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, kampferolhomorientinchrysin),

Harmane alkaloids (harmanharmalin, harmalolPyrone 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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Received on 28.05.2014          Accepted on 10.06.2014        

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Asian J. Pharm. Tech.  2014; Vol. 4: Issue 2, Pg 100-105