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8‐O‐Acetyl Shanzhiside Methylester Attenuates Cerebral Ischaemia/Reperfusion Injury through an Anti‐Inflammatory Mechanism in Diabetic Rats
Author(s) -
Zhang Liang,
Kan ZeChun,
Zhang XiuLi,
Fang Han,
Jiang WangLin
Publication year - 2014
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/bcpt.12266
Subject(s) - neuroprotection , medicine , ischemia , in vivo , pharmacology , blood–brain barrier , tumor necrosis factor alpha , inflammation , stroke (engine) , diabetes mellitus , brain damage , reperfusion injury , endocrinology , central nervous system , biology , mechanical engineering , microbiology and biotechnology , engineering
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 ( ND 01) on tumour necrosis factor‐α ( TNF ‐α)‐stimulated SH ‐ SY 5Y cell line in vitro and the experimental ischaemic diabetic stroke model in vivo . TNF ‐α‐stimulated SH ‐ SY 5Y cells were pre‐incubated with ND 01, 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 ‐ SY 5 Y cells with ND 01 blocked TNF ‐α‐induced nuclear transcription factor κB ( NF ‐κB) activation and decreased high‐mobility group box‐1 ( HMGB ‐1) expression. ND 01 40 mg/kg demonstrated significant neuroprotective effect even after delayed administration at 4 hr after I/R. ND 01 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 ND 01 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.