RESUMO
Heart failure (HF), a clinical syndrome with a high incidence due to various reasons, is the advanced stage of most cardiovascular diseases. Huangqi is an effective treatment for cardiovascular disease, which has multitarget, multipathway functions. Therefore, we used network pharmacology to explore the molecular mechanism of Huangqi in treating HF. In this study, 21 compounds of Huangqi, which involved 407 targets, were obtained and reconfirmed using TCMSP and PubChem databases. Moreover, we used Cytoscape 3.7.1 to construct compound-target network and screened the top 10 compounds. 378 targets related to HF were obtained from CTD and GeneCards databases and HF-target network was constructed by Cytoscape 3.7.1. The 46 overlapping targets of HF and Huangqi were gotten by Draw Venn Diagram. STRING database was used to set up a protein-protein interaction network, and MCODE module and the top 5 targets with the highest degree for overlapping targets were obtained. GO analysis performed by Metascape indicated that the overlapping targets were mainly enriched in blood vessel development, reactive oxygen species metabolic process, response to wounding, blood circulation, and so on. KEGG analysis analyzed by ClueGO revealed that overlapping targets were mainly enriched in AGE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, HIF-1 signaling pathway, c-type lectin receptor signaling pathway, relaxin signaling pathway, and so on. Finally, molecular docking showed that top 10 compounds of Huangqi also had good binding activities to important targets compared with digoxin, which was carried out in CB-Dock molecular docking server. In conclusion, Huangqi has potential effect on regulating overlapping targets and GE-RAGE signaling pathway in diabetic complications, IL-17 signaling pathway, HIF-1 signaling pathway, and so on to be a latent multitarget, multipathway treatment for HF.
RESUMO
Pruritus is one of the common side effects of intrathecal or epidural injection of opioids. The aim of this study was to test the antipruritic effect of acupuncture and its possible mechanism. We used electroacupuncture (EA), toll-like receptor (TLR)2/4 antagonist sparstolonin B (SsnB), and TLR2/4 agonist peptidoglycan (PGN) to precondition female wild-type BALB/c mice, and then prepared a morphine-induced pruritus model. The mRNA and protein expression levels of TLR2, TLR4, MyD88, and NF-κB were detected by RT-PCR and western blotting. The contents of interleukin (IL)-1, IL-6, IL-12, IL-10, and tumor necrosis factor-α in serum were measured by ELISA assays. Flow cytometry was performed to analyze the ratio of M1-phenotype to M2-phenotype macrophages. Our results showed that EA preconditioning improved pruritus; reduced the expressions of TLR2, TLR4, MyD88, and NF-κB both at the mRNA and protein levels (P<0.05); reduced the expression of proinflammatory cytokines IL-1, IL-6, IL-12, and tumor necrosis factor-α; and increased the expression of anti-inflammatory cytokine IL-10 (P<0.05). EA promoted M2-phenotype macrophage differentiation. Moreover, these results showed no significant difference between the SsnB group and the EA+SsnB group (P>0.05), but showed a significant difference between the PGN group and the EA+PGN group (P<0.05). Therefore, we propose that EA may be involved in the remission of pruritus in morphine-induced pruritus model mice through the TLR2/4-MyD88-NF-κB pathway. EA is a potential therapeutic treatment for pruritus.
