Purpose: Galuteolin is a substance extracted and purified from honeysuckle. The purpose of this study was to explore the protective effect of galuteolin on cerebral ischemia-reperfusion injury (CIRI) and reveal its potential molecular mechanism from the perspectives of anti-apoptosis, anti-oxidation, and anti-inflammation.
Materials and methods: One hundred and fifty rats were randomly divided into five groups: sham group, ischemia-reperfusion (I/R) group, 50 mg/kg galuteolin group, 100 mg/kg galuteolin group, and 200 mg/kg galuteolin group. Middle cerebral artery occlusion (MCAO) was used to establish a rat CIRI model, different doses of galtenolin were intraperitoneal injected 2 hrs after ischemia, and then reperfusion was performed for 24 hrs. Neurological function and cerebral water content were determined, and cerebral infarct volume was evaluated by TTC staining. TUNEL staining was used to detect the apoptosis of nerve cells. Western Blot was used to detect the expressions of Akt, p-Akt, Sod1, Sod2, catalase, caspase-3, Bcl-2, and Bax. Lipid hydrogen peroxide (LPO) was determined by kit assay. The contents of vascular endothelial growth factor (VEGF) and pro-inflammatory cytokines IL-1β and TNF-α were determined by ELISA.
Results: The results showed that galuteolin could significantly reduce the cerebral infarction volume, neurologic score, and cerebral water content in a dose-dependent manner. In addition, galuteolin obviously reduced the apoptosis rate of nerve cells and the expression levels of caspase-3 and Bax, meanwhile up-regulated the expression levels of p-Akt and Bcl-2. Furthermore, galuteolin apparently inhibited the levels of LPO, Sod1, Sod2, and catalase in the cerebral infarction tissues. Moreover, galuteolin also significantly reduced the levels of pro-inflammatory factors IL-1β and TNF-α in the cerebral infarction tissues. Finally, Galuteolin markedly inhibited the expression of VEGF in cerebral infarction tissues.
Conclusion: Galuteolin exerts neuroprotective effects against CIRI by inhibiting apoptosis, oxidation, and inflammation.
Keywords: galuteolin, ischemia, reperfusion, apoptosis, oxidation, inflammation