The Antiparkinsonian and Antidyskinetic Mechanisms of Mucuna pruriens in the MPTP-Treated Nonhuman Primate

Christopher A Lieu, Kala Venkiteswaran, Timothy P Gilmour, Anand N Rao, Andrew C Petticoffer, Erin V Gilbert, Milind Deogaonkar, Bala V Manyam, Thyagarajan Subramanian, Christopher A Lieu, Kala Venkiteswaran, Timothy P Gilmour, Anand N Rao, Andrew C Petticoffer, Erin V Gilbert, Milind Deogaonkar, Bala V Manyam, Thyagarajan Subramanian

Abstract

Chronic treatment with levodopa (LD) in Parkinson's disease (PD) can cause drug induced dyskinesias. Mucuna pruriens endocarp powder (MPEP) contains several compounds including natural LD and has been reported to not cause drug-induced dyskinesias. We evaluated the effects of Mucuna pruriens to determine if its underlying mechanistic actions are exclusively due to LD. We first compared MPEP with and without carbidopa (CD), and LD+CD in hemiparkinsonian (HP) monkeys. Each treatment ameliorated parkinsonism. We then compared the neuronal firing properties of the substantia nigra reticulata (SNR) and subthalamic nucleus (STN) in HP monkeys with MPEP+CD and LD+CD to evaluate basal ganglia circuitry alterations. Both treatments decreased SNR firing rate compared to HP state. However, LD+CD treatments significantly increased SNR bursting firing patterns that were not seen with MPEP+CD treatments. No significant changes were seen in STN firing properties. We then evaluated the effects of a water extract of MPEP. Oral MPWE ameliorated parkinsonism without causing drug-induced dyskinesias. The distinctive neurophysiological findings in the basal ganglia and the ability to ameliorate parkinsonism without causing dyskinesias strongly suggest that Mucuna pruriens acts through a novel mechanism that is different from that of LD.

Figures

Figure 1
Figure 1
Comparison of mUPDRS scores in parkinsonian primates with placebo, MPEP alone, MPEP+CD, and LD+CD demonstrates significant amelioration of parkinsonism after treatments. *P < 0.05, **P < 0.01.
Figure 2
Figure 2
(a) Firing rates of SNR and STN in the HP monkey in stable HP state (baseline) and on LD+CD (Levodopa) and MPEP+CD (Mucuna) (Kruskal-Wallis P < 0.01, **P < 0.01 rank-sum using Tukey's HSD correction, compared to baseline HP state). (b) Poisson comparison of SNR and STN neurons Pre-LD (stable baseline HP state) (Fisher's 2 × 2 two-sided exact test grouping “Poisson” category together with “regular,” *P = 0.0164), Post-LD (LD treatments), and Post-MP (MPEP+CD). (c) Coefficient of variation at HP state and with treatments (Kruskal-Wallis P < 0.05, *P < 0.05 rank-sum using Tukey's HSD correction, compared to baseline HP) (d–g) Measures of firing patterns in the SNR and STN in HP state and on treatments. (h) Sample entropy of SNR and STN.
Figure 3
Figure 3
(a) A water extract of MPEP (MPWE) significantly reduces parkinsonism in the parkinsonian primate at optimal doses similar to LD+CD (*P < 0.05) (b) and does not cause dyskinesias (P = 0.045, Chi-square test).

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