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.