Background: Cerebral ischemia-reperfusion (CUR) injury is a more serious brain injury caused by the recovery of blood supply after cerebral ischemia for a certain period of time. Rutaecarpine (Rut) is an alkaloid isolated from Evodia officinalis with various biological activities. Previous studies have shown that Rut has a certain protective effect on ischemic brain injury, but the specific molecular mechanism is still unknown.
Methods: In this study, a rat model of CUR was established to explore the effects and potential molecular mechanisms of Rut on CUR injury in rats.
Results: The results showed that Rut alleviated neuronal injury induced by CUR in a dose-dependent manner. Besides, Rut inhibited neuronal apoptosis by inhibiting the activation of caspase 3 and the expression of Bax. In addition, Rut alleviated the inflammatory response and oxidative stress caused by CUR through inhibiting the production of pro-inflammatory factors (IL-6 and IL-1 beta), lactate dehydrogenase (LDH), malondialdehyde (MDA) and ROS, and increased the levels of anti-inflammatory factors (IL-4 and IL-10) and superoxide dismutase (SOD). Biochemically, Western blot analyses showed that Rut inhibited the phosphorylation of ERK1/2 and promoted the expression of nuclear factor-erythroid 2 related factor 2 (Nrf2) pathway-related proteins (Nrf2, heme oxygenase 1 (HO-1) and NAD (P) H-quinone oxidoreductase 1) in a dose-dependent manner. These results show that Rut may alleviate brain injury induced by CUR by regulating the expression of ERK1/2 and the activation of Nrf2/HO-1 pathway.
Conclusion: In conclusion, these results suggest that Rut may be used as an effective therapeutic agent for damage caused by CUR.
[1]Second Peoples Hosp Dongying City, Dept Internal Med, Dongying 257335, Shandong, Peoples R China.
[2]Zoucheng Peoples Hosp, Dept Crit Care Med ICU, Zoucheng 273500, Shandong, Peoples R China.
[3]Fudan Univ, Shanghai Pudong Hosp, Dept Internal Neurol, Pudong Med Ctr, 2800 Gongwei Rd, Shanghai 201399, Peoples R China.
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