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HerbalGram The Journal of the American Botanical Council Issue: 56 Page: 40 5! Rhodiola rosea: A Phytomedicinal Overview HerbalGram" !00!

#56:40 5! American Botanical Council $Bu% This Issue& 'i(ebar: )Clinical Case 'tu(ies *" rosea) Rhodiola rosea: A Phytomedicinal Overview b% *ichar( P" Bro+n, -".", Patricia /" Gerbarg, -".", an( 0a1ir *ama2ano3, Ph".", ."'" Rhodiola rosea /", also 1no+n as )gol(en root) or )roseroot) belongs to the 4lant famil% Crassulaceae"5 R. rosea gro+s 4rimaril% in (r% san(% groun( at high altitu(es in the arctic areas of 6uro4e an( Asia"! The 4lant reaches a height of 5! to 70 inches $80cm& an( 4ro(uces %ello+ blossoms" It is a 4erennial +ith a thic1 rhi2ome, fragrant +hen cut" The Gree1 4h%sician, .ioscori(es, first recor(e( me(icinal a44lications of rodia riza in 88 C"6" in De Materia Medica.7 /innaeus rename( it Rhodiola rosea, referring to the rose li1e attar $fragrance& of the fresh cut rootstoc1"4 9or centuries, *" rosea has been use( in the tra(itional me(icine of *ussia, 'can(ina3ia, an( other countries" Bet+een 58!5 an( 5:60, 3arious me(icinal a44lications of R. rosea a44eare( in the scientific literature of '+e(en, ;or+a%, 9rance, German%, the 'o3iet <nion, an( Icelan("!,4 5! 'ince 5:60, more than 5=0 4harmacological, 4h%tochemical, an( clinical stu(ies ha3e been 4ublishe(" Although *" rosea has been e>tensi3el% stu(ie( as an a(a4togen +ith 3arious health 4romoting effects, its 4ro4erties remain largel% un1no+n in the ?est" In 4art this ma% be (ue to the fact that the bul1 of research has been 4ublishe( in 'la3ic an( 'can(ina3ian languages" This re3ie+ 4ro3i(es an intro(uction to some of the tra(itional uses of *" rosea, its 4h%tochemistr%, scientific stu(ies e>4loring its (i3erse 4h%siological effects, an( its current an( future me(ical a44lications" Rhodiola rosea in Traditional Medicine Tra(itional fol1 me(icine use( R. rosea to increase 4h%sical en(urance, +or1 4ro(ucti3it%, longe3it%, resistance to high altitu(e sic1ness, an( to treat fatigue, (e4ression, anemia, im4otence, gastrointestinal ailments, infections, an( ner3ous s%stem (isor(ers" In mountain 3illages of 'iberia, a bou@uet of roots is still gi3en to cou4les 4rior to marriage to enhance fertilit% an( assure the birth of health% chil(ren"! In -i((le Asia, R. rosea tea +as the most effecti3e treatment for col( an( flu (uring se3ere Asian +inters" -ongolian (octors 4rescribe( it for tuberculosis an( cancer"57 9or centuries, onl% famil% members 1ne+ +here to

har3est the +il( )gol(en roots) an( the metho(s of e>traction" ! 'iberians secretl% trans4orte( the herb (o+n ancient trails to the Caucasian -ountains +here it +as tra(e( for Georgian +ines, fruits, garlic, an( hone%" Chinese em4erors sent e>4e(itions to 'iberia to bring bac1 the )gol(en root) for me(icinal 4re4arations" /innaeus +rote of R. rosea as an astringent an( for the treatment of hernia, leucorrhoea $3aginal (ischarge&, h%steria, an( hea(ache"4,8 In 5855 R. rosea +as inclu(e( in the first '+e(ish Pharmaco4oeia" Ai1ings use( the herb to enhance their 4h%sical strength an( en(urance"54 German researchers (escribe( the benefits of R. rosea for 4ain, hea(ache, scur3%, hemorrhoi(s, as a stimulant, an( as an anti inflammator%"55,56 In 5:65, G"A" Br%lo3, a *ussian botanist an( ta>onomist in the .e4artment of Botan% at the ;o3osibirs1 Branch of the *ussian Aca(em% of 'ciences, le( an e>4e(ition to the ce(ar taiga in the Altai -ountains of southern 'iberia +here he locate( an( i(entifie( the )gol(en root) as Rhodiola rosea.58 6>tracts of the R. rosea root +ere foun( to contain 4o+erful a(a4togens" *esearch re3eale( that it 4rotecte( animals an( humans from mental an( 4h%sical stress, to>ins, an( col("!,58 The @uest for ne+ me(icines to treat (iseases such as cancer an( ra(iation sic1ness, an( to enhance 4h%sical an( mental 4erformance, le( to the (isco3er% of a grou4 of 4hen%l4ro4anoi(s that are s4ecific to R. rosea" $'ee Ph%tochemistr% section belo+"& Geographical Distribution and Taxonomy o Rhodiola rosea ?hile Rhodiola as a genus ma% ha3e originate( in the mountainous regions of 'outh+est China an( the Himala%as, 5= botanists ha3e establishe( that 3arious s4ecies of the genus Rhodiola naturall% (is4la% a circum4olar (istribution in mountainous regions in the higher latitu(es an( ele3ations of the ;orthern Hemis4here" In Central an( ;orthern Asia, the genus is (istribute( from the Altai -ountains across -ongolia into man% 4arts of 'iberia" 5: Accor(ing to Hegi, its (istribution in 6uro4e e>ten(s from Icelan( an( the British Isles across 'can(ina3ia as far south as the P%renees, the Al4s, the Car4athian -ountains an( other mountainous Bal1an regions" 'e3eral 3arieties of Rhodiola s4ecies ha3e also been i(entifie( across Alas1a, Cana(a, an( the northern mountains of the continental <nite( 'tates"!0 In fact, the +orl( (atabase of botanical literature sho+s man% citations i(entif%ing a broa( range of s4ecies of the genus Rhodiola, in some cases inclu(ing R. rosea, in man% (i3erse locations in northern latitu(es $see Table 5&" The current ta>onomical status of the genus Rhodiola has become @uite com4le>" Before ?orl( ?ar II, some ta>onomists se4arate( (ifferent s4ecies of Rhodiola into an in(e4en(ent genus, belonging to the subfamil% Sedoidae"!0 Then Rhodiola +as reclassifie( as a subgenus of the larger genus Sedum, +hich containe( about 50 s4ecies" In 5:67 Hegi i(entifie( more than 50 s4ecies of Rhodiola an( re establishe( them as a se4arate genus"!0 .ue to their mor4hological similarities, the% form a (istinct Rhodiola grou4"!5 There are still

(iffering o4inions among s4ecialists about +hich ne+ s4ecies shoul( or shoul( not be inclu(e( in the genus Rhodiola" The rationale an( (efining criteria for the boun(aries of the genus remain some+hat contro3ersial" This is not, in itself, necessaril% counter4ro(ucti3e, since the ac@uisition of botanical 1no+le(ge ine3itabl% stimulates ne+ un(erstan(ing an( insight, creating the nee( for re3ise( s%stems of classification" In the case of R. rosea, ho+e3er, this ta>onomic ambiguit% ma% ha3e une>4ecte( an( 4otentiall% negati3e conse@uences" Po4ulari2ing a 4h%tome(icinal 4lant li1e R. rosea can create confusion +hen the 4ublic is offere( a 3ariet% of )Rhodiola) 4ro(ucts using the general 4lant famil% name instea( of the full botanical name of the 4articular s4ecies" 9or e>am4le, 4ro(ucts calle( )Rhodiola s44", Tibetan Rhodiola or In(ian Rhodiola) ma% incorrectl% im4l% e@ui3alence +ith R. rosea e>tract" Because of significant s4ecies (e4en(ent 3ariation in 4h%tochemistr% an( 4harmacolog%, the use of )Rhodiola) as a general term is inaccurate an( mislea(ing" The correct i(entification of all Rhodiola s4ecies accor(ing to 4recise an( generall% acce4te( botanical, 4h%tochemical, an( genetic ta>onomic criteria is not merel% an abstract intellectual e>ercise" It is critical for both scientific an( 4h%to4harmacological accurac%, as +ell as for 4ro(uct labeling for the 4ublic" Consumers ma% nee( 4rofessional gui(ance to a3oi( 4urchasing ineffecti3e bran(s, 4articularl% those that (o not 4ro3i(e full information, inclu(ing the com4lete botanical name of the 4lant s4ecies" Com4anies ma% change their su44liers o3er time" Therefore, consumers shoul( 4erio(icall% chec1 in(e4en(ent sources of 4ro(uct e3aluation, as +ell as re@uesting information about @ualit% control an( content from manufacturers" The 4harmacological an( me(icinal 4ro4erties of Rhodiola are s4ecies (e4en(ent 4henomena"!! Cf all the Rhodiola s4ecies, R. rosea has been the 4re(ominant subDect of 4h%tochemical, animal, an( human stu(ies" !,5=,!7,!4 Table ! com4ares the research recor( of R. rosea +ith all other s4ecies of the genus Rhodiola" A44ro>imatel% 55 4ercent of all animal stu(ies an( :4 4ercent of all human stu(ies con(ucte( on 4lants in the genus Rhodiola are on the s4ecies R. rosea" Cnl% R. rosea has 4asse( e>tensi3e to>icological stu(ies an( has been certifie( safe for both animals an( humans"!5

Phytochemistry o Rhodiola rosea The in3estigation of the 4h%tochemistr% of R. rosea root has re3eale( the 4resence of si> (istinct grou4s of chemical com4oun(s:

Phen%l4ro4anoi(s: rosa3in, rosin, rosarin $s4ecific to R. rosea# Phen%lethanol (eri3ati3es: sali(rosi(e $rho(iolosi(e&, t%rosol# 9la3anoi(s: ro(iolin, ro(ionin, ro(iosin, acet%lro(algin, tricin# -onoter4ernes: rosiri(ol, rosari(in# Triter4enes: (aucosterol, beta sitosterol# Phenolic aci(s: chlorogenic an( h%(ro>%cinnamic, gallic aci(s"

The stan(ar(i2ation of R. rosea root e>tracts has gone through t+o (istinct 4hases" Initiall%, in the 5:80s, the com4oun( res4onsible for its uni@ue 4harmacological 4ro4erties +as belie3e( to be sali(rosi(e $rho(iolosi(e&" !,!7,!4,!6,!8 Therefore, the first generation of R. rosea tinctureEe>tracts a44ro3e( b% the *ussian Pharmaco4oeia Committee +as stan(ar(i2e( to a minimum of 0"= 4ercent sali(rosi(e content"!5 In the late 5:=0s, (eman( for R. rosea base( 4h%tome(icines (ramaticall% increase(" The +il( crafte( ra+ material +as o3er har3este(, resulting in a stea(% (ecline in the @ualit% an( effecti3eness of )Rhodiola) 4re4arations" 'cientific in3estigation re3eale( that other s4ecies of genus Rhodiola $+hich also containe( sali(rosi(e& +ere being substitute( for R. rosea" ?hile some of these mi>e( batches +ere highl% 3ariable in @ualit%, others ha( no 4harmacological effect" /ogicall%, the sus4icion arose that the sali(rosi(e stan(ar( +as ina(e@uate" Base( on com4arati3e anal%sis, the ob3ious h%4othesis +as that the original high 4otenc% 4ro(uct containe( other acti3e com4oun(s s4ecific to R. rosea that ha( not %et been i(entifie("

!peci ic compounds set Rhodiola rosea apart rom other Rhodiola species After more than a (eca(e of research, Bur1in an( colleagues 4resente( e3i(ence in 5:=6 that the chemical com4osition of R. rosea root is, in fact, (ifferent from the other s4ecies of genus Rhodiola"!7 <sing ne+l% (e3elo4e( metho(s of anal%sis, .ubiche3 an( colleagues (emonstrate( that R. rosea root contains three cinnam%l alcohol 3icianosi(es F rosa3in, rosin, an( rosarin F that are s4ecific to this s4ecies"!=,!: The term rosavins can be use( to inclu(e rosa3in, rosin, an( rosarin $see chemical figures&" It became e3i(ent that sali(rosi(e is 4resent in all chemicall% anal%2e( 4lants in the genus Rhodiola, an( in a +i(e 3ariet% of s4ecies outsi(e the genus"!,!5 74 The term salidroside is (eri3e( from Salix, the genus name for the +illo+s" 'ali(rosi(e +as first isolate( in 5:!6 from Salix triandra /" $'alicaceae&"77 'ince then it has been (etecte( in Vaccinium vitis-idaea /" $6ricaceae& an( in Rhododendron75,76 $4lants not belonging to the genus Rhodiola& in concentrations that can be higher than le3els foun( in Rhodiola s4ecies, inclu(ing R. rosea" Therefore, sali(rosi(e alone is not a useful mar1er com4oun( for (ifferentiating true R. rosea from other Rhodiola s4ecies# nor shoul( it be use( as the onl% mar1er com4oun( for the stan(ar(i2ation of R. rosea root e>tracts" Accor(ing to the re3ise( 5:=: 'o3iet Pharmaco4eia, 78 the e>tracts of R. rosea F 4rimaril% in the form of +aterEalcohol tinctures or (rie( root e>tract F are no+ stan(ar(i2e( for both rosa3ins an( sali(rosi(e" Although rosa3ins are no+ the acce4te( mar1er for geneticall% 4ure R. rosea $an( its e>tracts&, the% are not necessaril% the onl% 4harmacologicall% acti3e ingre(ients res4onsible for the efficac% obser3e( in clinical stu(ies" In fact, 4recise i(entification of the com4oun(s res4onsible for the numerous health benefits of R. rosea remains to be confirme(" R. rosea e>tracts use( in most human clinical stu(ies +ere stan(ar(i2e( to minimum 7 4ercent rosa3ins an( 0"= 5 4ercent sali(rosi(e because the naturall% occurring ratio of these com4oun(s in R" rosea root is a44ro>imatel% 7:5"

Rhodiola rosea in Modern Medicine 'ince 5:6:, R. rosea has been inclu(e( in official *ussian me(icine" The Pharmacological an( Pharmaco4oeia Committee of the 'o3iet -inistr% of Health recommen(e( me(icinal use an( in(ustrial 4ro(uction of li@ui( R. rosea e>tract" In 5:85, the 'o3iet -inistr% of Health a44ro3e( an( registere( 4re4aration ;o" 85E:77E54 as a me(icine an( tonic, allo+ing large scale 4ro(uction un(er the name *ho(iola 6>tract /i@ui(, an alcohol base( e>tract $40 4ercent eth%l alcohol&" -e(ical an( 4harmacological te>ts (escribe its use as a stimulant for asthenia $fatigue&, for somatic an( infectious illnesses, in 4s%chiatric an( neurological con(itions, an( in health% in(i3i(uals to relie3e fatigue an( to increase attention s4an, memor%, an( +or1 4ro(ucti3it%" The common (ose is 5 50 (ro4s ! 7 times a (a%, 55 70 minutes before eating for a 4erio( of 50 !0 (a%s" In 4s%chiatric (isor(ers +ith fatigue, a starting (ose of 50 (ro4s ! 7 times a (a% is gra(uall% increase( u4 to 70 40 (ro4s for 5 ! months" In '+e(en, R. rosea +as recogni2e( as an Herbal -e(icinal Pro(uct in 5:=5 an( has been (escribe( as an antifatigue agent in the Textbook of h!tomedicine for harmacists": In the te>tboo1 of 4harmacolog% for (is4enser training in '+e(en, R. rosea is mentione( as a 4lant +ith a stimulant action" Also, the harmaceutical "ook $#akemedelsboken :8E:=& mentions R. rosea as one of the most commonl% use( 4s%chostimulants in the grou4 of officiall% registere( herbal me(icinal 4ro(ucts"55 In .enmar1, R. rosea is registere( as a me(ical 4ro(uct in the categor% of botanical (rugs" *egistere( 4re4arations are e>tensi3el% use( in

'+e(en an( other 'can(ina3ian countries to increase mental +or1 ca4acit% (uring stress, as a 4s%chostimulant, an( as a general strengthener" Pharmacological and "linical !tudies The tra(itional use of R. rosea as a tonic in 'iberian an( *ussian me(icine stimulate( e>tensi3e research lea(ing to i(entification of R. rosea as an a(a4togen F a substance that nons4ecificall% increases the resistance of an organism an( (oes not (isturb normal biological 4arameters" 'tu(ies in cell cultures, animals, an( humans ha3e re3eale( antifatigue, anti stress, antih%4o>ic $4rotection against (amaging effects of o>%gen (e4ri3ation&, anticancer, antio>i(ant, immune enhancing an( se>ual stimulating effects" !,5=,!4,7= 40 'ince the *ussian an( Bulgarian literature is so e>tensi3e, this (iscussion +ill highlight seminal stu(ies an( maDor re3ie+s" The authors +ere fortunate to gain access to original re3ie+s, articles, an( (octoral theses" This o3er3ie+ relies hea3il% on monogra4hs an( 4eer re3ie+e( 4ublications" The research (ata containe( in these (ocuments are hel4ful for un(erstan(ing recent human stu(ies in normal an( 4athological con(itions" # ects upon the "entral $ervous !ystem The s%stematic stu(% of the 4harmacological effects of R. rosea, begun in 5:65, foun( that small an( me(ium (oses ha( a simulating effect, such as lengthening the time mice s+im an( remain on 3ertical 4erches to the limit of their abilities" In contrast, larger (oses +ere foun( to ha3e more se(ati3e effects" 'mall (oses increase( the bioelectrical acti3it% of the brain, 4resumabl% b% (irect effects on the brainstem ascen(ing an( (escen(ing reticular formation" !7 !6,7=,7:,45 9urther stu(ies sho+e( that me(ium range (oses, unli1e tran@uili2ers, enhance( the (e3elo4ment of con(itione( a3oi(ance refle>es in rats an( facilitate( learning base( on emotionall% 4ositi3e reinforcement"5=,4! 46 Overall% in small and medium doses% R. rosea stimulated norepinephrine &$#'% dopamine &DA'% serotonin &()*T'% and nicotinic cholinergic e ects in the central nervous system &"$!'+ ,t also enhanced the e ects o these neurotransmitters on the brain by increasing the permeability o the blood brain barrier to precursors o DA and ()*T+!,!7,4!,46 4: In com4aring stu(ies of R. rosea, Asian ginseng $ anax $insen$ C"A" -e%.% Araliaceae&, meclofeno>ate $centro4heno>ine&, 4iracetam, citicholine, an( other nootro4ics $substances that enhance cognition, 4rotect the brain, an( ha3e lo+ to>icit% an( fe+ si(e effects&, Pet1o3 an( colleagues note( that all of these agents enhance learning an( memor% in animal mo(els an( increase 5 HT le3els in the frontal cerebral corte>"46 50 .iagram 5 illustrates the 4ossible effects of R. rosea on neurotransmitters in multi4le neuronal 4ath+a%s" (- !tarting in the brain stem% R. rosea promotes release o $#% ()*T% and DA in ascending pathways that activate the cerebral cortex and the limbic system+.%/0%(1 "onse2uently% the cognitive &thin3ing% analy4ing% evaluating% calculating% and planning' unctions o the cerebral cortex and the

attention% memory% and learning unctions o the pre rontal and rontal cortex are enhanced+ Cther neuronal s%stems also contribute to the man% as4ects of memor%: enco(ing, sorting, storage, an( retrie3al" 9or e>am4le, the cholinergic s%stem uses the neurotransmitter acet%lcholine $Ach& an( contributes to memor% function 3ia 4ath+a%s ascen(ing from the memor% storage s%stems of the limbic s%stem to 3arious areas of the cerebral corte> $memor% retrie3al&" Agents that bloc1 Ach su44ress the acti3it% of these ascen(ing 4ath+a%s an( interfere +ith memor%" R. rosea re3erses this bloc1a(e"4:,50 The (eterioration of these s%stems +ith age results in age associate( memor% loss"5! R. rosea ma% 4re3ent or ameliorate some age relate( (%sfunction in these neuronal s%stems"

As an antio>i(ant,57 55 R. rosea ma% hel4 4rotect the ner3ous s%stem from o>i(ati3e (amage b% free ra(icals" 'tress interferes +ith memor% functions an(, o3er time, causes (eterioration in memor% s%stems" In a((ition to enhancing cogniti3e functions, learning, an( memor% b% stimulating ;6, .A, 5 HT, an( Ach neuronal s%stems, R. rosea may exert positive e ects on memory and cognition by improving resistance to physical and emotional stress " Thus, the (ual action of cogniti3e stimulation an( emotional calming creates benefits for both imme(iate cogniti3e an( memor% 4erformance an( for the long term 4reser3ation of brain functions"

The 4s%chostimulant effects of R. rosea +ere stu(ie( in 57 health% subDects an( 45! 4atients +ith neuroses an( asthenic s%n(romes $of both functional an( organic origin&"56 5= '%m4toms of asthenia $fatigue, (ecline in +or1 ca4acit%, trouble falling aslee4, 4oor a44etite, irritabilit%, an( hea(aches& res4on(e( fa3orabl% to R. rosea 50 mg three times a (a%" Treatment (urations range( from 50 (a%s to 4 months" The asthenic states inclu(e( both 4s%chiatric an( 4h%sical causes, for e>am4le, follo+ing influen2a or other illness" In an o4en stu(% of 5!= 4atients age( 58 55 %ears% R. rosea alleviated atigue% irritability% distractibility% headache% wea3ness and other vegetative symptoms in 5/ percent o cases+(6 ,mprovement was assessed by psychological testing and wor3 productivity" In 5=6: Bear( coine( the term )neurasthenia) to inclu(e 3arious forms of ner3ous asthenia" Contro3ers% o3er this term has centere( on the o3erla4 of s%m4tomatolog% an( co morbi(it% +ith other con(itions $e"g", (e4ression, neuroses, somatoform (isor(ers, an( chronic fatigue s%n(rome&" Although this (iagnosis has fallen out of fa3or in the <nite( 'tates an( no longer a44ears in The Dia$nostic and Statistical Manual of the &merican s!chiatric &ssociation $.'- IA&,5: it is still +i(el% use( throughout the +orl("60 67 ;eurasthenia is (efine( b% the ?orl( Health Crgani2ation in the 'nternational (lassification of Diseases $IC. 50&64 as:

either 4ersistent an( (istressing feelings of e>haustion after minor mental effort, or 4ersistent an( (istressing feelings of fatigue after minor 4h%sical effort# accom4anie( b% one or more of the follo+ing s%m4toms: muscular aches or 4ains# (i22iness# tension hea(aches# slee4 (isturbance# inabilit% to rela># an( irritabilit%# inabilit% to reco3er through rest, rela>ation, or enDo%ment# (oes not occur in the 4resence of organic mental (isor(ers, affecti3e (isor(ers or 4anic, or generali2e( an>iet% (isor(er"

In an o4en stu(% !8 health% stu(ents, 4h%sicians, an( scientists age( 5: 46 %ears +ere gi3en 50 (ro4s of R. rosea tincture $e@ui3alent to 500 550 mg R. rosea e>tract& once or t+ice a (a% for ! 7 +ee1s, beginning se3eral (a%s before intense intellectual +or1, such as final e>ams"5= The e>tract im4ro3e( the amount an( @ualit% of +or1 an( in all cases 4re3ente( asthenic (ecom4ensation $loss of +or1 ca4acit% (ue to fatigue&" A series of stu(ies using a 4roofrea(ing test sho+e( that a one time (ose of R. rosea (i( not significantl% increase the number of s%mbols correcte(, but very signi icantly decreased the percent o errors made% particularly over an 7)hour period"65,66 Positi3e results foun( in the stu(ies of 4roofrea(ing tests +ere base( on 700 mgE(a% or more" In me(ical treatments, the usual (oses are !00 600 mgE(a%" R. rosea increase( intellectual ca4acit% $4articularl% b% im4ro3ing 4erce4tion an( 4rocessing of information& to a greater (egree than an e>tract of eleuthero, formerl% calle( 'iberian ginseng $)leutherococcus senticosus *u4r" et -a>", Araliaceae&"5=

The (ecrease in 4h%sical an( mental 4erformance of 4h%sicians on 4rolonge( night call is +ell 1no+n" /o+ (ose $580 mgE(a%& R. rosea e>tract +as gi3en to 56 %oung, health% 4h%sicians on night call"5= The effect +as measure( as total mental 4erformance calculate( as )9atigue In(e>") The tests reflecte( an o3erall le3el of mental fatigue in3ol3ing com4le> cogniti3e functions, such as associati3e thin1ing, short term memor%, calculation, concentration, an( s4ee( of au(io 3isual 4erce4tion" These 4arameters +ere teste( before an( after night (ut% (uring three 4erio(s of t+o +ee1s each in a (ouble blin( crosso3er trial" A statisticall% significant im4ro3ement in mental 4erformance tests +as obser3e( in the treatment grou4 $R. rosea& (uring the first t+o +ee1 4erio(" Ho+e3er, at 6 +ee1s the effect a44eare( to be lost" ;o si(e effects +ere re4orte(" These results suggest that R. rosea e>tract can re(uce fatigue un(er certain stressful con(itions for some 4erio( of time" Possible reasons for the loss of efficac% o3er time ma% be the lo+ (ose use(, the crosso3er (esign, or the o3erall length of night (ut% +ith increase( fatigue b% +ee1s 5 an( 6" '4aso3 an( colleagues com4are( 500 mgE(a% R. rosea e>tract $'H* 5, '+e(ish Herbal Institute, Goteborg, '+e(en# stan(ar(i2e( to 7 4ercent rosa3in an( 0"= 4ercent sali(rosi(e& +ith 4lacebo in a (ouble blin( !0 (a% stu(% of 60 In(ian me(ical stu(ents stu(%ing in *ussia (uring their final e>am 4erio("7= .es4ite the lo+ (osage, in3estigators foun( significant im4ro3ements in general +ell being, 4h%sical fitness, mental fatigue, final e>am gra(es, an( coor(ination, but not in some as4ects of cogniti3e functioning in stu(ents ta1ing R. rosea e>tract com4are( to 4lacebo" In a (ouble blin( 4lacebo controlle( stu(% of 60 foreign stu(ents at a *ussian high school, a(ministration of a R. rosea e>tract $660 mgE(a% of a 4re4aration name( *o(a>on& resulte( in an increase in 4h%sical $3elergometric& +or1 ca4acit%, coor(ination, 1inesthetic sensiti3it%, an( general +ell being along +ith a (ecrease in 4s%chic fatigue an( situational an>iet%"7: <nfortunatel%, this stu(% 4ro3i(es no information on the amount of R. rosea in the *o(a>on 4re4aration" R. rosea +as beneficial in 4osttraumatic an( 3ascular lesions of the brain" It +as es4eciall% effecti3e in combination +ith 4iracetam for 4atients +ith mar1e( cogniti3e (%sfunction"56 Ho+e3er, it (i( not re(uce manic s%m4toms an( coul( +orsen 4aranoi( states" In one stu(% of more clearl% (e4resse( 4atients, R. rosea in combination +ith tric%clic anti(e4ressants $TCAs& 4ro(uce( significant im4ro3ement in the maDorit% of cases an( (ecrease( si(e effects of the TCAs" 68 <ltimatel%, some of these 4atients +ere able to res4on( to R. rosea alone" Anti4s%chotic me(ications use( in large (oses o3er man% %ears to treat schi2o4hrenic 4atients sometimes affect the (o4aminergic ner3es in the basal ganglia, the same ner3es that are (amage( in 4atients +ith Par1insonGs .isease" ?hen these ner3es are com4romise(, 4atients (e3elo4 a constellation of )Par1insonian) s%m4toms, inclu(ing stiffness, tremors, bra(%1inesia $slo+e( mo3ements&, an( others" Anticholinergic me(ications ha3e been use( to relie3e these s%m4toms +hen the% are cause( b% anti4s%chotic me(ication# ho+e3er,

the% sometimes fail to hel4" In schi2o4hrenic 4atients +hose anticholinergic me(ications ha( faile( to relie3e Par1insonian s%m4toms, R. rosea +as foun( to be of benefit"56,6= R. rosea ma% affect emotional tone b% influencing neurotransmitter monoamine le3els $;6, .A, 5 HT& in ner3e tracts in3ol3e( in the regulation of moo(, an>iet%, an( emotion in the am%g(ala, hi44ocam4us, h%4othalamus, an( mi(brain" The stimulation of nicotinic cholinergic acti3it% in the emotional circuits of the limbic s%stem $in the tem4oral lobe& ma% also contribute to these effects" Alterations in monoamine le3els un(erlie this com4le> s4ectrum of 4s%chotro4ic acti3it%: stimulating, tran@uili2ing, anti stress, an( anti(e4ressant" The authors ha3e foun( that R. rosea can hel4 4atients +ith (e4ressi3e s%n(romes, mental an( 4h%sical fatigue $secon(ar% to 4s%chiatric an( me(ical con(itions&, memor% loss an( cogniti3e (%sfunction from a 3ariet% of causes, se>ual (%sfunction, an( meno4ausal relate( (isor(ers" .r" Bro+n an( .r" Gerbarg ha3e successfull% treate( more than 550 in(i3i(uals +ith R. rosea e>tract $7 4ercent rosa3in an( 5 4ercent sali(rosi(e& an( ha3e su4er3ise( the treatment of more than 500 a((itional cases $'ee Case 'tu(ies&" # ects on Physical 8or3 "apacity A number of stu(ies ha3e sho+n that R. rosea increase( 4h%sical +or1 ca4acit% an( (ramaticall% shortene( the reco3er% time bet+een bouts of high intensit% e>ercise" These stu(ies inclu(e( normal in(i3i(uals e>4ose( to ma>imal +or1 on a bic%cle ergometer an( Cl%m4ic le3el cross countr% s1iers an( biathletes" 6: In one stu(%, 5! men $5= !4 %ears of age& +ere gi3en one (ose of either 55 (ro4s of R. rosea e>tract, ! ml eleuthero, or 5 ml of a 5 4ercent solution 4iri(rol $a stimulating 4s%chotro4ic similar to meth%l4heni(ate&" 9ifteen (ro4s of R. rosea e>tract is a44ro>imatel% e@ui3alent to 550 mg of (r% enca4sulate( root e>tract stan(ar(i2e( to 7 4ercent rosa3in an( 5 4ercent sali(rosi(e" After 70 minutes, the% 4e(ale( an electric bic%cle ergometer to 4ro(uce a 4recise amount of +or1 in(uce( baseline fatigue" After a 5 minute rest, the% 4erforme( further +or1 to (etermine the ma>imal (uration of +or1 the% coul( accom4lish at a s4ecific intensit%" .uring the secon( 4erio( of +or1, R. rosea (ro4s, eleuthero e>tract, an( 4iri(rol increase( +or1 ca4acit% b% : 4ercent, 6 4ercent, an( 6 4ercent res4ecti3el% $4H0"04& com4are( to 4lacebo controls" *eco3er% +as (efine( b% the time of normali2ation of heart rate an( arterial 4ressure" .uring the reco3er% 4erio(, at 50 minutes, the 4ulse slo+e( b% a factor of !"5 $68 beats 4er minute& in the R. rosea grou4 3ersus 5": $=8 beats 4er minute& in the control grou4" .uring the 7 (a% total reco3er% 4erio(, subDects gi3en 4iri(rol com4laine( of insomnia, e>citabilit%, an( irritabilit%# +hereas those gi3en R. rosea ha( no a(3erse si(e effects an( no com4laints" 6n(urance is the ca4acit% to maintain +or1 (es4ite fatigue" 9ort% t+o master le3el com4etiti3e s1iers $!0 !5 %ears of age& too1 either R. rosea e>tract or 4lacebo 70 60 minutes before training races $70 1m& an( a biathlon $!0 1m race

on s1is carr%ing a rifle an( shooting targets at sto4s&" Athletes gi3en R. rosea ha( statisticall% significant increase( shooting accurac%, less arm tremor an( better coor(ination" Thirt% minutes after +or1 4erformance, the heart rate in the R. rosea grou4 +as 504 506 4ercent of baseline, 3ersus 5!="8 4ercent in the 4lacebo grou4 $4H0"0!&" R. rosea im4ro3e( reco3er% time, strength, en(urance, car(io3ascular measures, an( coor(ination"6: A(a4togens (iffer from other stimulants (uring force(, e>hausti3e muscular +or1" ?ith classical stimulants the initial increase in +or1 ca4acit% is follo+e( b% a 4erio( of substantiall% (ecrease( $mar1e(l% belo+ a3erage& +or1 ca4acit%" *e4eate( use of C;' stimulants (e4letes brain catecholamines an( (ecreases con(itione( refle>es" In contrast, +ith e>tracts of R. rosea, the initial increase in +or1 ca4acit% is follo+e( b% a lesser (iminution, such that the +or1 ca4acit% continues to be abo3e a3erage"80 Animal stu(ies suggest mechanisms that ma% be in3ol3e( in these effects" R. rosea increase( essential energ% metabolites, a(enosine tri4hos4hate $ATP&, an( creatine 4hos4hate in the muscle an( brain mitochon(ria in mice ma(e to s+im to their limit"85 It ma% also enhance the ammonia reassimilation an( energ% metabolism of the cell b% increasing ATP, ribonucleic aci( $*;A&, 4rotein, an( amino aci( s%nthesis"8! In animal stu(ies, R. rosea increase( metabolism of fats t+ice as much as eleuthero87 an( im4ro3e( energ% metabolism in the brain (uring intensi3e muscular +or1loa(s"84 Adaptogenic% Anti)!tress% and $euroendocrine # ects In their classic 5:6= 4a4er, 'o3iet 4harmacologists Bre1hman an( .ar(%mo3 sur3e%e( the literature on 5=: me(icinal 4lants an( i(entifie( fi3e $inclu(ing R. rosea& that met the three (efining criteria for an a(a4togen:85

An adaptogen should be innocuous and cause minimal disturbance o the normal physiological unctions o an organism9 The action o an adaptogen should be nonspeci ic &i+e+% it should increase resistance to adverse in luences o a wide range o harm ul actors o physical% chemical% and biological nature'9 An adaptogen may possess normali4ing action irrespective o the direction o the preceding pathological changes &i+e+% i a body parameter is high% the adaptogen brings it down towards normal9 i a parameter is low% the adaptogen brings it up towards normal'+

The force( s+imming test, use( b% *ussian scientists to measure nons4ecific resistance to stress, +as later name( after Porsolt +ho assigne( s4ecific 4arameters such as +ater tem4erature an( the (imensions of the glass c%lin(er in +hich a mouse or rat +as force( to s+im to e>haustion $about 55 minutes&" After an initial 4erio( of 3igorous acti3it%, the ro(ent a(o4ts a characteristic immobile 4osture, ma1ing onl% the minimal mo3ements necessar% to sta% afloat" 86 The 3ali(it% of the Porsolt s+im test an( its relationshi4 to (e4ression ha3e been (iscusse( e>tensi3el%88,8= an( it subse@uentl% became a screening test for anti(e4ressant agents b% 4harmaceutical com4anies" Although (ifferent laboratories ha3e ma(e minor technical mo(ifications, the fun(amentals of the test remain the same" A(a4togens an( anti(e4ressants increase the amount of time the animal is able to 1ee4 s+imming acti3el%"85 Panossian an( colleagues 4ro4ose to u4(ate the (efinition of a(a4togen b% highlighting more s4ecific biochemical actions as metabolic regulators" 80 The +i(e range of me(ical benefits an( 4h%siological actions ma% be base( on the effects of a(a4togens on regulator% s%stems foun( in man% organs an( tissues $e"g", immune, hormonal, C;', car(io3ascular, muscular, etc"&" The% h%4othesi2e that a(a4togens re(uce (amage from stressors b% altering the reacti3it% of the organismGs (efense s%stem, inclu(ing the h%4othalamic 4ituitar% a>is $HPA& an( the efferent s%m4atho a(renal s%stem $'A'&"80 A recent stu(% sho+e( that R. rosea an( eleuthero 4rotecte( the embr%os of fresh+ater snails $#!mnaea sta$nalis& from a 3ariet% of en3ironmental stressors"8: 6nhancement in resistance +as stu(ie( b% a44l%ing 4h%to a(a4togen e>tracts for a 4erio( of !0 hours to 7 (a% ol( #. sta$nalis lar3ae" 'ubse@uentl% the lar3ae +ere e>4ose( to the follo+ing highl% to>ic en3ironmental stressors: a 4h%sical stress $heat shoc1: 47 (egrees C for 4 minutes&# an o>i(ati3e stress $su4ero>i(e ra(icals in(uce( b% mena(ione 600 micro- for ! hours&# an( hea3% metal in(uce( stress $co44er 50 micro- for 5 hour or ca(mium !0 micro- for 5 hour&" Both eleuthero an( R. rosea strongl% 4rotecte( snail embr%os from lethal heat shoc1, from the a(3erse effects of mena(ione in(uce( su4ero>i(e ra(icals, an( from to>ic e>4osure to hea3% metals $co44er an( ca(mium&" Although the (egree to +hich resistance +as enhance( (e4en(e( on the t%4e of stressor a44lie(, these results confirm the (efinition of 4h%to a(a4togens as being uni3ersal enhancers of non s4ecific resistance against (ifferent 1in(s of stress con(itions" The mechanisms of nons4ecific resistance are not entirel% clear, but

4robabl% in3ol3e im4ro3ements in cellular energ% metabolism, base( in 4art on ATP $as (iscusse( abo3e&" In higher animals an( humans, nons4ecific resistance ma% also be enhance( b% im4ro3ements in the neurological mechanisms of (ealing +ith stress $catecholamines, serotonin, an( en(or4hins&" The serotonin s%stem is necessar% for the stress res4onse reaction, a(a4tation to ne+ en3ironmental con(itions, an( tolerance of h%4o>ia" ;umerous stressors (ecrease serotonin in the h%4othalamus" Theoreticall%, the abilit% of R. rosea to increase the nons4ecific resistance of animals ma% be relate( to its ca4acit% to increase serotonin in the h%4othalamus an( mi(brain" A((itional research sho+e( that an intact h%4othalamic 4ituitar% a(renal a>is an( 4artici4ation of the gona(s an( th%mus +ere necessar% for this anti stress effect"! 9urthermore, R" rosea re(uces the acti3ation of se3eral com4onents of the stress res4onse s%stem" 9or e>am4le, it mo(estl% increase( serum beta en(or4hins that 4rotecte( rats against subse@uent stress in(uce( e>cess en(or4hin ele3ation" =0 In a((ition, R. rosea mo(erates the release of o4ioi( 4e4ti(es that occurs as 4art of the 4ituitar% a(renal a>is res4onse to stress" This re(uce( release 4rotects against su((en e>cess o4ioi( an( catecholamine $;6 an( .A& le3els $+hich interfere +ith normal brain functions an( can lea( to heart (amage&, +hile allo+ing a more mo(erate release that increases stress tolerance +ithout (amaging the central ner3ous s%stem or the car(io3ascular s%stem $see .iagram !&" R. rosea e>tracts also 4rotect the brain an( heart b% re(ucing the secretion of corticotro4hin releasing factor $C*9& un(er stress"=0,=5

#ndocrine and Reproductive # ects ;euroen(ocrine animal stu(ies sho+e( that R. rosea, li1e other a(a4togens, enhance( th%roi( function +ithout causing h%4erth%roi(ism"=5 In a((ition, the th%mus glan( functione( better an( +as 4rotecte( from the in3olution that

occurs +ith aging" The a(renal glan(s functione( +ith better reser3e an( +ithout the 1in( of h%4ertro4h% cause( b% other 4s%chostimulants" 6gg maturation +as enhance( in rats an( an anabolic effect in males $increase( muscle buil(ing an( gona( strengthening similar to effects of lo+ (ose testosterone& +as obser3e( in a number of s4ecies" A(ministration of rho(osin $e>tract of R. rosea for intra3enous, intramuscular, or 4eritoneal inDection& to se>uall% mature female mice o3er a 4erio( of 4 +ee1s 4rolonge( menstruation from 5"7 (a%s $control& to !"= (a%s $rho(osin treate(&, re(uce( the resting 4erio( from 7"= (a%s $control& to !"! (a%s $rho(osin treate(&, an( increase( the relati3e number of estrus (a%s from !: 4ercent to 56 4ercent" In the maDorit% of rho(osin treate( animals, the number of gro+ing follicles, the ooc%te 3olumes, the accumulation of *;A in ooc%te c%to4lasm, the 4roliferation of the lining an( glan(ular cells of the uterine horns, an( the 4re4aration of uterine mucosa for fertili2ation all increase(" In se>uall% mature mice, rho(osin increase( the mean +eight of the uterine horns from 7:"6I4"55 mg to 5:"5I5"5: mg an( the mean +eight of the o3aries from 6"4I0"65 mg to :"5I0"45 mg" Ho+e3er, the a(ministration of rho(osin to se>uall% immature female +hite mice for 7 +ee1s (i( not affect se>ual maturation, the onset of estrus, the +eight of o3aries or uterine horns, or the maturation of follicles" Thus, it is 4robable that the estrogenic effects of R. rosea 4re4arations (e4en( u4on a s4ecific hormonal milieu"=!,=7 These 4re clinical in3estigations le( to a stu(% of R. rosea e>tract in +omen suffering from amenorrhea $loss of menstrual c%cles&" 9ort% +omen +ith amenorrhea +ere gi3en R. rosea $either 500 mg R. rosea e>tract orall% t+ice a (a% for ! +ee1s, or 5 ml rho(osin intramuscularl% for 50 (a%s&" In some subDects the treatment c%cle +as re4eate( ! 4 times" ;ormal menses +ere restore( in !5 +omen, 55 of +hom became 4regnant" In those +ith normal menses, the mean length of the uterine ca3it% increase( from 5"5 cm to 8"0 cm $normal& after R. rosea treatment"=!,=7 Cne of the authors $.r" Bro+n& has treate( in his 4ractice se3eral +omen +ho ha( faile( to concei3e +ith stan(ar( fertilit% (rugs, an( +ho become 4regnant +ithin se3eral months of beginning R. rosea e>tract" These 4reliminar% clinical obser3ations +arrant controlle( follo+ u4 clinical trials" <sing the in vitro estrogen rece4tor com4etition assa%, Patricia 6agon, Ph"." $4ersonal communication, .ecember !005& recentl% foun( that R. rosea e>tract sho+e( strong estrogen bin(ing 4ro4erties that re@uire further characteri2ation" In an o4en stu(%, !6 out of 75 men +ith erectile (%sfunction an(Eor 4remature eDaculation $of 5 !0 %ears (uration& res4on(e( to R" rosea $550 !00 mgE(a% for 7 months& +ith substantiall% im4ro3e( se>ual function, normali2ation of 4rostatic flui(, an( an increase in 58 1etosteroi(s in urine"56,6: "ardioprotective # ects Car(io4rotecti3e effects of R. rosea inclu(e: 4re3ention of stress in(uce( car(iac (amage,=0,=5,=4 (ecrease( m%ocar(ial catecholamines an( c%clic a(enosine

mono4hos4hate $cA-P& le3els# an( re(uce( a(renal catecholamine release =0,=5 $see 9igure !&" 9urthermore, R. rosea acti3ation of mu o4iate rece4tors in heart muscle 4re3ente( re4erfusion arrh%thmias in animal hearts" This effect coul( be bloc1e( b% nalo>one inDection $1no+n to inhibit mu o4iate rece4tors&, thus confirming that the anti arrh%thmic effect of R. rosea is associate( +ith the mu o4iate rece4tors in m%ocar(ial $heart& muscle"=4

In a series of Doint '+e(ish an( *ussian (ouble blin(, ran(omi2e( 4lacebo controlle( stu(ies,=5 50 health% but se(entar% men $ages !0 75 %ears& +ere e3aluate(" T+ent% 4ercent of the subDects ha( a3erage 4h%sical +or1 ca4acit% as measure( b% Po+er ?or1 Ca4acit% $P?C 580& an( =0 4ercent ha( belo+ a3erage P?C 580, in(icating a lo+ le3el of 4h%sical training $P?C 580 is a calculation base( on the amount of +or1 4erforme( b% a man if his heart rate reaches 580 beats 4er minute, b4m&" A se@uence of com4le> 5 to 8 (a% trials com4are( the effects of an a(a4togen formula, a mi>ture of mono an( 4ol%4henolic a(a4togens $--PA&" 6ach tablet containe( the follo+ing ingre(ients: 7 mg rho(iolosi(e from R. rosea root e>tract, 50 mg# 7 mg total sum of isofra>i(ine , s%ringine , an( s%ringaresinoie gl%cosi(es from eleuthero root e>tract, 500 mg# an( 4 mg schi2an(rine an( gamma schi2an(rine from schisan(ra $ Schisandra chinensis $Turc2"& Baill", /amiaceae& fruit e>tract, 550 mg" .uring the 8 (a% a(a4togen trial, subDects +ere gi3en 7 ca4sules $containing a total of 550 mg R. rosea& t+ice a (a% on (a%s 5 7# 4 ca4sules $!00 mg R. rosea& t+ice a (a% on (a%s 4 6, an( 4 ca4sules once on (a% 8" The mean increase in 4h%sical +or1 ca4acit% +as != 4ercent +ith (ose( 4h%sical loa(s in subDects treate( +ith the a(a4togen formula" Thus, se(entar% subDects gi3en the a(a4togen +ere able to 4erform in the lo+er le3el of traine( athletes +ithout an% e>ercise training" Their heart rate 3ariabilit% an( inotro4ic $strength of heart muscle contractilit%& functions im4ro3e(" Both the s%m4athetic an( 4aras%m4athetic in4uts to the heart +ere enhance( such that the heart sho+e( increase( reser3es un(er stress of greater intensit%" The autonomic ner3ous s%stem controls automatic or in3oluntar% functions of the bo(%" It has t+o com4onents: the s%m4athetic an( the 4aras%m4athetic ner3es $see .iagram !&" The s%m4athetic ner3ous s%stem is the )fight or flight) s%stem

that hel4s the organism res4on( to stress $e"g", b% increasing heart rate, res4irator% rate, an( muscle tone&" The 4aras%m4athetic ner3ous s%stem conser3es an( restores energ% $e"g", b% slo+ing the heart rate, res4irator% rate, an( metabolism&" B% enhancing the functions of the s%m4athetic an( 4aras%m4athetic s%stems, R. rosea enables the organism to 4ut out more energ% (uring stress +hile at the same time maintaining higher energ% reser3es" Cne of the challenges 4resente( b% research on a multi ingre(ient formula is that it is not usuall% 4ossible to attribute the results to the acti3it% of an% one single herbal com4onent" Ho+e3er, the results of this stu(% are consistent +ith results of other research con(ucte( solel% on R. rosea mono4re4arations" Antioxidant and Anti)carcinogenic # ects R. rosea is rich in 4henolic com4oun(s, 1no+n to ha3e strong antio>i(ant 4ro4erties"57,=6 Animal stu(ies ha3e sho+n that R. rosea (ecreases to>icit% from c%clo4hos4hami(e, rubom%cin, an( a(riam%cin $anti cancer (rugs&, +hile it enhances their anticarcinogenic effects"=8 =: <(intse3 an( 'cha1ho3 stu(ie( the effect of R. rosea root e>tract $***6&, a tincture manufacture( accor(ing to the *ussian Pharmaco4oeia stan(ar(s $minimum 0"= 4ercent sali(rosi(e an( 7 4ercent rosa3in&, on tumor cells $trans4lante( into mice& an( normal bone marro+ cells in t+o mouse cancer mo(els":0 Cne grou4 of mice +ith 6hrlich ascites tumor $6AT& an( another grou4 +ith /e+is lung carcinoma $7//& +ere first treate( +ith 500 mgE1g c%clo4hos4hami(e $a chemothera4% agent& that su44resse( tumor gro+th to 75 7: 4ercent an( limite( 7// metastases to 5= 4ercent, +hile also re(ucing the number of normal bone marro+ cells, leucoc%tes, an( m%elo1arioc%tes, to 40 50 4ercent an( !0 !5 4ercent of normal, res4ecti3el%" In com4arison, ***6, 0"5 mgE1gE(a% gi3en orall% ! = (a%s after tumors ha( been trans4lante(, su44resse( gro+th of both tumors b% 5: !8 4ercent an( 7// metastases 56 4ercent" Ho+e3er, in contrast to c%clo4hos4hami(e, ***6 cause( no re(uction in normal bone marro+ cells" In animals gi3en both ***6 an( c%clo4hos4hami(e, the ***6 increase( the antimetastatic effect of c%clo4hos4hami(e b% 76 4ercent $4H0"05&" ***6 also increase( the number of leu1oc%tes b% 70 4ercent an( m%elo1arioc%tes b% 56 5= 4ercent"

In another mouse tumor mo(el, <(intse3 an( colleagues sho+e( that ***6 $minimum 0"= 4ercent sali(rosi(e an( 7 4ercent rosa3in& increase( the antitumor effect of the (rug a(riam%cin +hile substantiall% re(ucing its li3er to>icit%"=: -an% chemothera4% agents are hematoto>ic $re(uce the number of normal bloo( cell 4recursors in bone marro+& or he4atoto>ic $cause (amage to

the li3er&" These serious si(e effects +ere significantl% ameliorate( b% ***6" Thus, the research suggests that ***6 can both enhance tumor inhibition b% chemothera4eutic (rugs +hile alle3iating (angerous si(e effects"

'ubstances that re(uce the inci(ence of chromosomal aberrations are terme( antimutagenic" 'ali1ho3a an( colleagues foun( that in mice inDecte( +ith c%clo4hos4hami(e, ***6 $minimum 0"= 4ercent sali(rosi(e an( 7 4ercent rosa3in& ha( antimutagenic effects":5 Com4are( to 4lacebo controls, ***6 re(uce( the (e3elo4ment of chromosomal aberrations b% 50 4ercent an( re(uce( the inci(ence of cells +ith micronuclei b% more than 50 4ercent" ***6 also increase( in(ices of .;A re4air in bone marro+ cells after e>4osure to the mutagen ; nitroso ; meth%lurea $;-<&":5 In a small 4ilot stu(% of 5! 4atients +ith su4erficial bla((er carcinoma $TIG5 !&, treatment +ith ***6 $minimum 0"= 4ercent sali(rosi(e an( 7 4ercent rosa3in& im4ro3e( 4arameters of leu1oc%te integrines an( T cell immunit%" :! The a3erage fre@uenc% of rela4se +as re(uce(, but (i( not reach statistical significance" /arger 4lacebo controlle( stu(ies of R. rosea e>tracts to augment tumor inhibition an( re(uce to>ic effects of chemothera4% agents are nee(e(" Toxicity% !ide # ects% and "ontraindications R. rosea has a 3er% lo+ le3el of to>icit%" In rat to>icit% stu(ies, the /. 50 $lethal (ose at +hich 50 4ercent of animals (ie& +as calculate( to be !="6 mlE1g, a44ro>imatel% 7,760 mgE1g"!5 The e@ui3alent (osage in a 80 1g man +oul( be about !75 gm or !75,000 mg" 'ince the usual clinical (oses are !00 600 mgE(a%, there is a huge margin of safet%"=8 C3erall, R. rosea has 3er% fe+ si(e effects" -ost users fin( that it im4ro3es their moo(, energ% le3el, an( mental clarit%" 'ome in(i3i(uals, 4articularl% those +ho ten( to be an>ious, ma% feel o3erl% acti3ate(, Ditter%, or agitate(" If this occurs, then a smaller (ose +ith 3er% gra(ual increases ma% be nee(e(" R. rosea shoul( be ta1en earl% in the (a% because it can interfere +ith slee4 or cause 3i3i( (reams $not nightmares& (uring the first fe+ +ee1s" It is contrain(icate( in e>cite( states" Because R. rosea has an acti3ating anti(e4ressant effect, it shoul( not be use( in in(i3i(uals +ith bi4olar (isor(er +ho are 3ulnerable to becoming manic +hen gi3en anti(e4ressants or stimulants" <ntil this has been further stu(ie(, the

authors a(3ise caution in 4atients +ith bi4olar s4ectrum (isor(ers" The herb (oes not a44ear to interact +ith other me(ications, though it ma% ha3e a((iti3e effects +ith other stimulants" It is best absorbe( +hen ta1en on an em4t% stomach 70 minutes before brea1fast an( lunch" As +ith an% herbal 4re4aration, 4atients shoul( inform their 4rimar% healthcare 4ractitioner +hen ta1ing R. rosea"

Rhodiola in the :uture -ore scientific research is nee(e( to confirm the 4re3enti3e an( curati3e benefits of R. rosea" Controlle( stu(ies are +arrante( to e>4lore its use in anti(e4ressant augmentation, (isor(ers of memor% an( cognition, attention (eficit (isor(er, traumatic brain inDur%, Par1insonGs (isease, 4rotection against arrh%thmias, s4orts 4erformance, a3iation an( s4ace me(icine $enhancing 4h%sical an( mental 4erformance +hile re(ucing stress reactions&, en(ocrine (isor(ers $infertilit%, 4remenstrual (isor(er, meno4ause&, se>ual (%sfunction, (isor(ers of the stress res4onse s%stem $fibrom%algia, chronic fatigue s%n(rome, an( 4ost traumatic stress (isor(er&, an( enhancement of chemothera4%Era(iation +ith amelioration of to>icit%" In the course of e3olution, R. rosea has a(a4te( to the harsh con(itions of high altitu(e $e>treme col(, lo+ o>%gen, little rainfall, an( intense irra(iation from the sun& b% 4ro(ucing a grou4 of 4o+erful 4rotecti3e com4oun(s that ha3e (i3erse beneficial effects in animals an( humans" Cne is struc1 b% the 3ersatilit% of R. rosea, from its (escri4tion in Gree1 me(icine, !000 %ears ago to its use b% !0th centur% cosmonauts" It is time for mo(ern research, using controlle( clinical trials, to (e3elo4 the 4otential me(ical a44lications of this uni@ue 4h%to a(a4togen" Richard . "ro*n% M.D.% is &ssociate (linical rofessor of s!chiatr! at (olumbia +niversit! (olle$e of h!sicians and Sur$eons in ,e* -ork (it!. He received his M.D. in ./00 from (olumbia +niversit! (olle$e of h!sicians and Sur$eons in ,e* -ork. Dr. "ro*n com1leted his Residenc! in s!chiatr! and a 2ello*shi1 in s!chobiolo$! and s!cho1harmacolo$! at ,e* -ork Hos1ital. Dr. "ro*n is the reci1ient of numerous a*ards% includin$ a Mead-3ohnson ,euro1s!cho1harmacolo$! Travel 2ello*shi1% a Mallinckrodt Scholar a*ard% and a 2ello*shi1 in ,eurosciences and "rain 'ma$in$ from the Dana

2oundation. He has had a lon$standin$ interest in herbal and com1lementar! medicine% es1eciall! as relevant to 1s!chiatr!. 'n 4555% he co-authored the book% 'to4 .e4ression ;o+% *hich 1resents a holistic a11roach to the treatment of de1ression% includin$ S&M-e. Since .///% Dr. "ro*n has tau$ht a full da! course on Herbs and ,utrients in s!chiatr! at the annual meetin$s of the &merican s!chiatric &ssociation. Dr. "ro*n has no financial interest in *ho(iola rosea. atricia #. Gerbar$% M.D.% is &ssistant (linical rofessor in s!chiatr! at ,e* -ork Medical (enter. She $raduated from Harvard Medical School in ./06 and com1leted her s!chiatr! Residenc! at "eth 'srael Hos1ital in "oston in ./0/. She finished 1s!choanal!tic trainin$ at the "oston s!choanal!tic Societ! and 'nstitute in .//4 and has maintained a 1rivate 1s!chiatric 1ractice for 47 !ears. Dr. Gerbar$ has tau$ht and lectured on a ran$e of to1ics in 1s!chiatr! and 1s!choanal!sis. 8ver the 1ast ei$ht !ears she has been increasin$l! involved in research and *ritin$ about alternative and com1lementar! medicine in 1s!chiatr! and has co-authored numerous articles and book cha1ters *ith Dr. "ro*n. Dr. Gerbar$ has no financial interest in *ho(iola rosea" 9akir Ramazanov% h.D.% D.S.% is rofessor of "iochemistr! at #as almas Technolo$ical 'nstitute% S1ain. 'n ./0: he received a bachelor;s de$ree *ith a double ma<or in biochemistr! and 1lant 1h!siolo$! from ,orth (aucasian State +niversit! and in ./:. a h.D. in lant h!siolo$! and "iochemistr! from the Soviet &cadem! of Sciences. He has served as Senior Scientist and (hief of the De1artment of "iotechnolo$! at the Soviet &cadem! of Science and as (hairman of &l$al "iotechnolo$! Develo1ment. 'n .//. he acce1ted a research fello*shi1 at #ouisiana State +niversit!. The reci1ient of numerous research $rants% Dr. Ramazanov is kno*n for his *ork in s1ace biolo$!% the cultivation of 1hotos!nthetic or$anisms in s1ace stations% and the develo1ment of marine natural 1roducts from sea ve$etables. He has 1ublished more than .=5 scientific studies and co-authored t*o books> Arctic *oot $*ho(iola rosea& F The 4o+erful ne+ Ginseng Alternati3e ?.//:@ and 6ffecti3e ;atural 'tress an( ?eight -anagement <sing *ho(iola *osea an( *ho(o(en(ron Caucasicum ?.///@. Dr. Ramazanov is resident and ()8 of ,ational "iosciences (or1oration% (hester% ,-. &ckno*led$ement> The authors are $rateful to Dr. "ertalan Galambosi from &$rifood Research 2inland% )colo$ical roduction% of Mikkeli% 2inland% for 1rovidin$ the 1hoto$ra1hs of *ho(iola rosea. Re erences 5" 6ngler A" S!llabus der flanzenfamilien" Aol" !" Berlin, German%: Borntraeger# 5:64" 4" 5:: !00" !" 'arati1o3 A', Brasno3 6A" Rhodiola rosea is a valuable medicinal 1lant ?Golden Root&" Toms1, *ussia: Toms1 'tate <ni3ersit% Press# 5:=8"

7" -ell C." .%es, tannins, 4erfumes, an( me(icines from Rhodiola rosea" Textile (olorist 5:7=#60$855&:4=7 4" 4" /innaeus C" Materia Medica" /iber I" .e Plantis" 'toc1holm, '+e(en: /ars 'al3ius# 584:" 4" 56=" 5" /innaeus C" Artabok" 'toc1holm, '+e(en: Alm@uist an( ?i1sell# 58!5" 4" 5!8" 6" /innaeus C" lants of #a1land" <44sala, '+e(en: The *o%al 'cience Aca(em%Gs (ocuments# 5854" 4" 5=! 8" 8" /innaeus C" 2lora 8economica eller Hushalls-,!ttan af de i S*eri$e% Bildt *axande Arter" 'toc1holm, '+e(en: /ars 'al3ii# 584=" 4" 7::" =" /innaeus C, Tonning H" ,or*e$ian Rarities" <44sala, '+e(en: Johan 6(man# 586=" 4" 7 5:" :" 'an(berg 9, Bohlin /" 2!totera1i> vaxbaserade lakemedel JRemedies based on herbsK" 'toc1holm, '+e(en: Halso1ostra(ets farlag AB# 5::7" 4" 575" 50" Commission ;ationale (e la Pharmaco4ee 9ranaise" harmaco1ee 2raneaise" IL e(" Table al4habeti@ue re3isee (es (rogues 3egetales" Paris, 9rance: 9rench Agence (u -e(icament .irection (es 9rench /aboratoires et (es ContrMles, <nite Pharmaco4ee# 5:84" 4" II A!54 .5." 55" 'an(berg 9" Herbal Remedies and Herb Ma$ic" 'toc1holm, '+e(en: .et Basta# 5::=" 4" !!7" 5!" -ash1o3s1iD -." Doctor;s manual> medical dru$s" 5!th e(" Aol" 5" -osco+, *ussia: -e(it2ina# 5:86" 4" 565 5" 57" Bhai(ae3 0, -enshi1o3a TA" Medicinal lants in Mon$olian Medicine" <lan Bator, -ongolia# 5:8=" 54" -agnusson B" 2a$rin$ar> Vaxter som berar oss $"eaut!> herbs that touch us&" Nstersun(, '+e(en: Bern(tssons# 5::!" 4" 66 8" 55" Ho44e H" Dro$en kunde" Ban( 5, Angios4erm ="Berlin, German%: ?alter (e Gru%ter# 5:85" 4" :=6 8" 56" ;arr H" Ph%tochemical an( 4harmacological in3estigation of the a(a4togens: )leutherococcus senticocus% 8cimum sanctum% (odono1sis 1ilosula% Rhodiola crenulata J(issertationK" -unich, German%: 9acult% of Chemistr% an( Pharmac%, /u(+ig -a>imilians <ni3ersitat -Onchen# 5::7" 58" Br%lo3 GA" Herbs for #ife" ;o3osibirs1, *ussia: Aca(emic Press# 5:6:" 4" !64" 5=" .arbin%an A, Bte%an A, Panossian A, Gabrielian 6, ?i1man G, ?agner H" Rhodiola rosea in stress in(uce( fatigue: a (ouble blin( cross o3er stu(% of a stan(ar(i2e( e>tract 'H* 5 +ith a re4eate( lo+ (ose regimen on the mental 4erformance of health% 4h%sicians (uring night (ut%" h!tomedicine !000#8$5&:765 85" 5:" Bomaro3 A/, e(itor" 2lora of the +SSR" Aolume IL, Rosales an( Sarraceniales" Genus 6:=: Rhodiola /" /eningra(, *ussia: The <''* Aca(em% of 'ciences: 5:7:" Translation: Jerusalem, Israel: Israel Program for 'cientific Translation# 5:85" 4" !0 76" !0"Hegi G, e(itor" 'llustrierte 2lora von Mitteleuro1a" Aol"IAE!, /iefering !E7" HamburgEBerlin, German%# P" Pose%: 5:67" 4" :: 50!"

!5" Chba H" A re3ision of the eastern Himala%an s4ecies of the subgenus Rhodiola of the genus Sedum" In: Chashi H, e(itor" 2lora of )astern Himala!a, 7r( re4ort" To1%o, Ja4an: <ni3ersit% of To1%o Press# 5:85" 4" !=7 76!" !!" 'arati1o3 A', Brasno3 6A" Cha4ter I: Chemical com4osition of Rhodiola rosea" In: 'arati1o3 A', Brasno3 6A" Rhodiola rosea is a valuable medicinal 1lant $Golden Root&" Toms1, *ussia: Toms1 'tate <ni3ersit%# 5:=8" 4" 7 7:" !7" Bur1in AA, 0a4esochna%a GG" Chemical com4osition an( 4harmacological 4ro4erties of Rhodiola rosea" (hemical and harmaceutical 3ournal ?Mosco*@ 5:=6#!0$50&:5!75 44" !4" 'arati1o3 A'" Golden Root ?Rhodiola rosea@" Toms1, *ussia: Toms1 'tate <ni3ersit% Press# 5:84" !5" Bur1in AA, 0a4esochna%a GG" Chemical com4osition an( 4harmacological characteristics of Rhodiola rosea Jre3ie+K" 3ournal of Medicinal lants% Russian &cadem! of Science% Mosco* 5:=5#5!75 445" !6" 'arati1o3 A', Brasno3 6A, Bhni1ina /A, .u3i(son /-" Isolation an( chemical anal%sis of in(i3i(ual biologicall% acti3e constituents of Rhodiola rosea" Procee(ings of the 'iberian Aca(em% of 'ciences" "iolo$! 5:68#5:54 60" !8" The *ussian 9e(eration -inistr% of Health an( -e(ical In(ustr%" Russian ,ational harmaco1oeia" Pharmaco4oeia article: PA 4! !5!6 =7, li@ui( e>tract of *ho(iola rosea root an( rhi2ome" -osco+, *ussia: The *ussian 9e(eration -inistr% of Health an( -e(ical In(ustr%# 5:=7" !=".ubiche3 AG, Bur1in BA, 0a4esochna%a GG, Aornot2o3 6." 'tu(% of Rhodiola rosea root chemical com4osition using HP/C" (emicoarmaceutical 3ournal 5::5#!:5== :7" !:" Gan2era -, Pa%la P, Bhan IA" Anal%sis of the mar1er com4oun(s of Rhodiola rosea /" $gol(en root& b% re3erse( 4hase high 4erformance li@ui( chromatogra4h%" (hem harm "ull ?Tok!o@ !005#4:$4&:465 8" 70"0hang ', ?ang J, 0hang H" Chemical constituents of Tibetan me(icinal herb Rhodiola kirilo*ii $*eg"&" Gansu (hun$ Cuo (hun$ -ao Tsa (hih 5::5#56$=&:4=7, 55!" 75" ?ang ', ?ang 9P" 'tu(ies on the chemical com4onents of Rhodiola crenulata" -ao Hsueh Hsueh ao 5::!#!8$!&:558 !0" 7!" ?ang ', Pou LT, ?ang 9P" HP/C (etermination of sali(rosi(e in the roots of Rhodiola genus 4lants" -ao Hsueh Hsueh ao 5::!#!8$55&:=4: 5!" 77" Bri(el -, Beguin C" Isolation of rutosi(e, as4aragines an( a ne+ gl%cosi(e, h%(rol%sable b% emulsion, sali(rosi(e from Salix triandra /" Seances &cad Sci 5:!6#5=7:7!5 7" 74" 'hi /, -a P, Cai 0" Quantitati3e (etermination of sali(rosi(e an( s4ecnue2heni(e in the fruits of #i$ustrum lucidum b% high 4erformance li@ui( chromatogra4h%" "iomed (hromato$r 5::=#5!$5&:!8 70" 75" Thieme H" Cn the i(entit% of glucosi(e rho(iolosi(e an( sali(rosi(e" harmazie 5:6:#!4$!&:55= :" 76" Thieme H, ?ale+s1a 6, ?in1ler HJ" Isolation of sali(rosi(e from lea3es of Rhododendron 1onticum > cata*biense" harmazie 5:6:#!4$5!&:8=7"

78" The *ussian 9e(eration -inistr% of Health an( -e(ical In(ustr%" Russian ,ational harmaco1oeia" -osco+, *ussia: The *ussian 9e(eration -inistr% of Health an( -e(ical In(ustr%# 5:=:" 7="'4aso3 AA, ?i1man GB, -an(ri1o3 AB, -irono3a IA, ;eumoin AA" A (ouble blin(, 4lacebo controlle( 4ilot stu(% of the stimulating an( a(a4togenic effect of Rhodiola rosea 'H* 5 e>tract on the fatigue of stu(ents cause( b% stress (uring an e>amination 4erio( +ith a re4eate( lo+ (ose regimen" h!tomedicine !000#8$!&:=5 :" 7:" '4aso3 AA, -an(ri1o3 AB, -irono3a IA" The effect of the 4re4aration rho(iosin on the 4s%cho4h%siological an( 4h%sical a(a4tation of stu(ents to an aca(emic loa(" )ks1 Clin 2armakol !000#67$5&:86 =" 40"9urmano+a -, Cle(21a H, -ichals1a -, 'o1olnic1a I, *a(oms1a ." Cha4ter LLIII Rhodiola rosea /" $*oseroot&: 'n vitro regeneration an( the biological acti3it% of roots" Aol" 77" In: BaDaD PP', e(itor" "iotechnolo$! in &$riculture and 2orestr!" Aol" 77" Medicinal and aromatic 1lants" AIII" Berlin an( Hei(elberg, German%: '4ringer Aerlag# 5::5" 4" 45! !6" 45" 'arati1o3 A', Brasno3 6A" Cha4ter AII: A(a4togenic 4ro4erties of Rhodiola rosea" In: 'arati1o3 A', Brasno3, e(itors" Rhodiola rosea is a valuable medicinal 1lant $Golden Root&" Toms1, *ussia: Toms1 'tate <ni3ersit% Press# 5:=8" 4" 5:4 !55" 4!" Pet1o3 A., 'tanche3a '/, Tocuschie3a /, Pet1o3 AA" Changes in brain biogenic monoamines in(uce( b% the nootro4ic (rugs a(afeno>ate an( meclofeno>ate an( b% citicholine $e>4eriments on rats&" Gen harmacol 5::0#!5$5&:85 5" 47" Barano3 AB" 6>4erimental trials of herbal a(a4togen effect on the @ualit% of o4eration acti3it%, mental an( 4rofessional +or1 ca4acit%" Contract :7 55 655 'tage ! Phase I" -osco+, *ussia: *ussian 9e(eration -inistr% of Health Institute of -e(ical an( Biological Problems# 5::4" 44"Bomar AA, Bit '-, 'ischu1 /A, 'ischu1 A-" 6ffect of Rhodiola rosea on the human mental acti3it%" harmaceutical 3 5:=5#76$4&:6! 4" 45" 'tanche3a '/, -osharrof A" 6ffect of the e>tract of Rhodiola rosea /" on the content of the brain biogenic monoamines" Medecine h!siolo$ie (om1tes Rendus de l;&cademie "ul$are des Sciences 5:=8#40$6&:=5 8" 46"/a2aro3a -B, Pet1o3 A., -ar1o3s1a A/, Pet1o3 AA, -osharrof A" 6ffects of meclofeno>ate an( e>tr" Rhodiolae rosea /" on electrocon3ulsi3e shoc1 im4aire( learning an( memor% in rats" Methods 2ind )x1 (lin harmacol 5:=6#=$:&:548 5!" 48" Pet1o3 A., Pon1o3 ., -osharoff A, Bambouro3a T, Alo3a /, Pet1o3 AA, et al" 6ffects of alcohol a@ueous e>tract from Rhodiola rosea /" roots on learning an( memor%" &cta h!siol harmacol "ul$ 5:=6#5!$5&:7 56" 4="'arati1o3 A, -arina T9, 9isano3a //" 6ffect of gol(en root e>tract on 4rocesses of serotonin s%nthesis in C;'" 3ournal of "iolo$ical Sciences 5:8=#6:54!" 4:"-arina T9, Ale1see3a /P" 6ffect of Rhodiola rosea e>tract on electroence4halograms in rabbit" In" 'arati1o3 A', e(itor . Stimulants of the (entral ,ervous S!stem" Toms1, *ussia: Toms1 'tate <ni3ersit% Press# 5:6=" 4" !! 6"

50"-arina T9" 6ffect of Rhodiola rosea e>tract on bioelectrical acti3it% of the cerebral corte> isolate( to a (ifferent e>tent from the brain" In" 'arati1o3 A', e(itor" Stimulants of the (entral ,ervous S!stem" Toms1, *ussia: Toms1 'tate <ni3ersit% Press# 5:6=" 4" !8 75" 55" Bro+n *P, Gerbarg PG, -us1in P*" Alternati3e Thera4ies in Ps%chiatr%" In: Tasman A, /ieberman J, Ba% J, e(itors" s!chiatr!. !n( e( Jin 4ressK" ?est 'usse>, 6nglan(: ?ile% R 'ons, /t("# !00!" 5!" /u4ien 'J, (e /eon -, (e 'anti ', Con3it A, Tarshish C, ;air ;P, et al" Cortisol le3els (uring human aging 4re(ict hi44ocam4al atro4h% an( memor% (eficits" ,at ,eurosci 5::=#5$5&:6: 87" 57" 9urmano+a -, '1o4ins1a *o2e+s1a 6, *ogala 6, -algor2ata H" Rhodiola rosea in 3itro culture: 4h%tochemical anal%sis an( antio>i(ant action" &cta Societis "otanicorum oloniae 5::=#86$5&:6: 87" 54" .uran% ;, -unch G, -ichel T, *ie(erer P" In3estigations on o>i(ati3e stress an( thera4eutical im4lications in (ementia" )ur &rch s!chiatr! (lin ,eurosci 5:::#!4: 'u44l 7:6= 87" 55" Jose4h JA, 'hu1itt Hale B, .eniso3a ;A, Bielins1i ., -artin A, -c6+en JJ, et al" *e3ersals of age relate( (eclines in neuronal signal trans(uction, cogniti3e, an( motor beha3ioral (eficits +ith blueberr%, s4inach, or stra+berr% (ietar% su44lementation" 3 ,eurosci 5:::#5:$5=&:=554 !5" 56" 'arati1o3 A', Brasno3 6A" Cha4ter AIII: Clinical stu(ies of Rhodiola" In: 'arati1o3 A', Brasno3 6A, e(itors" Rhodiola rosea is a valuable medicinal 1lant $Golden Root&" Toms1, *ussia: Toms1 'tate <ni3ersit% Press# 5:=8" 4" !56 !8" 58" Brasi1 6., -oro2o3a 6', Petro3a BP, *agulina GA, 'hemeto3a /A, 'hu3ae3 AP" Thera4% of asthenic con(itions: clinical 4ers4ecti3es of a44lication of Rhodiola rosea e>tract $gol(en root&" In" roceedin$s Modern 1roblems in 1s!cho-1harmacolo$!. Bemero3o cit%, *ussia: 'iberian Branch of *ussian Aca(em% of 'ciences: 5:80" 4" !:= 770" 5=" Brasi1 6., Petro3a BP, *ogulina GA, 'hemeto3a /Pa, 'hu3a%e3a" ;e+ (ata on the thera4% of asthenic con(itions $clinical 4ros4ects for the use of Rhodiola e>tract&" Procee(ings of All *ussia Conference: <rgent Problems in Ps%cho4harmacolog% 5:80 -a% !6 !:" '3er(lo3s1, *ussia: '3er(lo3s1 Press# 5:80" 4" !55 8" 5:" American Ps%chiatric Association" Dia$nostic and Statistical Manual of Mental Disorders" 4th e( $.'- IA&" ?ashington, .C: American Ps%chiatric Association# 5::4" 60"Hic1ie I, .a3en4ort T, Issa1i(is C, An(re+s G" ;eurasthenia: 4re3alence, (isabilit%, an( healthcare characteristics in the Australian communit%" "r 3 s!chiatr! !00!#5=5:56 65" 65" -eri1angas B, Angst J" ;eurasthenia in longitu(inal cohort stu(% of %oung a(ults" s!cholo$ical Medicine 5::4#!4$4&:5057 !4" 6!" /in TP" ;eurasthenia re3isite(: its 4lace in mo(ern 4s%chiatr%" s!chiatric &nnals 5::!#!!$4&:587 =8" 67" 0heng PP, /in B-, Ta1euchi ., Burasa1i B', ?ang P, Cheung 9" An e4i(emiological stu(% of neurasthenia in Chinese Americans in /os Angeles" (om1rehensive s!chiatr! 5::8#7=$5&:!4: 5:"

64"<"'" .e4artment of Health an( Human 'er3ices" The 'nternational (lassification of Diseases" 50th *e3ision $IC. 50&" ?ashington, .C: <"'" .e4artment of Health an( Human 'er3ices# 5::!" 65" 0ato3a -I, Brilo3 GA, 'arati1o3 A'" Gol(en root: ne+ stimulati3e an( a(a4togenic (rug" roceedin$s of Siberian &cadem! of Sciences. "iolo$ical and Medical Sciences" 5:65#!:555 :" 66"'arati1o3 A'" 'creening for natural central ner3ous s%stem stimulants" In: 'arati1o3 A', e(itor" Stimulants of the (entral ,ervous S!stem" Aol" 5" Toms1, *ussia: Toms1 'tate <ni3ersit% Press# 5:66 4" 7 !7" 68" Brichen1o A', Bu4ri%ano3a I6, '1oro1ho3a T9" The use of herbal a(a4togens +ith tric%clic anti(e4ressants in 4atients +ith 4s%chogenic (e4ression" In: 'arati1o3 A', e(itor" Modern roblems of harmacolo$! and Search for ,e* Medicines" Toms1, *ussia: Toms1 'tate <ni3ersit% Press# 5:=6" 4" 5= 60" 6="-attson -P, Pe(ersen ?A, .uan ?, Culmsee C, Caman(ola '" Cellular an( molecular mechanisms un(erl%ing 4erturbe( energ% metabolism an( neuronal (egeneration in Al2heimerGs an( Par1insonGs (iseases" &nn , &cad Sci 5:::#=:7:554 85" 6:"'arati1o3 A', Brasno3 6A" Cha4ter III: 'timulati3e 4ro4erties of Rhodiola rosea" In: 'arati1o3 A', Brasno3 6A, e(itors" Rhodiola rosea is a valuable medicinal 1lant $Golden Root&" Toms1, *ussia: Toms1 'tate <ni3ersit%# 5:=8" 4" 6: :0" 80" Panossian A, ?i1man G, ?agner H" Plant a(a4togens" III" 6arlier an( more recent as4ects an( conce4ts on their mo(e of action" h!tomedicine 5:::#6$4&:!=8 700" 85" 'alni1 B<" 6ffect of se3eral stimulators on central ner3ous s%stem energ% metabolism (uring muscular +or1loa( J(issertationK" Toms1, *ussia: Toms1 'tate -e(ical Institute# 5:80" 8!" A(amchu1 /B" 6ffects of Rhodiola on the 4rocess of energetic reco3er% of rat un(er intense muscular +or1loa( J(issertationK" Toms1, *ussia: Toms1 'tate -e(ical Institute# 5:6:" 87" .anbue3a 6A" 6ffect of stimulators of the central ner3ous s%stem on li4i( metabolism at (ifferent muscular +or1loa(s J(issertationK" Toms1, *ussia: Toms1 'tate -e(ical Institute# 5:6=" 84" *e3ina TA" 6ffect of stimulators of the central ner3ous s%stem on carboh%(rate an( high energ% 4hos4hor%late( com4oun( metabolism in the brain (uring intense muscular +or1loa( J(issertationK Toms1, *ussia: Toms1 'tate -e(ical Institute# 5:6:" 85" Bre1hman II, .ar(%mo3 IA" ;e+ substances of 4lant origin +hich increase non s4ecific resistance" &nn Rev harmacol 5:6=#$:&:45: 70" 86" Porsolt *., Anton G, Bla3et ;, Jalfre -" Beha3ioral (es4air in rats: a ne+ mo(el sensiti3e to anti(e4ressant treatments" )ur 3 harmacol 5:8=#48$4&:78: :5" 88" Borsini 9, -eli A" Is the force( s+imming test a suitable mo(el for re3ealing anti(e4ressant acti3it%S s!cho1harmacolo$! ?"erl@ 5:==#:4$!&:548 60"

8=" ?illner P" The 3ali(it% of animal mo(els of (e4ression" s!cho1harmacolo$! ?"erl@ 5:=4#=7$5&:5 56" 8:" Boon ;iermeiDer 6B, 3an (en Berg A, ?i1man G, ?iegant 9A" Ph%to a(a4togens 4rotect against en3ironmental stress in(uce( (eath of embr%os from the fresh+ater snail #!mnaea sta$nalis" h!tomedicine !000#8$5&:7=: ::" =0"/ishmano3 IuB, Trifono3a 0hA, Tsibin A;, -aslo3a /A, .emente3a /A" Plasma beta en(or4hin an( stress hormones in stress an( a(a4tation" "iull )ks1 "iol Med 5:=8#507$4&:4!! 4" =5" -aslo3a /A, Bon(rate3 BIu, -aslo3 /;, /ishmano3 IuB" The car(io4rotecti3e an( antia(renergic acti3it% of an e>tract of Rhodiola rosea in stress" )ks1 Clin 2armakol 5::4#58$6&:65 7" =!"Gerasimo3a H." 6ffect of Rhodiola rosea e>tract on o3arian functional acti3it%" roc of Scientific (onference on )ndocrinolo$! and G!necolo$! " '3er(lo3s1, *ussia" 5:80 'e4t 55 56" 'iberian Branch of the *ussian Aca(em% of 'ciences" 4" 46 =" =7"'arati1o3 A', Brasno3 6A" Cha4ter AI: The influence of Rhodiola on en(ocrine glan(s an( the li3er" In: 'arati1o3 A', Brasno3 6A, e(itors" Rhodiola rosea is a valuable medicinal 1lant $Golden Root&" Toms1, *ussia: Toms1 'tate <ni3ersit%# 5:=8" 4" 5=0 :7" =4"-aimes1ulo3a /A, -aslo3 /;, /ishmano3 IuB, Brasno3 6A" The 4artici4ation of the mu , (elta an( 1a44a o4ioi( rece4tors in the reali2ation of the anti arrh%thmia effect of Rhodiola rosea" )ks1 Clin 2armakol 5::8#60$5&:7= :" =5" Barano3 AB" The res4onse of car(io3ascular s%stem to (ose( 4h%sical loa( un(er the effect of herbal a(a4togen" Contract :7 55 655 Phase I an( Phase II" -osco+: *ussian 9e(eration -inistr% of Health Institute of -e(ical an( Biological Problems# 5::4" =6"Bolsha1o3a IA, /o2o3s1aia 6/, 'a4e2hins1ii II" Antio>i(ant 4ro4erties of a series of e>tracts from me(icinal 4lants" "iofizika 5::8#4!$!&:4=0 7" =8" <(intse3 ';, 'cha1ho3 AP" .ecrease of c%clo4hos4hami(e haematoto>icit% b% Rhodiola rosea root e>tract in mice +ith 6hrlich an( /e+is trans4lantable tumors" )ur 3 (ancer 5::5#!8$:&:55=!" =="Boro3s1a%a TG, 9omina TI, Iaremen1o BA" A (ecrease in the to>ic action of rubom%cin on the small intestine of mice +ith a trans4lantable tumor through the use of a *ho(iola e>tract" &ntiobiot Chimioter 5:==#77$=&:655 8" =:"<(intse3 ';, Br%lo3a 'G, 9omina TI" The enhancement of the efficac% of a(riam%cin b% using he4ato4rotectors of 4lant origin in metastases of 6hrlichGs a(enocarcinoma to the li3er in mice" Vo1r 8nkol 5::!#7=$50&:5!58 !!" :0"<(intse3 ';, 'ha1ho3 AP" The role of humoral factors of regenerating li3er in the (e3elo4ment of e>4erimental tumors an( the effect of Rhodiola rosea e>tract on this 4rocess" ,eo1lasma 5::5#7=$7&:7!7 75" :5" 'ali1ho3a *A, Ale1san(ro3a IA, -a2uri1 AB, -i1hailo3 A9, <shen1o3a /;, Poroshen1o GG" 6ffect of Rhodiola rosea on the %iel( of mutation

alterations an( .;A re4air in bone marro+ cells" atol 2iziol )ks1 Ter 5::8#$4&:!! 4" :!" Bocharo3a CA, -at3ee3 BP, Bar%shni1o3 AIu, 9igurin B-, 'erebria1o3a *A, Bo(ro3a ;B" The effect of a Rhodiola rosea e>tract on the inci(ence of recurrences of a su4erficial bla((er cancer $e>4erimental clinical research&" +rol ,efrol ?Mosk@ 5::5#$!&:46 8"