Medicinal plants

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herbal plants
  Review Medicinal   plants   used   in   Iranian   traditional   medicine   to   treat   epilepsy ShamimSahranavard a,b, *,SaeedehGhafari b ,MahmoudMosaddegh a,b a Traditional   Medicine   and   Material   Medical   Research   Center,   Shahid   Beheshti   University   of    Medical   Sciences,   Tehran,   Iran b Department    of    Traditional   Pharmacy,   School   of    Traditional   Medicine,   Shahid   Beheshti   University   of    Medical   Sciences,   Tehran,   Iran 1.   Introduction The   long   term   use   of    herbs   introduced   in   traditional   medicinesconfirms   their   value   in   drug   discovery. 1,2 Based   on   historicalevidence,   herbal   therapies   were   used   to   treat   convulsive   seizuresfor   centuries. 3 Medicine   has   always   played   a   significant   role   inIranian   culture   and   civilization.   Thousands   of    years   of    history   andhundreds   of    books   have   placed   Iranian   traditional   medicine   amongthe   oldest   and   richest   alternative   medicines. 4,5 Epilepsy   is   an   important   issue   in   the   field   of    traditional   Persianneuroscience.   Iranian   scientists   such   as   Avicenna   (Ibn   Sina)   andRhazes   (Zakariya   al-Razi)   defined   epilepsy,   described   its   signs   andsymptoms,   and   gave   different   approaches   to   prevent   and   treat   it. 6 It   cannot   be   claimed   with   one   hundred   percent   certainty   thatwhat   was   described   in   Iranian   traditional   medicine   as   epilepsy(sar-e)   matches   the   same   illness   in   conventional   medicine,   becauseof    the   lack   of    diagnostic   equipment   in   that   time.   However,   somesigns   and   symptoms   in   both   sar-e   and   epilepsy   such   asunconsciousness   and   seizure   indicate   that   there   is   a   resemblanceand   make   the   assumption   more   reasonable.In   this   study,   we   investigated   remedies   listed   in   the   mostfamous   Iranian   traditional   medicine   books   as   treatments   for   sar-e,and   we   selected   those   which   were   used   most   and   were   effective   inmanaging   the   condition. 2.Material   and   method The   five   books   mentioned   above   were   among   the   mostimportant   Iranian   herbals   dating   from   between   the   10th   and18th   centuries.   In   all   the   reviewed   references,   the   term   denotingepilepsy   is   ‘sar-e’;   therefore,   it   was   the   main   keyword   searched   inthe   texts.First   the   Canon   of    Avicenna   was   searched,   as   it   is   the   mostcelebrated   book   in   medicine.   Thereafter,   the   plant   names   weresearched   in   other   books   to   find   their   usage   as   anticonvulsantremedies.   Then   these   herbal   medicines   were   scored   based   on   thefrequency   of    their   mention   in   order   to   recognize   the   most   valuableherbal   drugs   used   to   treat   epilepsy   through   hundreds   of    years.The   plants   used   to   treat   epilepsy   in   Iranian   traditional   medicinewere   identified   by   matching   their   names   with   scientific   namesusing   different   comprehensive   glossaries   including   comparativedescriptions   of    old   medicinal   plants. 7,8 A   substantial   search   of    scientific   databases   such   as   ‘‘GoogleScholar’’   and   ‘‘Medline’’   for   the   plant   names   in   combination   withthe   terms   ‘epilepsy’   and   ‘anticonvulsant’   was   performed   to   find   theplants’   possible   anticonvulsive   activities. 3.   Literature   sources  3.1.   The   Canon   of     Avicenna The   Canon,   which   means   ‘‘The   Law’’,   was   the   most   significantcontribution   made   by   the   most   famous   Persian   physician,   Ibn   Sina,known   as   Avicenna   in   the   western   world   (980–1037   AD).   It   isthe   most   influential   textbook   ever   written.   For   six   centuries,   it Seizure   23   (2014)   328–332 A   R    T   I   C   L    E   I   N   F   O  Articlehistory: Received   4   September   2013 Receivedinrevisedform14January2014 Accepted   16    January   2014 Keywords: Iranian   traditional   medicineEpilepsyMedicinal   plants A   B   S   T   R    A   C   T Antiepilepticdrugsusedtotreatepilepsycancausesevere,lifethreateningsideeffects.InIraniantraditionalmedicine,herbalremedieshavebeenusedforcenturiestotreatseizures.Inthisstudy,thefivemostimportantherbalsinIraniantraditionalmedicine,namelyCanon,al-Hawi,al-Abniah‘anHaqaeqalAdwia,Tuhfatal-Mu’minin,andMakhzanul-Adwia,weresearchedfortheterm‘‘sar-e’’,whichmeansepilepsy,toidentifytheherbsusedfortreatmentinancienttimes.Wealsosearchedscientificliteratureforpharmacologicalevidenceoftheireffectiveness.Twenty-fiveplantswereidentifiedasherbalremediestotreatepilepsy.Pharmacologicaldatarelatedtotheantiepilepticactivityofelevenoftheseplantsexists.Alargenumberoftheseplantswhichhavenotbeeninvestigatedpharmacologicallyforantiepilepticactivitywouldbegoodcandidatesforstudyinexploringnewherbalanticonvulsantremedies.  2014BritishEpilepsyAssociation.PublishedbyElsevierLtd.Allrightsreserved. * Corresponding   author   at:   Traditional   Medicine   and   Materia   Medica   ResearchCenter   (TMRC),   Shahid   Beheshti   University   of    Medical   Sciences,   P.O.   Box1516745811,   Tehran,   Iran.   Tel.:   +98   88773525;   fax:   +98   88776168. E-mail   address:   (S.   Sahranavard). Contents   lists   available   at   ScienceDirect Seizure jou   r   nalh   o   mepage:w   ww.elsevier   .co   m/loc   ate/yseiz 1059-1311/$   –   see   front   matter      2014   British   Epilepsy   Association.   Published   by   Elsevier   Ltd.   All   rights   reserved.  dominated   the   medical   schools   of    Asia   and   Europe.   The   Canonsurpassed   other   similar   books   on   medicine   and   is   considered   thebiggest   medical   encyclopedia   of    its   time. 9 Avicenna   was   the   first   person   in   medical   history   to   usethe   term‘epilepsy’,   which   means   ‘‘beingpossessed   by   an   outside   force’’   inLatin.   Ibn   al-Nafis,   a   great   Arab   physician   and   scientist   of    his   time,systematically   described   the   symptoms   and   recovery   of    ‘‘head   sick’’,which   is   a   synopsis   of    the   Canon   written   250   years   earlier. 10–12 The   Canon   consists   of    five   books.   The   first   book   is   about   generalprinciples   of    medicine;   the   second   book   comprises   the   materiamedica ,   which   lists   about   800   mineral,   herbal,   and   animal-basedmedicinal   materials;   the   third   book   is   on   therapy;   the   fourth   bookdiscusses   those   diseases   that   affect   the   body   and   are   not   restrictedto   a   single   part   of    the   body,   such   as   fevers;   the   final   book   presentsrecipes   for   compound   drugs. 13,14 Avicenna   assigned   a   chapter   of    the   Canon   to   epilepsy   under   thetitle   ‘Head   and   Brain   Disorders’.   From   his   point   of    view,   there   aretwo   types   of    epilepsy:   one   that   occurs   suddenly   and   is   over   quickly,and   one   that   is   intense   and   continuous   and   may   lead   to   death.   Inhis   opinion,   epilepsy   is   a   type   of    seizure   which   affects   the   brain.Avicenna   described   symptoms   of    epilepsy   as   being   weakness,forgetfulness,   depression,   nightmare,   yellow   tongue,   tongueparesthesia,   anger,   and   distress.   He   described   an   epileptic   attackas   follows:   ‘‘The   patient   feels   agitated   and   becomes   unconscious,turns   red,   and   stares   with   eyes   distorted;   respiration   is   impairedand   the   patient   becomes   cyanotic’’.   Muscle   contractions,   dizziness,salivation,   and   teeth   gnashing   are   other   symptoms   and   signs. 6 Avicenna   theorized   that   the   blockage   of    humors,   especiallyphlegm   and   black   bile,   was   a   possible   mechanism   of    epilepticconvulsions. 15 In   the   Canon,   he   classifies   epilepsy   based   on   age(children,   adults)   and   the   organ   in   which   the   attack   starts   (liver,stomach,   spleen,   or   uterus).   He   explains   that   some   precipitatingfactors   (environmental   temperature,   direct   solar   radiation,   bathingor   training   with   a   full   stomach,   overwhelming   anger,   fear   orsorrow,   and   dyspepsia)   provoke   epileptic   attacks.Avicenna   explains   the   general   recommendation   (to   avoidexcessive   heat   or   cold,   excess   sexual   intercourse,   swimming,and   postprandial   exercise)   and   states   that   therapy   is   based   on   thespecific   condition   of    the   patient.Plant-based   antiepileptic   therapy   constitutes   a   great   part   of    thetreatments   described   in   the   Canon   and   other   Iranian   traditionalmedicine   references. 16  3.2.    Al-Abniah   ‘an   Haqaeq   al    Adwia The   oldest   preserved   Persian   text   on   materia   medica   (10thcentury),   al-Abniah‘an   Haqaeq   al   Adwia   (principles   of    the   attributesof    plants)   written   by   Abu   Mansur   Movafaq   ibn   Ali   al-Heravi,is   anintroductory   treatise   on   medicine   and   pharmacy.   The   book   dealswith   584   mineral,herbal,   and   animal-based   drugs.   Each   monographincludes   the   name   of    the   drug   and   its   synonyms   in   Greek,   Indian,   andlocal   Persian   dialects,   its   therapeutic   effects,   methodsof    counteringthe   side   effects,   and   the   dosage   of    the   drug. 17,18  3.3.    Al-Hawi    fi   al-Tibb Before   Avicenna’s   Canon,   the   best   written   work   on   medicinewas   al-Hawi   fi   al-Tibb   (The   Comprehensive   Book   of    Medicine).   Itwas   written   by   Abu   Bakr   Mohammad   ibn   Zakariya   Razi,   known   asRhazes   (865–925   A.D.),   a   renowned   Iranian   physician,   philosopher,and   chemist   who   wrote   about   250   books   and   treatises.   Al-Hawi   isRhazes’   most   important   and   complete   book   in   which   he   surveyedGreek,   Syrian,   and   early   Arabic   medicine,   as   well   as   some   Indianmedical   knowledge.   Throughout   his   work,   he   added   his   ownconsidered    judgment   and   his   own   medical   experience   ascommentary.   It   was   repeatedly   printed   in   Europe   during   the15th   and   16th   centuries   under   the   title   ‘‘Liber   Continens’’,   and   ithad   a   major   influence   on   the   development   of    medical   practices   inEurope. 19–21  3.4.   Tuhfat    al-Mu’minin This   work   is   also   known   as   Tuhfeh-ye   Hakim   Mu’min   (1669AD).   It   is   a   medical   treatise   written   by   Mir   Muhammad   Mu’minHusaini   Tonekaboni,   known   as   Hakim   Mu’min,   the   physician   andpharmacist   to   the   court   of    the   Safavid   Shah   Sulayman   in   Persia.   Itcontains   5570   entries,   of    which   940   concern   plants   or   productsderived   from   plants. 22  3.5.   Makhzan   ul-Adwia Makhzan   ul-Adwia   (Drug   Treasure)   is   an   outstanding   workabout   traditional   medicine   and   medical   terminology   in   1772   AD.   Itwas   written   in   Persian   by   Mohammad   Hossein   Aghili   AlaviKhorasani,   a   famous   and   expert   physician.   The   book   has   14chapters   and   covers   poisons   and   antidotes,   temperaments,   food   asmedicine,   expiration   and   strengths   of    medicines.   In   it,   1744   simpledrugs   of    plant   or   animal   srcin   used   in   traditional   medicine   aredescribed   in   detail. 23 4.   Results The   sources   consulted   in   this   work   pointed   out   that   25   materiamedica   were   used   in   Iranian   traditional   medicine   to   treat   epilepsy.Table   1   shows   their   names,   parts   used,   administration,   and   thereferences   in   which   they   are   mentioned.In   the   following   section,   the   results   of    tests   performed   on   11plants   have   been   summarized;   attention   was   focused   on   theiranticonvulsant   activity. 4.1.   Paeonia   officinalis   L. The   root   extract   of    P.   officinalis   (peony   root)   was   identified   as   apotent   in   vitro   inhibitor   of    neuron   damage   in   the   CA1   area   of    thehippocampus   in   rats.   Data   indicated   that   peony   root   extract   hasexcellent   protective   effects   on   damaged   neurons   in   addition   toanticonvulsant   action   when   administered   orally. 24 4.2.   Bryonia   alba   L. Ethanolic   extract   of    the   aerial   parts   of    B.   alba   showed   moderateaffinity   to   the   benzodiazepine-site   of    the   GABA   receptor.   TheGABA A  -benzodiazepine   site   is   a   primary   target   in   the   treatment   of epilepsy   that   enhances   the   sensitivity   of    the   GABA A   receptor   forendogenous   GABA.   After   binding   GABA   to   the   receptor,   the   cell   isinhibited   and   an   anticonvulsant   activity   is   achieved.   Conversely,administration   of    the   aqueous   extracts   showed   no   affinity   for   theGABA–benzodiazepine   receptors. 25 4.3.   Ferula   persica   Willd. The   effects   of    ethanol   extract   of    the   aerial   parts   of    F.    persica   onepilepsy   have   been   evaluated   in   mice. 26 Results   indicated   that   adose   of    300   mg/kg   (i.p.)   of    ethanol   extracts   cannot   preventpentylenetetrazole   (PTZ)-induced   seizures;   therefore,   it   does   notpossess   anticonvulsant   effects   compared   with   the   untreatedanimals   at   the   used   dose. 4.4.   Lavandula   stoechas   L. The   effects   of    the   aqueous-methanolic   extract   of    L.   stoechas flowers   on   epilepsy   and   spasm   were   evaluated   in   mice.   Results S.   Sahranavard   et    al.    /    Seizure    23   (2014)    328–332   329  showed   that   treatment   with   600   mg/kg   of    extract   significantlydelayed   first   seizure   onset,   reduced   convulsion   severity,   andprolonged   the   onset   of    lethality   induced   by   PTZ.   A   prolongation   inthe   time   of    sodium   pentobarbital-induced   hypnosis   was   alsoobserved.   Possible   explanations   of    these   results   might   be   the   roleplant   extract   plays   as   a   calcium   channel   blocker. 27 4.5.   Ferula   asafoetida   L. Bagheri   et   al.   showed   that   the   oleo-gum-resin   of    F.   assafoetida (300   mg/kg,   i.p.)   could   not   prevent   PTZ-induced   seizures   in   mice.The   latency   of    hind   limb   tonic   extension   was   obtained   within   2–3   min,   and   the   percentage   of    mice   mortality   was   100%   in   the   PTZtest.   In   the   mentioned   study,   it   was   proposed   that   F.   assafoetida could   not   prevent   PTZ-induced   seizure. 26 4.6.   Coriandrum   sativum   L. The   aqueous   and   ethanolic   seed   extracts   of    C.   sativum   wereinvestigated   for   their   possible   anticonvulsant   effects   using   PTZ   and(maximal   electro   shock)   MES   tests.   The   results   indicated   that   bothextracts   have   an   anticonvulsant   effect,   and   the   maximum   non-fataldose   of    aqueous   and   ethanolic   extracts,   both   of    which   exertactivity,   were   0.5   g/kg   and   5   g/kg.   It   seems   that   the   anti-seizureprofile   might   be   related   in   part   to   the   coumarin   compoundsisolated   from   C.   sativum . 28 4.7.   Caesalpinia   bonducella   (L.)   Roxb. The   antiepileptic   activity   of    C.   bonducella   was   investigated   usingMES-,   PTZ-,   and   picrotoxin-induced   convulsion   models.   Petroleumether   extract   was   active   in   all   tests,   and   at   the   dose   of    600   mg/kg,   itincreased   the   threshold   for   convulsions   and   delayed   the   onset   of tonic   convulsions.   It   can   be   concluded   that   the   extract   showed   itseffectiveness   through   possibly   blocking   the   chloride   ion   channellinked   to   GABA   receptors. 29 4.8.   Ferula   gummosa   Boiss. The   effects   of    the   seed   acetone   extract   of    F.    gummosa   onepilepsy   and   sedation   were   evaluated.   Test   results   revealed   that   F. gummosa   protected   mice   against   tonic   convulsions   induced   byMES   and   PTZ.   It   produced   a   more   potent   protective   effect   againstseizures   induced   by   PTZ   (ED 50  =   55   mg/kg)   than   MES-inducedseizures   (ED 50  =   198.3   mg/kg).   Neurotoxicity   (sedation   and   motordeficit)   of    the   acetone   extract   assessed   by   the   rotarod   test   wereobtained   dose-dependently   with   a   TD 50  value   of    375.8   againstMES-   and   PTZ-induced   seizures. 30 In   another   study   Sayyah   et   al.   investigated   the   anticonvulsanteffect   of    fruit   essential   oil   of    F.    gummosa .The   study   revealed   thatthe   fruit   essential   oil   of    F.    gummosa   blocked   PTZ-induced   (thoughnot   MES-induced)   seizures   in   mice.   The   LD 50  (2.62   ml/kg)   value   of neurotoxicity,   however,   was   too   close   to   the   anticonvulsant   dose(2.5   ml/kg). 31 4.9.   Cuscuta   epithymum   Murray The   anticonvulsant   activity   of    hydro-alcoholic   extract   of    C.epithymum   was   investigated   using   the   PTZ   test.   Results   showedthat   at   a   dose   of    100   mg/kg,   C.   epithymum   significantly   increasedseizure   latency   and   percentage   of    survival,   but   no   significantdifference   between   convulsion   duration   with   plant   extract   and   thenegative   control   was   observed. 32 4.10.   Cedrus   deodara   Loudon Dhayabaran   et   al.   investigated   the   alcoholic   extract   of    heartwood   of    C.   deodara   (ALCD)   for   its   anxiolytic   effect   in   threeexperimental   models,   including   elevated   plus   maze   test,   light   darkmodel,   and   locomotor   activity   by   actophotometer   and   anticonvul-sant   activity   using   PTZ-   and   MES-induced   convulsions.   The   resultsshowed   that   pretreatment   with   ALCD   at   doses   of    100   and   200   mg/kg   (po)   significantly   delayed   the   onset   and   duration   of    seizures  Table   1 Plants   found   in   the   Iranian   ancient   herbals,   Al-Abniah   ‘an   Haqaeq   al   Adwia   (Abn),   Canon   (Ca),   al-Hawi   (Haw),   Makhzan   ul-Adwia   (Mak)   and   Tuhfat   al-Mu’minin   (Tuhf)   to   treatepilepsy.Traditional   name   Scientific   name   Family   Used   part   Herbals1Aftimoon   Cuscuta   epithymum   Murray   Convolvulaceae   Steam   Ca,   Haw,   Mak2   Azan-ol-far   Parietaria   cretica   L.   Urticaceae   Whole   part   Ca,   Mak,   Tuhf 3   Bandogh   Hendi   Caesalpinia   bonducella   (L.)   Roxb.   Caesalpiniaceae   Fruit   Ca,   Mak,   Tuhf 4   Balasa¯ n   Commiphora   opobalsamum   Engl.   Burseraceae   Seed,   gum   Abn,   Ca Balsamodendron   myrrha   kaunth Myroxylon   balsamum   L.   Fabaceae Myroxylon    pereirae   Klotzsch5   Divda¯ r   Cedrus   deodara   Loudon   Pinaceae   Steam   Ca,   Mak,   Tuhf 6   Eshghil   Urginea   maritima   Baker   Hyacinthaceae   Root   Abn,   Ca,   Mak,   Tuhf 7Fa¯ shera¯   Bryonia   dioica    Jacq.   Cucurbitaceae   Fruit,   leave   Abn,   Ca,   Haw,   Mak,   Tuhf 8   Fa¯ sherestin   Bryonia   alba   L.   Cucurbitaceae   Fruit,   leave   Ca,   Haw,   Mak,   Tuhf 9   Fa¯ vania   Paeonia   officinalis   L.   Paeoniaceae   Fruit,   root   Abn,   Ca,   Haw,   Mak,   Tuhf 10Gheradma¯ na¯   Lagoecia   cuminoides   L.   Apiaceae   Fruit   Ca,   Haw,   Tuhf 11Handaghughi   Trigonella   caerulea   (L.)   Ser.   Fabaceae   Leave,   seed   Ca,   Mak,   Tuhf  Trigonella   hamosa   L. Melilotus   sp.12   Heltit   Ferula   asa-foetida   L.   Apiaceae   Gum   Ca,   Haw,   Mak,   Tuhf 13   Hoor   Populus   nigra   L.   Salicaceae   Fruit   Ca,   Haw,   Mak,   Tuhf 14    Ja¯ vshir   Opopanax   chironium   Apiaceae   Gum   Abn,   Ca,   Mak,   Tuhf 15    Jawz   Roomi   Populus   alba   L.   Salicaceae   Fruit   Ca16   Kozborah   Coriandrum   sativum   L.   Apiaceae   Aerial   part   Abn,   Ca,   Haw17   Marzanjoosh   Origanum   majorana   L.   Lamiaceae   Leave   Ca,   Mak,   Tuhf 18   Moord   Esfarom   Ruscus   aculeatus   L.   Ruscaceae   Leave,   fruit   Abn,   Ca,   Mak,   Tuhf 19   Ostokhodos   Lavandula   stoechas   L.   Lamiaceae   Whole   part   Abn,   Ca,   Haw,   Mak,   Tuhf 20Qennah   Ferula    gummosa   Boiss.   Apiaceae   Gum   Ca,   Mak,   Tuhf 21   Sakbinaj   Ferula    persica   Willd.   Apiaceae   Gum   Abn,   Ca,   Haw,   Mak,   Tuhf 22   Sha¯ ba¯ bak   Inula   conyza   DC.   Asteraceae   Whole   part   Abn,   Ca,   Mak,   Tuhf 23   Sisalius   Seseli   tortuosum   L.   Apiaceae   Whole   part   Abn,   Ca,   Haw,   Mak,   Tuhf 24   Za¯ ra¯ vand   modahraj    Aristolochia   rotunda   L.   Aristolochiaceae   Root   Abn,   Ca,   Haw,   Mak,   Tuhf 25   Za¯ ra¯ vand   tavil    Aristolochia   longa   L.   Aristolochiaceae   Root   Abn,   Ca,   Haw,   Mak,   Tuhf  S.   Sahranavard   et    al.    /    Seizure    23   (2014)    328–332 330  induced   by   PTZ   and   MES   and   exhibited   significant   anxiolyticactivity   by   modulating   GABA   levels   in   the   brain   in   a   dose-dependent   manner. 33 4.11.   Origanum   majorana   L. Deshmane   et   al.   investigated   the   antiepileptic   and   sedativeproperties   of    different   extracts   of    aerial   parts   of    O.   majorana   usingPTZ   and   MES   tests.   All   the   extracts   delayed   the   onset   and   reducedthe   duration   of    seizures   in   the   PTZ   test   and   decreased   the   durationof    seizures   in   the   MES   test.   Chloroform   extract   exhibited   themaximum   reduction   in   the   seizure   duration   (48.5%   inhibition   at250   mg/mL).   Bioassay-guided   fractionation   led   to   the   identifica-tion   of    triterpenoic   acid   fraction   containing   substantial   amounts   of ursolic   acid   as   the   active   principle,   which   have   been   identified   as   amajor   compound   responsible   for   plant   activity   (55.6%   inhibition   at250   mg/mL).   The   test   extracts   also   decreased   latency   and   increasedthe   duration   of    total   sleeping   time   significantly. 34 5.   Discussion Epilepsy   continues   to   be   one   of    the   most   common   neurologicconditions   encountered   in   children   and   adults.   Hippocratesrecognized   epilepsy   as   an   organic   process   of    the   brain;   however,many   ancient   writers   considered   seizures   to   be   the   work   of supernatural   forces. 3 Natural   substances   derived   from   plant,   animal   and   mineralsrcins   have   provided   a   continuing   source   of    medicines   sinceancient   times,   and   their   use   has   been   perpetuated   for   centuries   intraditional   medicine. 35 In   this   study   we   reviewed   the   five   most   important   books   inIranian   traditional   medicine,   explored   antiepileptic   treatments,identified   the   plant   species,   and   discussed   what   is   known   abouttheir   potential   effectiveness.Although   all   possible   effort   was   taken   to   assign   the   correctscientific   names   to   plants,   in   some   cases   the   description   of    theplant   was   inadequate   or   different   genus   and   specious   matcheswere   made   with   one   explanation   in   ancient   texts,   which   madecorresponding   them   with   their   correct   scientific   and   Englishnames   very   difficult.As   one   of    the   most   important   textbooks   in   medieval   times,   theCanon   was   the   first   reference   searched   for   the   remedies   used   forepilepsy   in   those   times.   In   the   Canon,   48   natural   remedies   fortreating   epilepsy   with   animal,   herbal   and   mineral   srcin   wereidentified,   among   which   were   25   plants   from   different   families.   InTable   1,the   names   of    plants   based   on   information   such   astraditional   name,   which   parts   are   used,   and   their   administrationare   listed   in   alphabetical   order.   As   shown   in   Table   1,the   plants  Aristolochia   longa   L.,   Bryonia   dioica    Jacq.,   Ferula    persica   Willd., lavandula   stoechas   L.,   and   Paeonia   officinalis   L.   are   introduced   in   allof    the   books   as   treatments.   This   demonstrates   their   significancethrough   hundreds   of    years.   Seven   plants,   Caesalpinia   bonduc    (L.)Roxb.,   Cedrus   deodara   Loudon.,   Ferula    gummosa   Boiss.,   Origanummajorana   L.,   Parietaria   cretica   L.,   Populus   alba   L.,   and   Trigonellacaerulea   (L.)   Ser.   were   introduced   by   Avicenna,   and   only   three   of them   were   not   recommended   after   Avicenna   for   epilepsytreatment   ( Populus   alba   L.,   Coriandrum   sativum   L.,   and   Commiphoraopobalsamum   Engl.).As   mentioned   previously,   one   of    the   methods   used   to   classifyepilepsy   in   the   Canon   is   based   on   age.   There   are   also   differencesbetween   epilepsy   diagnosis   and   treatment   in   children   and   in   adultsin   modern   medicine. 36,37 Among   the   plants   listed,   Caesalpiniabonduc    (L.)   Roxb.,   Opopanax   chironium ,and   Paeonia   officinalis   L.have   been   prescribed   for   epilepsy   in   children.Most   of    the   administration   routes   of    the   plants   found   in   theherbals   was   oral,   but   Cedrus   deodara   Loudon   and   Origanummajorana   L.   were   administered   through   inhalation.   As   mentionedabove,   most   of    those   plants   studied   for   possible   anticonvulsantactivity   exerted   an   efficient   antiepileptic   ability.   They   eitherinteracted   with   GABA   receptors   or   had   anxiolytic   and   sedativeproperties,   although   other   pharmacological   mechanisms,   i.e.,neuroprotective   activity,   might   be   involved.Other   plants   have   still   not   been   investigated   for   theirpharmacological   effect   in   epilepsy,   and   they   would   be   goodcandidates   for   future   antiepileptic   evaluation.Surprisingly,   a   large   number   of    these   plants   were   traditionallyused   during   the   European   Renaissance   as   antiepileptic   treat-ments. 38 Overall,   some   plants   from   the   list   of    plant   species   used   inIranian   traditional   medicine   to   treat   epilepsy   have   been   pharma-cologically   investigated   for   their   antiepileptic   activity   and   haveshown   anticonvulsant   properties.   Other   plant   species   from   thatsame   list,   especially    Aristolochia   longa   L.,    Aristolochia   rotunda   L.,   and Seseli   tortuosum   L.   which   are   mentioned   in   all   herbals,   remain   to   beinvestigated   for   their   value   as   sources   of    antiepileptic   treatments. 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