The mechanism of Epimedium in the treatment of coronary atherosclerotic heart disease based on network pharmacology, molecular docking, and in vitro studies.

OBJECTIVE: There are many challenges related to the treatment of coronary atherosclerotic heart disease (CAD). Studies have confirmed that Epimedium extract inhibits myocardial injury induced by myocardial ischaemia, but the mechanism of action remains unclear. This study aimed at analysed the effective components and mechanisms of Epimedium in treating CAD based on network pharmacology and molecular docking studies and to verify the mechanism in vitro. MATERIALS AND METHODS: The TCMSP and UniProt databases were used to filter for the active components and drug targets of Epimedium. The GeneCards database was used to screen disease targets associated with CAD. The intersection of the drug targets of Epimedium and the disease targets of coronary heart disease was studied to identify the targets of Epimedium in the treatment of CAD. Cytoscape software was used to establish and analyse an activity-target network. The STRING database was used to analyse a protein-protein interaction (PPI) network, and proteins in the PPI network were visualized in the R language. Bioconductor software was used for GO function and KEGG pathway enrichment analyses, and visualization analysis was performed in the R language. PyMOL software was used to verify the molecular docking between selected active components of Epimedium and the targets of CAD, and the potential key effective components of Epimedium in the treatment of coronary heart disease were identified. The involvement of the PI3K/Akt pathway was validated by Western blot analysis. RESULTS: (1) Twenty-three active compounds, including Epimedium glycoside, quercetin, luteolin, and olive resin, were screened out. There were 68 common targets of Epimedium and CAD, including IL-6, ESR1, RELA, FOS, NCOA1, CCND1, EGFR, MAPK8, VEGFA, and CASP8. The potential signaling pathways involved in the treatment of CAD by Epimedium included the human cytomegalovirus infection pathway, the PI3K-Akt signaling pathway, the TNF signaling pathway, and the HIF-1 signaling pathway. (2) Luteolin, quercetin, sitosterol, and anhydroicaritin showed strong binding to targets of CAD based on molecular docking studies. (3) Epimedium extract increased the expression of PI3K, Akt and P-Akt but decreased the expression of IL-6  in vitro. CONCLUSIONS: (1) Icariin, quercetin and luteolin may act on target proteins, including IL-6, ESR1, EGFR, MAPK8, VEGFA and CASP8, to participate in the regulation of the human cytomegalovirus infection pathway, the PI3K-Akt signaling pathway, the TNF signaling pathway and other signaling pathways in order to effectively treat CAD. (2) In vitro studies confirmed that Epimedium extract can treat CAD by upregulating PI3K, Akt and P-Akt protein expression and downregulating IL-6 protein expression in SD rat cardiomyocytes.

Effect of integrative medicines on 28-day mortality from sepsis: a systematic review and network meta-analysis.

OBJECTIVE: The aim is to perform a network meta-analysis to evaluate the effect of different Chinese medicines combined with Western medicine treatment (WMT) on the 28-day mortality of patients with sepsis. MATERIALS AND METHODS: We searched multiple databases for randomized controlled trials (RCTs), using keywords such as sepsis, Shenfu, Shenmai, Shengmai, Dahuang Fuzi, Xuebijing, and mortality. The databases we searched included the China Knowledge Network (CNKI), Wanfang database, the Chinese scientific journal database (VIP), the Chinese biomedical literature database (CBM), PubMed, Embase and Cochrane. The collection time was from inception through September 22, 2020. Two researchers independently screened the articles, extracted data, and assessed the quality of the evidence. Stata15 was used for network meta-analysis, and Excel was used to summarize the list of adverse reactions. RESULTS: Twenty-nine studies with a total of 3201 patients were included in this study. Combined with WMT, Shenfu injection [OR = 0.63, 95% CI = (0.47, 0.83)] and Xuebijing injection [OR = 0.71, 95% CI = (0.52, 0.96)] can significantly reduce 28-day mortality among patients with sepsis, while Shenmai injection [OR = 0.40, 95% CI = (0.16, 1.03)] and Dahuang Fuzi decoction [OR = 1.00, 95% CI = (0.48, 2.10)] cannot significantly improve on the 28-day mortality. The efficacy ranking is as follows: Shenmai group (level of evidence: low) > Shenfu group (level of evidence: low) > Xuebijing group (level of evidence: very low) > WMT group > Dahuangfuzi group (level of evidence: very low). CONCLUSIONS: Combined with WMT, Shenfu injection or Xuebijing injection can reduce the 28-day mortality among patients with sepsis. The Shenfu group had the best effect on outcomes, and its level of evidence was higher than that of the Xuebijing group.