Plants against depression

5/24/2018 Plants against depression

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Natural Product Radian144

Review Article

Introduction

Mental depression is a chronicillness that affects a persons mood,thoughts, physical health and behaviour.Symptoms of depression includebiological and emotional components.Biological symptoms include retardationof thought and action, loss of libido, sleepdisturbance and loss of appetite.Emotional symptoms include misery,

apathy and pessimism, low self-esteemconsisting of feeling of guilt, inadequacyand ugliness, indecisiveness and loss ofmotivation. There are two types of mentaldepression, namelyunipolar depression,in which mood swings are always in thesame direction and is common (about75% of cases), non-familial, clearly

associated with stressful life events, and

accompanied by symptoms of anxiety andagitation. The second type is bipolardepression (about 25% of cases),sometimes also called as endogenousdepression, shows a familial pattern,unrelated to external stresses and usuallyappears in early adult life, and is muchless common, results in oscillatingdepression and mania over a period of afew weeks1. Patients with depression have

symptoms that reflect decrease in brainmonoamine neurotransmitters,specifically norepinephrine, serotonin anddopamine2. Reserpine, an antihypertensivedrug, isolated from Rauvol fiaserpentina Benth. ex Kurz, thatdepleted neuronal storage granules ofnorepinephrine, serotonin and dopamine,

produced clinically significant depressiin 15% or more of patients3.

Prevalence rate for all mendisorders in India was observed to 65.4/1000 population. Out of whiprevalence rate for affective disorders

estimated to be 31.2/1000 populatioDepression is the leading cause of diseasrelated disability among women in t

world today. Depression is much mocommon among women than men, w

female/male risk ratios roughly two : on

The prevalence of major depressionestimated to be 2% in the generpopulation over 65 years of age6. Abo11.2% school dropouts had severe

extreme grades of depression as again3% among school going and nil amocollege going adolescents7.

Although a number of synthe

drugs are being used as the standa

treatment for clinically depressed patien

they have adverse effects that c

compromise the therapeutic treatme

These common adverse effects include dmouth, fatigue, gastrointestinal

respiratory problems, anxiety agitatio

drowsiness, and cardiac arrhythmia

Several drug-drug interactions can al

occur. These conditions create

opportunity for alternative treatment

depression by use of medicinal plants

by plant-based antidepressa

formulations.

A review on antidepressant plants

Dinesh Dhingra* and Amandeep SharmaPharmacology Division, Department of Pharmaceutical Sciences

Guru Jambheshwar University, Hisar-125 001, Haryana, India*Correspondent author address, H. No. 207, Defence Colony, Hisar-125 001

E-mail: [email protected] 19 April 2005; Accepted 27 May 2005

AbstractDepression is a heterogeneous mood disorder that has been classified and treated in a

variety of ways. Although a number of synthetic drugs are being used as standard treatment forclinically depressed patients, they have adverse effects that can compromise the therapeutictreatment. Thus, it is worthwhile to look for antidepressants from plants with proven advantageand favourable benefit-to-risk ratio. A number of medicinal plantsper seand medicines derivedfrom these plants have shown antidepressant properties by virtue of their medicinal constituents.The causes of depression are decreased brain levels of monoamines like noradrenaline, dopamineand serotonin. Therefore, drugs restoring the reduced levels of these monoamines in the braineither by inhibiting monoamine oxidase or by inhibiting reuptake of these neurotransmittersmight be fruitful in the treatment of depression. The present review is focused on the medicinalplants and plant-based formulations having antidepressant activity in animal studies and inhumans.

Keywords: Depression, Medicinal plants, Antidepressants, Herbal medicine.

IPC code; Int. cl.7A61K 35/78, A61P 25/24


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Vol 5(2) March-April 2006 14

Review Articl

Medicinal plants as

antidepressants

The plants proved to possessantidepressant property are:Hypericum

perforatum Linn., Areca catechuLinn., Bacopa monnieri (Linn.)

Penn., Centella asiatica (Linn.)Urban, Clitoria ternatea Linn.,Cimicifuga racemosa(Linn.) Nutt.,Crocus sativus Linn., Curcuma

longa Linn., Evening Primerose(Oenotheraspp.) oil, Ginkgo biloba

Linn.,Magnolia officinalisRehder& E. H. Wilson, Mimosa pudica

Linn., Ocimum sanctum Linn.,

Withania somniferaDunal, Piper

methysticum

G. Forst.

(Kava Kava,

Siphocampylus

verticillatus

(Cham.) G.

D o n ,

R h a z y a

s t r i c t a

D e c n e ,

Apocynum

v e n e t u m

L i n n . ,

M o r i n d a

of fi ci na lis

H o w ,

P e r i l l a

fru tes cens( L i n n . )

Britton, and

R h i z o m a

a c o r i

tatarinowii.

Hyperi cum perforatum Linn.

(Family-Hypericaceae)

It is better known as St. Johnswort , ha s been used cl in ical ly fo rcenturies8. It is a perennial herbdistributed in Europe, Asia, North Africaand North America. Indian plant growsup to a height of 1m distributed in

western Himalayas at an altitude of 1000-3500m. It has been known for centuriesfor its putative medicinal properties,

including antidepressant, anxiolytic,diuretic, antibiotic, antimalarial, woundhealing and anthelmintic9, 10. Astandardized 50% aqueous ethanolicextract of Indian plant (100-200 mg/kgp. o.) once daily for 3 consecutive daysshowed significant antidepressant activityin behavioural despair test, tail-suspension

Clitoria ternatea

Cimicifuga racemosa

Curcuma longa

test, learned helplessness test anreserpine induced hypothermia test in rand mice. The observed antidepressaactivity of Indian plant was qualitativecomparable to that induced Imipramine11, 12. Indian plant has beshown to exert significant antioxidaactivity induced by augmented activityoxidative free radicals scavenging enzymsuperoxide dismutase, catalase aglutathione peroxide13. Hypericum extrastandardized to both hypericin anhyperforin, appears to have significant frradical scavenging properties in cell-fr

and human vascular systems14

. Thefavourable effects were achieved wH. perforatumhaving the ability to treboth depression and amnesia with lowpotential side effects15. Hypericum extraSTW 3 administered once daily in a doof 612 mg for up to 24 weeks producantidepressant effect equivalent Sertraline (50 mg) in patients of moderadepression16. Efficacy and tolerability Hypericum LI 160 was comparable

fluoxetine in mild to moderate depressiin a 4-week randomized, double-blitrial17. Thus, Hypericum extract can effective in routine treatment of mild moderate depressive disorders18.Howevit was not effective for treatment patients with major depression19.

Methanol extracts of the aerparts (blossom) ofH. canarienLinn.,H. grandifolium Choisy,Hglandulosum

Gilib.andH. reflexuLinn. f., found in Canary Island, show

antidepressant-like effect in mice20,

Hypericum contains numerocompounds with documented biologicactivity. Constituents that have stimulatthe most interest include tnaphthodianthrones namely hypericin a


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pseudohypericin22; phloroglucinols23

namely hyperforin and adhyperforin;flavonoids24like flavonol glycosides, viz.rutin, quercitrin, isoquercitrin, hyperin/hyperoside and aglycones, viz. kaempferol,luteolin, myricetin and quercetin;

xanthones namely kielkorin in roots25,1,3,6,7-tetrahydroxyxanthone in traceamounts in leaves and stems26. Manypharmacological activities appear to beattributable to hypericin and to theflavonoid constituents. However,hyperforin has been considered as animportant antidepressant constituent of

H. perforatum27-29 and this may beinvolved in inhibition of uptake ofserotonin, noradrenaline anddopamine30, 31. An increase of 5-HT level

was also observed in hypothalamus andhippocampus. The action of Hypericumextract is consistent with the notion thatserotonergic system is involved32. LI 160,standardized extract ofH. perforatumand pure substance hypericin showed weakinhibitory effect on MAO-A and MAO-B.It also markedly inhibited thesynaptosomal uptake of serotonin andnoradrenaline. However, dopamine uptakeand neuronal uptake of GABA andL-glutamate are also inhibited. Theseeffects may mainly be attributed tohyperforin present in the extract33, 34.

Areca catechuLinn.

(Family-Arecaceae)

It is widely cultivated in Indiaand Sri Lanka, South of China andPhilippines, in Malaysia, Indonesia andEastern Africa. Its nuts are being used bypeople for masticatory purposes indifferent parts of the world and it is a

very popular chewing nut in the Indo-Pak

subcontinent. It showed significantantidepressant activity in forced swim testand tail-suspension test in rodents35, 36.

Alkaloids such as arecaidine, arecoline,and a few other constituents, reported tobe present in areca nuts were found notto inhibit monoamine oxidase (MAO). Onthe other hand, dichloromethane fractionfrom areca nuts showed antidepressantactivity via MAO-A inhibition37.

Bacopa monnieri(Linn.) Penn.

(Family-Scrophulariaceae)

It is commonly known asBrahmi,and is found in wet, damp andmarshy places throughout India andsubtropical region up to 1000 m elevation.It has been used as nervine tonic and alsoenhances learning and memory. The activeconstituents are the alkaloids, namelybrahmine, herpestine and mixture of3 other alkaloids and also saponins,namely, bacoside A and B. Thestandardized methanolic extract (20 and40 mg/kg, p.o.) given once daily for 5days showed significant antidepressantactivity in forced swim test and learnedhelplessness models of depression andthis effect was comparable to that ofImipramine38.

Centella asiatica(Linn.) Urban

(Family-Apiaceae)

The drug consists of dried aerialparts (preferably leaves). It is distributedthroughout the tropical and subtropicalregions of India. Total triterpenesfrom the plant reduced the immobilitytime of mice in forced swimmingtest and thus had antidepressantactivity39.

Cimicifuga racemosa(Linn.) Nut

(Family-Ranunculaceae)

It is distributed in temperaHimalayas from Kashmir to Bhut(2300-4000 m), Eastern Europe anSiberia. Ethanolic-aqueous extracts C. racemosa (50 or 100 mg/ksignificantly decreased the period immobility in tail suspension test experimental animals and thus showantidepressant activity40.

Clitoria ternateaLinn.

(Family-Fabaceae)

A cosmopolitan herb found in ttropics. Methanolic extract of pladecreased the duration of immobility tail suspension test, thus possessiantidepressant activity via serotonergsystem41.

Crocus sativusLinn.(Family-Iridaceae)

Commonly known as Saffron,indigenous to Greece, Asia Minor aPersia in which it grows wildly. It is alcultivated in Spain, France, Greece, Persand India. Saffron at a dose of 30 mg/dTDS and BD was found to be effectisimilarly to Imipramine 100 mg/d(TDS) and Fluoxetine 20 mg/day (BDrespectively in the treatment of mild

moderate depression in adupatients42,43.

Curcuma longaLinn.(Family-Zingiberaceae)

This plant commonly known turmeric is native of Southern Asi


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cultivated in India, China and othertropical countries. The aqueous extractsadministered orally to the mice from 140to 560 mg/kg for 14 days, elicited dose-dependant reduction of immobility timein the tail suspension test and the forcedswimming test in mice. Turmeric hadsignificant antidepressant activity and thismay be mediated in part through MAO-Ainhibition in mouse brain44.

Evening Primerose oil

Evening Primerose oil is the fixed

oil obtained from the seeds ofOenothera species (Family-Onagraceae). The principle speciescultivated in the UK is O. biennisLinn.Evening Primerose oil (0.2 ml/20 g)showed significant antidepressant effecton all days of treatment in mouse modelof chronic fatigue syndrome (CFS) in

which mice were forced to swim everydayfor 7 days for 6 minutes session45.

Ginkgo bilobaLinn.

(Family-Ginkgoceae)

It is native of China andoccasionally cultivated in Indian gardens,particularly on Hills. A few trees are foundin Himachal Pradesh. Its extract (14 mg/kg, p.o.) restored restraint stress-inducedelevation in whole brain levels ofcatecholamines (norepinephrine,

dopamine) and serotonin46

. The extracthas a demonstrable effect in improvingmood in healthy older volunteers47. Thecombination of G. bilobaextract with

Venlafaxine enhanced the protection ofneurons and decreased damage to thebrain, while relieving the side effects ofsynthetic antidepressants48.

Magnolia officinalisLinn.(Family-Magnoliaceae)

The tree is distributed in centraland eastern Himalayas up to 1500m,Burma and Malay Peninsula. Acutetreatments with active metabolites suchas magnolol anddihydroxydihydromagnolol (50-100 mg/kg, i.p.) obtained from aqueous extractof the bark, attenuated the forced swim-induced experimental depression inmice49.

Mimosa pudicaLinn.(Family-Mimosaceae)

It is probably a native of tropicalAmer ica; na tu ra li zed more or le ssthroughout India. Aqueous extract fromdried leaves are employed to alleviatedepression in Mexico. The extract (6 mg/kg and 8 mg/kg, i.p.) reduced immobilityin the forced swimming test, thus showedantidepressant-like effect in rats50.

Ocimum sanctumLinn.(Family-Lamiaceae)

The plant known as Tulsi andSacred or Holy basil is a herbaceous, muchbranched annual plant found throughoutIndia. It helps in relieving the anxiety andagitation associated with depression51, 52.Tulsi also showed anti-aggressive and

calming effect53, 54

. Ethanolic extract of theleaves lowered the immobility in abehavioural despair involving forcedswimming in rats and mice. This action

was blocked by Haloperidol and Sulpiride,indicating a possible action involvingdopaminergic neurons55. Methanol extractfrom roots (400 mg/kg, i.p.) showed

increase in the swimming time, suggestiits antidepressant activity56.

Withania somnifera(Linn.) Duna(Family-Solanaceae)

The drug consists of dried rooof the plant, widely distributed in Nort

western India. In the Indian traditionsystem of medicine,it is widely regardas the Indian Ginseng. It is classified

Ayurveda, as a rasayana, a group of planderived drugs reputed to promote physicand mental health, augment resistance

the body against disease and diverse adverenvironmental factors, revitalize the boin debilitated conditions and increalongevity. Standardized extract of roots (and 50 mg/kg, p.o.), significanattenuated chronic stress induced mendepression, immunosuppressiocognitive deficit, male sexual dysfunctiohyperglycaemia, glucose intolerancincrease in plasma corticosterone levand gastric ulceration in rats. Thus,indicates significant antistress adaptogenactivity of the plant57, 58. A dose of (1mg/kg, p.o.) produced a significareduction in immobility period in a moumodel of chronic fatigue syndrome,

which mice were forced to swim forminutes session on each day for 15 daand the immobility period was recordeCo-administration of antioxidants aW. somnifera significantly reduc

lipid peroxidation and restored tglutathione levels decreased by chronswimming in mice59 . Bioactiglycowithanolides (20 and 50 mg/kp.o.), isolated from roots, administeronce daily for 5 days exhibitantidepressant effect, comparable withat induced by Imipramine (10 mg/k


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i.p.), in the forced-swimming inducedbehaviour despair and learnedhelplessness tests60.

Piper methysticumForst

(Family-Piperaceae)

In the South-Pacific islands, anaqueous extract of the roots of this plant,commonly known as Kava-Kava isconsumed as a ritual stimulant; large dosescause intoxication. The standardizedextract of kava-kava roots are used for thetherapy of anxiety, tension, insomnia and

restlessness. Kava pyrones, the majorconstituents of kava-kava, are generallyconsidered to be responsible for thepharmacological activity in humans andanimals. The inhibition of MAO-B by kavapyrones-enriched extract might be animportant mechanism for theirpsychotropic activity61, 62. Relaxing andeuphoric actions of the extract may becaused by the activation of the mesolimbic

dopaminergic neurons63.

alcoholic extract (100-1000 mg/kg, i.p.)elicited a significant antidepressant effect,

when assessed in the tail-suspension testand forced swimming test in mice. Thisantidepressant effect is most likely to bemediated through an interaction withadrenergic, dopaminergic, glutamatergicand serotonergic systems. The activeprinciple(s) responsible are so far, notknown, but much of the extract actioncould be related to the presence of thealkaloid, cis-8,10-di-n-propyllobelidiolhydrochloride dihydrate. Also otherconstituents like flavonoids (3-methoxy

luteolin), triterpenes (-amirin and-amirin), and steroids (campesterol,-sitosterol, stigmasterol and stigmasterolglycoside) could also be responsible, atleast in part, for the antidepressantproperties64.

Rhazya strictaDecne(Family-Apocynaceae)

It is a shrub plant which growscommonly in the Arabian Peninsula,Sind, Baluchistan and Afghanistan.

Aqueous ex tr ac t of le aves of th isplant showed antidepressant-likeactivity in forced-swimming test in ratsand this might be due to itsproperty of inhibiting both MAO-A andMAO-B. Anti depressant-like activity ofthe plant extract might be due to any ofthe constituents present, such as

alkaloids with -carboline nucleus(akuammidine, rhaziminine andtetrahydro secamine), flavonoids, namelyisorhamnetine, 3- (6-dirhamnosylgalactoside)-7-rhamnoside and3-(6-rhamnosyl galactoside)-7-rhamnoside65.

Apocynum venetumLinn.(Family-Apocynaceae)

A wild shrub widely distributin mid and Northwestern China. An extraof leaves significantly reduced immobiltime in the forced swimming test aftacute administration at a dosage of 1mg/kg, an effect which was comparabto that of synthetic antidepressaImipramine at a dosage of 20 mg/kg. Tantidepressant effect of the plant migbe due to hyperoside and isoquercitr

wh ich are ma jor fl avonoi ds in t

extract66

.

Morinda officinalis F.C. How

(Family-Rubiaceae)

It grows in humid areas of SouEast China. The ethanolic extract showantidepressant-like effect in animmodels of depression such as forceswimming test and learned helplessneparadigm. The antidepressant effect of t

extract could at least partly be due increase in serotonin levels at the neurlevel67, 68.

Piper methysticum

Morinda officinalis

Perilla frutescens

Siphocampylus verticillatus

(Cham.) G. Don

(Family-Campanulaceae)

It is a native species that growsabundantly in the south of Brazil. Hydro-


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Perilla frutescens(Linn.) Britton(Family-Lamiaceae)

The leaves ofP. frutescensvar.acuta Kudo (Perillae Herba) arefound in some traditional oriental herbalmedicines that are primarily used to treatdisorders such as depression and anxiety.

An oral administration of aqueous extractof the drug significantly reduced theduration of immobility in animal modelsof depression. Moreover, its 50%methanol extract of the aqueous extractand its 30% methanol extract also reduced

the duration of immobility. The extractwith anti-immobility effects was found tocontain abundant rosmarinic acid. Theoral and intraperitoneal administration ofrosmarinic acid significantly reduced theduration of immobility. The resultsuggested that rosmarinic acid may be themain component involved in theantidepressive effect of Perillae Herbain the forced swimming test69.

Rhizoma acori tatarinowii

The water decoction ofRhizoma acor itatar inowii, aChinese herb, significantly reduced theimmobility times in rat forced swimmingtest and mouse tail suspension test, thushaving antidepressant-like effect70.

Antidepressant polyherbal

formulations

Some polyherbal formulationsprescribed by medical practitioners are:Chaihu-Shugan-San, EuMil ,

Mentat, Siotone, Catuama, Banxia-houpu, Kami-shoyo-sanand Sho-ju-

sen. It has been observed that the mainingredients of these preparations include:Withania somnifera, Ocimum

sanctum,Asparagus racemosus

Willd.,Emblica officinalisGaertn.,Panax ginseng,Bacopamonnieri,

Centellaasiatica, Nardostachys

ja tamansi DC., Evolvulusalsino ides Linn., Valerianajatamansi Jones, Acorus calamusLinn., Tinospora cordifolia(Willd.)Miers. ex Hook. f. & Thoms.,Celastrus paniculatus Willd.,Saussurea lappa C.B. Clarke,

Terminalia chebula Retz.,Terminalia bellirica Roxb., SasakurinensisMakino et Sibata,PinusdensifloraSieb. et Zucc.andTribulusterrestrisLinn.71-81.

Conclusion

As mentioned above, there are anumber of medicinal plants andformulations that possess antidepressantactivity comparable to clinically effectivesynthetic antidepressants. Thus, plantbased formulations can be effectively usedfor the treatment of mild to moderatecases of depression, with fewer side effectsthan the older synthetic agents. However,except for Hypericum perforatum,more detailed clinical studies are requiredfor the plants showing antidepressantactivity in animal studies, so that

depression can be treated effectively byuse of plant-based formulations.

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