Article Publish Status: FREE
Abstract Title:

Luteolin Exerts NeuroprotectionModulation of the p62/Keap1/Nrf2 Pathway in Intracerebral Hemorrhage.

Abstract Source:

Front Pharmacol. 2019 ;10:1551. Epub 2020 Jan 21. PMID: 32038239

Abstract Author(s):

Xin Tan, Yi Yang, Jianguo Xu, Peng Zhang, Ruming Deng, Yiguang Mao, Jia He, Yibin Chen, Yan Zhang, Jiasheng Ding, Haiying Li, Haitao Shen, Xiang Li, Wanli Dong, Gang Chen

Article Affiliation:

Xin Tan


Upregulation of neuronal oxidative stress is involved in the progression of secondary brain injury (SBI) following intracerebral hemorrhage (ICH). In this study, we investigated the potential effects and underlying mechanisms of luteolin on ICH-induced SBI. Autologous blood and oxyhemoglobin (OxyHb) were used to establishandmodels of ICH, respectively. Luteolin treatment effectively alleviated brain edema and ameliorated neurobehavioral dysfunction and memory loss. Also,, we found that luteolin promoted the activation of the sequestosome 1 (p62)/kelch-like enoyl-coenzyme A hydratase (ECH)-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by enhancing autophagy and increasing the translocation of Nrf2 to the nucleus. Meanwhile, luteolin inhibited the ubiquitination of Nrf2 and increased the expression levels of downstream antioxidant proteins, such as heme oxygenase-1 (HO-1) and reduced nicotinamide adenine dinucleotide phosphate (NADPH): quinine oxidoreductase 1 (NQO1). This effect of luteolin was also confirmed, which was reversed by the autophagy inhibitor, chloroquine (CQ). Additionally, we found that luteolin inhibited the production of neuronal mitochondrial superoxides (MitoSOX) and alleviated neuronal mitochondrial injury, as indicatedtetrachloro-tetraethylbenzimidazol carbocyanine-iodide (JC-1) staining and MitoSOX staining. Taken together, our findings demonstrate that luteolin enhances autophagy and anti-oxidative processes in bothandmodels of ICH, and that activation of the p62-Keap1-Nrf2 pathway, is involved in such luteolin-induced neuroprotection. Hence, luteolin may represent a promising candidate for the treatment of ICH-induced SBI.

Study Type : Animal Study, In Vitro Study

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Sayer Ji
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