Background: Inflammatory activation plays a vital role in the pathophysiological mechanisms of stroke, exerting deleterious effects on the progression of tissue damage and may lead to the vascular damage in diabetes. The objectives of this study were to determine the effects of rosmarinic acid (RA) on a cultured neuronal cell line, SH-SY5Y in vitro and experimental ischemic diabetic stroke in vivo.

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-a (TNF-a)-stimulated SH-SY5Y cell line in vitro and the experimental ischaemic diabetic stroke model in vivo. TNFa-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-SY5Y cells with ND01 blocked TNF-a-induced nuclear transcription factor jB (NF-jB) 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-jB 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-jB signalling pathway.Ischaemic stroke is a leading cause of death and disability, resulting in reduced blood flow in a major brain artery. A large number of survivors experience permanent neurological damage that impacts the quality of life. The key recommendation of Stroke Treatment Academic Industry Roundtable (STAIR) VII is still to extend intravenous thrombolysis to a broader patient population, clarifying the risk and benefits of intra-arterial reperfusion therapies. However, STAIR proposes development of neuroprotective therapies [1].Diabetes mellitus (DM) is not only associated with microvascular and macrovascular diseases affecting several organs including brain, but also a major contributor to the incidence of stroke which is 2-5 times higher than for non-DM patients. Compared with the non-diabetic stroke patient, one year after stroke and mortality of DM patients with stroke significantly increased, long-term neurological defects are more obvious [2,3]. It is very serious that the number of Chinese diabetes patient has been growing fast for nearly 20 years [4]. Therefore, investigation of the neuroprotective effects on diabetic (streptozotocin induced) middle cerebral artery occlusion (MCAO) rats is warranted more than for the non-diabetic MCAO rats.The inflammatory response to brain injury and DM, especially nuclear transcription factor jB (NF-jB) activation, plays a vital role in the pathogenesis of ischaemic stroke and DM [5,6]. High-mobility group box-1 (HMGB-1) is a non-histone DNA-binding protein, which releases into the extracellular space immediately after an ischaemic insult and induce...