Impact of Plants having Potential
Action on CNS: An Overview
Tiwari Prashant*, Ahirwar Dheeraj, Dwivadi Shubhangi
School of Pharmacy, Chouksey
Engineering College, Bilaspur-495004, India
*Corresponding
Author E-mail: ptc_ptc15@rediffmail.com
ABSTRACT:
The
endeavor of the present study was to document the use of plants, probably
acting on the central nervous system. Plants have formed the basis for the treatment
of diseases in traditional medicine systems since many decades. However,
current investigation approaches to explore traditional medicine and medicinal
plants as a potential CNS stimulator and modulator for treating various
neuronal disorders like Epilepsy, Tardive Dyskinesia, Schizophrenia, Anxiety and Depression etc.
KEYWORDS: Central
Nervous System.
1. INTRODUCTION:
Medicinal plants, since times
immemorial, have been used in virtually all cultures as a source of medicine.
The widespread use of herbal remedies and healthcare preparations, as those
described in ancient texts such as the
Vedas and the bible, and obtained from commonly used traditional herbs and
medicinal plants, has been traced to the occurrence of natural products with
medicinal properties. The use of traditional medicine and medicinal plants in
most developing countries, as a normative basis for the maintenance of good
health, has been widely observed (UNESCO, 1996). Furthermore, increasing
reliance on the use of medicinal plants in the industrialized societies has
been traced to the extraction and development of several drugs and
chemotherapeutics from these plants as well as from traditionally used rural
herbal remedies (UNESCO, 1998). Moreover, in these societies, herbal remedies
have become more popular in the treatment of minor ailments, and also on
account of the increasing costs of personal health maintenance. Indeed, the
market and public demand has been so great that there is a great risk that many
medicinal plants today, face either extinction or loss of genetic diversity
[1].
Plants have
formed the basis for the treatment of diseases in traditional medicine systems
for thousands of years, and continue to play a major role in the primary health
care of about 80% of the world's inhabitants (world health organization
statistic). Approximately 119 pure chemical substances extracted from higher
plants are used in medicine throughout the world.
For the most part, the
discovery of the drugs stems from knowledge that their extracts are used to
treat one or more diseases in humans. The more interesting of the extracts are
then subjected to pharmacological and chemical tests to determine the nature of the active components. Therefore,
it should be of interest to ascertain just how important plant drugs are
throughout the world when used in the form of crude extracts. The world health
organization estimates that 80% of the people in developing countries of the
world rely on traditional medicine for their primary health care
needs, and about 85% of traditional medicine involves the use of plant
extracts. This means that about 3.5 to 4 billion people in the world rely on
plants as sources of drugs. Specific data in support of these estimates are
difficult to find [2].
Herbal and natural
products have enormous popularity as self-medication products. They are
perceived as natural, green, pure, and without side effects. Furthermore, their
popularity has resulted in more than 800 companies producing herbal products
and collecting revenues in excess of $4.5 billion. 89% of patients with cancer
or other chronic conditions use alternative therapies, often herbal or natural
products and 75% are secretive about alternative product use. Evidence shows
that healthcare consumer’s main source of information is lay sources and social
groups. Until recently, little evidence-based information was available on
interactions of herbs and natural products with diseases such as cancer or
cancer treatments, prescriptions, other herbs, and laboratory tests. This
information now is becoming available. A recent study showed that as many as
97% of healthcare professionals lack evidence-based resources for natural
products and herbs.
Herbal medicines are one of
the oldest remedies known to mankind. Herbs had been used by all cultures
throughout history but India has one of the oldest, richest and most diverse
cultural living traditions associated with the use of medicinal plants [3].
The use of traditional medicine and medicinal plants in most developing
countries, as a normative basis for the maintenance of good health, has been
widely observed. furthermore, an increasing reliance on the use of medicinal
plants in the industrialized societies has been traced to the extraction and
development of several drugs and chemotherapeutics from these plants as well as
from traditionally used rural herbal remedies moreover, in these
societies, herbal remedies have become more popular in the treatment of minor
ailments, and also on account of the increasing costs of personal health
maintenance. Indeed, the market and public demand has been so great that there
is a great risk that many medicinal plants today, face either extinction or
loss of genetic diversity.
Medicinal plants are
an important therapeutic aid for various ailments. [4]. In India, from ancient
times, different parts of medicinal plants have been used to cure specific ailments.
Today, there is widespread interest in drugs derived from plants. This interest
primarily stems from the belief that green medicine is safe and dependable,
compared with costly synthetic drugs that have adverse effects. Natural antimicrobials can be derived from
plants, animal tissues, or microorganisms [5]. The shortcomings of
the drugs available today, propel the discovery of new pharmacotherapeutic
agents in medicinal plants [6]. to
determine the potential and promote the use of herbal medicine, it is essential
to intensify the study of medicinal plants that find place in folklore. As the
use of antibacterial in present scenario is facing one of the major problems of
regular resistance development of bacterial strains toward different these agents.
Plants,
as extracts and in various other forms, are being used for centuries in
different traditional systems of medicine for the treatment of human ailments,
particularly those caused by pathogenic bacteria, fungi as well as viruses.
Plants and plant products have been used extensively throughout history to
treat medical problems.
Figure 1:
Traditional plants having medicinal activity .
Numerous
studies have been carried out to extract various natural products for screening
antimicrobial activity [7-11]. [Figure
1]
The use plant extracts against pathogens, though a relatively
recent practice, has gained momentum due to the well-known problems associated
with the generation of resistance for the purpose. Use of plant products for
the control of human and plant diseases has certain advantages, for instance,
the plants are generally readily available, production costs are low and, above
all, the products are biodegradable. The effective plant constituents can
combat human and plant pathogenic bacteria, fungi and viruses without toxic
side effects and environmental hazards. It is because of these reasons that
search for plant products having anti microbial properties has intensified in
recent years [12].
2. Plants having potential action on CNS
During the history of
mankind, drugs acting the central nervous system (CNS) have focused essentially
on those that bring relief to psychiatric disorders. Recently, a lot of focus
has been made on those likely to bring relief to those acting on Parkinsonism
and epilepsy and more potent analgesics etc. Drugs of plant origin are
important in all these areas although not usually for self-medication. Reserpine has
been a classical example where this anti-psychotic drug has revolutionized the
treatment of schizophrenia and has enabled patients to avoid hospitalization
before the introduction of drugs such as Chlorpromazine
and Olanzapine
and Risperidone.
Reserpine in the meantime has shown some side
effects in depleting the neurotransmitter levels in the brain thus causing
severe depression and has recently been involved in the development of breast
cancer. For milder psychiatric conditions, Phytotherapy
can still provide support when one takes into account the statistics whereby
depression and anxiety still affects one in six persons and that 40% or the
people having mental problems will also develop symptoms of anxiety and
depression. The latter is more prevalent in women than in men with associated
problems like sleep disturbances etc. It is in this context again that phytotherapy is called upon to re-establish a regular
pattern of sleep. Migraines, Dementia, Alzheimer disease are many of the
problems associated with the CNS, which are being addressed by plant extracts.
3. Plant as Hypnotics and sedatives
It has been reported that the
difference between a sedative and a hypnotic agent depends on the dose. Plant
products used in this way are not as potent as synthetic drugs but they do not
have as many disadvantages as their synthetic counter parts, which are often
recommended for short-term use. Valeriana officinalis (Valerianaceae) (Radix
valerianae).This plant has a long history in
traditional medicine as a digestive aid, and as adjuvant in Spasmolytic
states of smooth muscle and gastrointestinal pains of nervous origin. It has
also been used to treat Epilepsy, gum sores, headaches, nausea etc. This
herbaceous plant is being cultivated in many European countries, in the US and
also in Japan. The parts used pharmaceutically are the root, rhizome and stolons. Valerian has a characteristic smell, usually
described as unpleasant and is attributed to the presence of Valepotriate constituents and other volatile oils. [Figure
2]
Figure 2:
Valeriana officinalis
The main components of
the volatile oils are mono terpenes and sesquiterpenes including valeranone,
valerianol, valerenol, valerenal and valerenic acid and
derivatives. Among the valepotriate other compounds
are: valtrate, didrovaltrate
and isovaltrate, which are highly unstable
decomposing readily upon storage. The extracts of Valeriana officinalis also contain γ-aminobutyric acid (GABA), glutamine and tyrosine. Among the
modern medicinal uses for valerian roots are insomnia, stress and anxiety. The
sedative activity of V. officinalis has been
demonstrated in vitro and in vivo. In vitro studies have demonstrated the
binding of valerian extracts to GABA, adenosine, barbiturate and benzodiazepine
receptors. In vivo studies suggest that the sedative properties of the drug may
be due to high concentrations or glutamine in the extract. Glutamine is able to
cross the blood-brain barrier where it is taken up by nerve terminals and
subsequently metabolized to GABA. Increased GABA concentrations are associated
with decreased CNS activity, which may, at least, partly explain valerians
sedative activity (WHO, 1999). Recently several preparations containing
valerian root in combination with other herbs (e.g. hops) reputed to have
hypnotic and/or sedative effects have been tested [13]. Nonetheless the
required therapeutic dosage, the type or valerian preparations and the optimum
period or use for therapeutic effect still needs to be worked out [14].
The spasmolytic
activity of the valepotriates is principally due to valtrate or dihydrovaltrate.
These agents act on centers of the CNS and through direct relaxation or smooth
muscles, apparently by modulating ca2+ entry into the cells or by
binding to smooth muscle. Although the extracts have been clearly shown to
depress CNS activity, the identity of the active constituents still remains
controversial. Neither the valepotriates nor the sesquiterpenes valerinic acid and
valeranone, nor the volatile oil alone can account
for the overall sedative activity of the plant. It has been suggested that the baldrinals, degradation products or the valepotriates
may be responsible. It is clear unknown whether the activity of Valeriana offcinalis
resides in one compound, some unknown compounds or the synergistic activity of
several compounds. Piper Methysticum (piperaceae) in
the Pacific islands, the roots of kava (Piper
Methysticum) have been chewed for hundreds of
years. This small shrub with heart-shaped leaves has a thick woody root, which
is fermented to give the famous ceremonial drink, which has been offered to
important visitors namely the queen and even the pope. This drink is used to
induce a relaxed sociable state and nowadays it is used medicinally for its
tranquilizing properties as well as for other disparate complaints. Kava
dietary products have been sold worldwide for the treatment of nervous anxiety,
tension and restlessness.
Recent reports have showed the
potential association of kava usage and liver injuries [15]. The main
components of kava are the kavalactones (also known
as kavapyrones) and include kawain,
dihydrokavain, methysticin,
yangonin and desmethoxyyangonin
and dihydrokawain. Some of the medicinal uses have
been supported by clinical data and these include symptomatic treatment of mild
states of anxiety and insomnia due to nervousness, stress and tension. In vitro
studies had initially provided conflicting data on receptor interactions of
kava extract and isolated kava lactones. Current thinking is that kava lactones
potentiate GABA receptor activity. Other receptor binding studies demonstrate
no interaction with benzodiazepine receptors. Studies involving laboratory
animals given kava extract or purified kava lactones have demonstrated several
activities including behavioral effects, analgesic activity, neurological
effects, anti-convulsant and antispasmodic and
anti-microbial activities. Clinical trials have confirmed the efficacy of kava
extracts at relieving anxiety in double-blind and placebo controlled
experiments. Overall the randomized controlled trials involving patients with
anxiety have suggested that the kava extracts may be as effective as certain
benzodiazepines, although further research is needed to confirm these
observations. Recently pharmacological investigations of kava and pass flora
extract combination have shown there was a significant decrease of the
amphetamine-induced hyper motility and significant prolongation of the sleeping
phase induced by subcutaneous injections or barbiturates [16].[Figure 3]
Figure 3:
Kava
4. Toxicity
Kava extracts must not be
taken for more than the limited period without medical advice. Nonetheless
patients have been reported to complain about allergic reactions, hepatotoxicity and discoloration of the skin amongst some
or the symptoms. Hypericum perforatum (hypericaceae) (st. Johns wort,) this plant has had a long history of medicinal use.
This perennial, herbaceous plant native to Europe and Asia has been used
traditionally as a nervine tonic and eventually in
the treatment of nervous disorders. In recent years, herbal preparations
containing the aerial parts of st. Johns wort,
have been among the top selling herbal preparations. The active constituents
are thought to have been, initially, due to the presence of hypericin
as the major anti-depressant component of the drug. Experimentally and
clinically, it emerged that hyperforin is a major
component required for anti-depressant activity. The plant contains other
biologically active constituents such as flavonoids,
which may act in a synergistic manner with the above-mentioned constituents in
acting as an anti-depressant. Although the extracts of st.
Johns wort have manifested activity as a depressant,
the exact mode of action is unclear [17-18].
Biochemical and pharmacological studies have shown that the extracts
inhibit the synaptosomal uptake of the
neurotransmitters, serotonin (5-hydroxytryptamine, 5-ht), dopamine and
noradrenalin (nor-epinephrine) and GABA. Other effects of the extract of H. perforatum
include the ability to reduce the level or cholesterol in the blood of small
animals. The flavonoid-rich extract has been shown to
lower the serum triglycerides, total cholesterol and lipoprotein cholesterol as
well as slow lipid peroxidation and enhance
antioxidant enzyme activity [19].
5.
Plant parts used
Several plants parts have been
studied and their activities have been reported, which are summarized below
5.1 Root: the
fleshy or woody parts of many species are used medicinally. Roots may be
fibrous (Urtica dioica or u.
Radix of the urticaceae family, stinging nettle),
solid (Glycyrrhiza glabra of the
leguminosae family, liquorice)
or fleshy (Harpagophytum procrumbens of
the pedaliaceae family, devils claw).
5.2 Rhizome:
the rhizome is a woody or fleshy elongated stem that usually grows horizontally
below the ground, forming leaves above the ground and roots into the ground.
Medicinally important rhizomes include kava kava (Piper methysticum
of the piperaceae Family) and the ginger (Zingiber officinalis
of the zingiberaceae family).
5.3 Bulb: a
bulb is the fleshy structure made up of numerous layers of bulb scales which
are leaf bases. Bulbs which are popular for medicinal uses include the onion
and garlic (Allium cepa and A. Sativum respectively, both of the liliaceae
family).
5.4. Tuber: a
tuber is a swollen, fleshy structure below the ground, usually of stem origin
but often partly stem and partly roots.The African
potato (Hypoxis sp. Of the hypoxidaceae
family) is a well known example.
5.6 Bark: the
bark is the outer most protective layer of a tree trunk and is formed by layers
of living cells just above the wood itself. There are usually high concentrations
of the active ingredients in the bark and several examples of the bark exists
e.g. the quinine bark (Cinchona sp., rubiaceae) and cinnamon and camphor (Cinnamomum Camphora and C. camphora both of the lauraceae family).
5.7 Wood: the
wood is the thick stem or the wood itself. Important examples of useful woods
include sandalwood (Santalum album of the santalaceae
family).
5.8 Leaf: the
leaves can sometimes be used alone or mixed with the petiole. Example of plants
where only the leaves are used is the Gingko (Gingko biloba
of the ginkoaceae family).
5.9 Aerial parts: all parts of the plant found above the ground are referred to as
the aerial parts. Very often the plants, which have useful aerial parts, are
harvested when flowering. One such example is the st.
Johns wort (Hypericum perforatum of the hypericaceae
family).
5.10 Flowers:
flowers are very commonly used and popular in traditional medicine. Several
flowers commonly used in medicine include the clove (Syzygium aromaticum, myrtaceae),
camomille flower (Chamaemelum Nobile, asteraceae), Roselle (Hibiscus Sabdiriffa,
Meliaceae), and the marigold (Calendula officinalis, asteraceae).
5.11 Seeds:
seeds are contained in the fruit and in some instances are used by themselves.
Examples exist for the use of the seeds e.g. castor oil (Ricinus communis, Euphorbiaceae),
and the seeds of the fennel (Foeniculum vulgare, Apiaceae).
5.12 Gum:
gums are solids consisting of mixtures of polysaccharides. They are water
soluble and are partially digested by humans. Gums sometimes flow from a
damaged stem as a defense mechanism or sometimes as a protective system against
the invasion of bacterial and fungal rots. Well known examples of gums are gum
Arabic (Acacia senegal, leguminosae), Benjoin (Terminalia Bentzoe, Combretaceae) and
aloe gel (Aloe vera
gum of the liliaceae family mixed with water).
5.13 Resins:
resins are excreted from specialized cells or ducts in plants. They consist of
a mixture of essential oils and polymerized terpenes,
usually insoluble in water. Well-known examples of resins since biblical times
include frankincense (Boswellia sacra) and myrrh (Commiphora myrrha) both of the Burseraceae
family.
5.14 Fatty oils: these are non-volatile, insoluble oils pressed either from the
seeds or from the fruits of plants. Oils are often referred to as Acylglycerides because they are derived from glycerol
molecules. Olive oil is a useful example in as much as these oils over their
own therapeutic potential are also used in carriers as liquid formulations and
ointments.
Table No. 1: List of plants used in CNS diseases
|
S.No |
Name of plant (family) |
Part used |
Biomarker isolated |
|
1 |
Passiflora Incarnata |
Extract |
Flavonoids(as apigenin,Vitexin, kampferol, homorientin, chrysin), Harmane alkaloids (harman, harmalin, harmalol) Pyrone derivatives (malthol), |
|
2 |
Valeriana Officinalis |
Extract |
The Volatile oil
fraction containing bornyl salts, valeranone, Valeranal, valerenic acid and other monoterpenes
and sesquiterpenoids |
|
3 |
P methysticumg forst (kava-kava) |
Extract |
The lipid
extracts contain at least Seven Pyrones, known as kavalactones. |
Table No. 2: Plants traditionally used for
sedative and anticonvulsant
[28-36].
|
S.No |
Family
Species |
Traditional use, Ethnobotanical
information and known active constituents |
|
1 |
Adiantaceae(pteridaceae) Pellaea calomelanos |
Taken as an infusion or smoked to treat
convulsions in ZimbabweThe Kwena
and Kgatla administer milk decoctions of rhizome to
frightened children at link night presumably to calm them |
|
2 |
Amaryllidaceae Boophone disticha (l.f.) herb. Syn: b. Longepedicellata
pax |
Weak decoctions of bulb scales given to
sedate violent, psychotic patents . Traditional healers and patients in south africa drink bulb infusions to induce hallucinations for
divinatory purposes, and also as a medicine to treat mental illness |
|
3 |
Asclepiadaceae Gomphocarpu physocarpus e. |
Leaves used to ‘strengthen
body powdered leaf is used as sedative Roots of an unidentified species are
burned, the ash powdered and placed in incisions for febrile convulsions in
Zimbabwe. |
|
4 |
Asparagaceae Asparagus species: Asparagusvirgatus baker Syn: Protasparagus
Virgatus |
Asparagus africanus
lam. (syn:
Protasparagus Africanus
(lam.) Oberm.) It is used to treat mental
illness and disturbances in east africa. The Zulu
name Iphinganhloya means what
Suppresses the ill-omen; it is used as a protective charm to ward off the
effects of evil . In south africa
leaves, stems and roots of Aasparagus africanus are Pounded and soaked in water to make an
infusion. Drunken two to three times a day, it should relieve problems of
mental disturbance. |
|
5 |
Boraginaceae Lithospermum
cinereum dc. |
The plant is used as a sedative by the
Sotho. |
Table No. 3: Plants traditionally used for
treating depression and similar CNS ailments. [37-38]
|
S.
No |
Family
Species |
Traditional
use, Ethnobotanical information and known active
constituents |
|
1 |
Anacardiaceae Searsia
chirindensis (baker f.) Moffett |
Bark is used to strengthen the body,
stimulate circulation and for rheumatism bark decoctions are traditionally
administered for mental disturbances. |
|
2 |
Cunoniaceae Cunonia
capensis |
The Zulu regard this plant as a
strengthening medicine that is taken after the death of a kraal member. |
|
3 |
Rutaceae Clausena
anisata (willd.) |
Used by Xhosa to treat mental disease and
schizophrenia. Pounded roots of a plant known as Umnukambhiba
(z) reported to be Clausena anisata are used by the Zulu in an emetic for illness
believed to be inflicted by evil spirits or by the ancestors. |
|
4 |
Myrsinaceae Maesa
lanceolata forssk. |
Bark is used to make a stimulating drink
by the Masai of east Africa. Healers in south africa are reported to use this plant for spiritual
purposes associated with ancestral spirit (amadlozi)
worship |
5.15 Essential oil: these are volatile oils usually extracted from plants through a
process of either steam distillation or microwave extraction. They consist of terpenes (mono- and Sesquiterpenoids
and Coumarins). They are of considerable importance
as active ingredients of medicinal plants. Well known examples include
peppermint oil (Mentha X piperita, Lamiaceae), Ylang Ylang Oil (Cananga odorata, annonaceae) amongst
others.
6. Anxiolytic
plants
Anxiety is one of the most
common mental disorders affecting mankind its prevalence is increasing in
recent years due to the rather tense man’s zest to win nature [20], that is,
the rather tense life style imposed on man by the competitive and inhumane
atmosphere pervading everyday life. Anxiolytic
substances, mostly belonging to the benzodiazepine group, occupy a prominent
post in the ranking of the most utilized drugs by man [21]to minimize stress,
tension and anxiety [22] as a result of these effects, benzodiazepines are also
able to treat insomnia [23]. However, the anxiolytic
drugs have an unfavorable risk/benefit ratio, as they produce anterograde amnesia, dependence, abstinence syndrome,
paradoxical reaction in humans and decay of psychomotor functions [24-25] these
symptoms can lead to an increased possibility of car accidents and of fractures
[26-27]. As at present the etiologic factors responsible for anxiety and
tension are not expected to decrease; there is a need for new anxiolytic drugs with less potential to induce adverse
reaction
7. CONCLUSION:
It could be concluded from the above
article that there are significantly number of plants having action on CNS .If
proper research methodology is applied regarding the optimization,
standardization and commercialization of these plants, the ultimate aim of
maximum benefit and
minimum side effect could be achieved.
8. ACKNOWLEDGEMENT:
Authors
wish to thank the department of National Medical library, AIIMS, New Delhi to
carry out this work in a successful manner.
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