Arctigenin Alleviates Oxidative Stress in Cerebral Ischemia/Reperfusion Injury Rats by Keap1-Nrf2 Pathway

Background and Objective: Arctigenin, a phenylpropanoid dibenzyl butyrolactone lignan, is one of the major active components in Fructus Arctii, has protective effects in cerebral Ischemia/Reperfusion (I/R) injury. However, the role of arctigenin in cerebral I/R injury has not been fully understood. This study aimed to investigate the possible antioxidant stress effects of arctigenin and its mechanism on cerebral I/R injured rats. Material and Methods: A rat model of cerebral I/R injury was established and treated with arctigenin. The activity of SOD and the levels of MDA and ROS were determined by chemical analysis. The expressions of NQO1, HO-1, Nrf2 and Keap1 were detected in Cortex and hippocampus using Western blot. The binding affinity of the Keap1 to the arctigenin was assessed by molecular docking. Results: Current results indicated that arctigenin could remarkably restrict the brain infarction area and ameliorate neuronal functional deficit. After treatment, the activities of SOD were significantly up-regulated and the levels of MDA and ROS were significantly down-regulated in cortex tissue and hippocampus tissue. Meanwhile, increased Keap1, Nrf2, HO-1 and NQO1 expression levels were detected in cerebral I/R injury rats treated with arctigenin. Additionally, molecular docking revealed that potential interaction of arctigenin with the Nrf2-binding site in the Keap1 protein through hydrogen and hydrophobic interactions. Conclusion: This study suggested that arctigenin exerted a protective effect on cerebral ischemia/reperfusion injury in rats, which is probably related to activate Keap1-Nrf2 signaling pathway to alleviate oxidative stress damage.