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REVIEW
Mucuna pruriens seeds in treatment of Parkinson’s disease:
pharmacological review
Sanjay Kasture &Mahalaxmi Mohan &Veena Kasture
Received: 13 December 2012 /Accepted: 30 May 2013
#Institute of Korean Medicine, Kyung Hee University 2013
Abstract Medicinal plants have been a rich source of med-
icines. Mucuna pruriens is extensively used in Ayurveda to
treat kampavat (Parkinson’s disease in modern medicine), a
disease characterized by excess of Vata. Clinical and preclin-
ical studies have substantiated claims on its efficacy and
safety in PD and there are indications that it is more effective
than the levodopa in reducing dyskinesias. Several constitu-
ents of Mucuna seeds such as genistein, gallic acid, unsatu-
rated acids, nicotine, bufotenin, harmin alkaloids, lecithin,
etc. have been isolated which possess neuroprotective activ-
ity and support the antiPD activity of levodopa. The review
describes various constituents of Mucuna pruriens seeds in
context to therapeutic utility in treating Parkinson’s disease.
Since the conventional treatment of PD using levodopa with
other add-on drugs is very expensive and Mucuna pruriens
seeds are easily available and economic, the use of standard-
ized extract of Mucuna seeds may drastically reduce the cost
of treatment and also reduce the progression of disease. The
review emphasizes the importance of holistic approach of
Ayurveda in using the Mucuna pruriens in treatment of PD.
Further studies may provide an approach to understand the
mechanisms involved in treating PD with lesser adverse
effects.
Keywords Mucuna pruriens .Genistein .Neuroprotective .
Antioxidants .Unsaturated acids
Introduction
The diseases as described and defined in Modern medicine
were in existence globally since long times and were named
differently in various civilizations. Ayurveda, considered as
the oldest ‘Science of Life’describes various diseases and its
treatment with herbs, minerals, and parts of animals. The
Ayurveda describes various neurological diseases such as
kampavat (Parkinson’s disease), apasmar (epilepsy),
Unmad (schizophrenia), smrutinash (dementia), avsaada
(depression), manas mandata (mental retardation), etc.
Kampavata, (meaning tremors caused by excess of vata), is
characterized in Ayurveda by tremors, rigidity, akinesia,
dyskinesia, loss of olfaction, uncontrollable body move-
ments, difficulty in step initiation, difficulty in maintenance
of posture, etc. Mucuna pruriens is the most commonly used
herb in treatment of Kampavat, either alone or with other
herbs.
The incidence of Parkinson’s disease (PD) is very high in
aged population and levodopa is still the gold standard in
management of PD. Prolonged use of levodopa leads to
dyskinesias, toxicity, and diminishing efficacy (Cenci
2007; Chen et al. 2008). Despite of several advancements
in drug developments, the control over progression of neu-
rological damage is inadequate. Before the introduction of
modern medicine, every civilization had its own traditional
system of medicine. Several plants, minerals, and biochem-
ical substances were used in almost every traditional system
of medicine. The diseases, as defined by the modern system
of medicine, were described along with their symptoms in
the traditional system of medicine also.
Houghton and Howes (2005) and Song et al. (2012) have
reviewed plants having neuroprotective activity in rat model
of PD. The Ayurvedic physicians treat Kampavat using seeds
of Mucuna pruriens and some other medicinal plants such as
Celastrus paniculatus,Withania somnifera and Tinospora
cordifolia, Nardostachys jatamansi, etc. depending on the
S. Kasture (*):V. Kasture
Sanjivani College of Pharmaceutical Education & Research,
Dist. Ahmednagar, Kopargaon, India
e-mail: kasturesb1@gmail.com
S. Kasture :V. Kasture
Pinnacle Biomedical Research Institute, Bhopal, India
M. Mohan
Priyadarshini College of Pharmaceutical Sciences,
Narapally, Chowdaryguda, Hyderabad 500088, India
Orient Pharm Exp Med
DOI 10.1007/s13596-013-0126-2
symptoms (personal communication). There are pharmaco-
logical studies supporting therapeutic practice of using the
above mentioned plants. Godkar et al. (2004) have shown
that Celastrus paniculata protected neurons against gluta-
mate toxicity. Shanish et al. (2010) reported amelioration of
levodopa toxicities in 1-methyl-4-phenyl-1,2,3,6-
tetrahydropyridine- (MPTP) model of PD in rats. Naidu
et al. (2003) reported that Withania somnifera, the Rasayan
and cognitive enhancer (Bhattacharya et al. 1995) inhibits
haloperidol-induced catalepsy and orofacial dyskinesia.
Ahmed et al. (2005) have shown neuroprotective effect of
W. somnifera in 6-OHDA lesioned rats. Ahmed et al. (2006)
showed attenuation of 6-OHDA induced PD in rats by
Nardostachys jatamansi.
Traditionally, Mucuna pruriens is used as carminative,
hypertensive and hypoglycemic agent. It is also used as
aphrodisiac, diuretic, rubefacient, and vermifuge; used for
asthma, cancer, cholera, cough, diarrhea, dog bite, dropsy,
dysuria, insanity, mumps, pleuritis, ringworm, snakebite,
sores, syphilis, and tumors (Kirtikar and Basu 1985).
Vaidya et al. (1978) and Nagashayana et al. (2000) carried
out clinical studies using Mucuna pruriens in patients of PD
and reported seeds to be efficient. Mahajani et al. (1996)
performed bioavailability studies using Mucuna seed formu-
lation, HP-200 and showed similarity in pharmacokinetic
profile with that of L-dopa. Observations of clinical study
carried out by Katzenschlager et al. (2004) that Mucuna seed
powder exhibited rapid onset of action and longer on time
without simultaneous increase in dyskinesias suggest that
Mucuna contains such constituents that support activity of
L-dopa.
In preclinical studies, Manyam et al. (2004)reported
increased brain mitochondrial complex- I activity by MP
seed powder. The seed powder also restored the endogenous
levodopa, serotonin, and noradrenaline in the substantia
nigra of 6-hydroxydopamine (6-OHDA)-lesioned rats. The
previous studies have shown that Mucuna pruriens extract
used in doses that contain an equivalent amount of levodopa
is better than levodopa in increasing contralateral turning and
step initiation as well as step adjustment. The extract was
also more effective in reducing abnormal involuntary move-
ments in 6-OHDA lesioned rat models of PD (Kasture et al.
2009a; Lieu et al. 2010). Lieu et al. (2012) in MPTP treated
nonhuman primates showed antiparkinsonian activity with-
out induction of dyskinesia and have suggested that Mucuna
pruriens acts through a novel mechanism that is different
from that of levodopa. The medicinal effects of plants are
due to the presence of secondary metabolites and studies
have shown synergistic actions of various metabolites
(Ulrich-Merzenich et al. 2009,2010; Wagner and Ulrich-
Merzenich 2009). Pathan et al. (2011) have reported that
methanolic extract of Mucuna pruriens seed attunated halo-
peridol induced orofacial dyskinesia in rats.
Phytochemical studies Mucuna pruriens, also known as vel-
vet bean is a climbing legume endemic in India and other
tropical countries and has been in use since 1500 BC.
Mucuna seeds are in use much before they were known to
contain levodopa (Manyam 1990; Sathiayanarayanan and
Arulmozhi 2007). Levodopa (L-dopa) was first isolated from
the seeds of M. pruriens in 1937 by Damodaran and
Ramaswamy. Sridhar and Bhat (2007)andKalidassand
Mohan (2011) extensively investigated the phytocon-
stituents of M. pruriens seeds. The seeds in addition to the
levodopa also contained protein, lipid, dietary fibre and
carbohydrates, minerals such as sodium, potassium, calcium,
magnesium, iron, zinc, copper, manganese, and phosphorus.
The seeds also contain phenolics, tannins, and phytic acid.
The fatty acids found in the seeds were palmitic acid, stearic
acid, oleic acid, linoleic acid, linolenic acid and behenic acid.
The seeds also contained niacin and ascorbic acid. The
amino acids found in seeds were glutamic acid, aspartic acid,
serine, threonine, proline, alanine, glycine, valine, cystine,
methionine, isoleucine, leucine, tyrosine, phenylalanine, ly-
sine, histidine, tryptophan, and arginine. Sridhar and Bhat
(2007) have reported a number of value-added phytochem-
icals of Mucuna seeds of medicinal importance (e.g. alkaloids,
alkylamines, arachidic acid, beta-carboline, harmine, bufotenin,
dopamine, flavones, galactose, gallic acid, genistein, glutathi-
one, hydroxygenistein, 5-hydroxytryptamine, N,N-dimethyl-
tryptamine (DMT), 5-methoxy-dimethyltriptamine (5-MeO-
DMT), 6-methoxyharman, mucunadine, mucunain, mucunine,
myristic acid, nicotine, prurienidine, prurienine, riboflavin, sa-
ponins, serotonin, stizolamine, trypsin, tryptamine, vernolic
acid. Mucunadine, prurienine and prurieninine are the addition-
al alkaloids isolated from seed extracts (Mehta and Majumdar
1994).
N,N-dimethyltryptamine (DMT) is a hallucinogenic agent
and 5-HT
2A
/
2C
agonist (Smith et al. 1998; Yritia et al. 2002).
McKenna and Towers (1984) have reported 5-MeO-DMT
has high affinity for the serotonin 5-HT
1A
receptor, and it is
4- to 10-fold more potent than N,N-dimethyltryptamine
(DMT) in humans. In mice, 5-MeO-DMT induces head-
twitch and head-weaving responses via the activation of 5-
HT
2A
and 5-HT
1A
receptors, respectively (Matsumoto et al.
1997; Tricklebank et al. 1985). Several of these second-
ary metabolites have shown useful effects in treatment of
PD. Mucuna seeds are rich source of proteins (Bressani
2002; Fig. 1).
Since several constituents are present in small quan-
tities, a systematic pharmacological evaluation is daunting.
Further, it is difficult to compute the contribution of indi-
vidual constituent in the overall activity of the extract.
There are some studies carried out on individual constitu-
ents that support the antiparkinsonian activity of Mucuna
pruriens seeds (Table 1). Other activities unrelated to PD
are outside the scope of this review.
S. Kasture et al.
Neuroprotective effects of Mucuna pruriens
The mechanisms of neuroprotection and chemical structures of
substances having neuroprotective activity are diverse.
Common mechanisms include increased levels of stress, mito-
chondrial dysfunction, inflammatory changes, iron accumula-
tion, and excitotoxicity (Seidl and Potashkin 2011). Kovacsova
et al. 2010 have shown that antioxidants, inhibition of NADPH
oxidase, production of nitric oxide, and down regulation of
nuclear factor-kappa B plays important role in the
neuroprotective effect. PD patients have reduced mitochondrial
complex I activity in the substantia nigra (Schapira et al. 1990).
Manyam et al. (2004) reported neuroprotective effects of
Mucuna pruriens seed extract in 6-hydroxydopamine lesioned
rats. They suggested that neurorestorative benefit by Mucuna
pruriens cotyledon powder on the degenerating dopaminergic
N
N
H
Genistein Nicotine
N
H
N
N
H
C
H
2
C
H
2
N
β-Carboline N,N-Dimethyl tryptamine (DMT)
N
H
C
H
2
C
H
2
N
O
CH
3
N
OH N
CH
3
CH
3
5-Methoxy DMT Bufotenine
O
O
OH
OH
OH
OH
O
NH
2
N
H
O
N
H
O
SH
O
OH
O
O
O
O
O
O
P
O
OH
OH
P
O
OH
OH
P
O
OH
OH
P O
OH
OH
P
O
OH
OH
P
O
OH
OH
Glutathione Ph
y
tic acid
Fig. 1 Chemical structures of
constituents supporting
antiparkinsoanian activity
Mucuna pruriens seeds in treatment of Parkinson’s disease
neurons in the substantia nigra may be due to increased
complex-I activity and the presence of Nicotine adenine dinu-
cleotide (NADH) and coenzyme Q-10. Kooncumchoo et al.
(2006) have also reported that coenzyme Q-10 provides
neuroprotection of dopaminergic neurons. There are several
constituents of Mucuna seeds that possess neuroprotective ac-
tivity. Such constituents are genistein (Ma et al. 2010), gallic
acid (Ban et al. 2008), unsaturated fatty acids (Wang et al. 2006),
beta-carboline (Ruscher et al. 2007), phytic acid (Miyamoto
et al. 2000;Xuetal.2011), nicotine (Akaike et al. 2010).
Genistein
Chemically, genistein is 5, 7-dihydroxy-3- (4-hydroxyphenyl)-
4H-1-benzopyran-4-one, 4′, 5, 7-trihydroxyisoflavone.
Soybean is the best available source of genistein. Inhibition of
peripheral DOPA decarboxylation is necessary to achieve better
plasma and brain levels of levodopa. This is achieved by using
levodopa with carbidopa or benserazide. An isoflavonoid from
Mucuna seeds, genistein, prevents peripheral decarboxylation
of levodopa (Umezawa et al. 1975). Azcoitia et al. (2006); Liu
et al. (2008); and Baluchnejadmojarad et al. (2009) have re-
ported neuroprotective effect of genistein in rat models of PD.
Genistein is tyrosine kinase inhibitor and negative modulator of
the action of GABA on recombinant GABA
A
receptors
(Dunne et al. 1998; Huang et al. 1999; Campbell et al. 2004).
Zeng et al. (2004) showed that genistein ameliorates β-amyloid
peptide (25–35)-induced hippocampal neuronal apoptosis. It is
proposed that genistein inhibits protein tyrosine phosphoryla-
tion and improves neuronal plasticity (Mandel et al. 2005).
Many patients of PD develop dementia in later stages of
disease. Genistein can be useful in delaying onset of dementia.
Antioxidant principles in Mucuna pruriens seeds
Free radicals play an important role in the pathophysiology
of Parkinson’s disease. There is an imbalance between oxi-
dants and antioxidants in PD. There is dysregultion of iron
metabolism in sporadic as well as familial PD. Increase in
iron leads to generation of hydroxyl radical (Jenner and
Olanow 1996). In a nuclear microscopy study He et al.
(1996) and Double et al. (1998) reported increased iron
content in the substantia nigra of 6-OHDA induced parkin-
sonian rats. In PD, an increased deposition of iron occurs in
SNpc where copper is reduced (Riederer et al. 1989; Dexter
et al. 1991; Liochev and Fridovich 1994; Foley and Riederer
2000). Iron is bound to neuromelanin within the melanin
containing dopamine neurons of SNpc (Jellinger et al. 1990).
A similar change occurs in 6-OHDA (Hall et al. 1992) and
MPTP (Temlett et al. 1994) models of PD. There is depletion
of reduced glutathione (GSH) with subsequent decrease in
removal of hydrogen peroxide generated by oxidative
Table 1 Constituents of Mucuna pruriens seeds supporting antiparkinsonian activity of levodopa
Constituents Pharmacological action/use References
Genisten Inhibits dopa decarboxylase Umezawa et al. 1975
Neuroprotective Baluchnejadmojarad et al. 2009
Tyrosine kinase inhibitor Dunne et al. 1998
Improves neuronal plasticity Mandel et al. 2005
Phytic acid Iron chelator Graf and Eaton 1990
Suppresses MPTP induced hydroxyl radical
generation
Obata 2003
Glutathione Free radical scavenger Kidd 1997
Nicotine Reduces levodopa induced dyskinesia in rat
model of PD
Quik et al. 2009; Huang et al. 2011
Bufotenine, DMT,
5MeO-DMT
5-HT
1A
agonist, reduces dyskinesia Pytliak et al. 2011; Riahi et al. 2011,
Muñoz et al. 2008
β-carboline Neuroprotective, antioxidant, MAO inhibitor
facilitates activity of DMT
Maher and Davis 1996; Ruscher et al. 2007;
Moura et al. 2007;
Stearic acid, oleic acid,
linolenic acid
Neuroprotective: Activates peroxisome
proliferator-activated
receptor-gamma (arrest PD progression)
Lauritzen et al. 2000; Wang et al. 2006;
Bousquet et al. 2008; Schintu et al. 2009
Lecithin Decreased confusion, hallucinations and nightmares Barbeau 1980
Gallic acid Neuroprotective Lu et al. 2006; Sameri et al. 2011
Coenzyme- Q10 Slows functional decline in early stage of PD Shults et al. 2002
Harmine Glutamate receptor antagonist Serrano-Dueñas et al. 2001; Kari et al. 2009
L-tyrosine, L- tryptophan,
serotonin
Neutritional value Karobath et al. 1971; Charlton and Crowell 1992;
Zeevalk et al. 2007; Hinz 2009
S. Kasture et al.
processes (Halliwell 2001). Ben-Shachar et al. (1991)
showed that desferrioxamine retards 6-OHDA induced de-
generation of nigrostriatal dopamine neurons. Ben-Shachar
et al. (1991) have showed that desferrioxamine retards 6-
OHDA induced degeneration of nigrostriatal dopamine neu-
rons. Sekar et al. (2010) have reported antioxidant activity of
Mucuna pruriens as demonstrated by increased levels of
super oxide dismutase, glutathione, catalase, and decreased
lipid peroxidation along with decreased mitochondrial
permeability.
Mucuna pruriens seeds contain phytic acid (Kalidass and
Mohan 2011). Phytic acid (myo-inositol hexakisphosphate)
is a non-toxic iron chelator and has potent antioxidant activ-
ity (Ko and Godin 1990; Graf and Eaton 1990). The chela-
tion ability of phytic acid with minerals has been suggested
to have beneficial effects toward lowering serum cholesterol
and triglycerides and suppression of iron-mediated oxidation
(Lee et al. 2005). Obata (2003) have shown that phytic acid
suppresses MPTP-induced hydroxyl radical generation in rat
striatum. Xu et al. (2011) have also reported that phytic acid
protects against 6-OHDA induced dopaminergic neuron ap-
optosis in normal and iron excess conditions in a cell culture
model. Mucuna seeds contain gallic acid, a potent antioxi-
dant. Dhanasekaran et al. (2008) have reported that Mucuna
contains principles that scavenge DPPH radicals, ABTS
radicals and reactive oxygen species and also inhibits oxida-
tion of lipids. Further, Mucuna pruriens chelates divalent
iron and is devoid of any genotoxic or mutagenic effect on
the plasmid DNA. Dhanasekaran et al. (2008) suggested that
the neuroprotective and neurorestorative effect of Mucuna
pruriens may be related to its antioxidant activity indepen-
dent of the symptomatic effect.
Glutathione
Glutathione (GSH) depletion occurs early in the Parkinson’s
disease pathogenesis (Youdim et al. 1989;Pearceetal.1997)
showed that hydrogen peroxide generated in mitochondria is
largely detoxified by GSH-dependent mechanisms. GSH def-
icit exacerbates neuronal damage by impairing mitochondrial
function. Impairment of the GSH defense system thereby
reducing elimination of hydrogen peroxide from brain, results
in secondary mitochondrial dysfunction. PD patients have
deficiency of GSH ranging from 40 % to 90 % (Jenner
1998). Perry et al. (1982) suggested that PD is a disorder due
to GSH deficiency. Riederer et al. (1989) and Bains and Shaw
(1997) have demonstrated a link between GSH deficiency and
severity of neuron loss. Kidd in 1997 showed that GSH pro-
tects against free radical damage. Kidd (1999) suggested GSH
replacement as one of the ways of treating PD. Zeevalk et al.
(2008) have reviewed comprehensive role of glutathione in
PD. They commented that loss of GSH in the nigra in Lewy
body disease may be one of the earliest derangements to occur
in the early stages of PD. Sechi et al. 1996 demonstrated
improvement in untreated PD patients after intravenous ad-
ministration of 600 mg of GSH, twice daily for 30 days. In
another randomized, double blind clinical trial conducted on
21 patients by Hauser et al. (2009)GSHinadoseof1,400mg
(IV) three times a week was found to be effective and well
tolerated. The exact mechanism by which the GSH produces
relief is still unknown.
Gallic acid
Lu et al. (2006) reported neuroprotective effect of gallic acid
and its derivatives against 6-OHDA-induced neurotoxicity.
They have revealed that gallic acid derivatives with high
antioxidant activity and appropriate hydrophobicity were
more effective in preventing the injury of oxidative stress.
Sameri et al. (2011) evaluated effect of gallic acid on move-
ment disorder in 6-OHDA lesioned rats and found that gallic
acid improved motor dysfunctions. Kasture et al. (2009b)
have also reported putative antiparkinsonian activity of gallic
acid and its derivatives in rats.
Unsaturated fatty acids: stearic acid and oleic acid
Mucuna seeds contain many unsaturated fatty acids. Kala and
Mohan (2010) have analyzed fatty acid content of Mucuna
pruriens seeds and found to contain Palmitic acid: 26.8 %;
Stearic acid: 13.38 %; Oleic acid: 19.20 %; Linoleic acid :
31.48 %; Linolenic acid: 8.1 %; and Behenic acid: 1.84 %.
Dexter et al. (1989) showed that PD patients suffer from
deficiency of unsaturated fatty acids. Lauritzen et al. (2000)
reported that polyunsaturated fatty acids are neuroprotectors.
They observed that opening of background K
+
channels which
are activated by arachidonic acid and other polyunsaturated
fatty acids such as linolenic acid; play a significant factor in the
neuroprotective effect. These channels are abundant in the
brain, located both pre- and post-synaptically, and are sensitive
to unsaturated fatty acids only. Wang et al. (2006)demonstrat-
ed neuroprotective effects of stearic acid. Stearic acid is
converted to oleic acid in brain. Its neuroprotective effect
may be mainly mediated by the activation of peroxisome
proliferator-activated receptor-gamma (PPAR-γ). Schintu
et al. (2009) have reported PPAR-gamma agonists as a putative
anti-inflammatory therapy aimed at arresting PD progression.
Bousquet et al. (2008) showed that omega 3 fatty acid con-
taining linoleic acid and linolenic acid is beneficial in toxin
induced neuronal degeneration in an animal model of PD.
Beta-carboline
The family of β-carboline alkaloids affects multiple targets
such as muscular, cardiovascular and central nervous systems,
including monoamine oxidase inhibition (Rommelspacher
Mucuna pruriens seeds in treatment of Parkinson’s disease
et al. 1994; Kim et al. 1997; Herraiz and Chaparro 2005)and
binding to dopamine, benzodiazepine, serotonin, and
imidazoline receptors (Pimpinella and Palmery 1995;Grella
et al. 1998; Glennon et al. 2000;Husbandsetal.2001; Squires
et al. 2004). Maher and Davis (1996) and Ruscher et al. (2007)
demonstrated neuroprotective effect of β-carboline. Other
studies showed that these alkaloids exert a protective effect
on oxidative neuronal damage through a scavenging action on
reactive oxygen species (Lee et al. 2000; Tse et al. 1991). The
β-carboline alkaloid, harmine, has recently been reported to
be a high affinity inhibitor of dual-specificity tyrosine
phosphorylationregulated kinase 1A, (DYRK1A kinase) ac-
tivity (Gockler et al. 2009), suggesting that harmine, and
possibly other β-carboline derivatives, could alter tau phos-
phorylation. Frost et al. (2011) showed that the β-carboline
alkaloids inhibit DYRK1A kinase activity and reduce the
levels of multiple phosphorylated forms of tau protein that
are important in the pathological progression of Alzheimer’s
Disease (AD). PD patients may develop AD in later stages.
Polanski et al. (2011) have reported protection and regenera-
tion of dopaminergic neurons by 9-methyl-beta carboline.
Palmitic acid
Although Lauritzen et al. (2000)showedthatpalmiticacidisa
saturated fatty acid devoid of any neuroprotective effect
(Lauritzen et al. 2000), palmitic acid increased activity of
uncoupling protein–2 (UCP-2) in the mitochondria
(Mattiasson et al. 2003) and proposed that UCP-2 is an induc-
ible protein that offers neuroprotection by activating cellular
redox signaling or by inducing mild mitochondrial uncoupling
thereby preventing the release of apoptogenic proteins.
Lecithin
In late Parkinson’s disease, a relative cholinergic deficiency
develops because of accelerated aging and choline acetyl
transferase deficiency. This process is enhanced by chronic
levodopa therapy. A regimen of lecithin produced a clear
improvement in Kohs block design test (a test designed to
measure intelligence in humans) with a decrease in the
symptoms of confusion, hallucinations and nightmares.
Lecithin produced a decrease in levodopa-induced abnormal
movements, but at the expense of motor performance
(Barbeau 1980). Mucuna seeds contain lecithin (Duke 1981).
Nicotine
Dyskinesia is observed in patients receiving levodopa.
Bordia et al. (2008) and Huang et al. (2011) reported that
continuous and intermittent nicotine treatment reduces
levodopa-induced dyskinesias in a rat model of Parkinson’s
disease. Quik et al. (2009) have also shown that nicotine
administration improves L-dopa-induced dyskinesias in par-
kinsonian animal models. Importantly, nicotine did not mod-
ify the anti-parkinsonian effect of L-dopa in any parkinso-
nian animal model (Bordia et al. 2010). Further it is reported
that glutamate and other excitatory amino acids are respon-
sible for various neurodegenerative disorders such as
Alzhimer’sandParkinson’s disease and nicotine has
neuroprotective effect through alpha4- and alpha7-nACh
receptors on neurotoxicity induced by glutamate and other
excitatory amino acids (Akaike et al. 2010). Seidl and
Potashkin (2011) have reviewed neuroprotective activity of
various compounds of diverse chemical nature such as caf-
feine, nicotine, uric acid, urates, vitamin C, vitamine D,
vitamine E, riboflavine, β-carotene, Coenzyme-Q10,
Déhydroépiandrostérone, uridine, melatonin, glutathione,
phytic acid, NSAIDs, Rasagiline, and minocycline and opined
that these agents are promising neuroprotective agents with
potential to reduce progression of Parkinson’sdisease.
Bufotenin
5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT) present
in Mucuna seeds belongs to the family of naturally-
occurring psychoactive indolealkylamines. It is a nonselective
serotonin agonist. 5-MeO-DMT is O-demethylated by cyto-
chrome P450 2D6 (CYP2D6) to an active metabolite,
bufotenine, and mainly inactivated through the deamination
pathway mediated by monoamine oxidase A (MAO-A).
Simultaneous use of harmaline (present in Mucuna) reduces
deamination of 5-MeO-DMT which causes prolonged and
increased exposure to the parent drug 5-MeO-DMT, and
bufotenine. Harmaline, 5-MeODMT and bufotenine act ago-
nistically on serotonergic systems leading to serotonin toxicity
(Shen et al. 2010). May et al. (2003) observed 5-HT
1A
and 5-
HT
2A/2B/2C
agonist activity of Bufotenine. Pytliak et al. (2011)
have shown that bufotenin acts as a 5-HT
2A
agonist. Riahi
et al. (2011) demonstrated involvement of 5-HT
2A
receptors in
levodopa-induced dyskinesia. Muñoz et al. (2009)have
shown that 5-HT
1A
agonist reduces levodopa-induced abnor-
mal involuntary movements in 6-OHDA lesioned rats.
Nutritional substances in Mucuna pruriens
Amino acids
It is known that PD patients have low levels of tyrosine
hydroxylase activity (Charlton and Crowell 1992). Further,
administration of levodopa leads to depletion of L-tyrosine,
L-tryptophan, serotonin (Karobath et al. 1971; Borah et al.
2007), sulfur amino acids such as glutathione and S-
adenosylmethionine (Charlton 1997;Hinz2009). Fuller
et al. (1987) have shown that striatal afferents from
amygdale, parafascicilar nucleus may utilize excitatory
S. Kasture et al.
amino acids as a neurotransmitter. Kala and Mohan (2010)
have determined amino acid contents of Mucuna pruriens.
These amino acids are essential for protein synthesis. They
found Mucuna seeds to contain in terms of g/100 g following
amino acids: Glutamic acid–11.60; Aspartic acid–13.28;
Serine–4.54; Threonine–3.54; Proline–3.09; Alanine–4.16;
Glycine–5.22; Valine–3.63; Cystine–1.11; Methionine–
0.78; Isoleucine–6.68; Leucine–5.24; Tyrosine–3.31;
Phenylalanine–4.03; Lysine–5.20; Histidine–2.94;
Tryptophan–1.01; and Arginine–6.74. Levodopa inhibits ab-
sorption of tyrosine, phenylalanine, and tryptophan thereby
causing deficiency. Deficiency may also be due to reduced
food intake or due to reduced enzymic conversion from
phenylalanine (Charlton 1997). Growdon et al. (1982) and
Yamaguchi and Nagatsu (1983) have reported that PD pa-
tients may have impaired capacity to utilize L-tyrosine. The
mucuna seeds contain crude protein (30.63 ± 0.14 g/100 g);
Crude lipid (8.74±0.07 g/100 g); and total dietary fibre
(8.56±0.05 g/100 g). The caloric value contained in 100 g
seeds was 1641.78 kJ (Kala and Mohan 2010). This may
help in counteracting the body weight loss in PD patients.
Deficiency of various amino acids has been observed in
patients receiving levodopa (Hinz et al. 2011). Their study
has shown that 5-hydroxytriptophan and l-dopa when ad-
ministered in proper balance with l-tyrosine, l-cysteine and
other cofactors effectively controlled the l-dopa doses and
management of PD was better. Mucuna seeds contain 5-
hydroxytriptophan also (Kalidass and Mohan 2011).
Minerals & Vitamins present in Mucuna seeds (in
mg/100 g): Sodium (88.30±0.41); Potassium
(1964.24± 2.21); Calcium (659.0± 0.76); Magnesium
(348.10±0.33); Phosphorus (564.30 ± 0.58); Iron
(11.87± 0.14); Zinc (2.44 ± 0.03); Copper (0.44± 0.01);
Manganese (10.30±0.17); Niacin (54.32); and Ascorbic acid
(57.3) (Kala and Mohan 2010). Uitti et al. (1989) reported
very low levels of copper in the substantia nigra of the PD
patients whereas Johnson (2001) reported deficiency of mag-
nesium in PD. Ascorbic acid (Vit C) is a well known
neuroprotective agent. (Seidl and Potashkin 2011).
Manganese is reported to have neuroprotective action
(Williams et al. 2010) whereas copper, zinc, and iron can
be neurotoxic (Horning et al. 2000; Seidl and Potashkin
2011). However, these minerals may be chelated by phytic
acid (Lee et al. 2005) present in Mucuna seeds.
Conclusion
Thus the review of scientific data clearly indicates that
Mucuna pruriens seeds contain various substances that pos-
sess antioxidant and neuroprotective activities which support
the antiparkinsonian activity of levodopa. The review also
emphasizes the importance of holistic approach of Ayurveda
in using the Mucuna pruriens in treatment of PD. Further
studies on these phytoconstituents with the objective of
revealing their mode of action will help in understanding
the treatment of PD.
Conflicts of interest None
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