Assessment of symptomatic and neuroprotective efficacy of Mucuna pruriens seed extract in rodent model of Parkinson's disease.
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.
Kasture
Sanjay
S
Department of Pharmacology, MGV's Pharmacy College, Nashik 422 003, India.
Pontis
Silvia
S
Pinna
Annalisa
A
Schintu
Nicoletta
N
Spina
Liliana
L
Longoni
Rosanna
R
Simola
Nicola
N
Ballero
Mauro
M
Morelli
Micaela
M
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D000704:Analysis of Variance; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology / Q000627:therapeutic use; D039481:CD11b Antigen / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007568:Jaw / Q000503:physiopathology; D007980:Levodopa / Q000627:therapeutic use; D008124:Locomotion / Q000187:drug effects / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009068:Movement / Q000187:drug effects; D031299:Mucuna / Q000737:chemistry*; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D016627:Oxidopamine / Q000633:toxicity; D010277:Parasympathomimetics / Q000009:adverse effects; D010300:Parkinson Disease / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D008517:Phytotherapy / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012639:Seeds / Q000737:chemistry; D013565:Sympatholytics / Q000633:toxicity; D013619:Tacrine / Q000009:adverse effects; D013997:Time Factors; D014738:Vibrissae / Q000502:physiology
D000978:Antiparkinson Agents; D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D018696:Neuroprotective Agents; D010277:Parasympathomimetics; D013565:Sympatholytics; D007980:Levodopa; D013619:Tacrine; D016627:Oxidopamine; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine