Protective effect of astragaloside IV on lipopolysaccharide-induced cardiac dysfunction via downregulation of inflammatory signaling in mice

Evidence-Based Complementary and Alternative Medicine

et al. 2020

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.

Section: Resultsmentioning

confidence: 99%

Exploring Molecular Mechanism of Huangqi in Treating Heart Failure Using Network Pharmacology

Tao

Huang

Evidence-Based Complementary and Alternative Medicine

et al. 2020

“…In vitro studies have demonstrated that AST IV is a strong scavenger of superoxide radicals and hydroxyl radicals (Zhao et al 2015). The antioxidant properties of AST IV are likely derived from the phenyl hydroxyl group and cyclic propane group in the saponin molecule (Zhao et al 2015a(Zhao et al , 2015b. Another pharmacological property of AST IV is its anti-inflammatory activity.…”

Section: Discussionmentioning

confidence: 99%

Astragaloside IV attenuates inflammatory reaction via activating immune function of regulatory T-cells inhibited by HMGB1 in mice

Liu

Huang

et al. 2016

Pharmaceutical Biology

“…It is used for the treatment of a variety of diseases including cardiac13, hepatic141516 and neurological disorders171819. The protective effect of AS-IV has been mechanically linked to its inhibition of Akt and its downstream pathways202122. Notably, recent studies have shown that AS-IV preserves renal function in a mouse model of type 1 diabetes2324.…”

mentioning

confidence: 99%

Astragaloside IV ameliorates renal injury in db/db mice

Sun

Han

et al. 2016

Sci Rep

Diabetic nephropathy is a lethal complication of diabetes mellitus and a major type of chronic kidney disease. Dysregulation of the Akt pathway and its downstream cascades, including mTOR, NFκB, and Erk1/2, play a critical role in the development of diabetic nephropathy. Astragaloside IV is a major component of Huangqi and exerts renal protection in a mouse model of type 1 diabetes. The current study was undertaken to investigate the protective effects of diet supplementation of AS-IV on renal injury in db/db mice, a type 2 diabetic mouse model. Results showed that administration of AS-IV reduced albuminuria, ameliorated changes in the glomerular and tubular pathology, and decreased urinary NAG, NGAL, and TGF-β1 in db/db mice. AS-IV also attenuated the diabetes-related activation of Akt/mTOR, NFκB, and Erk1/2 signaling pathways without causing any detectable hepatotoxicity. Collectively, these findings showed AS-IV to be beneficial to type 2 diabetic nephropathy, which might be associated with the inhibition of Akt/mTOR, NFκB and Erk1/2 signaling pathways.