Network Pharmacology Experiments Show That Emodin Can Exert a Protective Effect on MCAO Rats by Regulating Hif-1α/VEGF-A Signaling

Abstract

Modern pharmacological studies have shown that emodin, the main effective component of rhubarb, has good anti-inflammatory and antioxidant effects, but its pharmacodynamic mechanism remains unclear yet. This study aims to elucidate the multitarget action mechanism of emodin in ischemic stroke through network pharmacology and in vivo experiments. Sprague–Dawley rats were randomly divided into control (normal saline), sham (normal saline), model (normal saline), and emodin groups ( n = 9 per group). Emodin was administered at 40 mg/kg/d for 3 consecutive days. The rats were subjected to middle cerebral artery occlusion for 2 h, followed by reperfusion for 24 h to establish the cerebral ischemia–reperfusion injury. To search for relevant studies in databases, emodin, ischemic stroke, and stroke were used as keywords. Subsequently, protein–protein interaction networks and complex disease target networks were established, and an enrichment analysis and molecular docking of core targets were performed. Gene expression was detected through western blotting and reverse-transcription polymerase chain reaction. Localization and expression of proteins were detected through immunohistochemistry. Furthermore, the neurological function, 2,3,5-triphenyltetrazolium chloride staining, levels of brain tissue inflammatory factors, the role of the blood–brain barrier (BBB), and relevant signaling pathways were assessed in vivo . The molecular docking of core targets revealed that the docking between vascular endothelial growth factor A (VEGF-A) and emodin was the most efficient. Emodin pretreatment decreased the neurological score from 2.875 to 1.125. Moreover, emodin inhibited the degradation of occludin and claudin-5 caused by matrix metalloprotein kinase (MMP)-2/MMP-9, thereby protecting the BBB. Additionally, related proteins such as hypoxia-inducible factor-1α/VEGF-A and nuclear factor kappa B were down-regulated. Thus, emodin may play a protective role during cerebral ischemia reperfusion through mediation of the Hif-1α/VEGF-A signaling pathway to inhibit the expression of inflammatory factors.

Marine-Derived Leads as Anticancer Candidates by Disrupting Hypoxic Signaling through Hypoxia-Inducible Factors Inhibition

“…Emodin (37) is widely reputed for its anticancer effects and the interference with a series of molecular events underlying cancer development and progression [205]. The interference with the HIF-1 pathway emerges as a common mechanism underlying an array of potential therapeutic effects of 37, ranging from neuroprotection and anti-inflammatory effects to the preservation of intestinal barrier function and amelioration of pulmonary inflammation [206][207][208][209][210]. Similarly, the response to the hypoxic environment in the cancer microenvironment has also been commonly reported.…”

Investigating the Protective Effects of Rhubarb on Cerebral Ischemic Stroke Rats Using Network Pharmacology and Molecular Docking

“…[11][12][13][14] Rhubarb is a TCM drug that has been historically used to treat blood stasis syndrome, including diabetes, 15 atherosclerosis, 16 ischemia, 17 and inflammation. 18 Furthermore, it has been reported to possess anti-inflammatory and antioxidative properties that may facilitate the treatment of cerebral ischemia, 19,20 but its specific mechanism in the treatment of CIS remains elusive.…”