title: A novel caffeoyl triterpene attenuates cerebral ischemic injury with potent anti-inflammatory and hypothermic effects.
abstract: Despite the intense efforts in searching for stroke therapies, an urgent need still exists to explore novel neuroprotective agents for ischemic stroke that have high efficacy and wide therapeutic time-window. Here, we provide the first demonstration that 28-O-caffeoyl betulin (B-CA), a novel derivative of naturally occurring caffeoyl triterpene, could significantly alleviate brain infarction and neurological deficit when given as late as 6 h after transient middle cerebral artery occlusion in the rat. Moreover, post-ischemia B-CA administration exhibited long-term (14 days post stroke) protective effects on both brain infarction and functional (i.e., motor and sensory) deficits. Protective B-CA effects correlated with decreased inflammatory responses as indicated by inhibition of microglia and astrocyte activation [stained with ionized calcium-binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) antibody, respectively], as well as suppression of tumor necrosis factor-α, interleukin-1β, and cyclooxygenase-2 overproduction in the ipsilateral cortex of ischemic rat. B-CA administration caused significant hypothermia in the focal cerebral ischemic rat, which may contribute to its ameliorative effects on brain damage and inflammation. In view of its potency in wide therapeutic time-window, robust anti-inflammatory and hypothermic effects, this novel caffeoyl triterpene derivative may lead toward the development of effective therapeutic strategies for the treatment of ischemic stroke.
authors.affiliation: CAS Key Laboratory of Receptor Research, Department of Pharmacology, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Ruan
authors.forename: Hong Min
authors.initials: HM
authors.lastname: Wang
authors.forename: Xiao Tian
authors.initials: XT
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Fu
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.forename: Chun Yan
authors.initials: CY
authors.lastname: Ye
authors.forename: Jin Long
authors.initials: JL
authors.lastname: Li
authors.forename: Lei
authors.initials: L
authors.lastname: Wu
authors.forename: Qi
authors.initials: Q
authors.lastname: Gong
authors.forename: Wei Min
authors.initials: WM
authors.lastname: Zhao
authors.forename: Hai Yan
authors.initials: HY
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000473:pathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000188:drug therapy; D014315:Triterpenes / Q000627:therapeutic use*; D002109:Caffeic Acids; D000094062:Betulinic Acid
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D018696:Neuroprotective Agents; D014315:Triterpenes; C000597780:28-O-caffeoyl betulin; D002109:Caffeic Acids; D000094062:Betulinic Acid
keywords: caffeoyl triterpene; hypothermia; inflammation; ischemic stroke; neuroprotection; therapeutic time window