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- Title
8-O-Acetyl Shanzhiside Methylester Attenuates Cerebral Ischaemia/Reperfusion Injury through an Anti-Inflammatory Mechanism in Diabetic Rats.
- Authors
Zhang, Liang; Kan, Ze‐Chun; Zhang, Xiu‐Li; Fang, Han; Jiang, Wang‐Lin
- Abstract
Inflammatory activation plays a vital role in the pathophysiological mechanisms of stroke and diabetes mellitus ( DM), exerts the deleterious effects on the progression of the brain and leads to vascular damage in diabetic stroke. The objectives of this study were to investigate the effects of 8- O-acetyl shanzhiside methylester ( ND01) on tumour necrosis factor-α ( TNF-α)-stimulated SH- SY5Y cell line in vitro and the experimental ischaemic diabetic stroke model in vivo. TNF-α-stimulated SH- SY5Y cells were pre-incubated with ND01, then analysed protein expression. For in vivo experiment, the diabetic rats were subjected to middle cerebral artery occlusion ( MCAO) for 30 min. followed by reperfusion for 23 hr. Treatment of SH- SY5 Y cells with ND01 blocked TNF-α-induced nuclear transcription factor κB ( NF-κB) activation and decreased high-mobility group box-1 ( HMGB-1) expression. ND01 40 mg/kg demonstrated significant neuroprotective effect even after delayed administration at 4 hr after I/R. ND01 40 mg/kg attenuated the histopathological damage, decreased brain swelling, inhibited NF-κB activation and reduced HMGB-1 expression in ischaemic brain tissue. These data show that ND01 protects diabetic brain against I/ R injury with a favourable therapeutic time-window by alleviating diabetic cerebral I/ R injury and attenuating blood-brain barrier ( BBB) breakdown, and its protective effects may involve HMGB-1 and NF-κB signalling pathway.
- Subjects
METHYLESTERASES; CEREBRAL ischemia treatment; TREATMENT of reperfusion injuries; TUMOR necrosis factors; ANIMAL models of diabetes; LABORATORY rats
- Publication
Basic & Clinical Pharmacology & Toxicology, 2014, Vol 115, Issue 6, p481
- ISSN
1742-7835
- Publication type
Article
- DOI
10.1111/bcpt.12266