Network analysis to explore the pharmacological mechanism of Shenmai injection in treating granulocytopenia and evidence-based medicine approach validation

• Published in: Medicine (Baltimore) Vol. 102; no. 20; p. e33825
• Main Authors: Hou, Xianbing, Chen, Dandan, Wang, Yao, Cui, Bixian, Xu, Hui, Wang, Yuanyuan, Chen, Hongzhou, Wang, Dan, Chen, Ying, Cheng, Tongfei, Dai, Xiaojun
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 19.05.2023
• Subjects: Agranulocytosis; Drugs, Chinese Herbal - pharmacology; Drugs, Chinese Herbal - therapeutic use; Humans; Leukopenia; Phosphatidylinositol 3-Kinases; Systematic Review and Meta-Analysis; Chinese medicine; granulocytopenia; network pharmacology; evidence-based medicine; Shenmai injection
• DOI: 10.1097/MD.0000000000033825
• ISSN: 0025-7974; 1536-5964

Background: Shenmai injection is frequently utilized in China to clinically treat granulocytopenia in oncology patients following chemotherapy. Despite this, the drug's therapeutic benefits remain a topic of contention, and its active components and potential treatment targets have yet to be established. The present study utilizes a network pharmacology approach to investigate the drug's active ingredients and possible therapeutic targets, and to evaluate the effectiveness of Shenmai injection in treating granulocytopenia through meta-analysis. Methods: In our subject paper, we utilized the TCMID database to investigate the active ingredients present in red ginseng and ophiopogon japonicus. To further identify molecular targets, we employed SuperPred, as well as OMIM, Genecards, and DisGeNET databases. Our focus was on targets associated with granulocytopenia. The DAVID 6.8 database was utilized to perform gene ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. Additionally, a protein-protein interaction network was established. The resulting "drug-key component-potential target-core pathway" network was used to predict the mechanism of action of Shenmai injection in the treatment of granulocytopenia. In order to evaluate the quality of the studies included in our analysis, we utilized the Cochrane Reviewers' Handbook. We then conducted a meta-analysis of the clinical curative effect of Shenmai injection for granulocytopenia, utilizing the Cochrane Collaboration's RevMan 5.3 software. Results: After conducting a thorough screening, the study identified 5 primary ingredients of Shenmai injection - ophiopogonoside a, β-patchoulene, ginsenoside rf, ginsenoside re, and ginsenoside rg1-that can potentially target 5 essential proteins: STAT3, TLR4, PIK3CA, PIK3R1, and GRB2. Additionally, Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed that Shenmai injection can be beneficial in treating granulocytopenia by interacting with pathways such as HIF-1 signaling, T-cell receptor signaling, PI3K-Akt signaling, chemokine signaling, and FoxO signaling. The results of meta-analysis indicate that the treatment group exhibited superior performance in terms of both efficiency and post-treatment leukocyte count when compared to the control group. Conclusion: In summary, studies in network pharmacology demonstrate that Shenmai injection exerts an impact on granulocytopenia via various components, targets, and mechanisms. Additionally, evidence-based studies provide strong support for the effectiveness of Shenmai injection in preventing and treating granulocytopenia.