title: Tricin 7-glucoside protects against experimental cerebral ischemia by reduction of NF-κB and HMGB1 expression.
abstract: There have been several studies of nuclear factor-κB (NF-κB) and high-mobility group box1 (HMGB1) associated with the pathophysiology of cerebral ischemia. Tricin 7-glucoside, a major bioactive compound extracted from Sedum sarmentosum Bunge. The objectives of this study were to determine the effects of Tricin 7-glucoside on a cultured neuronal cell line, SH-SY5Y in vitro and experimental ischemic stroke in vivo. For oxygen-glucose deprivation (OGD) and tumor necrosis factor-α (TNF-α) stimulated SH-SY5Y cell line in vitro, SH-SY5Y cells were incubated with Tricin 7-glucoside. For in vivo experiment, rats were subjected to middle cerebral artery occlusion (MACO) for 1h, then followed by reperfusion for 23 h. Treatment of SH-SY5Y cells with Tricin 7-glucoside reduced the OGD-induced apoptosis and cytotoxicity, blocked TNF-α-induced NF-κB and IκB-α phosphorylation, and decreased HMGB1 expression. At doses higher than 50mg/kg, Tricin 7-glucoside produced a significant neuroprotective potential in rats with ischemia and reperfusion (I/R). Tricin 7-glucoside (100mg/kg) demonstrated significant neuroprotective activity even after delayed administration at 2h and 4h after I/R. Tricin 7-glucoside 100mg/kg attenuated histopathological damage, decreased brain edema, inhibited NF-κB activation and reduced HMGB1 expression. These data show that Tricin 7-glucoside protects brain against I/R injury with a favorable therapeutic time-window by alleviating cerebral I/R injury and attenuating blood-brain barrier (BBB) breakdown, and its protective effects may involve HMGB1 and NF-κB signaling pathway.
authors.affiliation: School of Pharmaceutical Sciences and Institute of Material Medica, Binzhou Medical University, Yantai 264003, PR China.
authors.forename: Wang-Lin
authors.initials: WL
authors.lastname: Jiang
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.forename: Shu-Ping
authors.initials: SP
authors.lastname: Zhang
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Zhu
authors.forename: Jian
authors.initials: J
authors.lastname: Hou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000503:physiopathology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D005419:Flavonoids / Q000008:administration & dosage / Q000627:therapeutic use*; D005960:Glucosides / Q000008:administration & dosage / Q000627:therapeutic use*; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D005419:Flavonoids; D005960:Glucosides; D024243:HMGB1 Protein; C104200:Hbp1 protein, rat; D016328:NF-kappa B; D018696:Neuroprotective Agents; C017769:tricin