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揭示胃卫兵 1 号治疗胃炎的作用机制及分子靶点:基于网络药理学结合 GEO 数据库分析。

Uncovering the Mechanisms and Molecular Targets of Weibing Formula 1 against Gastritis: Coupling Network Pharmacology with GEO Database.

机构信息

Department of Traditional Chinese Medicine, People's Hospital of Xinjin District, Chengdu, China.

Department of Rehabilitation Medicine, China MCC5 Group Corp. Ltd. Hospital, China.

出版信息

Biomed Res Int. 2021 Aug 21;2021:5533946. doi: 10.1155/2021/5533946. eCollection 2021.

Abstract

Weibing Formula 1, a classic traditional formula, has been widely used clinically to treat gastritis in recent years. However, the potential pharmacological mechanism of Weibing Formula 1 is still unclear to date. A network pharmacology-based strategy was performed to uncover the underlying mechanisms of Weibing Formula 1 against gastritis. Furthermore, we structured the drug-active ingredients-genes-disease network and PPI network of shared targets, and function enrichment analysis of these targets was carried out. Ultimately, Gene Expression Omnibus (GEO) datasets and real-time quantitative PCR were used to verify the related genes. We found 251 potential targets corresponding to 135 bioactive components of Weibing Formula 1. Then, 327 gastritis-related targets were known gastritis-related targets. Among which, 60 common targets were shared between potential targets of Weibing Formula 1 and known gastritis-related targets. The results of pathway enrichment analysis displayed that 60 common targets mostly participated in various pathways related to Toll-like receptor signaling pathway, MAPK signaling pathway, cytokine-cytokine receptor interaction pathway, chemokine signaling pathway, and apoptosis. Based on the GSE60427 dataset, 15 common genes were shared between differentially expressed genes and 60 candidate targets. The verification results of the GSE5081 dataset showed that except for DUOX2 and VCAM1, the other 13 genes were significantly upregulated in gastritis, which was consistent with the results in the GSE60427 dataset. More importantly, real-time quantitative PCR results showed that the expressions of PTGS2, MMP9, CXCL2, and CXCL8 were significantly upregulated and NOS2, EGFR, and IL-10 were downregulated in gastritis patients, while the expressions of PTGS2, MMP9, CXCL2, and CXCL8 were significantly downregulated and NOS2, EGFR, and IL-10 were upregulated after the treatment of Weibing Formula 1. PTGS2, NOS2, EGFR, MMP9, CXCL2, CXCL8, and IL-10 may be the important direct targets of Weibing Formula 1 in gastritis treatment. Our study revealed the mechanism of Weibing Formula 1 in gastritis from an overall and systematic perspective, providing a theoretical basis for further knowing and application of this formula in the future.

摘要

胃痛方 1 号是一种经典的传统方剂,近年来在临床上广泛用于治疗胃炎。然而,胃痛方 1 号的潜在药理机制至今仍不清楚。本研究采用网络药理学策略来揭示胃痛方 1 号治疗胃炎的潜在机制。此外,构建了药物-活性成分-基因-疾病网络和共享靶点的 PPI 网络,并对这些靶点进行了功能富集分析。最后,使用基因表达综合 (GEO) 数据集和实时定量 PCR 来验证相关基因。我们发现胃痛方 1 号对应 135 种生物活性成分的 251 个潜在靶点。然后,已知的 327 个胃炎相关靶点。其中,胃痛方 1 号的潜在靶点和已知的胃炎相关靶点之间有 60 个共同靶点。通路富集分析的结果表明,60 个共同靶点主要参与 Toll 样受体信号通路、MAPK 信号通路、细胞因子-细胞因子受体相互作用通路、趋化因子信号通路和细胞凋亡等多种途径。基于 GSE60427 数据集,差异表达基因和 60 个候选靶点之间有 15 个共同基因。GSE5081 数据集的验证结果表明,除了 DUOX2 和 VCAM1 外,其他 13 个基因在胃炎中均显著上调,与 GSE60427 数据集的结果一致。更重要的是,实时定量 PCR 结果表明,在胃炎患者中 PTGS2、MMP9、CXCL2 和 CXCL8 的表达明显上调,NOS2、EGFR 和 IL-10 的表达下调,而在胃痛方 1 治疗后,PTGS2、MMP9、CXCL2 和 CXCL8 的表达明显下调,NOS2、EGFR 和 IL-10 的表达上调。PTGS2、NOS2、EGFR、MMP9、CXCL2、CXCL8 和 IL-10 可能是胃痛方 1 治疗胃炎的重要直接靶点。本研究从整体和系统的角度揭示了胃痛方 1 号治疗胃炎的作用机制,为进一步了解和应用该方剂提供了理论依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98d8/8405302/0b83cd9a952b/BMRI2021-5533946.001.jpg

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