Nature: Anxiolytics in the Lap of Nature

Article ID: WMC002140 2046-1690

Nature: Anxiolytics in the Lap of NatureCorresponding Author:Dr. Zulfiqar Ali Bhat,Sr. Asst. Professor, Department of Pharmaceutical sciences, University of Kashmir, Hazaratbal, Srinagar,J&K-190006, India, 190006 - India

Submitting Author:Mr. Dinesh Kumar,Major Project Fellow, Department of Pharmaceutical sciences, University of Kashmir, Hazaratbal, 190006 - India

Article ID: WMC002140

Article Type: Review articles

Submitted on:01-Sep-2011, 06:54:52 PM GMT Published on: 02-Sep-2011, 04:41:24 PM GMT

Article URL: http://www.webmedcentral.com/article_view/2140

Subject Categories:PHARMACEUTICAL SCIENCES

Keywords:Anxiety, Anxiolytics, Traditional medicines, Neurotransmitters

How to cite the article:Kumar D , Bhat Z , Kumar V , Shah M . Nature: Anxiolytics in the Lap of Nature .WebmedCentral PHARMACEUTICAL SCIENCES 2011;2(9):WMC002140

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Nature: Anxiolytics in the Lap of NatureAuthor(s): Kumar D , Bhat Z , Kumar V , Shah M

Abstract

BackgroundA large number of populations depend on traditionalpractitioners, who in turn are dependent on medicinalplants, to meet their primary health care needs. Today"traditional medicine," characterized by the use ofherbs and other natural products, still remains aregular component of health care in the world.AimsTo explore the natural and traditional medicines inrelation to anxieolyticsMethodElectronic literature searches were conducted usingthe following databases: AMED, Cinahl, Embase,Elsevier, Medline, PsychInfo, PubMed (all frominception to August 2004), Google scholar and manyimportant text books. The terms used for the electronicsearches were limited to important receptors andneurotransmitters present in brain which help tomodulate anxiety, plants with neurological bioactivityand bioactive compounds with respective receptorsand mechanism of action along with few chemicalstructures involved in the treatment of anxiety. ResultsSystematic review were located with the above searchstrategy Discussion and conclusionThe review covered all aspects of traditional medicinesand revealed that a detailed study is required toexplore the plants and their uses to treat seriouscomplication of central nervous system. Nature andtradition both is wonder agent of God for the treatmentof diseases. The review will pave a way for new drugsearch.Keywords: Anxiety, Anxiolytics, Traditional medicines,Neurotransmitters.

Introduction

There is a high prevalence of mental and neurologicaldisorders worldwide; these account for 13% of totaldisability adjusted life years (DALYs) lost due to alldiseases and injuries in the world. WHO estimates that450 million persons suffer from mental illness. Anxietyis widespread, with lifetime prevalence rates ranging

from 13.6 to 28.8% in Western countries. Individualsaged between 10 and 25 years are at highest risk fordeveloping an anxiety condition. These conditions areamong the most common mental diseases, and theirprevalence and disease course are reasonably welldocumented. On the other hand, WHO launched itsfirst-ever comprehensive traditional medicine strategyin 2002 with the objective of recognizing traditionalmedicine in the treatment of public health problems [1].Anxiety is a feeling of uneasiness, uncertainty or fear,in response to a real or imagined danger. The bodyresponds to anxiety by releasing a number of "stress"hormones, like adrenaline and cortisol, which have aneffect on almost every organ in the body. Mild forms ofanxiety caused by emotional conflict or life stress arecommon and unproblematic. Anxiety disorders are agroup of conditions in which the feelings of anxiety arenot associated with a real or appropriate threat, or aremuch more intense and long lasting than they shouldbe. People feel frightened and distressed for noapparent reason. This condition can paralyze theindividual into inactivity or withdrawal, and candramatically reduce productivity and significantlydiminish a person's quality of life. Anxiety disordersare common - nearly 25% of people will experienceanxiety disorders at some time in their lives. Physicalsymptoms of anxiety disorders are due to releasedstress hormones. These may increase blood pressure,cause heart palpitations, chest pain, rapid breathing orbreathlessness, sweating, increased muscle tension orirritability. Intestinal blood flow decreases, resulting innausea or diarrhoea. There is often a decreased sexdrive. Children may also have a fear of being awayfrom the family, a refusal to go to school, a fear ofstrangers, a fear of falling asleep or have recurrentnightmares. Specific anxiety disorders each have theirown particular pattern of symptoms and additionalbehavioural characteristics Figure 1.

Depression and Anxiety

The simultaneous occurrence of depression andanxiety is very common. Figures show that between60% and 90% of people with depression also havesymptoms of anxiety. The combination is wellrecognized and can significantly increase the disabilityand disruption of normal function suffered by thepatient. The anxiety associated with depression cantake many forms including panic attacks, obsessive



compulsive disorder, post-traumatic stress disorder,social anxiety disorder or a generalized anxietydisorder. Fortunately medication is available which caneffectively relieve both depression and anxiety.Anxiety is different type like Panic Disorder, Phobias,Post-Traumat ic Stress Disorder (PTSD),Obsessive-Compulsive Disorder (OCD), GeneralisedAnxiety Disorder (GAD).Anxiety disorders in a modern society have relativelyhigh prevalence affecting between10 and 30% of thegeneral population with considerable financialresources. Excessive anxiety can debilitate anddamage the quality of life. In the clinical treatment ofanxiety benzodiazepines, GABAAreceptor agonist andbuspirone, 5-HT1A receptor agonist, are mainlyprescribed as first choice treatment. Chronicadministration of benzodiazepines, however result inphysical dependence such as sedation, myelorelaxation, ataxia, amnesia and pharmacologicaldependence. More over buspirone also results indizziness, headache, nervousness, paresthesia,diarrhea, excitation and sweating as adverse.Therefore, research has been conducted to identifysafer, more specific medications possessing anxiolyticeffect without the complications. In past few years,several herbal medicines have been used for themanagement of anxiety in the world [2].

Methods

Electronic literature searches were conducted usingthe following databases: AMED, Cinahl, Embase,Elsevier, Medline, PsychInfo, PubMed (all frominception to August 2004), Google scholar and manyimportant text books. The terms used for the electronicsearches were limited to important receptors andneurotransmitters present in brain which help tomodulate anxiety, plants with neurological bioactivityand bioactive compounds with respective receptorsand mechanism of action along with few chemicalstructures involved in the treatment of anxiety.

Results

Systematic review was located with the above searchstrategy. Nature and tradition in relation to anxieolytics4.1 Neurotransmiter involve in the CNS disorderespecially in anxietyThere are approximately 50 neurotransmittersidentified. There are billions of nerve cells located inthe brain, which do not directly touch each other.Nerve cells communicate messages by secreting

neurotransmitters. Neurotransmitters can excite orinhibit neurons (nerve cells). Some commonneurotransmitters are acetylcholine, norepinephrine,dopamine, serotonin and gamma aminobutyric acid(GABA). Acetylcholine and norepinephrine areexcitatory neurotransmitters while dopamine, serotonin,and GABA are inhibitory. Each neurotransmitter candirectly or indirectly influence neurons in a specificportion of the brain, thereby affecting behaviour.Cholecystokinin (CCK) is a neurotransmitter in thebrain closely related to anxiety.4.2 Mechanism of impulse transmissionNeurotransmitters are chemicals that transmitmessages from one nerve cell (neuron) to another.The nerve impulse travels from the first nerve cellthrough the axon—a single smooth body arising fromthe nerve cell— to the axon terminal and the synapticknobs. Each synaptic knob communicates with adendrite or cell body of another neuron, and thesynaptic knobs contain neurovesicles that store andrelease neurotransmitters. The synapse lies betweenthe synaptic knob and the next cell. For the impulse tocontinue traveling across the synapse to reach thenext cel l , the synapt ic knobs release theneurotransmitter into that space, and the next nervecell is stimulated to pick up the impulse and continue it.Any changes in its normal function may cause CNSdisorders Figure 2.The mechanism of action and localization ofneurotransmitters in the brain has provided valuableinformation concerning the cause of many mentaldisorders, including clinical depression and chemicaldependency, and in researching medications thatallow normal flow and movement of neurotransmittermolecules.4.3 Noradrenaline; Dysregulation of norepinephrine indepression and adaptation with treatment:Noradrenaline is one of the neurotransmitter in thebrain and its proper regulation helps to normalize thebrain. Any change in regulation leads to disturbancesin the brain system and leads to psychologicaldiseases.In the 1960s, based on over a decade of accumulatingdata, a consensus was forming that catecholamines,specifically norepinephrine (NE), played a crucial rolein affective disorders. “Some, if not all, depressionsare associated with an absolute or relative deficiencyof catecholamines, particularly norepinephrine, atfunctionally important adrenergic receptor sites in thebrain. Elation conversely may be associated with anexcess of such amines” Figure 4.4.4 Role of Norepinephrine in Mood Disorders:Norepinephrine is highly involved in mood disordersFigure 3 and 4.



4.4.1 Receptor in the brain responsible foranxiety/antianxietyBenzodizepine Receptors:BDZ-Rs; The specific antagonist of the BDZ-R, RO15-1788, blocks the anxiolytic effects while theagonists or partial agonists Potentiate the anxiolyticeffects e.g: Flavonoids.Drawback of benzodiazepines:BDZs is oftenassociated with tolerance development and withdrawalsymptoms, which poses a risk of relapse upondiscontinuation.Serotonin receptors (5-hydroxytriptamine):5-hydroxytryptamine1A (5-HT1A); 5-HT1Areceptorsare located at the presynaptic and postsynaptic sites.The somatodendritic autoreceptor, when activated bysystemic stimulation, is believed to exert anxiolytic-likeeffects and to reduce 5- HT release both in the cellbody and in the terminal regions of the serotonergicneurons. The other 5-HT1A receptor is localizedpostsynaptically to the serotonergic neurons in thehippocampus, septum, amygdala, and cortex, where itincreases signal transfer, which leads to an inhibitionof the firing activity. Thus (5-HT1A) receptor is viewedas a relevant target for the treatment of psychiatricdisorders, notably anxiety and depression.5-HT3 receptor:5-HT3 receptor antagonism contributes the anxiolyticeffect .Select ive 5-HT reuptake inhibi tors(SSRIs).y-aminobutyric acid receptor (GABA): GABAAreceptor; GABA is a major inhibitory transmitter in thecentral nervous system. The γ-aminobutyric acid typeA (GABAA) receptor, the chloride ion channel complexand the central benzodiazepine receptors located onthe neuronal membranes within this complex havebeen suggested to play an important role in theregulation of the stress and anxiety states. GABAAreceptors possess binding sites for several drugs,such as anxiolytics, anticonvulsants, generalanesthetics, barbiturates, ethanol, and neurosteroids,which are known to elicit at least some of theirpharmacological effects via the GABAA receptors.GABAA-benzodiazepine receptorHistamine receptor(H-receptor):Histamine receptor plays an important role in anxietyand other CNS disorder With reference to H1, H2, H3receptors.Opioid receptors:Endogenous opioid peptides such as enkephalins,dynorphins and endomorphins, and their receptorshave been found in the peripheral and central nervoussystems. Various bioactive peptides are known to bederived from enzymatic digests of food proteins.Among them, several bioactive peptides derived fromfood proteins such as bovine casein and wheat gluten

show analgesic activities through opioid receptors.Three kinds of opioid receptors are known: µ, deltaand k receptors. In general, opioids were reported toimpair learning and memory and they are also playrole in anxiety and antianxiety.Adenosine A1 receptors:Adenosine functions as a neuromodulator in thecentral nervous system (CNS), acting throughcell-surface receptors. Adenosine receptors wererecognised on the basis of the ability of caffeine to actas an antagonist at A1 and A2 receptors. At themoment, four adenosine receptor subtypes (A1, A2A,A2B and A3) have been cloned and characterisedfrom several mammalian species, including humansand mice, and they all belong to the G-protein coupledreceptor (GPCR) family. In addition, many studiesusing selective adenosine receptor agonists andantagonists have demonstrated that adenosine A1receptors, localised in brain areas essential for motorcontrol such as the striatum, the cerebellum and themotor cortex, are the primary site where adenosinemodulates the incoordination induced by ethanol.Adenosine A1 receptor agonist shows ananxiolytic-like profile or receptors modulateanxiolytic-like actions of ethanol. Dopaminergic Receptor: (D2) receptors; They haveplayed role in psychological diseases and may havethe role in anxiety.Somodendritic autoreceptors:GAC treatment on behavioural perturbations in anxietymodels may involve the somodendritic autoreceptorsof raphae nuclei, leading to decreased centralserotonergic and augmented catecholaminergicfunction. Our fndings reflect the positive attributes ofginkgolic acid conjugates in the actions of Ginkgobiloba [20].Adrenergic receptors: These receptors also play a keyrole in the nervous system. They might be a coreceptor for the anxiety.CCK receptor: Cholecystokinin (CCK) was firstidentified (initially characterized as a 33-amino-acidlong peptide) in the gastrointestinal tract and later itwas found to be one of the most widely distributedpept ides in the bra in where i t acts as aneurotransmitter.H1, H2, H3 receptors:Brain histamine localizes in both histamine neuronsand non-neuronal mast cells, with the mast cellsstoring approxi-mately 50% of whole brain histaminelevels. Histaminergic neurons project to almost allregions of the mammalian brain f rom thetuberomammillary nucleus of the posteriorhypothalamic region. Clinically effective anxiolyticdrugs, diazepam, benzodiazepines and buspirone,



serotonin (5-HT1A) agonists have been found todecrease turnover rate of brain histamine in mice andrats. These findings suggest that histaminergic systemin the brain plays an important role in the regulation ofanxiety. Furthermore, Imaizumi and Onodera havedemonstrated that anxiety-like behavioral activity isinduced or enhanced by the combined administrationof thioperamide, a neuronal histamine releaser havinginhibitory effect of histamine H3autoreceptors, withzolanitidine, a histamine H2 receptor antagonist. Inaddition it has also demonstrated that anxiety likebehavioral activity is also induced by co-injection ofnon-neuronal selective mast cell histamine releaser,Compound 48/80, with a histamine H2receptorantagonist, cimetidine. These neuronal andnon-neuronal histaminergics induced experimentalanxiety models in mice are useful for assessing theeffect of any drug on brain histaminergic system in astate of anxiety.Role of histaminergic system in anxiety: Role ofhistaminergic system in anxiety showed in Table 1.CCK receptor subtypes:CCK1 and CCK2: High densities of CCK-binding sitesin several areas including the cerebral cortex, striatum,olfactory bulb and tubercle, and certain amygdaloidnuclei. Moderate levels were observed in thehippocampus, claustrum, substantia nigra, superiorcolliculus, periaqueductal gray matter, and pontinenuclei. Low densities were reported in several thalamicand hypothalamic nuclei and in the spinal cord. Withthe advent of specific radioligands that coulddifferentiate between the two types of CCK receptors,it has become apparent that the distributions of CCK1and CCK2/gastrin receptors within the CNS areoverlapping and yet distinct. CCK2 receptors are thepredominant subtype in the CNS, with CCK1 receptorsrestricted to some discrete nuclei. The widespreaddistribution of CCK2 receptors in the CNS is consistentwith the diverse functions attributed to neural CCK,including the regulation of feeding (satiety), the controlof learning and memory, behavioral expression ofanxiety, mediation of pain, cardiovascular regulation,neuroendocr ine contro l , osmot ic s t ress,neuropsychiatric disorders (such as panic attacks) andmodulation of dependence and withdrawal processesas well as functions controlled by the dopaminergic,serotonergic, and opioid systems.4.5 Tradition and nature helps to treat diseasesDuring the last decade, there has been a growinginterest in traditional and alternative systems ofmedicine in many developed countries. Medicinalplants are the oldest known health-care products.Their importance is still growing although it variesdepending on the ethnological, medical and historical

background of each country. Herbal medicines areassuming greater importance in the primary healthcare of individuals and communities in manydeveloped as well as developing countries and therehas been an increase in international trade in herbalmedicines. India has 45000 diverse plant speciesspread over 16 different agro-climatic zones, 10vegetation zones, 25 biotic provinces and 426 habitatsof specific spices. Besides, India has up to 18,000flowering plants, 2500 algae, 23,000 fungi, 1600 typesof lichen and 1,800 varieties of bryophytes. Of thisvast quantum around 15,000 to 20,000 are ofmedicinal value, but out of this only, 7,000 to 7,500plants are used by traditional medicine systems inIndia.The use of natural products with therapeuticproperties is as ancient as human civilization and, fora long time, mineral, plant and animal products werethe main sources of drugs. The Industrial Revolutionand the development of organic chemistry resulted ina pre ference for synthet ic products fo rpharmacological treatment. The reasons for this werethat pure compounds were easily obtained, structuralmodifications to produce potentially more active andsafer drugs could be easily performed and theeconomic power of the pharmaceutical companieswas increasing. Furthermore, throughout thedevelopment of human culture, the use of naturalproducts has had magical-religious significance anddifferent points of view regarding the concepts ofhealth and disease existed within each culture.Obviously, this approach was against the new modusVivendi of the industrialized western societies, inwhich drugs from natural resources were consideredeither an option for poorly educated or low incomepeople or simply as religious superstition of nopharmacological value. However, even if we onlyconsider the impact of the discovery of the penicillin,obtained from micro-organisms, on the development ofanti-infection therapy, the importance of naturalproducts is clearly enormous. About 25% of the drugsprescribed worldwide come from plants, 121 suchactive compounds being in current use. Of the 252drugs considered as basic and essential by the WorldHealth Organization (WHO), 11% are exclusively ofplant origin and a significant number are syntheticdrugs obtained from natural precursors. Examples ofimportant drugs obtained from plants are digoxin fromDigitalis spp., quinine and quinidine from Cinchonaspp., vincristrine and vinblastine from Catharanthusroseus, atropine from Atropa belladonna and morphineand codeine from Papaver somniferum. It is estimatedthat 60% of anti-tumour and anti-infectious drugsalready on the market or under clinical trial are ofnatural origin. The vast majority of these cannot yet be



synthesized economically and are still obtained fromwild or cultivated plants. Natural compounds can belead compounds, allowing the design and rationalplanning of new drugs, biomimetic synthesisdevelopment and the discovery of new therapeuticproperties not yet attributed to known compounds [24].In addition, compounds such as muscarine,physostigmine, cannabinoids, yohimbine, forskolin,colchicines and phorbol esters, all obtained fromplants, are important tools used in pharmacological,physiological and biochemical studies.Plants have been used by human beings sinceimmemorial times to cure diseases and to promoterelief from ailments There were times when they werethe most important sources of medicines for peopleHowever, beginning in the late 1940s, this old form oftherapeutics began to lose its importance, being moreand more replaced by synthetic remedies The lessonsfrom millennia were forgotten and were considered‘‘unscientific.’’ Many species of plants possessingactivity on the central nervous system (CNS) In fact,they cover the whole spectrum of central activity suchas psychoanaleptic, psycholeptic and psychodyslepticeffects, and several of these plants are currently usedin therapeutics to treat human ailments. Mind-alteringdrugs, especially plants, have always fascinatedhuman beings Surrounded by mystic superstitions,magic thoughts and religious rituals, they have alwaysoccupied man’s attention Among the plants used byhumans, those able to alter the conscience and thesensorium have drawn special consideration In fact,due to their astonishing effects, the psychodyslepticdrugs (hallucinogenic drugs) have occupied much ofthe researchers’ time, directed most of their thoughtsand efforts towards attempts to understand theirmechanism of action and hence, to understand humanbehavior, thoughts, humor, sensations etc.4.6 Traditional medicines previously evaluated for theirclaims as anxiolytics:Plants has been evaluated for the treatment of anxietyshowed in Table 2 along with their parts used,traditional claims related to anxiety, constituentsisolated from respective plants.4.7 Plant drugs and isolated compounds as anxiolyticsPlant drugs as extract and their single molecules/compounds helps to reduce anxiety has been showedin Table 3 along with their capacity for receptor siteand mechanism of action [2, 6, 16, 17, 20, 28--32,61-63].4.8 Chemical structure of natural isolates responsiblefor treatment of anxiety:The structure of natural isolatesshowed in Figure 5,6and 7 which have the potential to treat anxiety andshowed anxieolytic effects.

Discussion and Conclusion

During the past decade, the indigenous or traditionalsystem of medicine has gained importance in the fieldof medicine. In most of the developing countries, alarge number of populations depend on traditionalpractitioners, who in turn are dependent on medicinalplants, to meet their primary health care needs.Although modern medicines are available, herbalmedicines have retained their image for historical andcultural reasons. As the usage of these herbalmedicines has increased, issues and the mottoregarding their quality, safety, and efficacy inindustrialized and developing countries have croppedup [64]. The search for new molecules that act on the centralnervous system (CNS) and that can be used fortherapeutic purposes started with several studies inthe 19th century. In fact, the first drugs used to treatpathologic conditions of the CNS were based onnatural resources, specifically on plants. However,studies targeting plants with this type of bioactivityrepresent only a very small percentage of thoseinvestigations. In a review of the existing literature, itappears that plants with molecules that produce thiskind of activity are increasingly attractive targets forthe development of new drugs [20]. Flavonoids haverecently increased in importance because they havebeen identified as a new type of ligand with in vivoanxiolytic properties. Different plant species utilized intraditional medicine have been submitted toneuropharmacological evaluation (among others, theEPM) in which sedative effects have beendemonstrated [65]. The flavones chrysin and apigenin,obtained from medicinal plants, have shown ananxiolytic effect in rodents exposed to behavioral tests.Apparently, these compounds modulate thegama-aminobutyric acid (GABA)ergic system toproduce the biological effect [66-67]. Many studieshave examined the use of native plants for morespecific, lower cost treatments with fewer harmfuleffects. The review covered all aspects of traditionalmedicines and revealed that a detailed study isrequired to explore the plants and their uses to treatserious complication of central nervous system.Medicines are hiding in the lap of nature and traditionalways helps to shine the medicines for the treatmentof human illness. Nature and tradition both is really awonder agent of God for the treatment of diseases.This review helps to understand the anxiety or centralnervous system disorders along with treatment bynatural medicines. This review also stimulates the



young researchers and students to search out thenovel drug from the lap of nature and tradition.

Acknowledgments

Dinesh Kumar, ZA Bhat, and MY Shah would like tothank the Department of Pharmaceutical Sciences,University of Kashmir, Srinagar-190006 (India) andUGC - Delhi for their interest and help with thismanuscript.

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Illustrations

Illustration 1

Figure 4: Dysregulation of norepinephrine in depression and adaptation with treatment.

Illustration 2

Figure 2: Mechanism of impulse transmission



Illustration 3

Figure 1: Symptoms of anxiety

Illustration 4

Figure 3. Regulation and function of the norepinephrine modulatory system.



Illustration 5

Figure 5: Structure of chrysin, apigenin, Sinapic acid, Sanjoinine A

Illustration 6

Figure 6: Flavonols, Flavanones, Flavanoid glycoside (1-12) showed anxiolytic activity



Illustration 7

Figure 7: Structure of Trideca-7, 9, 1-,trienoic acid and Cardiospermin

Illustration 8

Table 1: Histaminergic system in anxiety



Biological source Part used Traditional uses related to anxiety Compounds having

anxiolytic activity

Ficus religiosa Linn.

(Moraceae)

Roots, stem,

barks

Nervous disorders, nervine tonic, epilepsy, unconsciousness, and

drug addiction (bhang and opium)

Uncaria rhynchophylla

(Rubiaceae)

Stem Anti-hypertensive, anti-epileptic, and neuroprotective activities

Tilia americana var.

Mexicana (Tiliaceae)

Anxiolytic-like effect Quercetin, kaempferol,

flavonoids

Rubus brasiliensis Martius

(Rosaceae)

Leaf Nervous breakdown treatment

Zizyphi Spinosi Semen

(ZSS), the dried seed of

Zizyphus jujuba Mill var.

spinosa (Rhamnaceae),

Seed Analgesic, tranquilizer and anticonvulsant anxiolyticlike

effect

Sanjoinine A

Magnolia obovata Thrombotic stroke, headache and anxiety Honokiol, magnolol,

obovatol

Valeriana Officinalis L. Roots Tranquilizer insomnia, anxiety and sleep inducer

Sphaeranthus indicus Linn Flower Epileptic, hypotensive, peripheral vasodilatory and convulsions,

Illustration 9

Table 2: Traditional medicines as anxiolytics



Asteraceae mental illnesses and hemicranias

Turnera aphrodisiaca Ward

(Turneraceae)

Anxiety neurosis, and as an aphrodisiac Apigenin

Spondias mombin L.

(Anacardiacaea)

leaves Psychiatric disorders

Casimiroa pringlei (S.

Watson) Engl. (Rutaceae)

Leaves

Casimiroa edulis Llave and

Lex.

Bark, leaves Induce sleep and as an anxiolytic

Matricaria recutita L Sedative and anticonvulsant properties

Passiflora incarnata L. Flower Anxiolytic and sedative properties

Piper methysticum Forst Anxiolytic and sedative properties

Valeriana officinalis L. Anxiolytic and sedative properties, insomnia

Euphorbia hirta L.

(Euphorbiaceae)

Whole herb Anxiolytic and sedative properties

Lavandula angustifolia Linalyl acetate and linalool are considered to have sedative and local

anesthetic effects

Linalool

Cecropia glazioui Sneth

(Moraceae)

leaves Antihypertensive, cardiotonic, and antiasthmatic

Butea frondosa

(Leguminosae)

leaves Rejuvenato and stress treatment



Bacopa monniera Whole herb Cognitive functions of the brain

Azadirachta indica Leaves Cognitive functions of the brain

Withania somnifera Roots and

Whole plant

Cognitive functions of the brain

Ocimum sanctum Whole plant Cognitive functions of

the brain

Annona muricata

(Annonaceae)

Leaves Anticonvulsant activity, tranquilizing and sedative properties

Annona Cherimolia

(Annonaceae)

Tranquilizing and sedative properties

A. glabra (Annonaceae) tranquilizing and sedative properties

A. Montana (Annonaceae) tranquilizing and sedative properties

Annona diversifolia

(Annonaceae)

Leaves Anticonvulsant activity

Salvia reuterana Boiss.

(Labiatae)

Arial part of

the plant

Anti-anxiety herbal drugs

Portulaca oleracea L.

(Portulacaceae)

Anxiolytic agent

Kaempferia parviflora

Zingiberaceae

Rhizomes Impotent symptoms and promote longevity



Elaeocarpus sphaericus

(Elaeocarpaceae)

Fruits Sedative, hypnotic, transquillizing, antiepileptic, and

antihypotensive properties

Citrus paradisi var. starruby Fruits Mood enhancer, anxiety Essential oils

Citrus paradisi Fruits Mood enhancer, anxiety Essential oils

CitrusLimon Fruits Mood enhancer, anxiety Essential oils

Citrus bergamia Fruits Mood enhancer, anxiety Essential oils

Citrus Aurantifolia Fruits Mood enhancer, anxiety Essential oils

Citrus nobilis Fruits Mood enhancer, anxiety Essential oils

Citrus aurantium Fruits Mood enhancer, anxiety Essential oils

Passiflora incarnata

L.(Passifloraceae)

whole plants Sedative, anxiolytic and antispasmodic purpose

Echium amoenum L.

(Boraginaceae)

Flower Anxiolytic

Tilia americana var.

mexicana (Tiliaceae)

Aerial parts Relieve sleeplessness, headache, and nervous excitement Flavonoids

Alstonia scholaris

Linn.R.Br., (Apocynaceae)

leaves Mental illnesses

Ginkgo biloba Linn.

(Ginkgoaceae)

leaves Cerebrovascular insu¦ciency, cardiovascular malfunction and

bronchitis

G i n k g o l i c a c i d

conjugates

Clerodendrum philippinum

schauer, (Verbenaceae)

Flower Treatment of neuropsychological

diseasesWebmedCentral > Review articles of 22


Angelica sinensis

(Umbelliferaceae)

Whole plant Sedative and antianxiety activities Essential oil

Aniba riparia (Nees) Mez,

(Lauraceae)

Fruit Sedative and antianxiety activities

Aethusa cynapium L.

(Umbelliferae/Apiaceae)

Aerial parts Convulsions, mental tension, sleep disorders,

delirium

Trideca-7,9,11-

trienoic acid

C a r d i o s p e r m u m

halicacabum

Roots Curing diseases related to the nervous system Cardiospermin

Nardostachys jatamansi

(Valerianaceae)

Roots Nervous system

Bacopa monnieri L.

(Scrophulariaceae)

Anxiety, poor cognition and a lack of concentration

Centella asiatica (Apiaceae) Nervine tonic in various brain diseases, In parts of India it is given

with milk to improve memory against dementia and aging.



Plant extracts/drugs Natural isolates or

compounds

Binding Receptor/ compete/

Mimick Action receptor

Mode of action

Chrysin

[5,7-dihdroxyflavone]

BDZ-Rs Partial agonists

Apigenen

[5,7,41trihydroxyflavone]

BDZ-Rs Partial agonists

50% EtOH extract of

Cinnamomum cassia

(stem barks)

S o m a t o d e n d r i t i c

autoreceptors (5-HT1A)

WAY100635, a somatodendritic 5-HT1A antagonist,

enhances serotonergic system activity via complete

blockade of the somatodendritic autoreceptors and

possesses anxiogenic activity.The anxiolytic-like effect

of C. cassia was significantly blocked by WAY100635

at 0.3 and 1.0 mg/kg and the above mentioned that the

action of extract is due to 5-HT1A receptor.

50% EtOH extract of

Cinnamomum cassia

(stem barks)

GABAA receptors GABAA receptors are potentially inhibited by

picrotoxin bicuculline and SR95531 (compitative

antagonist) and the anxiolytic-like effect of C. cassia

was significantly blocked by (+)-bicuculline at 0.1, 0.3,

Illustration 10

Table 3: Plant drugs and isolated compounds as anxiolytics



and 1.0 mg/kg.

Cinnamic acid of

p h e n y l p r o p a n o i d

compounds

--------------

p-Coumaric acid, caffeic

acid, and ferulic acid of

cinnamic acid derivatives

----------------

U n c a r i a

r h y n c h o p h y l l a

aqueous extract

5-HT1A 5-HT1A receptor activation.

Quercetin and kaempferol ___________

cinnamic acid, p-coumaric

acid, caffeic acid and

ferulic

acid

sinapic acid GABAA receptor, Agonist of GABAA receptor

Magnolol and Honokiol Histaminergic system

Saiboku-to Histaminergic system By acting on H-receptor

Sanjoinine A GABA receptor Sanjoinine A may exert its anxiolytic effect by

increasing GABA synthesis via GAD65/67 activation

and increasing receptors for benzodiazepine or GABAWebmedCentral > Review articles of 22


by influencing GABA receptor subunit compositions.

Hexanic fraction of

Rubus brasiliensis

GABAA-benzodiazepine

receptor complex

By acting as an agonist on GABAA-benzodiazepine

receptor complex.

Obovatol GABAA/benzodiazepine

receptor complex

Anxiolytic effect mediated by GABA-benzodiazepine

receptors-activated Cl-channel opening.

Trideca-7,9,11-

trienoic acid

Antianxiety activity was confirmed using the

mCPP-induced hypolocomotion test.

Cardiospermin

valerenic acid GABAA-minergic system Valerenic acid interacts with the GABAA-ergic system,

a mechanism of action similar to benzodiazepine drugs.

Ginkgolic acid conjugates

(GAC) (6-alkylsalicylates,

namely n-tridecyl-,

n - p e n t a d e c y l - ,

n-heptadecyl-,

n-pentadecenyl- and

n-heptadecenylsalicylates)

5-HT1, receptor, dopamine

D2 receptor

Indian Ginkgo biloba extracts (unpuriÞed) containing

GAC have been found to decrease the serotonin 5-HT1,

receptor binding activity in the frontal cortex and

dopamine D2 receptor binding activity in corpus

striatum.



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