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.
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http://dx.doi.org/10.1016/j.parkreldis.2010.04.015 | DOI Listing |
Int J Pharm
December 2024
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, Palestine.
Aim: This study focuses on the design and investigation a transethosomal formulation for enhanced topical delivery and improved analgesic activity of caryophyllene oxide. In addition, this work explores new potential mechanisms of analgesic activity of the active compound including alpha-amino-3-hydroxy-5-methyl-4-isooxazole-propionic acid (AMPA) and Cyclooxygenase 2 (COX-2).
Methods: The transethosomal system containing various caryophyllene concentrations was prepared.
Int J Biol Sci
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Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
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View Article and Find Full Text PDFAnn Med
December 2024
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Sensors (Basel)
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Department of Mechanical and Industrial Engineering (DIMI), University of Brescia, Via Branze 38, 25123 Brescia, Italy.
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