综合运用荟萃分析、网络药理学和分子对接方法探讨丹红注射液治疗特发性肺纤维化的疗效及分子机制。

Exploring the efficacy and molecular mechanism of Danhong injection comprehensively in the treatment of idiopathic pulmonary fibrosis by combining meta-analysis, network pharmacology, and molecular docking methods.

机构信息

Department of Preclinical Medicine, Guizhou University of Traditional Chinese Medicine, Guiyang, China.

出版信息

Medicine (Baltimore). 2024 May 10;103(19):e38133. doi: 10.1097/MD.0000000000038133.

DOI:10.1097/MD.0000000000038133

PMID:38728523

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11081554/

Abstract

BACKGROUND

Danhong injection, a compound injection of Chinese herbal medicine, has been widely used in idiopathic pulmonary fibrosis (IPF) at present as an adjuvant treatment. However, the clinical efficacy and molecular mechanism of IPF are still unclear. This study will evaluate and explore the clinical efficacy and molecular mechanism of Danhong injection in the treatment of IPF.

METHODS

In meta-analysis, the computer was used to search 8 databases (PubMed, EMbase, CENTRAL, MEDLINE, CBM, CNKI, WanFang, and VIP) to collect the RCTs, and RevMan 5.3 and Stata 14.0 were used for statistical analysis. It has been registered on PROSPERO: CRD42020221096. In network pharmacology, the main chemical components and targets of the chemical components of Danhong injection were obtained in TCMSP and Swiss Target Prediction databases. The main targets of IPF were obtained through Gencards, Disgenet, OMIM, TTD, and DRUGBANK databases. The String platform was used to construct PPI networks. Cytoscape 3.8.2 was used to construct the "Danhong components - IPF targets-pathways" network. The molecular docking verification was conducted by Auto Dock.

RESULTS

Twelve RCTs were finally included with a total of 896 patients. The meta-analysis showed that Danhong injection could improve the clinical efficiency ([OR] = 0.25, 95% CI [0.15, 0.41]), lung function, arterial blood gas analysis, inflammatory cytokines, and serum cytokines associated with pulmonary fibrosis of IPF patients, respectively (P < .05). The core active components of Danhong injection on IPF were Luteolin, Quercetin, and Kaempferol, and the core targets were PTGS2, AR, ESR1, PPARG, and RELA. Danhong injection mainly improved IPF through PD-L1 expression and PD-1 checkpoint path in cancer, pathways in cancer, PI3K-Akt signaling pathway, etc.

CONCLUSION

These results provided scientific basis for the clinical use of Danhong injection for the treatment of IPF, and provided a new direction to explore the potential mechanism of action of Danhong injection.

摘要

背景

丹红注射液是一种中药复方注射液，目前已广泛用于特发性肺纤维化（IPF）的辅助治疗。然而，IPF 的临床疗效和分子机制仍不清楚。本研究将评估和探讨丹红注射液治疗 IPF 的临床疗效和分子机制。

方法

在荟萃分析中，计算机检索 8 个数据库（PubMed、EMbase、CENTRAL、MEDLINE、CBM、CNKI、万方和 VIP），收集 RCTs，采用 RevMan 5.3 和 Stata 14.0 进行统计分析。该研究已在 PROSPERO 上注册：CRD42020221096。在网络药理学中，通过 TCMSP 和 Swiss Target Prediction 数据库获取丹红注射液的主要化学成分和靶点，通过 Gencards、Disgenet、OMIM、TTD 和 DRUGBANK 数据库获取 IPF 的主要靶点。使用 String 平台构建 PPI 网络，使用 Cytoscape 3.8.2 构建“丹红成分-IPF 靶点-通路”网络。采用 Auto Dock 进行分子对接验证。

结果

最终纳入 12 项 RCT，共 896 例患者。Meta 分析结果显示，丹红注射液可提高 IPF 患者的临床疗效[OR=0.25，95%CI（0.15，0.41）]、肺功能、血气分析、炎症因子和与肺纤维化相关的血清因子（P<.05）。丹红注射液治疗 IPF 的核心活性成分有木犀草素、槲皮素和山奈酚，核心靶点有 PTGS2、AR、ESR1、PPARG 和 RELA。丹红注射液主要通过 PD-L1 表达和癌症中的 PD-1 检查点通路、癌症通路、PI3K-Akt 信号通路等改善 IPF。