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A Study of Unani Formulation Majoon-e-Baladur for effect on Drug Induced Catatonia in Rats

N.A. !an" M.Nasiruddin #" M.Mu$affar. and IA %asmi


De&artment of Ilmul Ad'ia" A. . (i))iya College" De&artment of *!armacology# +. N. Medical College" A.M.U." Aligar! ,U*-" INDIA

Abstract D. antagonists are associated /it! e0tra &yramidal sym&toms /!ic! are 'ery distressing. (!e drugs a'aila)le in modern medicine for t!era&y of *ar1insonism and drug induced e0tra&yramidal sym&toms are also not free from ad'erse effects. (!e Unani formulation ,Majoon-e-Baladur- is one of t!e 1no/n formulations /!ic! contains .2 com&ounds and used in Unani system of medicine as ner'ine tonic" in tremors for years. But t!ere is no scientific )asis for its use. (!e study /as &lanned to e'aluate its effect in drug ,!alo&eridol- induced catatonia. (!e effect /as com&ared /it! standard drug i.e. )en$!e0ol. (!is study /as conducted on adult al)ino rats /eig!ing 234 5 .44 gm of eit!er se0. (!ey /ere di'ided into four grou&s of si0 animals eac!. (!e animals /ere &ro'ided standard diet and /ater ad li)itum. (!e animals in grou& I /ere administered distilled /ater. 6rou&s II" III and I7 /ere administered )en$!e0ol majoon and alco!olic e0tract of Unani formulation in t!e dose of 4.23mg" 284mg and 24mg9244gm )ody /eig!t" res&ecti'ely. (!e treatment /as gi'en &.o. once daily for :4 days. ;n :4t! day 83 minutes after treatment all animals in different grou&s /ere administered !alo&eridol in t!e dose of 4.:4mg9244gm )ody /eig!t intra&eritoneally. All t!e animals /ere tested for t!e intensity of catatonia at e'ery t/enty minutes for a &eriod of t!ree !ours. (!e &ercent in!i)ition of catatonia in test and standard drug /as calculated and com&ared /it! control. It /as found t!at t!ere /as significant decrease in duration of catatonia in test grou& and standard drug treated grou&s as com&ared /it! control at different inter'al of time. It can )e concluded t!at t!e Unani formulation in e0tract form /as more effecti'e t!an majoon in drug induced catatonia Key words: *ar1insonism" Semecar&us anacardium

Introduction Neurole&tics and some &ro1inetics are often associated /it! distressing and se'ere e0tra &yramidal side effects ,Casey D<".444 = ul1arni S " Naidu *S".442- 2".. (!e &!enomenon to induce catatonia in rodents )y ty&ical neurole&tics ,*!enot!ia$ines"!alo&eridol- is ro)ust )e!a'ioral model to study nigrostriatal function,(urner" 2>?3:" Al)ina A".44@8-. Aert! et al ,2>3B-3 di'ided catatonia into 8 stages de&ending u&on increasing intensity. Ce o)ser'ed t!at t!e drugs a)le to antagoni$e catatonia of stage III and I7 &ossessed good anti&ar1insons acti'ity. Neurole&tics are most commonly used drugs in sc!i$o&!renia and ot!er affecti'e disorders ,Alfred 6oodman 6ilman" .44?-?. *ro1inetic drugs ,metoclo&ramide- also induce catale&sy in mice ,A!tee D" 2>@8-@. (!e drugs a'aila)le in modern medicine for t!e t!era&y of *ar1insonism and drug induced e0tra&yramidal sym&toms are also !a'ing limitations to )e used due to t!eir ad'erse drug reactions. (!e Unani Formulation ,Majoon.-e- Baladur- is one of t!e 1no/n formulations /!ic! contains .2 com&ounds and used in Unani system of medicine as ner'ine tonic" in tremors for years. But t!ere is no scientific )asis for its use. (!e study /as &lanned to e'aluate its effect in drug ,!alo&eridol- induced catatonia. (!e effect /as com&ared /it! standard drug i.e" )en$!e0ol. Material & Methods (!e study /as conducted in t!e De&artment of Ilmul Ad'ia" A. . (i))iya College" AMU" Aligar! in colla)oration /it! t!e De&artment of *!armacology" +. N. Medical College" AMU" Aligar!" after o)taining &ermission from Institutional Animal <t!ical Committee. Animals 5 Al)ino rats of eit!er se0 ,Aistar Strain- Aeig!ing 234 5 .44 gm. /ere di'ided into four grou&s of ? animals eac!. (!e animals /ere &ro'ided standard diet ,Di&ton India- and /ater and li)itum. (!e tem&erature at .? E . 4C and 2. !rs dar1 and lig!t cycles /ere maintained. Drugs : (!e ingredients as descri)ed in National Formulary of Unani Medicine" *art I

,Anonymous 2>B2-B ,ta)le 5 2-/ere &rocured from Da/a1!ana (i))iya College AMU" Aligar! and /ere identified )y com&arison for its macrosco&ic and microsco&ic c!aracters /it! aut!entic s&ecimens of t!e ingredients at t!e Botanical sur'ey of India" De!radun and Forest Researc! Institute De!radun" India. (!e ingredients /ere administered in t/o forms ,a- Majoon and ,)-

34F alco!olic e0tract. (!e amount of ingredients as mentioned in National Formulary of Unani Medicine" *art I /ere mi0ed in Majoon and for e0tract. Ben$!e0ol /as o)tained from Sigma &!armaceuticals. Calo&eridol /as o)tained from (orrent &!armaceuticals. Preparation of Majoon: All t!e ingredients e0ce&t Crocus sati'us" Dinn ,Gafran- and *istacia lentiscus" Dinn ,mastagi- /ere &o/dered in an electric grinder and sie'ed B4 No mes!. *.lentiscus /as &o/dered se&arately in &orcelain mortar )y slo/ and lig!t mo'ement and C. sati'us /as ground in 34 ml rose /ater se&arately in a c!ina clay mortar . %i/am ,sugary )ase- /as &re&ared from sugar and !oney )ot! " sugar ,:34gm) /as dissol'ed in .44 ml of /ater at )oiling stage" t!ereafter !oney,2 1g- /as added in t!e sugar solution and t!e mi0ture /as !eated . *o/dered ingredients /ere added in t!e Hi/am ,sugary )ase- and mi0ed /ell. After cooling *. lentiscus &o/der and ground C. sati'us in rose /ater /ere added to t!e a)o'e syru& containing all ot!er ingredients and made !omogenous )y stirring. Preparation of !tract: All t!e ingredients e0ce&t !oney" sugar" *. lentiscus and C. sati'us /ere &o/dered in electric grinder. *. lentiscus /as &o/dered se&arately in mortar. (!e &o/dered ingredients and C sati'us /ere e0tracted in So0!letIs a&&aratus for ? !rs in 34F alco!ol. (!e e0tract /as filtered and dried on /ater )at!. (!e yield &ercentage of e0tract /as calculated /it! reference to crude drug and /as found to )e B.3?F. (!e animal dose of Majoon and e0tract /ere calculated in t!e usual manner )y di'iding t!e Unani Clinical dose )y 34 t!en multi&lying )y @ for al)ino rats ,D!a/an" 2>B.->. Doses of the "nani formulation and drugs in rats Majoon 5 284 mg 9 244gm )ody /eig!t & o 34F alco!ol e0tract 24mg 9 244gm )ody /eig!t & o Ben$!e0ol 4.23 mg 9 244 gm & o Calo&eridol 5 4.:4mg 9 244gm )ody /eig!t i.&. Methods 5 (est /as carried out )y t!e met!od of Mor&ugro ,2>?.- 24. (!e animals /ere di'ided into four grou&s of ? animals eac!. (!e animals in grou& I /ere administered distilled /ater and ser'ed as control. (!e animals in grou& II /ere treated /it! )en$!a0ol 4.23 mg 9 244gm once

daily. (!e dose of )en$!e0ol in !uman is ?-2. mg9day ,Alfred 6oodman 6ilman".44?- 22 (!e animals in grou&s III and I7 /ere administered majoon and alco!olic e0tract in t!e dose of 284 mg and 24mg 9 244gm )ody /eig!t once daily &.o. (!e animals of all grou&s /ere treated for :4 days. ;n t!e :4t! day 83 minutes after administration of distilled /ater" standard drug = test drug" all animals in different grou&s /ere administered !alo&eridol in t!e dose 4.:4 mg 9 244 gm )ody /eig!t intra&eritoneally. (!e ma0imum dose of !alo&eridol in !uman is .4 mg 9day ,Alfred 6oodman 6ilman" .44?-2.. (!e dose of )en$!e0ol and !alo&eridol in rats /as calculated )y formula gi'en )y D!a/an" 2>B.>. All t!e animals /ere tested for t!e intensity of anticatatonia at e'ery .4 minutes for a &eriod of : !rs. (!e rig!t and left fore lim)s of eac! animal /as successi'ely &laced on : cm !ig! o)ject. If t!e animal retained t!e &osition for 24 seconds a score of 4.3 /as gi'en ,for eac! fore lim)-. Dater t!e lim)s /ere &laced on ? cm !ig! o)ject. If t!e animal retained t!e &osture for 24 seconds a score of 2 /as gi'en ,for eac! lim)-. (!us ma0imum score for a rat /as :. (!e &ercent in!i)ition of catatonia in test drug and standard drug /as calculated in com&arison /it! control grou& )y t!e formula. 244 0 ,2 5 a 9 )A!ere JaI is t!e mean anti-catatonic score of t!e test 9 standard animals and J)I is t!e mean anticatatonic score of t!e control animals. (!e mean score of 'arious grou& of animals /ere

statistically com&ared for determine significance of difference )y using one-/ay AN;7A follo/ed )y DunnettIs test /as &erform )y using 6ra&! *ad soft/are" 'ersion :.44 "San Diego California" USA.

#esultK It /as o)ser'ed t!at &ercentage of in!i)ition of catatonia after .4 min. of !elo&eridol administration in grou& II ,)en$!e0ol treated grou&-" III = I7 /ere ?>" 38 = ?. res&ecti'ely. (!ere /as !ig!ly significant increase in duration of catatonia in grou& II" III = I7 as com&ared /it! control grou& ,&L4.42- de&icted in ta)le . = gra&!2" .. After 84 min. of !alo&eridol administration t!e &ercentage in!i)ition in catatonia in grou& II" III = I7 /ere @8" 3> = ?@ res&ecti'ely as com&ared /it! control. (!e increase in duration of catatonia in all t!ree grou&s /ere !ig!ly significant ,&L4.42-. (!e o)ser'ation /as recorded for :

!ours at t!e inter'al of .4 min and it /as o)ser'ed t!at t!e increase in duration of catatonia in grou&s II" III = I7 /ere !ig!ly significant statistically. DiscussionK (!e test formulation ,Majoon e )aladur- is a &otent Unani formulation and mainly used in CNS disorders )ut it /as not used in *ar1insons disease or drug induced e0tra&yramidal sysm&toms. (!e test formulation !as significant catatonia antagoni$ing acti'ity &roduced )y !alo&eridol. (!e antagonism of catatonia &roduced )y &!enot!ia$ines is a good inde0 of anti&ar1insons acti'ity ,(urner" 2>?3-:. In t!e &resent study it /as o)ser'ed t!at all t!e test formulations ,Majoon and alco!olic e0tract- = standard drug ,)en$!e0ol- in t!e dose of 284 mg" 24 mg and 4.23 mg9244gm )ody /eig!t res&ecti'ely &roduced significant in!i)ition of catatonia t!roug!out t!e testing &eriod ,&L4.42-. (!e unani formulation in Majoon form &roduced &ea1 and significant in!i)ition ,@3Fat ?4 min ,&L4.42- )ut least in!i)ition at .4 min after !alo&eridol administration ,&L4.42-. 34F alco!olic e0tract &roduced &ea1 and !ig!ly significant ,B8F- in!i)ition in catatonia at ?4 min of !alo&eridol administration ,&L4.42-. (!e standard drug ,)en$!a0ol- &roduced &ea1 and !ig!ly significant ,BBF- at ?4 min of !alo&eridol administration /!ile &roduced !ig!ly significant in!i)ition t!roug!out t!e testing &eriod. 34F alco!olic e0tract treated grou& s!o/ed almost similar res&onse to )en$!e0ol treated grou&. It can )e concluded t!at t!e Unani formulation in e0tract form /as as effecti'e as )en$!e0ol in drug induced catatonia. Its mec!anism of action and safety &rofile can )e e0&lored in furt!er studies. Ac$nowledgement Ae are grateful to *rofessor . M. Musuf Amin de&artment of Ilmul Ad'ia"A. . (i))iya College" AMU for !is !el& and assistance.

Table-1 Ingredient of Majoon-e-Baladur


%.&o. *. .. :. 8. 3. ?. @. B. >. 24. 22. 2.. 2:. 28. 23. 2?. 2@. 2B. 2>. .4. .2. 'ontent unjad Mag!$-e-(u1!um-e-Baladur Mag!$-e-Badam Mag!$-e-C!ilg!o$a Asgand AHarHar!a !ulanjan +au$a)u/a Bis)asa Ganja)eel Sala) Misi Filfil Dara$ Mastagi (u1!m-e-!aliyun (u1!m-e-6a$ar (u1!m-e-Anjra (u1!m-e- onc! Gafran Samundar So1! %and Safaid Asal (otanical &ame Sasamum Indicum Dinn. Semecar&us anacardium Dinn. *runus amygdalus" Baill *inus gerardiana" Aall Ait!ania somnifera" Dunal Anacyclus *yret!rum DC Al&inia galanga" /illd Myristica fragrans" Coutt. Myristica fragrans" Coutt. Gingi)er officinal" Roscae ;rc!is latifolia" Dinn. *i&er longum Dinn. *istacia lentiscus Dinn. As&aragus officinalis Dinn. Daucus carota Dinn. Ble&!aris edulis *ers. Mucuna *ruriens Ba1. Crocus sati'us Dinn. Argyreia s&eciosa" s/eet Sacc!arum officimarum" Dinn. A&is mellifera.Dinn )eight :4 gm :4 gm :4 gm :4 gm :4 gm :4 gm :4 gm :4 gm :4 gm .4 gm .4 gm 23 gm 23 gm 23 gm 24 gm 24 gm 24 gm 24 gm 3 gm :@3 gm 2 g

FI6-2

FI6-.

#eferences 2. Casey D<. (ardi'e dys1inesiaK *at!o&!ysiology and animal models. + Clin *syc!iat .444N ?2K3->. .. :. ul1arni S " Naidu *S. (ardi'e dys1inesiaK An u&date. Drugs (oday .442N :@K >@ 5 22>. (urner ARK Screening met!ods in *!armacology. Academic *ress" Ne/ Mor1 and Dondon 2>?3N .:2 5 :.. 8. Al)ina A" 7inod N" C N 6o&ala1ris!na"M Nandini. <'aluation of t!e antio0idant &otential of NR-ANO-C,a &oly!er)al formulation- and its indi'idual constituents in re'ersing !alo&eridol- induced catale&sy in mice" Indian + *!armacol" .44@N:>K :K23238. 3. Airt! A" 6oss/ald R" Carlein U" Risse C and reis1ott CK *!arma1ologie acylierter

&!enot!ia$in-deri'ati'e" Arc!. Intern. *!armacodynamic 2>3BN 223K 2->. ?. A 6oodman 6ilmanK (!e &!armacological )asis of t!era&eutics" Ross .+. Baldessarini and Fran1 I (ara$i" *!armacot!era&y of *syc!osis and ania"c!a&ter-2B Mc 6ra/ Cill" USA" <le'ent! International <dition" .44?" 8?2-8B3. @. A!tee D" Buncom)e 6. Metoclo&ramide induces catale&sy and increases striatal !omo'anillic acid content in mice.Acta *!armacol (o0icol 2>@8N :3K 8.>-8:.. B. >. AnonymousK National Formulary Unani medicine. *art I" First edition 2>B2N 2@?-2@>. D!a/an BN" Duley M*" Me!rotra BN" Rastogi R* and (ondon +SK Screening of Indian *lants for Biological Acti'ity" *art IO" Indian +. <0& Biol 2>B.N 2B K 3>8-3>@. 24. Mor&urgo" CK <ffect of Anti&ar1inson drugs on a &!enot!ia$ine induced catatonic reaction" Arc!. Intern. *!armacodynamic 2>?." 2:@N B8 5 >8.

22.

A 6oodman 6ilmanK (!e &!armacological )asis of t!era&eutics" Da'id 6 Standaert and Anne B Moung" (reatment of Central Ner'ous System Degenerati'e Disorder" c!a&ter.4" Mc 6ra/ Cill" USA" <le'ent! International <dition" .44?" 3::-3:@.

2..

A 6oodman 6ilmanK (!e &!armacological )asis of t!era&eutics" Ross .+. Baldessarini and Fran1 I (ara$i" *!armacot!era&y of *syc!osis and ania"c!a&ter-2B" Mc 6ra/ Cill" USA" <le'ent! International <dition" .44?" 8@3-8@@.

+able,-

.%tudy for Anti,Par$inson Acti/ity of Majoon,e,(aladur0

Inter/al of +esting .Minutes0 -2 min &.'alue Mean Score E S.<. F of In!i)ation. 32 min &.'alue Mean Score E S.<. F of In!i)ation. 42 min F of In!i)ation.. &.'alue Mean Score E S.<. 52 min &.'alue Mean Score E S.<. F of In!i)ation. *22 min &.'alue Mean Score E S.<. F of In!i)ation. *-2 min &.'alue Mean Score E S.<. F of In!i)ation. *32 min &.'alue Mean Score E S.<. F of In!i)ation. *42 min &.'alue Mean Score E S.<. F of In!i)ation. *52 min Mean Score E S.<. F of In!i)ation. @8 ?: @4

1roup

1roup ,I

..2@ E 4..2 4.?@ E 4.24 2

...3 E 4..3 4.3B E 4.B:

..?@ E 4.24 4.:: E 4.24

..@3 E 422 4.8. E 4.4B

..3B E 4.4B 4.34 E 4.44

..34 E 4... 4.34 E 4.2.

..8. E 4..4 4.3B E 4..:

..:: E 4.2? 4.3B E 4.4B

...3 E 4.22 4.3B E 4.22

1roup ,II
dd

?>

@8

BB

B3

B2

B4

@?

@3

1roup ,III

E 4... 4.B: E 4.24

38

4.>. E 4..4

3>

4.?@ E 4.24

@3

4.@3 E 4.2@

@:

4.@3 E 4.2@

@2

4.B: E 4.2?

?:

4.>. E 4.23

?.

4.>. E 4.4B

?2

4.B: E 4.2?

1roup ,I6

?.

4.@3 E 4.22

?@

4.8. E 4.4B

B8

4.34 E 4.44

B.

4.3B E 4.4B

@B

4.?@ E 4.24

@:

4.@3 E 4.22

?>

4.@3 E 4.2@

?B

4.?@ E 4.24

6rou&-I K Control 6rou&-IIK Standard ,Ben$!e0ol- 4.23 gm 6rou&-IIIK MB 284mg9244gm 6rou&-I7K 34F Alc!olic <0tract ,MB- 24mg9244gm

,(!e data /ere analy$ed using one-/ay AN;7A follo/ed )y DunnettIs test.-

&.'alue &L4.42 &L4.42 &L4.42

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