Abstract: Objective To explore the possible mechanism of rhamnetin on protecting brain damage in rats with diabetes mellitus (DM) undergoing cerebral ischemia-reperfusion (CI/ R). Methods The model of DM rats was constructed, and CI/ R was prepared by suture-occluded method. They were administered intragastrically with rhamnetin (50, 100, 200 mg / kg). The brain water content, brain index, cell apoptosis, serum inflammatory factors, markers for cell apoptosis and inflammatory response, expression levels of Notch1 and P38 mitogen-activated protein kinase (P38 MAPK) proteins were detected 14 days after administration. Notch1 activator Jagged1 was applied to observe the changes of expression levels of Notch1 and P38 MAPK proteins. Results After intervention with medium- and high- doses of rhamnetin, the number of error times in step-down test, the brain index and brain water content, the apoptosis rate, the levels of IL-6, IL-1β, TNF-α, and the expression levels of cleaved caspase-3 / caspase-3, cleaved caspase-9 / caspase-9, p-Notch1 / Notch1 and p-P38 MAPK/ P38 MAPK were decreased, while the number of times that the rat entering extraneous arms and the level of IL-10 were increased (P< 0. 05). Rhamnetin could inhibit the Jagged1 induced activation of Notch1-p38 MAPK signaling (P<0. 05). Conclusion Rhamnetin can protect DM rats undergoing CI/ R from brain tissue damage, its mechanism may be related to the alleviation of inflammatory response through down-regulation of Notch1-p38 MAPK signaling.

Key words: rhamnetin, diabetes mellitus, cerebral ischemia-reperfusion, inflammatory response, Notch1-P38 MAPK signaling axis