Abulaiti Kailibinuer, Aikepa Miheleayi, Ainaidu Mireguli, Wang Jiaxin, Yizibula Maiwulanijiang, Aikemu Maihesumu
Institute of Traditional Uyghur Medicine, Xinjiang Medical University, Urumqi 830017, China.
Central Laboratory Institute, Xinjiang Medical University, Urumqi 830011, China.
Chin Herb Med. 2024 Mar 26;16(4):599-611. doi: 10.1016/j.chmed.2024.02.001. eCollection 2024 Oct.
To investigate the mechanisms that underlie the anti-asthmatic effects of (DBJJ, Dabao Jingjie in Chinese) in rats by integrating metabolomics and network pharmacology.
In this study, the rat model of asthma was induced by ovalbumin (OVA), and the rats were treated with a decoction of . Pathological changes in lung tissue were observed, and the quantification of eosinophils (EOS) and white blood cells (WBC) in bronchoalveolar lavage fluid was performed. Furthermore, the serum levels of asthma-related factors induced by OVA were assessed. H NMR spectroscopy serum metabolomics method was utilized to identify differential metabolites and their associated metabolic pathways. UPLC-QE-MS/MS combined with network pharmacology was employed to predict the core targets and pathways of DBJJ in its action against asthma. The anti-asthmatic properties of DBJJ were investigated using an integrated approach of metabolomics and network pharmacology. The findings were validated through molecular docking and Western blotting analysis of the key targets.
The administration of DBJJ effectively alleviated OVA-induced lung histopathological changes and decreased the number of EOS and WBC in BALF. Additionally, DBJJ inhibited the OVA-induced elevation of TNF-α, IL-18, Ig-E, EOS, IL-1β, MDA, VEGF-A, and TGF-β1. A total of 21 biomarkers and 10 pathways were found by metabolomics analysis. A total of 29 compounds were identified by UPLC-QE-MS/MS, in which 13 active components were screened by oral availability and Caco-2 cell permeability, the 120 targets and 173 KEGG pathways were predicted. The integration of metabolomics and network pharmacological analysis revealed that DBJJ's main constituents, including ferulic acid and ursolic acid, exerted their effects on four targets, namely DAO and NOS2, as well as their associated metabolites and pathways. The active constituents of DBJJ demonstrated a high binding affinity towards DAO and NOS2. Furthermore, DBJJ was observed to decrease the protein expression and phosphorylation levels of NOS2, MAPK, and STAT3.
The administration of DBJJ demonstrates notable anti-asthma properties in rats with allergic asthma. This effect can be attributed to the modulation of various targets, including NOS2, MAPK, and STAT3, by primary constituents such as ferulic acid and ursolic acid.
通过整合代谢组学和网络药理学研究大宝经解（DBJJ，中文）对大鼠抗哮喘作用的潜在机制。
本研究中，用卵清蛋白（OVA）诱导大鼠哮喘模型，并用大宝经解水煎剂对大鼠进行治疗。观察肺组织的病理变化，并对支气管肺泡灌洗液中的嗜酸性粒细胞（EOS）和白细胞（WBC）进行定量分析。此外，评估OVA诱导的哮喘相关因子的血清水平。采用核磁共振氢谱血清代谢组学方法鉴定差异代谢物及其相关代谢途径。采用超高效液相色谱-四极杆-串联质谱联用（UPLC-QE-MS/MS）结合网络药理学预测大宝经解抗哮喘作用的核心靶点和途径。采用代谢组学和网络药理学的综合方法研究大宝经解的抗哮喘特性。通过对关键靶点的分子对接和蛋白质印迹分析验证研究结果。
给予大宝经解有效减轻了OVA诱导的肺组织病理变化，并减少了BALF中EOS和WBC的数量。此外，大宝经解抑制了OVA诱导的TNF-α、IL-18、Ig-E、EOS、IL-1β、MDA、VEGF-A和TGF-β1升高。代谢组学分析共发现21种生物标志物和10条途径。通过UPLC-QE-MS/MS鉴定出29种化合物，其中通过口服生物利用度和Caco-2细胞通透性筛选出13种活性成分，预测出120个靶点和173条KEGG途径。代谢组学和网络药理学分析的整合表明，大宝经解的主要成分，包括阿魏酸和熊果酸，对四个靶点即DAO和NOS2及其相关代谢物和途径发挥作用。大宝经解的活性成分对DAO和NOS2表现出高结合亲和力。此外，观察到大宝经解降低了NOS2、MAPK和STAT3的蛋白表达和磷酸化水平。
给予大宝经解对过敏性哮喘大鼠具有显著的抗哮喘特性。这种作用可归因于阿魏酸和熊果酸等主要成分对包括NOS2、MAPK和STAT3在内的多种靶点的调节。
