Abstract
Danshen (Salvia miltiorrhiza) preparations such as Danhong injection, Danshen injection, Salvianolate injection, compound Danshen injection and Sodium Tanshinone IIA Sulfonate (STS) injection are widely used in China to treat stable angina (angina pectoris) caused by coronary heart disease. In this study we compared the network pharmacological mechanisms of the 5 Danshen preparations. Following a literature search performed in PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI) database, China Biology Medicine (CBM) database, China Conference Paper Database, Wanfang Database, VIP Database and Conference Proceedings Citation Index (through January 2015), 444 randomized controlled trial publications detailing the use of the 5 Danshen-based injections for treating stable angina were identified, and their combined data were analyzed using a network meta-analysis. All of the 5 Danshen-based preparations were effective in treating stable angina with clinical improvement rates of 72.4%–91.6% and electrocardiogram (ECG) improvement rates of 54.5%–71.6%. According to both clinical improvement and ECG improvement, the 5 Danshen-based preparations were ranked as follows: Danhong injection > Salvianolate injection > STS injection > compound Danshen injection > Danshen injection. There were no significant differences among the safety profiles of the 5 Danshen preparations. The meta-analysis results were further examined using a network pharmacology approach and functional enrichment analysis, which revealed that Danshen and Danhong injections affected 4 and 15 signaling pathways, respectively, and that the 4 signaling pathways affected by Danshen were a subset of those influenced by Danhong. Therefore, Danhong injection affected some unique signaling pathways that might regulate lipoprotein metabolism, oxidation, and inflammation, and protect vascular endothelia, reflecting the multi-component and multi-target characteristics of this traditional formula and its strengths in treating complex diseases.
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Acknowledgements
This study was supported by National 11th Five-year Plan Supporting R&D Project (No 2006BAI08B04-06).
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Supplementary information is available at the website of Acta Pharmacologica Sinica.
Supplementary information
Supplementary Table S1
The difference between the five drugs (DOC 9 kb)
Supplementary Table S2
The included data items extracted from the literature. (DOC 87 kb)
Supplementary Table S3
The Cochrane quality assessment criteria. (DOC 132 kb)
Supplementary Table S4
Age, gender, and follow-up time and found that these factors were not significant effect modifiers. (DOC 59 kb)
Supplementary Table S5
Consistent and inconsistent network meta-analysis models produced similar indices. (DOC 55 kb)
Supplementary Table S6
The paired-comparisons of the effects of the five Danshen-based preparations on the clinical efficacy. (DOC 77 kb)
Supplementary Table S7
The paired-comparisons of the effects of the five Danshen-based preparations on ECG improvement. (DOC 78 kb)
Supplementary Table S8
The OMIM database yielded 19 genes that were associated with chronic stable angina, resulting in a total of 94 corresponding associated genes. (DOC 45 kb)
Supplementary Table S9
The associated genes of Danshen and safflower in UniProt, TCMSP, and PubMed were identified: 31 and 41 genes associated with Danshen and safflower, respectively. (DOC 68 kb)
Supplementary Table S10
Three overlapping pathways, amyotrophic lateral sclerosis (ALS), arginine and proline metabolism, and calcium signaling pathway, were identified as being affected by both Danshen alone and Danhong (DOC 116 kb)
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Zhang, Gx., Zhang, Yy., Zhang, Xx. et al. Different network pharmacology mechanisms of Danshen-based Fangjis in the treatment of stable angina. Acta Pharmacol Sin 39, 952–960 (2018). https://doi.org/10.1038/aps.2017.191
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DOI: https://doi.org/10.1038/aps.2017.191
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