Combination Treatment of Icariin and L-DOPA Against 6-OHDA-Lesioned Dopamine Neurotoxicity.
Combination Treatment of Icariin and L-DOPA Against 6-OHDA-Lesioned Dopamine Neurotoxicity.
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淫羊藿苷和左旋多巴联合治疗 6-OHDA 损伤的多巴胺神经毒性
DOI：
10.3389/fnmol.2018.00155
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发表时间：
2018
影响因子：
4.8
通讯作者：
Zhang F
中科院分区：
文献类型：
--
作者：
Lu DS;Chen C;Zheng YX;Li DD;Wang GQ;Liu J;Shi J;Zhang F
迄今为止，多巴胺（DA）前体，L-3，4-二羟基苯丙氨酸（L-DOPA）仍然是帕金森病（PD）患者有效药物治疗的金标准。然而，长期长期服用左旋多巴会导致药效丧失和严重的不良反应，例如左旋多巴诱导的运动障碍（LID）。淫羊藿苷（伊卡）是从淫羊藿中提取的一种黄酮类化合物，已被证明对PD动物模型中DA神经元丢失具有神经保护作用。本研究观察伊卡和L-DOPA联合应用对6-羟基多巴胺（6-OHDA）引起的DA神经毒性和L-DOPA引起的运动功能障碍的影响。应用PC 12细胞研究伊卡和L-DOPA联合治疗对6-OHDA损伤的神经毒性的影响。此外，通过立体定向注射6-OHDA诱导的DA神经元损伤，观察伊卡联合L-DOPA对DA神经元的保护作用。通过异常不自主运动（AIM）评分分析确定L-DOPA引发的病理性运动。在PC 12细胞中，伊卡与L-DOPA组合比伊卡或L-DOPA单独处理对6-OHDA诱导的神经毒性产生更好的神经保护。在帕金森病6-OHDA损伤大鼠中，伊卡作为单一疗法赋予DA神经保护作用，并在每日给予L-DOPA和伊卡21天后增强L-DOPA治疗的益处。此外，伊卡改善了LID的发展，如降低的AIM评分所证明的，而不影响L-DOPA介导的功效。此外，伊卡在体内减弱6-OHDA诱导的DA神经元损失和LID发展中的神经炎症。总之，这些研究结果表明伊卡可能是一种潜在的有前途的佐剂，以提高左旋多巴的疗效和减轻左旋多巴产生的不良反应在PD。
Until now, the dopamine (DA) precursor, L-3,4-dihydroxyphenylalanine (L-DOPA), remains the gold standard effective drug therapy for Parkinson’s disease (PD) patients. Nevertheless, long-term chronic L-DOPA administration leads to the drug efficacy loss and severe adverse effects, such as L-DOPA-induced dyskinesia (LID). Icariin (ICA), a flavonoid that is extracted from Epimedium, has been proved to evoke neuroprotection against DA neuronal loss in PD animal models. Here, the present study detected the effects of ICA combined with L-DOPA on 6-hydroxydopamine (6-OHDA)-elicited DA neurotoxicity and L-DOPA-induced motor dysfunction as well. PC12 cells were applied to investigate the combination treatment of ICA and L-DOPA against 6-OHDA-lesioned neurotoxicity. In addition, rat substantia nigral stereotaxic injection of 6-OHDA-induced DA neuronal injury was performed to explore the neuroprotective effects mediated by ICA combined with L-DOPA. The pathological movement triggered by L-DOPA was determined by the abnormal involuntary movements (AIM) scores analysis. In PC12 cells, ICA combined with L-DOPA produced better neuroprotection from 6-OHDA-induced neurotoxicity than ICA or L-DOPA alone treatment. In parkinsonian 6-OHDA lesioned rats, ICA conferred DA neuroprotection as monotherapy and an enhancement benefit of L-DOPA treatment after daily administration of L-DOPA and ICA for 21 days. Moreover, ICA ameliorated the development of LID as evidenced by the lowered AIM scores without affecting L-DOPA-mediated efficacy. Furtherly, ICA attenuated neuroinflammation in 6-OHDA-induced DA neuronal loss and the development of LID in vivo. In conclusion, these findings suggest ICA might be a potential promising adjuvant to enhance L-DOPA efficacy and attenuate L-DOPA-produced adverse effects in PD.
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影响因子：
7.9
作者：
Chen, Wen-Fang;Wu, Lin;Wong, Man-Sau
通讯作者：
Wong, Man-Sau
影响因子：
4.7
作者：
Ostock CY;Hallmark J;Palumbo N;Bhide N;Conti M;George JA;Bishop C
通讯作者：
Bishop C
DOI：
10.1124/jpet.111.179416
发表时间：
2011-06-01
影响因子：
3.5
作者：
Lindenbach, David;Ostock, Corinne Y.;Bishop, Christopher
通讯作者：
Bishop, Christopher
影响因子：
4.8
作者：
Zhang, Wei;Shin, Eun-Joo;Kim, Hyoung-Chun
通讯作者：
Kim, Hyoung-Chun
影响因子：
3.4
作者：
Carta, Anna R.;Mulas, Giovanna;Del-Bel, Elaine
通讯作者：
Del-Bel, Elaine