title: Ursolic Acid Ameliorates Early Brain Injury After Experimental Traumatic Brain Injury in Mice by Activating the Nrf2 Pathway.
abstract: Previous studies have indicated oxidative stress and inflammatory injury as significant contributors to the secondary damage associated with traumatic brain injury (TBI). Ursolic acid (UA) has been demonstrated to exert anti-oxidative and anti-inflammatory effects on cerebral ischemia by activating the nuclear factor-erythroid 2-related factor 2 (Nrf2) pathway. However, the effects of UA on TBI remain unclear. The aim of this study is to evaluate the potential roles of UA in the activation of the Nrf2 pathway using an experimental TBI model and the underlying mechanism. Wild-type (WT) and Nrf2(-/-)mice were divided into eight groups: (1) sham; (2) TBI; (3) TBI + vehicle; (4) TBI + 50 mg/kg UA; (5) TBI + 100 mg/kg UA; (6) TBI + 150 mg/kg UA; (7) TBI + Nrf2(-/-)+ vehicle; (8) TBI + Nrf2(-/-)+ UA. All mice underwent the TBI with the exception of the sham group. The neurologic outcomes of the mice were evaluated at 24 h after TBI, as well as the expression of Nrf2, NQO1, HO1,SOD, GPx, and MDA. Treatment of UA significantly ameliorated brain edema and the neurological insufficiencies after TBI. In addition, UA treatment markedly strengthened the nuclear translocation of Nrf2 protein and increased the expression of NQO1 and HO1. Moreover, UA significantly increased the expression of AKT, an Nrf2 upstream factor, suggesting that UA play a neuroprotective role through the activation of the Nrf2-ARE signal pathway. On the contrary, UA showed no neuroprotective effect on the Nrf2(-/-)mice. These data indicated that UA increases the activity of antioxidant enzymes and attenuated brain injury via Nrf2 factor.
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu, 210002, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ding
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu, 210002, People's Republic of China. njhdwang@hotmail.com.
authors.forename: Handong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu, 210002, People's Republic of China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing University, 305 East Zhongshan Road, Nanjing, Jiangsu, 210002, People's Republic of China.
authors.forename: Wuting
authors.initials: W
authors.lastname: Wei
mesh_terms: D000818:Animals; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014315:Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D000097245:Ursolic Acid
chemical_list: D051267:NF-E2-Related Factor 2; D014315:Triterpenes; D000097245:Ursolic Acid; C495636:Nfe2l2 protein, mouse
keywords: Neuroprotection; Nrf2; Traumatic brain injury; Ursolic acid