title: Gastrodin alleviates cerebral ischemic damage in mice by improving anti-oxidant and anti-inflammation activities and inhibiting apoptosis pathway.
abstract: Gastrodin (GAS), an active constituent of the Chinese herbal medicine Tianma, has anti-oxidant and anti-inflammation activities but its protective effect to the prevention of neurotoxicity induced by ischemic stroke is unclear. In the present study, middle cerebral artery occlusion (MCAO) was used to establish a mice ischemic stroke model. Infarct volume ratio and neurobehavioral score were evaluated, Nissl staining was performed and the expression of cleaved Caspase 3, Bax and B cell lymphoma 2 (Bcl-2) were assessed at 24 h or 7 days after reperfusion. In addition, the total superoxide dismutase (SOD) activity and malondialdehyde (MDA) content, as well as the expression of Nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), SOD1, phospho-Akt and total Akt and TNF-α and IL-1β in the ischemic hemispheres were also observed at 6 h after reperfusion to assess oxidative stress and inflammatory changes after GAS treatment. It was found that GAS, especially at high dose (100 mg/kg) reduced tested neuronal injury and neurobehavioral deficient in MCAO mice. Enhanced expression of cleaved Caspase 3 and Bax and decreased expression of Bcl-2 by MCAO were also reversed by GAS. Moreover, GAS treatment decreased the MDA content and the expression of TNF-α and IL-1β, and increased amount of SOD activity and the expression of HO-1 and SOD1 in GAS-treated ischemic brain. Furthermore, GAS significantly increased Akt phosphorylation and Nrf2 expression. These results support the neuroprotective effects of GAS, and the activation of Akt/Nrf2 pathway may play a critical role in the pharmacological action of GAS.
authors.affiliation: Department of Toxicology, Shaanxi Key Lab of Free Radical Biology and Medicine, The Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical University, Xi'an, 710032, China.
authors.forename: Zhengwu
authors.initials: Z
authors.lastname: Peng
authors.forename: Shiquan
authors.initials: S
authors.lastname: Wang
authors.forename: Guanjie
authors.initials: G
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Cai
authors.forename: Rui
authors.initials: R
authors.lastname: Liu
authors.forename: Jiao
authors.initials: J
authors.lastname: Deng
authors.forename: Jiangzheng
authors.initials: J
authors.lastname: Liu
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Qingrong
authors.initials: Q
authors.lastname: Tan
authors.forename: Chunxu
authors.initials: C
authors.lastname: Hai
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001592:Benzyl Alcohols / Q000494:pharmacology*; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016207:Cytokines / Q000037:antagonists & inhibitors; D005960:Glucosides / Q000494:pharmacology*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001592:Benzyl Alcohols; D016207:Cytokines; D005960:Glucosides; D018836:Inflammation Mediators; C045345:gastrodin