei Yanghe Decoction attenuate allergic airway inflammation by suppressing group 2 innate lymphoid cells responses.
Wang Y, Cui J, Jiang Y, Zhang S, Chen L, Ma Z, Yang D, Zhang Z, Huang X, Yang Y, Guo J, Lu Z, Li C.
Abstract
BACKGROUND:Jiawei 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.
OBJECTIVE：To investigate the therapeutic effect as well as the underlying mechanisms of JWYHD on asthmatic mice.
METHODS:The 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.
RESULTS:JWYHD 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.
CONCLUSION:Our 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.
上一篇：
哮喘治疗的精准医学：释放表观基因组和微生物组的潜力
下一篇：
接受手术的生物治疗2型弥漫性/嗜酸性粒细胞慢性鼻窦炎患者疾病持续存在的预测因素
