4.7 Article

Evodiamine prevents traumatic brain injury through inhibiting oxidative stress via PGK1/NRF2 pathway

期刊

BIOMEDICINE & PHARMACOTHERAPY
卷 153, 期 -, 页码 -

出版社

ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
DOI: 10.1016/j.biopha.2022.113435

关键词

Traumatic brain injury; Apoptosis; Oxidative stress; PGK1/NRF2; Evodiamine

资金

  1. National Natural Science Foundation of China [82104611, 81901254]
  2. Suzhou Science and Technology Plan Project grants (People's Livelihood Science and Technology) [SYS2020067]

向作者/读者索取更多资源

This study demonstrates that evodiamine (Evo) improves outcomes after traumatic brain injury (TBI) by targeting the PGK1/NRF2 signaling pathway to regulate oxidative stress.
Background: Traumatic brain injury (TBI) is a leading cause of death and disability worldwide as well as a risk factor for neurodegenerative diseases later in life. Evodiamine (Evo), a compound derived from Evodia rutaecarpa, is known to possess pharmacological activities. However, whether Evo confers protection after TBI remains unknown. Objective: To study whether Evo protects against TBI through inhibiting oxidative stress via the phosphoglycerate kinase 1 (PGK1)/nuclear factor erythroid 2-related factor 2 (NRF2) pathway. Materials and methods: In vivo, adult male C57BL/6J mice were subjected to controlled cortical impact (impact velocity: 6 m/s; penetration depth: 2 mm) to establish a murine model of TBI. Evodiamine was administrated at 24 h, 30 min prior to TBI and 2, 24, 48, 72 h post TBI. In vitro, pheochromacytoma 12 (PC12) cells were pre-treated with Evo for 24 h, then exposed to 300 mu M H2O2 stimulation for another 24 h to induce oxidative stress. Furthermore, transfection of PGK1 overexpressing vectors or PGK1 siRNAs was performed to decipher the role of PGK1 in Evo-produced effect in TBI. Results: Treatment with Evo alleviated TBI-induced neurological dysfunction, BBB breakdown, histopathological changes in H&E staining, and increased apoptosis. Importantly, Evo enhanced catalase (CAT) and superoxide dismutase (SOD) activities, and reduced reactive oxygen species (ROS) generation through PGK1 inhibition-induced activation of the NRF2/heme oxygenase-1 (HO-1) signaling in TBI mice or H2O2-exposed PC12 cells. Of note, the protective effect of Evo in the in vitro TBI was similar to that of PGK1 siRNAs; overexpression of PGK1 compromised Evo-produced protection in H2O2-stimulated PC12 cells. Discussion and conclusions: Taken together, we demonstrated that Evo improved the outcomes after TBI by targeting the PGK1/NRF2 signaling-regulated oxidative stress. Evo may represent a potential therapy to promote recovery from TBI.

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