Abstract
Mucuna pruriens
(Fabaceae) is an established herbal drug used for the management of
male infertility, nervous disorders, and also as an aphrodisiac. It has
been shown that its seeds are potentially of substantial medicinal
importance. The ancient Indian medical system, Ayurveda, traditionally
used M. pruriens, even to treat such things as Parkinson's disease. M. pruriens
has been shown to have anti-parkinson and neuroprotective effects,
which may be related to its anti-oxidant activity. In addition,
anti-oxidant activity of M. pruriens has been also demonstrated in vitro by its ability to scavenge DPPH radicals and reactive oxygen species. In this review the medicinal properties of M. pruriens are summarized, taking in consideration the studies that have used the seeds extracts and the leaves extracts.
Keywords: Mucuna pruriens, Phytochemicals, Antioxidant, Parkinson's disease, Skin, Diabetes
Introduction
The genus Mucuna,
belonging to the Fabaceae family, sub family Papilionaceae, includes
approximately 150 species of annual and perennial legumes. Among the
various under-utilized wild legumes, the velvet bean Mucuna pruriens
is widespread in tropical and sub-tropical regions of the world. It is
considered a viable source of dietary proteins (Janardhanan et al.,
2003; Pugalenthi et al., 2005) due to its high protein concentration
(23–35%) in addition its digestibility, which is comparable to that of
other pulses such as soybean, rice bean, and lima bean (Gurumoorthi et
al., 2003). It is therefore regarded a good source of food.
The dozen or so cultivated Mucuna
spp. found in the tropics probably result from fragmentation deriving
from the Asian cultigen, and there are numerous crosses and hybrids
(Bailey and Bailey, 1976). The main differences among cultivated species
are in the characteristics of the pubescence on the pod, the seed
color, and the number of days to harvest of the pod. “Cowitch” and
“cowhage” are the common English names of Mucuna types with
abundant, long stinging hairs on the pod. Human contact results in an
intensely itchy dermatitis, caused by mucunain (Infante et al., 1990).
The nonstinging types, known as “velvet bean” have appressed, silky
hairs.
The plant M. pruriens, widely known as
“velvet bean,” is a vigorous annual climbing legume originally from
southern China and eastern India, where it was at one time widely
cultivated as a green vegetable crop (Duke, 1981). It is one of the most
popular green crops currently known in the tropics; velvet beans have
great potential as both food and feed as suggested by experiences
worldwide. The velvet bean has been traditionally used as a food source
by certain ethnic groups in a number of countries. It is cultivated in
Asia, America, Africa, and the Pacific Islands, where its pods are used
as a vegetable for human consumption, and its young leaves are used as
animal fodder.
The plant has long, slender branches;
alternate, lanceolate leaves; and white flowers with a bluish-purple,
butterfly-shaped corolla. The pods or legumes are hairy, thick, and
leathery; averaging 4 inches long; are shaped like violin sound holes;
and contain four to six seeds. They are of a rich dark brown color, and
thickly covered with stiff hairs. In India, the mature seeds of Mucuna bean are traditionally consumed by a South Indian hill tribe, the Kanikkars, after repeated boiling to remove anti-nutritional factors. Most Mucuna
spp. exhibit reasonable tolerance to a number of abiotic stresses,
including drought, low soil fertility, and high soil acidity, although
they are sensitive to frost and grow poorly in cold, wet soils (Duke,
1981). The genus thrives best under warm, moist conditions, below 1500 m
above sea level, and in areas with plentiful rainfall. Like most
legumes, the velvet bean has the potential to fix atmospheric nitrogen
via a symbiotic relationship with soil microorganisms.
Mucuna
spp. have been reported to contain the toxic compounds L-dopa and
hallucinogenic tryptamines, and anti-nutritional factors such as phenols
and tannins (Awang et al., 1997). Due to the high concentrations of
L-dopa (4–7%), velvet bean is a commercial source of this substance,
used in the treatment of Parkinson's disease. The toxicity of
unprocessed velvet bean may explain why the plant exhibits low
susceptibility to insect pests (Duke, 1981). Velvet bean is well known
for its nematicidic effects; it also reportedly possesses notable
allelopathic activity, which may function to suppress competing plants
(Gliessman et al., 1981).
Despite its toxic properties, various species of Mucuna
are grown as a minor food crop. Raw velvet bean seeds contain
approximately 27% protein and are rich in minerals (Duke, 1981). During
the 18th and 19th centuries, Mucuna was
grown widely as a green vegetable in the foothills and lower hills of
the eastern Himalayas and in Mauritius. Both the green pods and the
mature beans were boiled and eaten. In Guatemala and Mexico, M. pruriens
has for at least several decades been roasted and ground to make a
coffee substitute; the seeds are widely known in the region as
“Nescafé,” in recognition of this use.
Mucuna pruriens as a traditional medicine
M. pruriens
is a popular Indian medicinal plant, which has long been used in
traditional Ayurvedic Indian medicine, for diseases including
parkinsonism (Sathiyanarayanan et al., 2007). This plant is widely used
in Ayurveda, which is an ancient traditional medical science that has
been practiced in India since the Vedic times (1500–1000 BC). M. pruriens
is reported to contain L-dopa as one of its constituents (Chaudhri,
1996). The beans have also been employed as a powerful aphrodisiac in
Ayurveda (Amin, 1996) and have been used to treat nervous disorders and
arthritis (Jeyaweera, 1981). The bean, if applied as a paste on scorpion
stings, is thought to absorb the poison (Jeyaweera, 1981).
The
non-protein amino acid-derived L-dopa (3,4-dihydroxy phenylalanine)
found in this under-utilized legume seed resists attack from insects,
and thus controls biological infestation during storage. According to
D’Mello (1995), all anti-nutritional compounds confer insect and disease
resistance to plants. Further, L-dopa has been extracted from the seeds
to provide commercial drugs for the treatment of Parkinson's disease.
L-Dopa is a potent neurotransmitter precursor that is believed, in part,
to be responsible for the toxicity of the Mucuna seeds (Lorenzetti et al., 1998). Anti-epileptic and anti-neoplastic activity of methanol extract of M. pruriens has been reported (Gupta et al., 1997). A methanol extract of MP seeds has demonstrated significant in vitro anti-oxidant activity, and there are also indications that methanol extracts of M. pruriens may be a potential source of natural anti-oxidants and anti-microbial agents (Rajeshwar et al., 2005).
All parts of M. pruriens
possess valuable medicinal properties and it has been investigated in
various contexts, including for its anti-diabetic, aphrodisiac,
anti-neoplastic, anti-epileptic, and anti-microbial activities
(Sathiyanarayanan et al., 2007). Its anti-venom activities have been
investigated by Guerranti et al. (2002) and its anti-helminthic activity
has been demonstrated by Jalalpure (2007). M. pruriens has
also been shown to be neuroprotective (Misra and Wagner, 2007), and has
demonstrated analgesic and anti-inflammatory activity (Hishika et al.,
1981).
Functional components of Mucuna pruriens
In addition to the low levels of sulfur-containing amino acids in M. pruriens
seeds, the presence of anti-physiological and toxic factors may
contribute to a decrease in their overall nutritional quality. These
factors include polyphenols, trypsin inhibitors, phytate, cyanogenic
glycosides, oligosaccharides, saponins, lectins, and alkaloids.
Polyphenols (or tannins) are able to bind to proteins, thus lowering
their digestibility. Phenolic compounds inhibit the activity of
digestive as well as hydrolytic enzymes such as amylase, trypsin,
chymotrypsin, and lipase. Recently, phenolics have been suggested to
exhibit health related functional properties such as anti-carcinogenic,
anti-viral, anti-microbial, anti-inflammatory, hypotensive, and
anti-oxidant activities.
Trypsin inhibitors belong to
the group of proteinase inhibitors that include polypeptides or proteins
that inhibit trypsin activity. Tannins exhibit weak interactions with
trypsin, and thus also inhibit trypsin activity. Phytic acid
[myoinositol-1,2,3,4,5,6-hexa(dihydrogen phosphate)] is a major
component of all plant seeds, which can reduce the bioavailability of
certain minerals such as zinc, calcium, magnesium, iron, and phosphorus,
as well as trace minerals, via the formation of insoluble complexes at
intestinal pH. Phytate-protein complexes may also result in the reduced
solubility of proteins, which can affect the functional properties of
proteins.
Cyanogenic glycosides are plant toxins that
upon hydrolysis, liberate hydrogen cyanide. The toxic effects of the
free cyanide are well documented and affect a wide spectrum of organisms
since their mode of action is inhibition of the cytochromes of the
electron transport system (Laurena et al., 1994). Hydrogen cyanide (HCN)
is known to cause both acute and chronic toxicity, but the HCN content
of M. pruriens seeds is far below the lethal level. Janardhan et al. (2003) have investigated the concentration of oligosaccharides in M. pruriens
seeds, and verbascose is reportedly the principal oligosaccharide
therein (Siddhuraju et al., 2000). Fatty acid profiles reveal that
lipids are a good source of the nutritionally essential linoleic and
oleic acids. Linoleic acid is evidently the predominant fatty acid,
followed by palmitic, oleic, and linolenic acids (Mohan and Janardhanan,
1995; Siddhuraju et al., 1996). The nutritional value of linoleic acid
is due to its metabolism at tissue levels that produce the hormone-like
prostaglandins. The activity of these prostaglandins includes lowering
of blood pressure and constriction of smooth muscle. Phytohemagglutinins
(lectins) are substances possessing the ability to agglutinate human
erythrocytes.
The major phenolic constituent
of M. pruriens beans was found to be L-dopa (5%), along with minor
amounts of methylated and non-methylated tetrahydroisoquinolines (0.25%)
(Sidhuraju et al., 2001; Misra and Wagner, 2004). However, in addition
to L-dopa, 5-indole compounds, two of which were identified as
tryptamine and 5-hydroxytryptamine, were also reported in M. pruriens
seed extracts (Tripathi and Updhyay, 2001). Mucunine, mucunadine,
prurienine, and prurieninine are four alkaloids that have been isolated
from such extracts (Mehta and Majumdar, 1994).
Pharmacological effects of Mucuna pruriens extracts
All parts of the Mucuna plant possess medicinal properties (Sathiyanarayanan and Arulmozhi, 2007). In vitro and in vivo studies on M. pruriens
extracts have revealed the presence of substances that exhibit a wide
variety of pharmacological effects, including anti-diabetic,
anti-inflammatory, neuroprotective and anti-oxidant properties, probably
due to the presence of L-dopa, a precursor of the neurotransmitter
dopamine (Misra and Wagner, 2007). It is known that the main phenolic
compound of Mucuna seeds is L-dopa (approximately 5%) (Vadivel and Pugalenthi, 2008). Nowadays, Mucuna
is widely studied because L-dopa is a substance used as a first-line
treatment for Parkinson's disease. Some studies indicate that L-dopa
derived from M. pruriens has many advantages over synthetic
L-dopa when administered to Parkinson's patients, as synthetic L-dopa
can have several side effects when used for many years.
In
small amounts (approximately 0.25%) L-dopa corresponds to methylated
and non-methylated tetrahydroisoquinoline (Siddhuraju and Becker, 2001;
Misra and Wagner, 2004). These substances are present in the Mucuna roots, stems, leaves, and seeds. Other substances are present in different parts of the plant, among which are N,N-dimethyl
tryptamine and some indole compounds (Tripathi and Updhyay, 2001).
Alcoholic extracts of the seeds were shown to have potential
anti-oxidant activity in in vivo models of lipid peroxidation induced by
stress (Tripathi and Updhyay, 2001). On the other hand, Spencer et al.
(1996) have reported that the pro-oxidant and anti-oxidant actions of
L-dopa and its metabolites promote oxidative DNA damage and could also
be harmful to tissues damaged by neurodegenerative diseases, namely
parkinsonism. Moreover, a study using in vitro models revealed
that L-dopa significantly increases the levels of oxidized glutathione
in rat brain striatal synaptosomes (Spina et al., 1988). The observed
depletion of reduced glutathione (GSH) could be due to the generation of
reactive semiquinones from L-dopa (Spencer et al, 1995).
Protective effect of Mucuna pruriens seeds against snake venom poisoning
M. pruriens
is one of the plants that have been shown to be active against snake
venom and, indeed, its seeds are used in traditional medicine to prevent
the toxic effects of snake bites, which are mainly triggered by potent
toxins such as neurotoxins, cardiotoxins, cytotoxins, phospholipase A2 (PLA2),
and proteases (Guerranti et al., 2002). In Plateau State, Nigeria, the
seed is prescribed as a prophylactic oral anti-snakebite remedy by
traditional practitioners, and it is claimed that when the seeds are
swallowed intact, the individual is protected for one full year against
the effects of any snake bite (Guerranti et al., 2001). The mechanisms
of the protective effects exerted by M. pruriens seed aqueous
extract (MPE), were investigated in detail, in a study involving the
effects of Echis carinatus venom (EV) (Guerranti et al., 2002). In vivo
experiments on mice showed that protection against the poison is evident
at 24 hours (short-term), and 1 month (long term) after injection of
MPE (Guerranti et al., 2008). MPE protects mice against the toxic
effects of EV via an immune mechanism (Guerranti et al., 2002). MPE
contains an immunogenic component, a multiform glycoprotein, which
stimulates the production of antibodies that cross-react with (bind to)
certain venom proteins (Guerranti et al., 2004). This glycoprotein,
called gpMuc (see Table 1),
is composed of seven different isoforms with molecular weights between
20.3 and 28.7 kDa, and pI between 4.8 and 6.5 (Di Patrizi et al., 2006).
Anti-microbial properties of Mucuna pruriens leaves
Various
parts of certain plants are known to contain substances that can be
used for therapeutic purposes or as precursors for the production of
useful drugs (Sofowora, 1982). Plant-based anti-microbials represent a
vast untapped source of medicines and further investigation of plant
anti-microbials is needed. Anti-microbials of plant origin have enormous
therapeutic potential. Phytochemical compounds are reportedly
responsible for the anti-microbial properties of certain plants (Mandal
et al., 2005). While bioactive compounds are often extracted from whole
plants, the concentration of such compounds within the different parts
of the plant varies. Parts known to contain the highest concentration of
the compounds are preferred for therapeutic purposes. Some of these
active components operate individually, others in combination, to
inhibit the life processes of microbes, particularly pathogens. Crude
methanolic extracts of M. pruriens leaves have been shown to have mild activity against some bacteria in experimental settings (Table 1),
probably due to the presence of phenols and tannins (Ogundare and
Olorunfemi, 2007). Further studies are required in order to isolate the
bioactive components responsible for the observed anti-microbial
activity.
Neuroprotective effect of Mucuna pruriens seeds
In India, the seeds of M. pruriens
have traditionally been used as a nervine tonic, and as an aphrodisiac
for male virility. The pods are anthelmintic, and the seeds are
anti-inflammatory. Powdered seeds possess anti-parkinsonism properties,
possibly due to the presence of L-dopa (a precursor of neurotransmitter
dopamine). It is well known that dopamine is a neurotransmitter. The
dopamine content in brain tissue is reduced when the conversion of
tyrosine to L-dopa is blocked. L-Dopa, the precursor of dopamine, can
cross the blood-brain barrier and undergo conversion to dopamine,
restoring neurotransmission (Kulhalli, 1999). Good yields of L-dopa can
be extracted from M. pruriens seeds (Table 1) with EtOH-H2O (1:1), using ascorbic acid as a protector (Misra and Wagner, 2007). An n-propanol extract of M. pruriens
seeds yields the highest response in neuroprotective testing involving
the growth and survival of DA neurons in culture. Interestingly,
n-propanol extracts, which contain a negligible amount of L-dopa, have
shown significant neuroprotective activity, suggesting that a whole
extract of M. pruriens seeds could be superior to pure L-dopa with regard to the treatment of parkinsonism.
Anti-diabetic effect of Mucuna pruriens seeds
Using
a combination of chromatographic and NMR techniques, the presence of
d-chiro-inositol and its two galacto-derivatives,
O-α-d-galactopyranosil-(1→2)-d-chiro-inositol (FP1) and O-α-d-galactopyranosil-(1→6)-O-α-d-galactopyranosil-(1→2)-D-chiro-inositol (FP2), was demonstrated in M. pruriens
seeds (Donati et al., 2005). Galactopyranosyl d-chiro-inositols are
relatively rare and have been isolated recently from the seeds of
certain plants; they constitute a minor component of the sucrose
fraction of Glycine max (Fabaceae) and lupins, and a major component of Fagopyrum esculentum
(Polygonaceae) (Horbovitz et al., 1998). Although usually ignored in
phytochemical analyses conducted for dietary purposes, the presence of
these cyclitols is of interest due to the insulin-mimetic effect of
d-chiro-inositol, which constitutes a novel signaling system for the
control of glucose metabolism (Larner et al., 1998; Ortmeyer et al.,
1995). According to Anktar et al., (1990), M. pruriens seeds
used at a dose of 500 mg/kg reduced plasma glucose levels. These and
other data demonstrated that the amount of seeds necessary to obtain a
significant anti-diabetic effect contain a total of approximately 7 mg
of d-chiro-inositol (including both free, and that derived from the hydrolysis of FP1 and FP2). The anti-diabetic properties of M. pruriens seed EtOH/H2O 1:1 extract are most likely due to d-chiro-inositol and its galacto-derivatives (Table 1).
Anti-oxidant activity of Mucuna pruriens
Free
radicals that have one or more unpaired electrons are produced during
normal and pathological cell metabolism. Reactive oxygen species (ROS)
react readily with free radicals to become radicals themselves.
Anti-oxidants provide protection to living organisms from damage caused
by uncontrolled production of ROS and concomitant lipid peroxidation,
protein damage and DNA strand breakage. Several substances from natural
sources have been shown to contain anti-oxidants and are under study.
Anti-oxidant compounds such as phenolic acids, polyphenols, and
flavonoids, scavenge free radicals such as peroxide, hydroperoxide or
lipid peroxyl, and thus inhibit oxidative mechanisms. Polyphenols are
important phytochemicals due to their free radical scavenging and in vivo
biological activities (Bravo, 1998); the total polyphenolic content has
been tested using Folin-Ciocalteau reagent. Flavonoids are simple
phenolic compounds that have been reported to possess a wide spectrum of
biochemical properties, including anti-oxidant, anti-mutagenic and
anti-carcinogenic activity (Beta et al., 2005). The hydrogen donating
ability of the methanol extract of M. pruriens was measured in
the presence of 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical. In a
recent study, Kottai Muthu et al. (2010) found that ethylacetate and
methanolic extract of whole M. pruriens plant (MEMP), which
contains large amounts of phenolic compounds, exhibits high anti-oxidant
and free radical scavenging activities. These in vitro assays
indicate that this plant extract is a significant source of natural
anti-oxidant, which may be useful in preventing various oxidative
stresses. It has been reported (Ujowundu et al., 2010) that methanolic
extracts of M. pruriens leaves have numerous biochemical and physiological activities, and contain pharmaceutically valuable compounds (Table 1).
Possible usage of Mucuna pruriens for skin treatments
The skin is one of the main targets of several exogenous insults such as UV radiation, O3,
and cigarette smoke, and all of these exert toxicity via the induction
of oxidative stress (Valacchi et al., 2000). Several skin pathologies,
such as psoriasis, dermatitis, and eczema, are related to increased
oxidative stress and ROS production (Briganti and Picardo, 2003), and
research investigating novel natural compounds with anti-oxidant
proprieties is an expanding field. As mentioned above, certain
plant-derived compounds have been an important source of traditional
treatments for various diseases, and have received considerable
attention in more recent years due to their numerous pharmacological
proprieties.
Recent preliminary
studies from our group have shown that human keratinocytes treated with a
methanolic extract from MP leaves exhibit downregulation of total
protein expression. In addition, treatment with MP significantly
decreased the baseline levels of 4HNE present in human keratinocytes
(Lampariello et al., 2011). This preliminary study suggests that
evaluating the effect that topical MP methanolic extract treatment may
have on skin diseases would be worthwhile, as would further work aimed
at clarifying the mechanisms involved in such effects.
Conclusions
Mucuna pruriens
is an exceptional plant. On the one hand it is a good source of food,
as it is rich in crude protein, essential fatty acids, starch content,
and certain essential amino acids. On the other hand, it also contains
various anti-nutritional factors, such as protease inhibitors, total
phenolics, oligosaccharides (raffinose, stachyose, verbascose), and some
cyclitols with anti-diabetic effects. In fact, all parts of the Mucuna plant possess medicinal properties. The main phenolic compound is L-dopa (5%), and M. pruriens seeds contain some components that are able to inhibit snake venom. In addition, methanolic extracts of M. pruriens
leaves have demonstrated anti-microbial and anti-oxidant activities in
the presence of bioactive compounds such as phenols, polyphenols and
tannins, and preliminary studies on keratinocytes support its possible
topical usage to treat redox-driven skin diseases. Collectively, the
studies cited in this review suggest that this plant and its extracts
may be of therapeutic value with regard to several pathologies, although
further work is needed to investigate in more detail the mechanisms
underlying the pharmacological activities of MP.