PHYTOTHERAPY RESEARCH

Phytother. Res. 18, 706–712 (2004)

706 Published online in Wiley InterScience (www.interscience.wiley.com).
B. V. MANYAM ET AL. DOI: 10.1002/ptr.1514

Neuroprotective Effects of the Antiparkinson

Drug Mucuna pruriens

Bala V. Manyam1*, Muralikrishnan Dhanasekaran1 and Theodore A. Hare2

1
Department of Neurology, Scott & White Memorial Hospital and Clinic; Scott, Sherwood and Brindley Foundation; and the
Texas A&M University System, Health Science Center College of Medicine, Temple, TX, USA
2
Department of Chemistry and Biochemistry, Messiah College, Grantham, PA, USA

Mucuna pruriens possesses significantly higher antiparkinson activity compared with levodopa in the 6-
hydroxydopamine (6-OHDA) lesioned rat model of Parkinson’s disease. The present study evaluated the
neurorestorative effect of Mucuna pruriens cotyledon powder on the nigrostriatal tract of 6-OHDA lesioned
rats. Mucuna pruriens cotyledon powder significantly increased the brain mitochondrial complex-I activity but
did not affect the total monoamine oxidase activity (in vitro). Unlike synthetic levodopa treatment, Mucuna
pruriens cotyledon powder treatment significantly restored the endogenous levodopa, dopamine, norepinephrine
and serotonin content in the substantia nigra. Nicotine adenine dinucleotide (NADH) and coenzyme Q-10,
that are shown to have a therapeutic benefit in Parkinson’s disease, were present in the Mucuna pruriens
cotyledon powder. Earlier studies showed that Mucuna pruriens treatment controls the symptoms of Parkinson’s
disease. This additional finding of a neurorestorative benefit by Mucuna pruriens cotyledon powder on the
degenerating dopaminergic neurons in the substantia nigra may be due to increased complex-I activity and the
presence of NADH and coenzyme Q-10. Copyright © 2004 John Wiley & Sons, Ltd.

Keywords: Mucuna pruriens; Parkinson’s disease; complex-I activity; neuroprotection; nigrostriatal tract; 6-hydroxydopamine;
NADH and coenzyme Q-10.

tion following 6-hydroxydopamine (Beal, 1998). Vari-

INTRODUCTION
Parkinson’s disease is a degenerative neurological dis-
order that is prevalent throughout the world. The very
first description and treatment of Parkinson disease
was found in Ayurveda, the ancient Indian medical
system under the name Kampavata (Manyam, 1990).
Numerous factors including reactive oxygen species
induced damage, excitotoxicity, mitochondrial dysfunc-
tion and inflammation-mediated cell injury are consid-
ered in the etiology of this disorder (Reiss and Kruger,
1999). Neuronal toxins such as 6-hydroxydopamine
(Ungerstedt and Arbuthnott, 1970), 1-methyl-4-phenyl-
1, 2,3,6-tetrahydropyridine (Langston et al., 1984) and
rotenone (Jenner, 2001) can induce Parkinsonism in
animals.
6-Hydroxydopamine-induced neurotoxicity is medi-
ated by its ability to inhibit complex-I, leading to the
mitochondrial energy crisis of adenosine triphosphate
(ATP) depletion and generation of reactive oxygen
species. 6-Hydroxydopamine also inhibits tyrosine
hydroxylase, which is the rate-limiting enzyme for
dopamine synthesis (Perese et al., 1989). N-methyl-d-
aspartate mediated toxicity and calcium accumulation
are also involved in dopaminergic neurodegenera-
* Correspondence to: Dr B. V. Manyam, Department of Neurology, Scott
& White Clinic/Texas A&M University, 2401 South 31st Street, Temple,
Texas, 76508 USA.
E-mail: bmanyam@swmail.sw.org
Contract/grant sponsor: National Institutes of Health Office of Alter-
native Medicine; Contract/grant number: RFA 00-93-002.
Contract/grant sponsor: Helen Vosburg McCrillus Plummer and Robert
Edward Lee Plummer, Jr. Endowed Fund.
Copyright © 2004 John Wiley & Sons, Ltd.
Copyright © 2004 John Wiley & Sons, Ltd.
ous neurotoxic mechanisms are implicated in
6-hydroxydopamine-induced neuronal impairment
resulting in the development of a valid model for
Parkinson’s disease to test various drugs and formula-
tions for its antiparkinson activity (Kaakkola and
Teravainen, 1990).
The major drug in the treatment of Parkinson’s
disease is levodopa, the physiological amino acid pre-
cursor of dopamine. Levodopa has been reported to
be neurotoxic in vitro (Basma et al., 1995) and impairs
the survival of metabolically stressed neurons in vivo
(Naudin et al., 1995). Levodopa dose-dependently
increased hydroxyl radical formation leading to the
inhibition of mitochondrial complex-I activity (Smith
et al., 1994). There is evidence that levodopa treatment
is not toxic (Murer et al., 1998). Mucuna pruriens
seeds contain a small amount of levodopa in addition
to other unknown compounds and have been used in
the treatment of Parkinson’s disease patients in
Ayurvedic medicine (Manyam, 1990).
A distinctive approach for the treatment of Parkinson
disease was the reduced form of nicotinamide aden-
ine dinucleotide (NADH) to increase mitochondrial
complex-I activity and endogenous dopamine syn-
thesis, since NADH indirectly supplies reducing
equivalents to the rate-limiting tyrosine hydroxylase-
catalysed step of dopamine synthesis (Birkmayer and
Birkmayer, 1989). The primary role of NADH is in
the electron transport chain to synthesize the high-
energy molecule, ATP. In earlier studies with the raw
powder obtained from Mucuna pruriens, increased
dopamine synthesis was shown (Manyam et al., in press).
Coenzyme Q-n (ubiquinone, 2-methyl-5, 6-dimethoxy-1,
Received
Phytother. 23706–712
Res. 18, February(2004)
2004
Accepted 21 April 2004
 MUCUNA PRURIENS ON 6-OHDA NEUROTOXICITY
4-benzoquinone) is a biologically occurring fat-soluble
quinone and is vital to the optimal functioning of an
organism. Coenzyme Q-10 primarily helps to transfer
electrons between redox components of the electron
transport chain to form a proton gradient across
the inner mitochondrial membrane to synthesize ATP.
Numerous studies have confirmed that patients with
Parkinson’s disease have reduced complex-I activity in
the brain and platelets. Platelet mitochondria from
parkinsonian patients were found to have lower levels
of coenzyme Q-10 than mitochondria from age/sex-
matched controls (Gotz et al., 2000). Coenzyme Q-10
is also known as ubiquinone due to its ubiquitous pres-
ence. This study investigated the presence of NADH
and coenzyme Q-10 in Mucuna pruriens cotyledon
powder.
Mucuna pruriens belongs to the family Leguminosae
and is a twiner with trifoliate leaves, purple flowers and
pods covered with hairs. Seeds from Mucuna pruriens
(Atmagupta) have been described as a useful therapeu-
tic agent in various diseases of the human nervous and
reproductive system including Parkinson’s disease in
the ancient Indian medical system, Ayurveda. The pres-
ence of a small amount of levodopa in Mucuna pruriens
seeds is known, however, the amount of Mucuna
pruriens seed preparation used by the Ayurvedic phy-
sicians was much too small to account for the improve-
ment of Parkinson’s disease symptoms in the patients.
Mucuna pruriens seeds, in addition to levodopa,
contain several known compounds. However, none
of the compounds have proven antiparkinson activity.
The details are discussed elsewhere (Manyam et al., in
press). Mucuna pruriens showed significantly higher
antiparkinson activity compared with levodopa in the
6-hydroxydopamine lesioned rat model of Parkinson’s
disease (Hussain and Manyam, 1997). Mucuna pruriens
has proven to be effective in the treatment of patients
with Parkinson’s disease in modern times (HP-200 in
Parkinson’s Disease Study Group, 1995). The present
study examines the neuroprotective effects of Mucuna
pruriens cotyledon powder on 6-hydroxydopamine-
induced neurotoxicity in the rat brain.
MATERIALS AND METHODS
Animals. Male Sprague-Dawley rats were purchased
from Harlan Sprague-Dawley (Indianapolis, IN). The
weight of the animals at the start of the study was in
the range of 200–225 g and the animals were housed
two per cage, at 25° ± 2 °C and humidity was main-
tained at 55%. Water was available ad libitum and
12 h day/night cycles were maintained. All the animal
procedures were conducted in compliance with the
United States National Institutes of Health Guide for the
Care and Use of Laboratory Animals after obtaining
approval from the Institutional Animal Experimenta-
tion Committee.
6-Hydroxydopamine lesioning. 6-Hydroxydopamine was
injected into the right hemisphere following anesthesia
using a stereotaxic frame (David Kopf Instruments,
Tujunga, CA) in the established manner (Perese et al.,
1989). The incision site was cleaned with Betadine
solution and closed with wound clips.
Copyright © 2004 John Wiley & Sons, Ltd.
707
Validation of the Parkinson’s disease model. The
efficacy of 6-hydroxydopamine lesions was tested
with amphetamine 1 week after surgery at a dose of
2.5 mg/kg. i.p. and 5 mg/kg i.p., and during weeks 2–4
using an automated rotometer for rotational behavior
(Ungerstedt and Arbuthnott, 1970). Following admin-
istration of amphetamine, the rats were placed in trans-
lucent plastic buckets and allowed to rotate. With the
destruction of nigrostriatal dopaminergic neurons
on the right side, amphetamine induces the animals
to turn ipsilaterally. The number of complete rota-
tions, ipsilateral and contralateral to the side of 6-
hydroxydopamine lesions was recorded. Rats having
more than seven ipsilateral rotations per minute were
considered to be valid animal models of Parkinson’s
disease.
Mucuna pruriens cotyledon powder treatment. Mucuna
pruriens cotyledon powder was prepared in a single
batch from the same harvest of organically cultivated
plant material (free of foreign material), uniformly
mixed to maintain consistency of active compounds
required and shipped to our location. Validated 6-
hydroxydopamine treated rats were randomized to five
groups (n = 6, each group). Mucuna pruriens cotyledon
powder at 2.5 or 5.0 g/kg/day dose or synthetic levodopa
125 or 250 mg/kg body wt/day were blended with
powdered rat chow and administered orally ad libitum
for 4 weeks prior to necropsy. The dose of levodopa
was kept constant whether in the ‘synthetic’ or the
‘natural’ form, as the Mucuna pruriens cotyledon
powder at a dose of 2.5 g contained 125 mg of levodopa
and the 5.0 g dose contained 250 mg of levodopa
(Mahajani et al., 1996). The control group received
no drug and was fed only powdered rat chow (Purina
Mills, Inc.). The mean body weight and the mean
feed intake were used to calculate the amount of drugs
for each group of animals. Brains were removed and
immediately frozen following 4 weeks of treatment.
They were stored at −70 °C until analysis.
Neurochemical determinations. The frozen brain
sections were thawed and further sectioned to obtain
striatum and substantia nigra. Each of the above
tissues (0.1–0.3 g net weight) was homogenized in
0.1 N perchloric acid (105 µL). After centrifugation, the
clear supernatant (25–75 µL) was processed for further
analysis. The HPLC-electrochemical detector method
was used for all estimations of neurotransmitters and
its metabolites. The system consisted of a Coulochem
electrode Array ESA460 HPLC with auto-sampler
equipped with Neslab refrigerated circulating water bath
to control temperature below 4 °C during the automated
run. The gradient elution was performed using two ESA
420 dual piston HPLC pumps and Kontron M800 gra-
dient mixer. The C18 (Octadecyl silica) column 3 µm,
8 cm × 4.6 mm (i.d.) was used for the separation of the
monoaminergic neurotransmitters and its metabolites.
Preparation of mitochondrial (P2) fraction. Mito-
chondrial (P2) fraction was obtained by homogenizing
the whole rat brain, with a glass-teflon homogenizer
in 0.32 m sucrose in cold 10 mm potassium phosphate
buffer (pH 7.2). The homogenate was centrifuged at
1000 × g for 10 min at 4 °C using a Sorvall centrifuge.
The supernatant was again centrifuged at 10 000 × g for
Phytother. Res. 18, 706–712 (2004)
708 B. V. MANYAM ET AL.
30 min. The pellets were resuspended in cold 50 mm
Tris buffer and were centrifuged at 10 000 × g for 30 min.
This step was repeated once more. The pellets thus
obtained were resuspended in cold 10 mm potassium
phosphate buffer (pH 7.2) and kept overnight at −20 °C.
Prior to analysis, the suspension was sonicated at low
energy until the pellets were uniformly dispersed. This
suspension was used to evaluate the effect of Mucuna
pruriens cotyledon powder on total monoamine oxidase
activity and complex-I activity. Different doses of
Mucuna pruriens cotyledon powder were incubated with
the mitochondrial (P2) fraction for 1 h to evaluate the
effect on total monoamine oxidase and complex-I
activity.
Total mitochondrial monoamine oxidase activity. 4-
Hydroxy-quinoline formed by the oxidation of
kynuramine was measured fluorimetrically and the
monoamine oxidase activity was expressed as 4-hydroxy-
quinoline formed/h/mg protein (Morinan and Garratt,
1985).
Mitochondrial complex-I activity. Mitochondrial
complex-I activity (NADH dehydrogenase activity)
was based on the NADH oxidation. The oxidation of
NADH was measured spectrophotometrically at 340 nm
(Ramsay et al., 1986). Complex-I activity was expressed
as NADH oxidized/mg protein.
Quantification of coenzyme Q-10 in Mucuna pruriens.
Mucuna pruriens cotyledon powder was sonicated in
ethanol (10% w/v) and mixed with hexane (2:5 ethanol:
hexane v/v). The above mixture was shaken for 10 min
in the dark. The hexane layer was removed by centrifu-
gation and evaporated using a Meyer N-EVAP analyti-
cal evaporator. It was then redissolved in the mobile
phase (methanol 75% and hexane 25%). Coenzyme Q-
10 was separated on a C-18 Hypersil-ODS silica based
column. Hypersil ODS phases are based on completely
porous spherical silica particles with a pore size of 120Å.
The column length was 125 mm, and the diameter was
3 mm. Coenzyme Q-10 was quantified using a flow rate
of 0.3 mL/min and UV-detection at 275 nm (Rousseau
and Varin, 1988). A standard curve was obtained for
coenzyme Q-10 and the amount of coenzyme Q-10
present in Mucuna pruriens cotyledon powder was quan-
tified using the standard curve.
Figure 1. 6-ODHA caused significant levodopa depletion in the nigrostriatal tract (* p < 0.05, compared with the control). Mucuna
pruriens cotyledon powder (5.0 g/kg) significantly restored the levodopa in the nigrostriatal tract (a p < 0.05, compared with the 6-
OHDA-treated group). Values represent levodopa pmole/mg protein, mean ± SEM, n = 6.
Copyright © 2004 John Wiley & Sons, Ltd.
Quantification of NADH in Mucuna pruriens. NADH
content was measured colorimetrically using the method
of Stern et al. (2002). The reaction mixture for the
assay consisted of Tris-HCl pH 8.2, alcohol
dehydrogenase, phenazineethosulfate, ethanol and 3-
(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bro-
mide. The change in absorbance after 10 min of
incubation was noted at 570 nm. A standard curve was
obtained using NADH and the amount of NADH
present in Mucuna pruriens cotyledon powder was quan-
tified using the standard curve.
Protein estimation. Protein was assayed using the
Coomassie plus protein assay reagent kit (Pierce,
Rockford, IL). Bovine serum albumin (BSA) was used
as the standard for protein measurement.
Statistical analysis. Sigma stat. (2.03) one way ANOVA
was used for finding significant differences between two
means. Values of p less than or equal to 0.05 were
considered significant.
RESULTS
Mucuna pruriens cotyledon powder treatment did not
produce any behavioral abnormalities or significant
difference in weight of the animals compared with
the control group.
Effect of Mucuna pruriens cotyledon powder on
6-hydroxydopamine-induced levodopa depletion in
nigrostriatal tract
6-Hydroxydopamine significantly depleted levodopa in
the substantia nigra by 58% (p < 0.03) and in the
striatum by 67% (p < 0.007) (Fig. 1). Oral administra-
tion of the 5.0 g/kg Mucuna pruriens cotyledon powder
significantly restored the endogenous levodopa content
in the substantia nigra (p < 0.03) and striatum (p <
0.004) while an equivalent amount (by weight present
in Mucuna pruriens cotyledon powder) of synthetic
levodopa treatment (250 and 500 mg/kg) and a lower
dose Mucuna pruriens cotyledon powder (2.5 g/kg) did
not have any effect.
Phytother. Res. 18, 706–712 (2004)
 MUCUNA PRURIENS ON 6-OHDA NEUROTOXICITY 709

Figure 2. 6-ODHA caused significant dopamine depletion in the substantia nigra (* p < 0.05, compared with the control). Mucuna
pruriens cotyledon powder (5.0 g/kg) significantly restored the dopamine in the substantia nigra (a p < 0.05, compared with the
6-OHDA-treated group). Values represent dopamine pmole/mg protein, mean ± SEM, n = 6.

Figure 3. 6-ODHA caused significant norepinephrine depletion in the nigrostriatal tract (* p < 0.05, compared with the control).
Mucuna pruriens cotyledon powder (2.5 and 5.0 g/kg) and levodopa (500 mg/kg) significantly restored the norepinephrine content
(a p < 0.05, compared with the 6-OHDA-treated group). Values represent norepinephrine pmole/mg protein, mean ± SEM, n = 6.

Table 1. Mucuna pruriens cotyledon powder (2.5 and 5.0 g/kg) and levodopa (250 and 500 mg/kg) significantly restored the DOPAC
content in substantia nigra following 6-OHDA induced DOPAC depletion

Levodopa Levodopa MPCP MPCP

Control 6-OHDA (250 mg/kg) (500 mg/kg) (2.5 g/kg) (5.0 g/kg)

Substantia nigra 14.49 ± 2.38 3.66 ± 1.37a 15.01 ± 3.21b 13.22 ± 2.13b 7.34 ± 1.49b 12.16 ± 2.23b
Nucleus caudatus putamen 26.08 ± 2.08 14.33 ± 1.41a 9.98 ± 1.41a 11.63 ± 3.13a 13.05 ± 2.67a 7.95 ± 2.41a

DOPAC pmole/mg protein; mean ± SEM; n = 6; a p < 0.05, compared with the control; b
p < 0.05, compared with the 6-OHDA-treated
group.

Effect of Mucuna pruriens cotyledon powder on Effect of Mucuna pruriens cotyledon powder
6-hydroxydopamine-induced dopamine and its on 6-hydroxydopamine-induced norepinephrine
metabolite (DOPAC) depletion in nigrostriatal tract depletion in nigrostriatal tract

Dopamine, like its precursor, was also significantly de-
pleted in the substantia nigra by 83% (p < 0.002) and
in the striatum by 75% (p < 0.001) due to treatment
with 6-hydroxydopamine (Fig. 2). Mucuna pruriens coty-
ledon powder (5.0 g/kg) treatment significantly restored
the dopamine content only in the substantia nigra (p <
0.01) and had no effect on the dopamine content in the
striatum. However, levodopa treatment did not restore
the dopamine content in both tissues analysed. 6-
Hydroxydopamine significantly (p < 0.008) reduced the
DOPAC content in the substantia nigra by 75% (Table
1). Mucuna pruriens cotyledon powder (5.0 g/kg) and
levodopa (250 and 500 mg/kg) significantly reversed
the 6-hydroxydopamine-induced toxicity. However,
both synthetic levodopa and Mucuna pruriens cotyle-
don powder administration did not effect the 6-
hydroxydopamine-induced DOPAC depletion (44%,
p < 0.01) in the striatum.
Copyright © 2004 John Wiley & Sons, Ltd.
6-Hydroxydopamine significantly depleted norepine-
phrine in the substantia nigra by 60% (p < 0.03) and
in the striatum by 65% ( p < 0.04) (Fig. 3). Mucuna
pruriens cotyledon powder significantly restored the
norepinephrine content in the nigrostriatal tract at both
doses of 2.5 g/kg (p < 0.01) and 5.0 g/kg (p < 0.07)
while synthetic levodopa restored the norepinephrine
content at a dose of 500 mg/kg (p < 0.02) in the striatum
only.
Effect of Mucuna pruriens cotyledon powder on 6-
hydroxydopamine-induced serotonin depletion in the
substantia nigra
The mean ± SEM serotonin level in the substantia nigra
was 35.11 ± 4.53 pmol/mg protein in the control animals.
6-OHDA lesioning reduced the levels to 11.33 ±
Phytother. Res. 18, 706–712 (2004)
710 B. V. MANYAM ET AL.
Figure 4. Mucuna pruriens cotyledon powder (1 mg) increased the mitochondrial complex-I activity (* p < 0.05, compared with the
control). Values represent ng of NADH oxidized/min/mg protein, mean ± SEM, n = 6.
2.43 pmol/mg protein. This was significant at p < 0.05
by t-test. Synthetic levodopa treatment at 250 mg/kg
resulted in a substantia nigra serotonin level of 14.32 ±
0.9 pmol/mg protein and a dose of 500 mg/kg resulted
in a level of 16.69 ± 3.99 pmol/mg protein. Both were
not significant. Mucuna pruriens cotyledon powder treat-
ment at a dose of 2.5 g/kg resulted in a level of 18.29 ±
2.7 pmol/mg protein and a dose of 5.0 g/kg resulted
in a level of 23.31 ± 2.32 pmol/mg protein. This was
significant at the p < 0.05 level compared with the 6-
OHDA-treated group showing that Mucuna pruriens
cotyledon powder significantly restored the serotonin
content in the dopaminergic cell body of the nigrostriatal
tract following 6-ODHA induced serotonin depletion.
Effect of Mucuna pruriens cotyledon powder on
mitochondrial complex-I and monoamine oxidase
activity
Mucuna pruriens cotyledon powder dose-dependently
increased the rat brain mitochondrial complex-I activ-
ity (p < 0.05) (Fig. 4) and had no effect on the total
monoamine oxidase activity.
Estimation of coenzyme Q-10 and NADH in Mucuna
pruriens cotyledon powder
NADH and coenzyme Q-10 have been used in the
therapeutic treatment of Parkinson’s disease due to their
capacity to enhance mitochondrial respiration and anti-
oxidant ability. NADH and coenzyme Q-10 were
present in significant amounts in Mucuna pruriens coty-
ledon powder. The amount of NADH quantified was
1.41 ± 0.14 µg/mg powder. The amount of coenzyme
Q-10 quantified was 2.32 ± 0.33 ng/mg powder.
DISCUSSION
Mucuna pruriens treatment is known to increase the
dopamine content in the rat brain (Manyam et al.,
2004). Mucuna pruriens exhibited twice the anti-
parkinsonian activity compared with synthetic levodopa
suggesting that Mucuna pruriens may contain uniden-
tified antiparkinsonian compounds in addition to
levodopa, or that it may have adjuvants that enhance
the efficacy of levodopa. The present study identified
Copyright © 2004 John Wiley & Sons, Ltd.
the presence of antioxidant and mitochondrial energy
enhancing compounds such as coenzyme Q-10 and
NADH.
The medication for Parkinson’s disease has mainly
focused on alleviating motor symptoms. However, the
current major focus of research is the development
of drugs to slow the degeneration of the dying
dopaminergic neurons or their regeneration. Coenzyme
NADH has been used in an open label trial as a novel
medication in patients with Parkinson’s disease, using
a parenteral administration technique (Birkmayer
and Birkmayer, 1989). Support for using NADH in
Parkinson’s disease treatment includes claims that
NADH stimulates tyrosine hydroxylase and dopamine
biosynthesis in tissue culture and in humans. A bene-
ficial clinical effect was observed. The best results were
obtained with a dose of 25 to 50 mg every second day
by intravenous administration. Concomitantly with the
improvement in disability, urine homovanillic acid level
increased significantly, indicating a stimulation of en-
dogenous levodopa biosynthesis (Birkmayer et al., 1990).
The orally applied form of NADH also yielded an over-
all improvement and was comparable to that of the
parenterally applied form (Birkmayer et al., 1993). Most
Parkinson’s disease treatments palliate symptoms by
increasing nigrostriatal dopaminergic tone (Birkmayer
et al., 1989). This may be due to the presence of NADH.
Mucuna pruriens cotyledon powder also has a sig-
nificant amount of NADH and hence it can possibly
increase the mitochondrial complex-I activity and
dopamine synthesis benefiting Parkinson’s disease
patients.
The antioxidant and neuroprotective activity of
coenzyme Q-10 was also proved in animal models where
coenzyme Q-10 administered orally prior to treatment
with MPTP was found to protect the nigrostriatal
dopaminergic system (Beal et al., 1998). Coenzyme Q-
10 also can protect against striatal lesions produced
by both malonate and nitropropionic acid (Matthews
et al., 1998). Phase II studies of high dose synthetic
coenzyme Q-10 suggested a retardation of Parkinson’s
disease progression possibly through increased complex-
I activity (Shults et al., 1997). Mucuna pruriens cotyle-
don powder contains natural coenzyme Q-10. Despite
smaller quantities, it may have an adjuvant effect and
thus enhance the therapeutic effect of Mucuna pruriens
cotyledon powder in Parkinson’s disease.
Recombinant lentiviral vector has been used for
gene delivery of glial cell line-derived neurotrophic
factor (GDNF) to the specific regions of the brain
Phytother. Res. 18, 706–712 (2004)
 MUCUNA PRURIENS ON 6-OHDA NEUROTOXICITY
and assessed for its neuroprotective effects in 6-
hydroxydopamine lesioned rat model of Parkinson’s
disease. GDNF significantly protected the nigral
dopamine neurons against 6-hydroxydopamine lesions
(Georgievska et al., 2002). Neurotrophic factors pro-
vide selective protection for basal ganglia circuits that
are affected in nigrostriatal degenerative disorders, in-
cluding Parkinson’s disease. This raises the possibility
of alternative mechanisms for Mucuna pruriens
cotyledon powder to render neuroprotection, such as a
neurotrophic-like effect for its neurorestorative effect
against 6-hydroxydopamine-induced toxicity.
Dopamine agonists such as bromocriptine (Calne
et al., 1974) and SKF-38393 (Muralikrishnan and Ebadi,
2001) have neuroprotective properties due to their anti-
oxidant capabilities. Kavapyrone extracts from Piper
methysticum with an antiglutamatergic effect (Schmidt
and Ferger, 2001), salicylic acid (Mohanakumar et al.,
2000) and deprenyl with its hydroxyl radical scavenging
property (Muralikrishnan et al., 2003), render protec-
tion against MPTP-induced neuronal toxicity. Similarly,
Mucuna pruriens cotyledon powder, due to its anti-
oxidants and increased complex-I activity, might
have a protective effect on the 6-hydroxydopamine
damaged nigral neurons. Another possible mechanism
could be monoamine oxidase inhibition providing a
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711
neuroprotective effect. Mucuna pruriens did not have
any effect on the mitochondrial monoamine oxidase
activity, thus eliminating the possibility of monoamine
oxidase inhibition leading to neuroprotection. There is
evidence that Mucuna pruriens seeds have an anti-
oxidant effect (Tripathi and Upadhyay, 2002).
In conclusion, the present study shows that Mucuna
pruriens cotyledon powder significantly restored the
monoaminergic neurotransmitter levels in the substantia
nigra and had a better neuroprotective effect compared
with levodopa. The mechanism of Mucuna pruriens
cotyledon powder induced neuroprotection may be
mediated by increasing the mitochondrial complex-I
activity and by scavenging the free radicals. These re-
sults suggest that Mucuna pruriens cotyledon powder
in addition to a symptomatic benefit to patients with
Parkinson’s disease may also provide neuroprotection
through antioxidant activity.
Acknowledgements
We thank K. M. Parikh, B Pharm, D Sc, Zandu Pharmaceutical Works,
for Mucuna pruriens cotyledon powder; Du Pont Pharma for
carbidopa; Ghazala Hussain, PhD, Shari B Randall and Charles
Rodarte, for technical assistance, Glen Cryer and Jacqueline
Whetteckey for editorial assistance.
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