Pharmacology Lab, Department of Pharmaceutical Sciences and Technology (DPST), Institute of Chemical Technology (ICT), N. P. Marg, Matunga (E), Mumbai 400019, India.
Medicinal and Natural Product Research Laboratory, Department of Pharmaceutical Sciences and Technology (DPST), Institute of Chemical Technology (ICT), N. P. Marg, Matunga (E), Mumbai 400019, India.
Cytokine. 2018 Oct;110:78-86. doi: 10.1016/j.cyto.2018.04.018. Epub 2018 Apr 26.
Lipopolysaccharide (LPS), an endotoxin from the outer membrane of Gram negative bacteria has been reported to cause neuroinflammation and learning and memory deficits. There are reports describing the beneficial effects of Imperatorin (IMP), a naturally occurring furanocoumarin in central nervous system (CNS) disorders such as anxiety and epilepsy.
In the current study, we investigated whether IMP protects against LPS mediated memory deficits and neuroinflammation.
Mice pretreated with IMP (5, 10 mg/kg po) were administered LPS (250 μg/kg ip) for 7 days. Memory was evaluated in the Morris water maze (MWM) and Y maze. The mice were euthanised and different biochemical assessments were carried out to measure oxidative stress and acetyl choline esterase (AChE). Further, evaluation of proinflammatory cytokines such as tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) levels and brain derived neurotrophic factor (BDNF) in hippocampus and cortex of brain were performed.
LPS administration caused poor memory retention in both, MWM and Y maze, and caused distinct oxidative stress since decrease in superoxide dismutase (SOD), reduced glutathione (GSH) levels and increased lipid peroxidation were observed. Also, a significant rise was observed in the levels of AChE. Moreover, a rise in TNF-α and IL-6 levels and depleted levels of BDNF were noted. IMP pretreatment reversed LPS induced behavioral and memory disturbances and significantly decreased the oxidative stress and AChE levels. It also reduced TNF-α and IL-6 levels and caused a significant upregulation of BDNF levels.
Present study highlights the potential neuroprotective role of IMP against LPS mediated cognitive impairment and neuroinflammation.
脂多糖（LPS）是革兰氏阴性细菌外膜的内毒素，已被报道可引起神经炎症和学习记忆障碍。有报道描述了天然呋喃香豆素素补骨脂素（IMP）在中枢神经系统（CNS）疾病中的有益作用，如焦虑和癫痫。
在本研究中，我们研究了 IMP 是否可以预防 LPS 介导的记忆障碍和神经炎症。
用 IMP（5、10mg/kg 口服）预处理的小鼠给予 LPS（250μg/kg 腹腔注射）7 天。使用 Morris 水迷宫（MWM）和 Y 迷宫评估记忆。处死小鼠，并进行不同的生化评估，以测量氧化应激和乙酰胆碱酯酶（AChE）。此外，还评估了海马体和大脑皮层中的促炎细胞因子，如肿瘤坏死因子（TNF-α）和白细胞介素 6（IL-6）水平以及脑源性神经营养因子（BDNF）。
LPS 给药导致 MWM 和 Y 迷宫的记忆保留能力下降，并引起明显的氧化应激，因为观察到超氧化物歧化酶（SOD）、还原型谷胱甘肽（GSH）水平降低和脂质过氧化增加。此外，AChE 水平显著升高。此外，还观察到 TNF-α和 IL-6 水平升高和 BDNF 水平降低。IMP 预处理逆转了 LPS 诱导的行为和记忆障碍，并显著降低了氧化应激和 AChE 水平。它还降低了 TNF-α和 IL-6 水平，并显著上调了 BDNF 水平。
本研究强调了 IMP 对 LPS 介导的认知障碍和神经炎症的潜在神经保护作用。
