Sachdeva Anand Kamal, Misra Shubham, Pal Kaur Indu, Chopra Kanwaljit
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Eur J Pharmacol. 2015 Jan 15;747:132-40. doi: 10.1016/j.ejphar.2014.11.014. Epub 2014 Nov 20.
Neuroinflammation is a prominent feature of Alzheimer disease (AD) and other chronic neurodegenerative disorders. Intracerebroventricular (ICV) streptozotocin (STZ) induced-cognitive impairment has been widely used as an experimental paradigm of Alzheimer׳s disease. Sesamol is a potent inhibitor of cytokine production as well as an antioxidant. The present study was designed to evaluate the effectiveness of sesamol in ICV-STZ-induced cognitive deficits in rats by incorporating it into solid lipid nanoparticles (SLNs). ICV-STZ administration produced significant cognitive deficits as assessed by both Morris water maze and elevated plus maze task which is accompanied by significantly enhanced nitrodative stress, altered acetylcholinesterase in rat brain along with significantly increased serum TNF-α levels. Chronic treatment with sesamol and sesamol loaded SLNs dose dependently restored cognitive deficits in ICV-STZ rats along with mitigation of nitrodative stress and cytokine release. Effectiveness of SLNs to deliver sesamol to the brain was shown by a significantly better alleviation of the oxidative stress parameters. Our findings demonstrate that loading of sesamol in SLNs is an effective strategy to mitigate ICV-STZ-induced neuronal dysfunction and memory deficits.
神经炎症是阿尔茨海默病（AD）和其他慢性神经退行性疾病的一个显著特征。脑室内（ICV）注射链脲佐菌素（STZ）诱导的认知障碍已被广泛用作阿尔茨海默病的实验模型。芝麻酚是一种有效的细胞因子产生抑制剂以及抗氧化剂。本研究旨在通过将芝麻酚载入固体脂质纳米粒（SLNs）来评估其对ICV-STZ诱导的大鼠认知缺陷的有效性。通过莫里斯水迷宫和高架十字迷宫任务评估，ICV-STZ给药导致显著的认知缺陷，同时伴有大鼠脑内显著增强的硝基氧化应激、乙酰胆碱酯酶改变以及血清TNF-α水平显著升高。用芝麻酚和载有芝麻酚的SLNs进行慢性治疗可剂量依赖性地恢复ICV-STZ大鼠的认知缺陷，同时减轻硝基氧化应激和细胞因子释放。SLNs将芝麻酚递送至脑内的有效性表现为对氧化应激参数的显著更好的缓解。我们的研究结果表明，将芝麻酚载入SLNs是减轻ICV-STZ诱导的神经元功能障碍和记忆缺陷的有效策略。
