Gentiopicroside Ameliorates Cerebrovascular Angiogenesis, Neuronal Injury and Immune Disorder in Rats with Cerebral Ischemia/Reperfusion Injury via VEGF and Phosphorylated Nrf2 Elevation.

Background: Cerebral ischemia-reperfusion (CI/R) injury is induction of blood flow restoration after an ischemic stroke. Gentiopicroside (GPC) is the principal active secoiridoid glycoside of . This research aimed to illuminate the function of GPC and its mechanism in CI/R injury.

Methods: After CI/R injury models were constructed, GPC (25, 50 or 100 mg/kg) was then administered by gavage to rats. Rats were grouped into Sham, CI/R, CI/R+25 mg/kg GPC, CI/R+50 mg/kg GPC, and CI/R+100 mg/kg GPC. Neuronal cells were exposed to oxygen-glucose deprivation and reperfusion (OGD/R) injury to establish ischemic-like conditions , and cells were further treated with 25, 50, or 100 μM GPC. Cells were grouped into control, OGD/R, OGD/R+25 μM GPC, OGD/R+50 μM GPC, and OGD/R+100 μM GPC. GPC's function on rat cerebral injury, angiogenesis, oxidative stress, neuronal injury and immune dysfunction was estimated using hematoxylin-eosin staining, Western blot, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, commercial kits and enzyme linked-immunosorbent assay. Meanwhile, GPC's mechanism in CI/R injury was examined via Western blot. GPC's function was estimated via Cell Counting Kit-8 assay, 5-ethynyl-2'-deoxyuridine (EdU) staining, flow cytometry.

Results: GPC alleviated cerebral injury through decreasing cerebral infarction volume, cerebral indexes, brain water contents ( < 0.05). GPC reduced oxidative stress and boosted cerebral angiogenesis in CI/R rats ( < 0.05). Meanwhile, GPC weakened neuronal cell apoptosis, and decreased neuron-specific enolase and S100beta protein levels in CI/R rats. GPC reduced inflammatory cytokines contents in serum and brain tissues of CI/R rats ( < 0.05). Moreover, GPC increased the viability and proliferation in OGD/R-treated neuronal cells, but decreased cell apoptosis ( < 0.05). Mechanistically, GPC upregulated vascular endothelial growth factor (VEGF) and phosphorylated nuclear factor E2-related factor 2 (p-Nrf2) levels in CI/R rat brain tissues ( < 0.05).

Conclusions: GPC reduced cerebrovascular angiogenesis, neuronal injury and immune disorder in CI/R injury through elevating VEGF and p-Nrf2.