Abstract：
BACKGROUND: Asthma is a complex disease with mechanisms involving multiple factors, and there is still a lack of highly effective and low-side-effect drugs. Traditional Chinese medicine Fagopyrum Dibotrys Rhizoma (FDR) has been applied for the treatment of acute and chronic bronchitis as well as bronchial asthma due to its favorable pharmacological activity. However, the exact mechanism of FDR remains unclear.
OBJECTIVE: A mouse model of asthma was created using OVA and HDM. To investigate the mechanism of FDR in asthma treatment, a combination of network pharmacology, lipidomics, and molecular biology approaches was employed.
METHODS: To evaluate the therapeutic effects of FDR on asthma, we established two distinct models of asthma in C57BL/6 J mice using OVA and HDM, respectively. We then employed LC-MS to analyze the major chemical constituents in FDR. Next, the network pharmacology approach was used to predict the potential targets and mechanisms of FDR in asthma treatment. Additionally, lipidomics analysis of mouse serum was conducted using LC-MS. Finally, the impact of FDR on the ERK -cPLA2 signaling pathway was investigated through Western Blotting assay.
RESULTS: FDR treatment has been shown to improve histomorphological changes, lung function and inflammation in models of OVA and HDM-induced asthma. Using UPLC/LTQ-Orbitrap-MS, we were able to identify 12 potential active components. Network pharmacology analysis revealed that FDR shares 75 targets with asthma. Further analysis using GO and KEGG pathways demonstrated the involvement of key pathways such as PI3K-Akt, TNF, and MAPK. Additionally, lipidomics analysis of the serum from OVA and HDM induced asthma mice showed disturbances in lipid metabolism, which were effectively ameliorated by FDR treatment. Mechanistically, FDR inhibits ERK1/2-cPLA2, leading to a reduction in lysophospholipids and restoration of lipid balance, thereby aiding in the treatment of asthma.
CONCLUSIONS: FDR has been shown to improve lipid metabolism disorder in the serum of asthmatic mice, thereby potentially serving as a treatment for asthma. This can be achieved by regulating the activation levels of ERK1/2 and p38MAPK. Consequently, the production of lysophosphatide is reduced, thereby alleviating the disorder of lipid metabolism and achieving the desired therapeutic effect in asthma treatment.
OBJECTIVE: A mouse model of asthma was created using OVA and HDM. To investigate the mechanism of FDR in asthma treatment, a combination of network pharmacology, lipidomics, and molecular biology approaches was employed.
METHODS: To evaluate the therapeutic effects of FDR on asthma, we established two distinct models of asthma in C57BL/6 J mice using OVA and HDM, respectively. We then employed LC-MS to analyze the major chemical constituents in FDR. Next, the network pharmacology approach was used to predict the potential targets and mechanisms of FDR in asthma treatment. Additionally, lipidomics analysis of mouse serum was conducted using LC-MS. Finally, the impact of FDR on the ERK -cPLA2 signaling pathway was investigated through Western Blotting assay.
RESULTS: FDR treatment has been shown to improve histomorphological changes, lung function and inflammation in models of OVA and HDM-induced asthma. Using UPLC/LTQ-Orbitrap-MS, we were able to identify 12 potential active components. Network pharmacology analysis revealed that FDR shares 75 targets with asthma. Further analysis using GO and KEGG pathways demonstrated the involvement of key pathways such as PI3K-Akt, TNF, and MAPK. Additionally, lipidomics analysis of the serum from OVA and HDM induced asthma mice showed disturbances in lipid metabolism, which were effectively ameliorated by FDR treatment. Mechanistically, FDR inhibits ERK1/2-cPLA2, leading to a reduction in lysophospholipids and restoration of lipid balance, thereby aiding in the treatment of asthma.
CONCLUSIONS: FDR has been shown to improve lipid metabolism disorder in the serum of asthmatic mice, thereby potentially serving as a treatment for asthma. This can be achieved by regulating the activation levels of ERK1/2 and p38MAPK. Consequently, the production of lysophosphatide is reduced, thereby alleviating the disorder of lipid metabolism and achieving the desired therapeutic effect in asthma treatment.
摘要：
背景：哮喘是一种复杂的疾病，其机制涉及多种因素，仍然缺乏高效和低副作用的药物。由于具有良好的药理活性，中药FagopyrumDibotrysRhizoma（FDR）已被用于治疗急性和慢性支气管炎以及支气管哮喘。然而,FDR的确切机制尚不清楚.
目的：使用OVA和HDM建立哮喘小鼠模型。探讨FDR在哮喘治疗中的作用机制,网络药理学的结合，脂质组学，采用了分子生物学方法。
方法：为了评估FDR对哮喘的治疗效果，我们使用OVA和HDM在C57BL/6J小鼠中建立了两种不同的哮喘模型，分别。然后，我们使用LC-MS分析了FDR中的主要化学成分。接下来,网络药理学方法用于预测哮喘治疗中FDR的潜在靶点和机制.此外,使用LC-MS进行小鼠血清的脂质组学分析。最后,通过蛋白质印迹法研究FDR对ERK-cPLA2信号通路的影响。
结果：FDR治疗已被证明可以改善组织形态学变化，OVA和HDM诱导的哮喘模型的肺功能和炎症。使用UPLC/LTQ-Orbitrap-MS，我们能够识别出12种潜在的活性成分.网络药理学分析显示，FDR与哮喘共享75个目标。使用GO和KEGG通路的进一步分析表明，PI3K-Akt等关键通路参与，TNF,和MAPK。此外,对OVA和HDM诱导的哮喘小鼠血清的脂质组学分析显示脂质代谢紊乱，通过FDR治疗得到有效改善。机械上,FDR抑制ERK1/2-cPLA2，导致溶血磷脂减少和恢复脂质平衡，从而有助于哮喘的治疗。
结论：FDR可改善哮喘小鼠血清脂质代谢紊乱，从而有可能作为哮喘的治疗方法。这可以通过调节ERK1/2和p38MAPK的活化水平来实现。因此,溶血磷脂的产量减少，从而在哮喘治疗中减轻脂质代谢紊乱并达到期望的治疗效果。
目的：使用OVA和HDM建立哮喘小鼠模型。探讨FDR在哮喘治疗中的作用机制,网络药理学的结合，脂质组学，采用了分子生物学方法。
方法：为了评估FDR对哮喘的治疗效果，我们使用OVA和HDM在C57BL/6J小鼠中建立了两种不同的哮喘模型，分别。然后，我们使用LC-MS分析了FDR中的主要化学成分。接下来,网络药理学方法用于预测哮喘治疗中FDR的潜在靶点和机制.此外,使用LC-MS进行小鼠血清的脂质组学分析。最后,通过蛋白质印迹法研究FDR对ERK-cPLA2信号通路的影响。
结果：FDR治疗已被证明可以改善组织形态学变化，OVA和HDM诱导的哮喘模型的肺功能和炎症。使用UPLC/LTQ-Orbitrap-MS，我们能够识别出12种潜在的活性成分.网络药理学分析显示，FDR与哮喘共享75个目标。使用GO和KEGG通路的进一步分析表明，PI3K-Akt等关键通路参与，TNF,和MAPK。此外,对OVA和HDM诱导的哮喘小鼠血清的脂质组学分析显示脂质代谢紊乱，通过FDR治疗得到有效改善。机械上,FDR抑制ERK1/2-cPLA2，导致溶血磷脂减少和恢复脂质平衡，从而有助于哮喘的治疗。
结论：FDR可改善哮喘小鼠血清脂质代谢紊乱，从而有可能作为哮喘的治疗方法。这可以通过调节ERK1/2和p38MAPK的活化水平来实现。因此,溶血磷脂的产量减少，从而在哮喘治疗中减轻脂质代谢紊乱并达到期望的治疗效果。
