Division of Pharmacology, Central Drug Research Institute, CSIR, Lucknow, UP, India.
Behav Brain Res. 2011 Aug 1;221(1):207-15. doi: 10.1016/j.bbr.2011.02.041. Epub 2011 Mar 4.
Recently, silibinin, a clinically used hepatoprotectant, has been reported to prevent amyloid beta induced memory impairment by reducing oxidative stress and inflammation in mice brain. However, the exact mechanism of neuroprotective effect of silibinin has not been properly studied especially in context of brain energy metabolism and cholinergic functions, the essential factors that undergo impairment in Alzheimer's disease. Therefore, the present study investigated the effect of silibinin on impairment in memory, brain energy metabolism and cholinergic function following intracerebral (IC) streptozotocin (STZ) administration in mice. STZ (0.5mg/kg), administered twice at an interval of 48h, caused significant memory impairment tested by Morris water maze. Further, STZ significantly decreased ATP and increased synaptosomal calcium level in mice brain. Increased oxidative and nitrosative stress was also observed in IC STZ injected mice brain. STZ IC induced memory impairment is associated with increased activity and mRNA expression of acetylcholinesterase (AChE) and decreased α-7 nicotinic acetylcholine receptor (α-7-nAChR) mRNA expression in mice brain. Pretreatment with silibinin (100 and 200mg/kg, po) attenuated STZ induced memory impairment by reducing oxidative and nitrosative stress and synaptosomal calcium ion level. Further, silibinin dose dependently restored ATP level indicating improvement in brain energy metabolism. The activity and mRNA expression of AChE was restored by silibinin. Moreover, α-7-nAChR mRNA expression was significantly increased by silibinin in STZ treated mice brain. The present study clearly demonstrates that beneficial effects of silibinin in STZ induced memory impairment in mice is due to improvement in brain energy metabolism and cholinergic function.
最近，临床使用的肝保护剂水飞蓟素被报道可通过降低小鼠大脑中的氧化应激和炎症来预防淀粉样β诱导的记忆障碍。然而，水飞蓟素的神经保护作用的确切机制尚未得到适当研究，特别是在阿尔茨海默病中发生损伤的脑能量代谢和胆碱能功能方面。因此，本研究探讨了水飞蓟素对脑内（IC）链脲佐菌素（STZ）给药后小鼠记忆损伤、脑能量代谢和胆碱能功能的影响。两次间隔 48 小时给予 STZ（0.5mg/kg）可导致 Morris 水迷宫测试中出现明显的记忆损伤。此外，STZ 还显著降低了小鼠大脑中的 ATP 并增加了突触体钙水平。还观察到 IC STZ 注射小鼠大脑中的氧化和硝化应激增加。IC STZ 诱导的记忆损伤与小鼠大脑中乙酰胆碱酯酶（AChE）的活性和 mRNA 表达增加以及α-7 烟碱型乙酰胆碱受体（α-7-nAChR）mRNA 表达降低有关。水飞蓟素（100 和 200mg/kg，po）预处理可通过降低氧化和硝化应激以及突触体钙离子水平来减轻 STZ 诱导的记忆损伤。此外，水飞蓟素剂量依赖性地恢复了 ATP 水平，表明脑能量代谢得到改善。AChE 的活性和 mRNA 表达通过水飞蓟素得到恢复。此外，水飞蓟素可显著增加 STZ 处理小鼠大脑中的α-7-nAChR mRNA 表达。本研究清楚地表明，水飞蓟素在 STZ 诱导的小鼠记忆损伤中的有益作用是由于改善了脑能量代谢和胆碱能功能。
