Molecular Mechanism of Epimedium Extract against Ischemic Stroke Based on Network Pharmacology and Experimental Validation

Abstract

Ischemic stroke exhibits high morbidity, disability, and mortality, and treatments for ischemic stroke are limited despite intensive research. The potent neuroprotective benefits of Epimedium against ischemic stroke have gained lots of interest. Nevertheless, systematic research on the direct role and mechanisms of Epimedium in ischemic stroke is still lacking. Network pharmacology analysis coupled with experimental verification was utilized to systematically evaluate the potential pharmacological mechanism of Epimedium against ischemic stroke. The TCMSP database was used to mine the bioactive ingredients and Epimedium’s targets. The DrugBank, OMIM, and GeneCards databases were employed to identify potential targets of ischemic stroke. GO and KEGG pathway analyses were also carried out. The interaction between active components and hub targets was confirmed via molecular docking. An experimental ischemic stroke model was used to evaluate the possible therapeutic mechanism of Epimedium. As a result, 23 bioactive compounds of Epimedium were selected, and 30 hub targets of Epimedium in its function against ischemic stroke were identified, and molecular docking results demonstrated good binding. The IL-17 signaling pathway was revealed as a potentially significant pathway, with the NF-κB and MAPK/ERK signaling pathways being involved. Furthermore, in vivo experiments demonstrated that Epimedium treatment could improve neurological function and reduce infarct volume. Additionally, Epimedium reduced the activation of microglia and astrocytes in both the ischemic penumbra of the hippocampus and cerebral cortex following ischemic stroke. Western blot and RT–qPCR analyses demonstrated that Epimedium not only depressed the expression of IL-1β, TNF-α, IL-6, and IL-4 but also inhibited the NF-κB and MAPK/ERK signaling pathways. This study applied network pharmacology and in vivo experiment to explore possible mechanism of Epimedium’s role against ischemic stroke, which provides insight into the treatment of ischemic stroke.

The Diagnostic Model of Ligusticum Chuanxiong Hort. Against Cerebral Stroke Using Network Pharmacology and Transcriptomics Analyses

“…IL-17 is a signature cytokine of Th17 cells and plays an important role in ischemic stroke [31]. The IL-17 signaling pathway has been demonstrated to be a potentially significant pathway in ischemic stroke [32]. LCH has been reported to have anti-inflammatory effects [33].…”

Integrating molecular pathway with genome-wide association data for causality identification in breast cancer

“…Subsequently, KEGG enrichment analysis was conducted using the enrichKEGG function to identify significant biological pathways based on DEGs. Finally, the outcomes of the enrichment analyses were visually represented through bubble diagrams [ 23 ]. Significance was found out by adjusted P-value of < 0.05.…”

USP10 is a potential mediator for vagus nerve stimulation to alleviate neuroinflammation in ischaemic stroke by inhibiting NF-κB signalling pathway

“…The tMCAO model was successfully established if the regional cerebral blood flow decreased to 20% after occlusion and returned to more than 80% of baseline after reperfusion, as measured by a laser Doppler flowmeter (PeriFlux 5000, Perimed AB, Sweden). Meanwhile, mice were evaluated by Longa scoring ( 21 ) for neurological defects immediately after resuscitation, and those scoring 2 or 3 were enrolled in the study and the mice that did not meet the required score were excluded from the study ( 25 ). The number of deaths in each group at 72h after tMCAO: sham (0), tMCAO (4), tMCAO+VNS (2), tMCAO+VNS+LV-scramble (2), and tMCAO+VNS+LV-shUSP10 (3).…”

“…2,3,5-triphenyltetrazolium chloride (TTC, Sigma-Aldrich, USA) staining was performed to detect cerebral infarct volumes at 72hr after tMCAO ( 25 ). The mice were euthanized, and the brains were rapidly removed and frozen at -20°C for 20 mins.…”