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评估黎豆种子提取物在帕金森病啮齿动物模型中的症状和神经保护功效。

Assessment of symptomatic and neuroprotective efficacy of Mucuna pruriens seed extract in rodent model of Parkinson's disease.

机构信息

Department of Pharmacology, MGV's Pharmacy College, Nashik 422 003, India.

出版信息

Neurotox Res. 2009 Feb;15(2):111-22. doi: 10.1007/s12640-009-9011-7. Epub 2009 Feb 20.

Abstract

Mucuna pruriens (MP) has long been used in Indian traditional medicine as support in the treatment of Parkinson's disease. However, no systematic preclinical studies that aimed at evaluating the efficacy of this substance are available to date. This study undertook an extensive evaluation of the antiparkinsonian effects of an extract of MP seeds known to contain, among other components, 12.5% L: -dihydroxyphenylalanine (L: -DOPA), as compared to equivalent doses of L: -DOPA. Moreover, the neuroprotective efficacy of MP and its potential rewarding effects were evaluated. The results obtained reveal how an acute administration of MP extract at a dose of 16 mg/kg (containing 2 mg/kg of L: -DOPA) consistently antagonized the deficit in latency of step initiation and adjusting step induced by a unilateral 6-hydroxydopamine lesion, whereas L: -DOPA was equally effective only at the doses of 6 mg/kg. At the same dosage, MP significantly improved the placement of the forelimb in vibrissae-evoked forelimb placing, suggesting a significant antagonistic activity on both motor and sensory-motor deficits. The effects of MP extract were moreover investigated by means of the turning behavior test and in the induction of abnormal involuntary movements (AIMs) after either acute or subchronic administration. MP extract acutely induced a significantly higher contralateral turning behavior than L: -DOPA (6 mg/kg) when administered at a dose of 48 mg/kg containing 6 mg/kg of L: -DOPA. On subchronic administration, both MP extract (48 mg/kg) and L: -DOPA (6 mg/kg) induced sensitization of contralateral turning behavior; however, L: -DOPA alone induced a concomitant sensitization in AIMs suggesting that the dyskinetic potential of MP is lower than that of L: -DOPA. MP (48 mg/kg) was also effective in antagonizing tremulous jaw movements induced by tacrine, a validated test reproducing parkinsonian tremor. Furthermore, MP induced no compartment preference in the place preference test, indicating the lack of components characterized by rewarding effects in the extract. Finally, in a subchronic mice model of 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine hydrochloride (MPTP)-induced dopamine neuron degeneration, MP extract did not prove capable of preventing either tyrosine hydroxylase decrease induced by MPTP or astroglial or microglial activation as assessed by means of GFAP and CD11b immunohistochemistry, supporting the absence of neuroprotective effects by MP. Characterization MP extract strongly supports its antiparkinsonian activity.

摘要

黎豆(MP)长期以来一直被用于印度传统医学中,作为治疗帕金森病的辅助药物。然而,目前尚无针对该物质疗效的系统临床前研究。本研究对一种已知含有 12.5%L-二羟基苯丙氨酸(L-DOPA)的 MP 种子提取物进行了广泛的抗帕金森作用评估,与等效剂量的 L-DOPA 进行了比较。此外,还评估了 MP 的神经保护作用及其潜在的奖赏作用。研究结果表明,急性给予 MP 提取物 16mg/kg(含 2mg/kg 的 L-DOPA)剂量可一致拮抗单侧 6-羟多巴胺损伤引起的起始潜伏期和调整步长缺陷,而 L-DOPA 仅在 6mg/kg 剂量时才具有同等疗效。在相同剂量下,MP 显著改善了触须诱发的前肢放置中前肢的放置,表明其对运动和感觉运动缺陷均具有显著的拮抗作用。通过旋转行为测试和急性或亚慢性给药后异常不自主运动(AIMs)的诱导,进一步研究了 MP 提取物的作用。当给予包含 6mg/kg 的 L-DOPA 的 48mg/kg 剂量时,MP 提取物比 L-DOPA(6mg/kg)急性诱导出显著更高的对侧旋转行为。在亚慢性给药时,MP 提取物(48mg/kg)和 L-DOPA(6mg/kg)均诱导了对侧旋转行为的敏化;然而,仅 L-DOPA 诱导了 AIMs 的伴随敏化,表明 MP 的运动障碍潜力低于 L-DOPA。MP(48mg/kg)还能有效拮抗他克林诱导的震颤下巴运动,他克林是一种验证性测试,可再现帕金森震颤。此外,MP 在位置偏好测试中没有引起隔间偏好,表明提取物中没有具有奖赏作用的成分。最后,在 1-甲基-4-苯基-1,2,3,6-四氢吡啶盐酸盐(MPTP)诱导的多巴胺神经元变性的亚慢性小鼠模型中,MP 提取物不能预防 MPTP 诱导的酪氨酸羟化酶减少或 GFAP 和 CD11b 免疫组化评估的星形胶质细胞或小胶质细胞激活,这支持了 MP 缺乏神经保护作用。MP 提取物的特性强烈支持其抗帕金森作用。

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