Department of Neurology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Parkinsonism Relat Disord. 2010 Aug;16(7):458-65. doi: 10.1016/j.parkreldis.2010.04.015. Epub 2010 May 31.
Dopaminergic anti-parkinsonian medications, such as levodopa (LD) cause drug-induced dyskinesias (DID) in majority of patients with Parkinson's disease (PD). Mucuna pruriens, a legume extensively used in Ayurveda to treat PD, is reputed to provide anti-parkinsonian benefits without inducing DID. We compared the behavioral effects of chronic parenteral administration of a water extract of M. pruriens seed powder (MPE) alone without any additives, MPE combined with the peripheral dopa-decarboxylase inhibitor (DDCI) benserazide (MPE+BZ), LD+BZ and LD alone without BZ in the hemiparkinsonian rat model of PD. A battery of behavioral tests assessed by blinded investigators served as outcome measures in these randomized trials. In experiment 1, animals that received LD+BZ or MPE+BZ at high (6mg/kg) and medium (4mg/kg) equivalent doses demonstrated significant alleviation of parkinsonism, but, developed severe dose-dependent DID. LD+BZ at low doses (2mg/kg) did not provide significant alleviation of parkinsonism. In contrast, MPE+BZ at an equivalent low dose significantly ameliorated parkinsonism. In experiment 2, MPE without any additives (12mg/kg and 20mg/kg LD equivalent dose) alleviated parkinsonism with significantly less DID compared to LD+BZ or MPE+BZ. In experiment 3, MPE without additives administered chronically provided long-term anti-parkinsonian benefits without causing DID. In experiment 4, MPE alone provided significantly more behavioral benefit when compared to the equivalent dose of synthetic LD alone without BZ. In experiment 5, MPE alone reduced the severity of DID in animals initially primed with LD+BZ. These findings suggest that M. pruriens contains water-soluble ingredients that either have an intrinsic DDCI-like activity or mitigate the need for an add-on DDCI to ameliorate parkinsonism. These unique long-term anti-parkinsonian effects of a parenterally administered water extract of M. pruriens seed powder may provide a platform for future drug discoveries and novel treatment strategies in PD.
多巴胺能抗帕金森病药物，如左旋多巴（LD），会导致大多数帕金森病（PD）患者出现药物诱导的运动障碍（DID）。在阿育吠陀中广泛用于治疗 PD 的豆科植物 Mucuna pruriens 据称具有抗帕金森病的功效，而不会引起 DID。我们比较了单独给予 M. pruriens 种子粉水提取物（MPE）、MPE 与外周多巴脱羧酶抑制剂（DDCI）卡比多巴（MPE+BZ）、LD+BZ 和没有 BZ 的 LD 在 PD 半帕金森大鼠模型中的行为效应。由盲法研究者评估的一系列行为测试作为这些随机试验的结果测量。在实验 1 中，接受高（6mg/kg）和中（4mg/kg）等效剂量 LD+BZ 或 MPE+BZ 的动物表现出帕金森病的显著缓解，但出现严重的剂量依赖性 DID。低剂量（2mg/kg）的 LD+BZ 没有显著缓解帕金森病。相比之下，MPE+BZ 的低等效剂量显著改善了帕金森病。在实验 2 中，没有任何添加剂的 MPE（12mg/kg 和 20mg/kg LD 等效剂量）与 LD+BZ 或 MPE+BZ 相比，缓解帕金森病的 DID 明显减少。在实验 3 中，没有添加剂的 MPE 长期给药可提供长期的抗帕金森病作用，而不会引起 DID。在实验 4 中，与没有 BZ 的等效剂量的合成 LD 相比，单独的 MPE 提供了显著更多的行为获益。在实验 5 中，单独的 MPE 可减少最初用 LD+BZ 启动的动物 DID 的严重程度。这些发现表明，M. pruriens 含有水溶性成分，这些成分要么具有内在的 DDCI 样活性，要么减轻了对附加 DDCI 的需求，以改善帕金森病。这种经肠给予 M. pruriens 种子粉水提取物的独特的长期抗帕金森病作用可能为 PD 的未来药物发现和新的治疗策略提供平台。
