School of Pharmacy, Shanghai University of Medicine and Health Sciences, Shanghai 201318, China.
School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Comput Biol Chem. 2021 Aug;93:107535. doi: 10.1016/j.compbiolchem.2021.107535. Epub 2021 Jun 25.
Banxia Xiexin decoction (BXD), a traditionally prescribed Chinese medicine, has been used to treat chronic gastritis for many years. However, the underlying mechanism and targets for its effects remain unknown. In the present study, we predicted the targets and active compounds of BXD in the treatment of chronic gastritis through network pharmacology and ultra-performance liquid chromatography coupled with linear trap quadrupole-Orbitrap mass spectrometry (UPLC-LTQ-Orbitrap MS).
A chronic gastritis model was established in rats by oral administration of 56 % ethanol. BXD was orally administered for 7 days. Stomach tissues were collected for histopathological analysis, and tumour necrosis factor (TNF)-α, interleukin (IL)-2, IL-8, and lactate dehydrogenase (LDH) levels were measured by enzyme-linked immunosorbent assay. UPLC-LTQ-Orbitrap MS was established to analyse compounds in rat plasma following oral BXD administration. The absorbed ingredients were selected as candidate active compounds. The chronic gastritis-related targets were screened using multiple databases. The potential targets for the treatment of chronic gastritis were used to construct a protein-protein interaction (PPI) network and were also analysed using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Finally, molecular docking was used to uncover the interaction between multi-components and putative targets, and the results were verified by surface plasmon resonance (SPR).
Intragastric administration of BXD ameliorated stomach injury resulting from chronic gastritis in rats and decreased the levels of TNF-α, IL-2, IL-8, and LDH. A comprehensive systematic strategy was used to successfully identify 38 candidate targets and 14 active compounds in BXD. Based on the network of compounds-targets and PPI, three hub genes that were associated with BXD therapy for chronic gastritis were selected and included intercellular adhesion molecule-1, peroxisome proliferator-activated receptor gamma and mitogen-activated protein kinase 14. The results of molecular docking and SPR demonstrated that the active compounds in BXD demonstrate affinity for these targets. Additionally, an enrichment analysis revealed that treatment of chronic gastritis with BXD primarily involves cytokine activation, the inflammatory response and nuclear factor-kappa B, hypoxia-inducible factor-1, phosphatidylinositol-3-kinase-protein-serine-threonine kinase and Janus kinase-signal transducer and activator of transcription signalling pathways, which may mediate the effects of BXD in the treatment of chronic gastritis.
BXD exhibits a therapeutic effect in ethanol-induced gastritis through multi-compound, multi-target and multi-pathway mechanisms. A strategy of network pharmacology combined with SPR may provide a feasible approach to explore the targets of herbal medicine and uncover novel bioactive components.
半夏泻心汤（BXD）是一种传统的中药方剂，多年来一直用于治疗慢性胃炎。然而，其作用的潜在机制和靶点尚不清楚。在本研究中，我们通过网络药理学和超高效液相色谱-线性阱四极杆-Orbitrap 质谱联用（UPLC-LTQ-Orbitrap MS）预测 BXD 治疗慢性胃炎的靶点和活性化合物。
通过灌胃 56%乙醇建立大鼠慢性胃炎模型。BXD 灌胃 7 天。收集胃组织进行组织病理学分析，酶联免疫吸附法检测肿瘤坏死因子（TNF）-α、白细胞介素（IL）-2、IL-8 和乳酸脱氢酶（LDH）水平。建立 UPLC-LTQ-Orbitrap MS 分析大鼠灌胃 BXD 后血浆中的化合物。选择吸收成分作为候选活性化合物。使用多个数据库筛选与慢性胃炎相关的靶点。利用蛋白质-蛋白质相互作用（PPI）网络对潜在的治疗慢性胃炎靶点进行分析，并使用基因本体（GO）和京都基因与基因组百科全书（KEGG）数据库进行分析。最后，分子对接用于揭示多成分与假定靶点之间的相互作用，并通过表面等离子体共振（SPR）进行验证。
BXD 灌胃可改善慢性胃炎大鼠的胃损伤，降低 TNF-α、IL-2、IL-8 和 LDH 水平。采用综合系统策略，成功鉴定出 BXD 中的 38 个候选靶点和 14 个活性化合物。基于化合物-靶点网络和 PPI，选择了与 BXD 治疗慢性胃炎相关的三个关键基因，包括细胞间黏附分子-1、过氧化物酶体增殖物激活受体γ和丝裂原活化蛋白激酶 14。分子对接和 SPR 的结果表明，BXD 中的活性化合物与这些靶点具有亲和力。此外，富集分析表明，BXD 治疗慢性胃炎主要涉及细胞因子激活、炎症反应和核因子-κB、缺氧诱导因子-1、磷脂酰肌醇-3-激酶-丝氨酸-苏氨酸激酶和 Janus 激酶-信号转导和转录激活因子信号通路，这些通路可能介导 BXD 治疗慢性胃炎的作用。
BXD 通过多成分、多靶点和多途径机制对乙醇诱导的胃炎发挥治疗作用。网络药理学结合 SPR 的策略可能为探索中药靶点和发现新的生物活性成分提供一种可行的方法。
