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- Title
A novel caffeoyl triterpene attenuates cerebral ischemic injury with potent anti-inflammatory and hypothermic effects.
- Authors
Ruan, Zhi; Wang, Hong Min; Huang, Xiao Tian; Fu, Yan; Wu, Jian; Ye, Chun Yan; Li, Jin Long; Wu, Lei; Gong, Qi; Zhao, Wei Min; Zhang, Hai Yan
- 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.
- Subjects
CEREBRAL ischemia; TRITERPENES; BETULIN; ANTI-inflammatory agents; HYPOTHERMIA; STROKE treatment; THERAPEUTICS
- Publication
Journal of Neurochemistry, 2015, Vol 133, Issue 1, p93
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/jnc.13046