Neurotherapeutics Lab, Department of Pharmaceutics, Indian Institute of Technology (Banaras Hindu University), Varanasi 221 005, U.P., India.
Amity Institute of Biotechnology, Amity University, Lucknow 226010, India.
Pharmacol Biochem Behav. 2014 Feb;117:92-103. doi: 10.1016/j.pbb.2013.12.008. Epub 2013 Dec 15.
Silymarin commonly known for its hepatoprotective effect is reported to show protection against 6-hydroxydopamine-induced neurotoxicity. Silibinin forms the major active constituent of silymarin. Therefore, the neuroprotective effect of silibinin (50, 100 and 200 mg/kg) was evaluated in the unilaterally injected 1-methyl-4-phenylpyridinium (MPP(+))-induced dopaminergic neurotoxicity in male rats. A battery of tests such as elevated plus maze (EPM), narrow beam walk, open field, bar catalepsy, grip strength, and foot print analysis was performed to evaluate the behavioral symptoms of striatal dopaminergic toxicity. Furthermore, the mechanism of action of silibinin was investigated by evaluating the mitochondrial complex enzyme activities, mitochondrial integrity and oxidative status. Striatal caspase-3 and NFκB were expressed to evaluate the effect of silibinin on apoptosis and inflammation respectively. Silibinin (100 and 200 mg/kg) protected against MPP(+)-induced dopamine depletion in striatum. Silibinin reversed MPP(+)-induced decrease in transfer latency indicating memory consolidation in the EPM test. Silibinin (100 and 200 mg/kg) attenuated MPP(+)-induced motor deficits, such as fine motor movements and gait. MPP(+)-induced mitochondrial dysfunction, loss of integrity and oxidative stress were attenuated by silibinin. Silibinin decreased striatal caspase-3 and NFκB expression indicating potential anti-apoptotic and anti-inflammatory effects respectively. Hence, silibinin exhibited neuroprotective effect in the MPP(+) induced striatal toxicity augmenting dopamine levels. The mechanism of action may be linked to maintenance of mitochondrial bioenergetics and integrity apart from anti-apoptotic and anti-inflammatory activities.
水飞蓟素以其护肝作用而闻名，据报道，它具有对抗 6-羟多巴胺诱导的神经毒性的保护作用。水飞蓟宾是水飞蓟素的主要活性成分。因此，评估了水飞蓟宾（50、100 和 200mg/kg）对雄性大鼠单侧注射 1-甲基-4-苯基吡啶（MPP(+））诱导的多巴胺能神经毒性的神经保护作用。进行了一系列测试，如高架十字迷宫（EPM）、狭窄光束行走、开阔场、巴氯芬、握力和足迹分析，以评估纹状体多巴胺毒性的行为症状。此外，通过评估线粒体复合物酶活性、线粒体完整性和氧化状态来研究水飞蓟宾的作用机制。还表达了纹状体 caspase-3 和 NFκB，以评估水飞蓟宾对细胞凋亡和炎症的影响。水飞蓟宾（100 和 200mg/kg）可预防 MPP(+）诱导的纹状体多巴胺耗竭。水飞蓟宾逆转了 MPP(+）诱导的转移动作潜伏期降低，表明 EPM 测试中的记忆巩固。水飞蓟宾（100 和 200mg/kg）减轻了 MPP(+）诱导的运动缺陷，如精细运动和步态。水飞蓟宾减轻了 MPP(+）诱导的线粒体功能障碍、完整性丧失和氧化应激。水飞蓟宾降低了纹状体 caspase-3 和 NFκB 的表达，表明其具有潜在的抗细胞凋亡和抗炎作用。因此，水飞蓟宾在 MPP(+)诱导的纹状体毒性中表现出神经保护作用，增加了多巴胺水平。其作用机制可能与维持线粒体生物能学和完整性有关，除了具有抗细胞凋亡和抗炎作用。
