PEG-scutellarin prodrugs: Synthesis, water solubility and protective effect on cerebral ischemia/reperfusion injury

Fifteen PEG-scutellarin prodrugs were synthesized by modifying carboxyl and phenolic hydroxyl groups of scutellarin with mPEG of different molecular weight (400–3000). The water solubility of prodrugs increased remarkably and reached the maximum value of 783.88 mg/mL (scutellarin, 0.02 mg/mL). The anti-infarct effects of four PEG prodrugs with high water solubility were evaluated by Cerebral Ischemia/Reperfusion in the Middle Cerebral Artery Occlusion (MCAO) model. The results showed that the prodrug 7e could significantly reduce the infarct area from 27.2% to 12.2% (33.3% for the control) and decrease the neurological deficit score from 2.77 to 1.32 (2.85 for the control). The half-life (18.62 min) of the prodrug 7e was significantly longer than that of scutellarin (3.03 min).

Graphical abstractThe prodrug 7e could significantly reduce the infarct area from 27.2% to 12.2% and decrease the neurological deficit score from 2.77 to 1.32 compared with scutellarin.Figure optionsDownload full-size imageDownload as PowerPoint slide