1. Withanolide A (WA), a major constituent phytochemical of the Ayurvedic herb Withania somnifera reportedly combats neurodegeneration in Alzheimer’s disease and Parkinson’s disease. But no study has yet reported the ability of WA in crossing the blood–brain barrier (BBB). The present study analyses the brain penetration ability of WA after intra-nasal administration and assesses its neuroprotective ability in cerebral ischemia-reperfusion injury in adult mice model.

2. Brain penetration of WA after intranasal administration in cortex and cerebellum was assessed using HPLC-UV. Three different doses (1 mg/kg, 5 mg/kg and 10 mg/kg) of the phytochemical were used to study the neuroprotective ability of WA by evaluating the brain damage, changes in cerebral neurotransmitter levels and brain tissue morphology.

3. Intranasal administration of the phytochemical facilitates its penetration in the cortex and cerebellum. Post-treatment with WA significantly reduced cerebral infarction, restored BBB disruption and cerebral oedema. The WA post-treatment also lowered the ischemia-induced elevated neurotransmitter and biochemical levels in brain compartments. The highest dose (10 mg/kg) of WA also markedly reduced the morphological damages, apoptotic and necrotic cell death in brain tissue occurring due to cerebral ischemia pathophysiology.

4. Intra-nasal administration enables brain penetration of WA and allows the phytochemical to exert neuroprotective ability in the global cerebral ischemia model.

1. Withanolide A（WA），是阿育吠陀草药Withania somnifera的主要植物化学成分，据报道可抵抗阿尔茨海默氏病和帕金森氏病的神经退行性变。但是，尚无研究报道WA具有穿越血脑屏障（BBB）的能力。本研究分析了鼻内给药后WA的脑穿透能力，并评估了其在成年小鼠模型中对脑缺血-再灌注损伤的神经保护能力。

2.使用HPLC-UV评估鼻内给药皮质和小脑后WA的脑渗透性。通过评估脑损伤，脑神经递质水平的变化和脑组织形态，使用三种不同剂量（1 mg / kg，5 mg / kg和10 mg / kg）的植物化学物质来研究WA的神经保护能力。

3.鼻内施用植物化学物质有助于其渗透到皮层和小脑中。WA的后处理可显着减少脑梗死，恢复BBB破坏和脑水肿。WA后处理还降低了局部脑缺血引起的神经递质和生化水平升高。WA的最高剂量（10 mg / kg）也显着减少了由于脑缺血病理生理而引起的脑组织形态损害，凋亡和坏死细胞死亡。

4.鼻内给药使WA的脑部渗透并允许植物化学物质在整体脑缺血模型中发挥神经保护能力。