Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Department of Integrative Medicine, Huashan Hospital, Fudan University, Shanghai, China; Institute of Integrative Medicine, Fudan University, Shanghai, China.
J Ethnopharmacol. 2022 Aug 10;294:115351. doi: 10.1016/j.jep.2022.115351. Epub 2022 May 6.
Loki zupa (LKZP) decoction, a traditional Uyghur medicine prescription, has been commonly used to treat numerous respiratory ailments in the Xinjiang region of western China, especially chronic airway inflammatory diseases such as allergic asthma. Due to its complex chemical composition, however, the mechanism of action of LKZP has yet to be fully elucidated.
Based on the balanced regulation theory of pro-inflammation and anti-inflammation, we tried to investigate the effectiveness of LKZP on asthma and its related protective mechanisms.
In this study, an experimental model of asthma was established using ovalbumin (OVA) in BALB/c mice to assess the effects of LKZP. The potential mechanism of LKZP anti allergic asthma were researched by the combination of in silico systems pharmacology and in vivo transcriptomics.
Our data revealed that LKZP exerted a therapeutic effect against OVA-induced asthma by reducing airway hyperresponsiveness (AHR), peribronchial inflammation, and mucus hypersecretion. Meanwhile, LKZP downregulated the expression of OVA-induced IgE, interleukin (IL)-4, IL-5, IL-13, and tumor necrosis factor (TNF)-α and concurrently promoted the expression of interferon (IFN)-γ in serum and bronchoalveolar lavage fluid (BALF). Systems pharmacology analysis identified 10 core bioactive ingredients and 26 hub targets of LKZP against asthma. Transcriptomic analysis confirmed 246 differentially expressed genes (DEGs) after LKZP treatment. These were mainly expressed in cytokine-cytokine receptor interactions and immune and inflammatory response-related signaling pathways. Additionally, the real-time quantitative PCR (qPCR) results for the nine selected DEGs matched those of the RNA-seq analysis. Nuclear factor (NF)-κB and hypoxia-inducible factor (HIF)-1 signaling pathways were identified as candidate targets involved in the action of LKZP on allergic asthma, which was highly consistent with the findings in silico. By qPCR, Western blot, and immunohistochemical analysis, it was verified that LKZP treatment dramatically inhibited the activation of NF-κB p65 and HIF-1α stimulated by OVA in asthmatic mice.
Taken together, our experimental data revealed that LKZP could be a candidate for the treatment of allergic asthma via NF-κB and HIF-1 signaling pathways.
Loki zupa (LKZP) 汤，一种传统的维吾尔医药方，在中国西部新疆地区被广泛用于治疗多种呼吸道疾病，特别是过敏性哮喘等慢性气道炎症性疾病。然而，由于其复杂的化学成分，LKZP 的作用机制尚未完全阐明。
基于炎症和抗炎的平衡调节理论，我们试图研究 LKZP 对哮喘的治疗效果及其相关的保护机制。
本研究采用卵清蛋白 (OVA) 在 BALB/c 小鼠中建立哮喘模型，评估 LKZP 的作用。结合计算机系统药理学和体内转录组学研究 LKZP 抗过敏性哮喘的潜在机制。
我们的数据显示，LKZP 通过降低气道高反应性 (AHR)、支气管周围炎症和粘液分泌过度，对 OVA 诱导的哮喘发挥治疗作用。同时，LKZP 下调了 OVA 诱导的 IgE、白细胞介素 (IL)-4、IL-5、IL-13 和肿瘤坏死因子 (TNF)-α 的表达，并促进了血清和支气管肺泡灌洗液 (BALF) 中干扰素 (IFN)-γ的表达。系统药理学分析确定了 LKZP 治疗哮喘的 10 种核心生物活性成分和 26 个关键靶标。转录组分析证实，LKZP 治疗后有 246 个差异表达基因 (DEGs)。这些基因主要在细胞因子-细胞因子受体相互作用和免疫及炎症反应相关信号通路中表达。此外，通过实时定量 PCR (qPCR) 对 9 个选定的 DEGs 的检测结果与 RNA-seq 分析结果一致。核因子 (NF)-κB 和缺氧诱导因子 (HIF)-1 信号通路被鉴定为参与 LKZP 治疗过敏性哮喘的候选靶点，这与计算机模拟结果高度一致。通过 qPCR、Western blot 和免疫组织化学分析，证实 LKZP 治疗可显著抑制 OVA 刺激哮喘小鼠 NF-κB p65 和 HIF-1α 的激活。
综上所述，我们的实验数据表明，LKZP 可通过 NF-κB 和 HIF-1 信号通路成为治疗过敏性哮喘的候选药物。
