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Rutaecarpine may improve neuronal injury, inhibits apoptosis, inflammation and oxidative stress by regulating the expression of ERK1/2 and Nrf2/HO-1 pathway in rats with cerebral ischemia-reperfusion injury

Authors Han M, Hu L, Chen Y

Received 17 May 2019

Accepted for publication 31 July 2019

Published 20 August 2019 Volume 2019:13 Pages 2923—2931

DOI https://doi.org/10.2147/DDDT.S216156

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Tuo Deng


Meiyu Han,1,* Lin Hu,2,* Yang Chen3

1Department of Internal Medicine, The Second People’s Hospital of Dongying City, Dongying City, Shandong Province 257335, People’s Republic of China; 2Department of Critical Care Medicine ICU, Zoucheng People’s Hospital, Zoucheng, Shandong Province 273500, People’s Republic of China; 3Department of Internal Neurology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Pudong, Shanghai 201399, People’s Republic of China

Correspondence: Yang Chen
Department of Internal Neurology, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, 2800 Gongwei Road, Huinan Town, Pudong, Shanghai 201399, People’s Republic of China
Tel +86 1 356 895 4215
Email l8nz03s78@sina.com

*These authors contributed equally to this work

Background: Cerebral ischemia-reperfusion (CI/R) 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 CI/R was established to explore the effects and potential molecular mechanisms of Rut on CI/R injury in rats.
Results: The results showed that Rut alleviated neuronal injury induced by CI/R 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 CI/R through inhibiting the production of pro-inflammatory factors (IL-6 and IL-1β), 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 CI/R 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 CI/R.

Keywords: cerebral ischemia-reperfusion, rutaecarpine, nuclear factor-erythroid 2 related factor 2, extracellular regulated protein kinases

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