A study of the pharmacological actions of Dioclea grandiflora martius ex bentham

R ita M a tte ', J o s e R o b e rto L e ite , S e rg io T u fik

A s tu d y o f th e p h a rm a c o lo g ic a l

a c tio n s

o f D io c le a g ra n d iflo ra m a rtiu s e x b e n th a m

Departament

of Psychobiology,

Escola Paulista de Medicina - Siio Paulo, Brazil

D io c/e a g ra n d iflo ra M a rt. e x B e n t., kn o w n a s M u cu n a o r M u cu n a o f sto n e , is a m e m b e r o f th e L e g u m in o sa e fa m ily, p o p u la rly u se d fo r its p o ssib le e ffe cts o n th e C e n tra l N e rvo u s S yste m (C N S ). R e p o rts m e n tio n se d a tive , to n ic, a n d a lso a n ti e p ile p tic p ro p e rtie s fo r th is p la n t. In th is p a p e r a scre e n in g fo r C N S a ctio n w a s d o n e w ith a q u e o u s e xtra cts o f th e se e d s. T h is stu d y w a s ca rrie d o u t u sin g so m e a n im a l m o d e ls fo r th e stu d y o f se d a tive , h yp n o tic, a n xio lytic, a n tico n vu lsiva n t a n d n e u ro le p tic a ctivity. T h e re su lts sh o w e d th a t D io cle a g ra n d iflo ra M a rt. e x B e n t. d e m o n stra te s th e g e n e ra l p ro file o f a C N S d e p re ssa n t d ru g . H o w e ve r, th e e xtra ct d id n o t e xh ib it a n y o f th e sp e cific p ro file s te ste d . M o re o ve r, th e re su lts su g g e st a p o ssib le to xicity ste m m in g fro m th e p o p u la r o r fo lk u se o f

th is p la n t. .

U N IT E R M S : D io cle a g ra n d iflo ra . M u cu n a . P h a rm a co lo g ic scre e n in g .

IN T R O D U C T IO N

V

a r i o u s s p e c i e s o f t h e L e g u m i n o s a e f a m i l y a r e f r e q u e n t l y u s e d i n p o p u l a r o r f o l k r e m e d i e s . D i o c l e a G r a n d i f l o r a M a r t . e x B e n t . i s a t a l l c l i m b i n g p l a n t , w i t h l e a v e s c o m p o s e d o f t h r e e s m a l l o b l o n g l e a f l e t s a n d l a r g e s e e d s . I n B r a z i l i t i s f o u n d i n t h e s a v a n n a h o r s c r u b o f t h e s t a t e s o f B a h i a , C e a r a , P a r a f b a , a n d P e r n a m b u c o ( B e n t h a m , 1 8 5 9 a n d M a x w e l l , 1 9 6 9 ) . I t i s a l s o k n o w n a s M u c u n a o r " M u c u n a d o c a r o ~ o " , a n d i t i s i n d i c a t e d a s a f o l k r e m e d y d u e t o i t s p o s s i b l e e f f e c t s o n t h e c e n t r a l n e r v o u s s y s t e m s u c h a s : t o n i c a c t i o n , c a l m a n t

A d d re s s fo r c o rre s p o n d e n c e : R ita M a tte i

D e p a rta m e n to d e P s ic o b io lo g ia - E s c o la P a u lis ta d e M e d ic in a R u a B o tu c a tu , 8 6 2 -C a ix a P o s ta l 2 0 3 9 9

S a o P a u lo - S P - B ra s il - C E P 0 4 0 3 4 -0 6 2

a n d p o s s i b l y a n t i e p i l e p t i c a c t i o n ( I n v e n t a r i o d e P l a n t a s M e d i c i n a i s B A , 1 9 7 9 ) . H o w e v e r , n o s y s t e m a t i c s t u d y h a s b e e n m a d e w i t h t h e i n t e n t o f c o n f i r m i n g t h e s e a c t i o n s . T h e o b j e c t i v e o f t h i s p a p e r w a s t o s t u d y t h e p h a r m a c o l o g i c a l a c t i o n s o f a q u e o u s e x t r a c t s o f t h e s e e d s o f D i o c l e a g r a n d i f l o r a M a r t . e x B e n t . I n o r d e r t o d o t h i s , v a r i o u s s p e c i f i c t e s t s w e r e p e r f o r m e d w i t h a n i m a l m o d e l s a n d t h e p o s s i b l e s e d a t i v t ? , a n t i c o n v u l s i v a n t , n e u r o l e p t i c , a n x i o l y t i c a n d h y p n o t i c a c t i o n s w e r e d e t e r m i n e d .

M A T E R IA L S A N D M E T H O D S

B o t a n i c a l M a t e r i a l - T h e s e e d s o f D i o c l e a g r a n d i f l o r a M a r t . e x B e n t . w e r e s u p p l i e d b y t h e A l b a n o M a r t i n s L t d a . c o m p a n y o f S a o P a u l o , w h i c h h a d t h e m b r o u g h t f r o m

B a h i a s t a t e , a n d w e r e l a t e r i d e n t i f i e d b y P r o f e s s o r L u c i a n o

P a g a n u c c i d e Q u e i r o z , c u r a t o r o f t h e 'H U E F S h e r b a r i u m

o f t h e S t a t e U n i v e r s i t y o f F e i r a d e S a n t a n a , B a h i a , w h o

c o n c l u d e d t h a t t h e y w e r e i n d e e d s e e d s o f t h e D i o c l e a

g r a n d i f l o r a M a r t . e x B e n t ( h e r e a f t e r r e f e r r e d t o s i m p l y a s

D i o c l e a g r a n d i f l o r a ) . I n o r d e r t o d o t h i s t h e s h o r t e r s i z e o f

t h e h i l u m o f t h e s e e d s w a s c o n s i d e r e d , t h i s b e i n g a d i f f e r i n g

c h a r a c t e r i s t i c , a s t h e o t h e r s p e c i e s e x h i b i t a h i l u m m o r e

t h a n 2 / 3 t h e c i r c u m f e r e n c e o f t h e s e e d . T h i s d i s t i c t i o n i s

o n l y v a l i d f o r m a t e r i a l s c o m i n g f r o m t h e e a s t o f B r a z i l

( P e r n a m b u c o t o P a r a n a ) .

P r e p a r a t i o n a n d L i o p h i l i z a t i o n - T h e s e e d s w e r e

g r o u n d u s i n g a k n i f e g r i n d e r , r e s u l t i n g i n a f i n e p o w d e r

t h r o u g h t a m i s n o . 1 8 0 a s r e c o m m e n d e d b y t h e

P h a r m a c o p e i a o f 1 9 7 7 . B a s e d o n n o n - o f f i c i a l s o u r c e s s u c h

a s v a r i o u s f o l k r e c i p e s a n e x t r a c t w a s p r e p a r e d c o n t a i n i n g

3 .3 g . o f p o w d e r i n 1 5 0 m l . o f b o i l i n g w a t e r a g i t a t e d f o r

1 2 0 m i n u t e s . T h i s e x t r a c t w a s d r i e d a f t e r f i l t e r i n g . T h e

d o s e s o f t h e e x t r a c t u s e d i n t h e e x p e r i m e n t s f o l l o w e d t h e

c r i t e r i a f o r a p h a r m c o l o g i c a l s c r e e n i n g , a n d r e p r e s e n t

a p r o x i m a t e l y 2 0 , 5 0 , 7 5 , a n d 1 0 0 t i m e s t h e d o s e s u s e d b y

h u m a n b e i n g s , w h i c h i s e q u i v a l e n t t o 1 5 0 , 3 4 2 , 5 2 0 , a n d

6 8 5 m g / k g r e s p e c t i v e l y .

A n i m a l s - M a l e a l b i n o S w i s s m i c e w e i g h i n g b e t w e e n

3 0 a n d 4 0 g . a n d m a l e W i s t a r r a t s w e i g h i n g b e t w e e n 3 0 0

a n d 4 0 0 g ., a n d 3 t o 4 m o n t h s o l d w e r e u s e d . T h e s e a n i m a l s

w e r e r a i s e d i n t h e v i v a r i u m o f t h e D e p a r t m e n t o f

P s y c h o b i o l o g y o f t h e E s c o l a P a u l i s t a d e M e d i c i n a .

1. Preliminary

Tests

M e a s u r e m e n t o f M o t o r A c t i v i t y

5 g r o u p s o f 1 0 h o u s e m i c e e a c h r e c e i v e d b y v i a ( i .p .)

s a l i n e s o l u t i o n a n d d i f f e r e n t d o s e s o f t h e e x t r a c t o f D i o c l e a

g r a n d i f l o r a , r e s p e c t i v e l y o f 1 5 0 , 3 4 2 , 5 2 0 , a n d 6 8 5 m g /

k g . T h e a n i m a l s w e r e t h e n i n d i v i d u a l l y p l a c e d i n b o x e s

e q u i p p e d w i t h p h o t o e l e c t r i c c e l l s i n o r d e r t o r e g i s t e r t h e i r

m o v e m e n t s f o r 6 0 m i n u t e s ( C a r l i n i , 1 9 7 2 ) .

M e a s u r e m e n t o f M o t o r C o o r d i n a t i o n

3 g r o u p s o f 1 0 m i c e , e a c h p r e v i o u s l y t r a i n e d , r e c e i v e d

r e s p e c t i v e l y , s a l i n e s o l u t i o n , D i a z e p a m 2 .5 m g / k g , a n d

e x t r a c t o f D i o c l e a g r a n d i f l o r a i n a d o s e o f 6 8 5 m g / k g ( i .p .) .

T h e y w e r e t h e n s u b j e c t e d t o a t e s t b y p l a c i n g t h e m o n t h e

s p i n n i n g b a r o f a r o t a - r o d a p p a r a t u s , a f t e r 6 0 , 1 2 0 a n d

1 8 0 m i n u t e s . T h e t i m e e a c h a n i m a l r e m a i n e d o n t h e

s p i n n i n g b a r w a s t h e n e v a l u a t e d ( C a r l i n i a n d B u r g o s ,

1 9 7 9 ) .'

2. Evaluation of the Anticonvulsivant

Action

P r e v e n t i o n o f E l e c t r o s h o c k - i n d u c e d C o n v u l s i o n

3 g r o u p s o f 1 0 m i c e r e c e i v e d , r e s p e c t i v e l y , s a l i n e

s o l u t i o n , 2 0 m g / k g o f d i p h e n y l h y d a n t o i n , a n d e x t r a c t o f

6 8 5 m g / k g D i o c l e a g r a n d i f l o r a ( i .p .) . T r a n s c o r n e a l

e l e c t r o s h o c k ( 8 m A / 0 .2 s e c o n d s ) w a s a p p l i e d 1 2 0 m i n u t e s

a f t e r t h e t r e a t m e n t , b e i n g t h e n r e c o r d e d t h e n u m b e r s o f

a n i m a l s w h i c h e x h i b i t e d t o n i c c o n v u l s i o n s a n d t h e n u m b e r

o f d e a t h s .

P r e v e n t i o n o f P e n t y l e n e t e t r a z o l - i n d u c e d C o n v u l s i o n s

4 g r o u p s o f 1 0 m i c e e a c h w e r e t r e a t e d w i t h s a l i n e

s o l u t i o n a n d 3 d i f f e r e n t d o s e s ( 3 4 2 , 5 2 0 , a n d 6 8 5 m g / k g )

o f D i o c l e a g r a n d i f l o r a ( i .p .) . A f t e r 6 0 m i n u t e s 1 0 0 m g / k g

o f p e n t y l e n e t e t r a z o l w a s a p p l i e d ( s .c .) . T h e l a t e n c y t i m e s

f o r c l o n i c a n d t o n i c c o n v u l s i o n s , a n d t h e n u m b e r o f d e a t h s

w e r e t h e n r e c o r d e d ( V a l e a n d L e i t e , 1 9 8 3 ) .

3. Evaluation of Neuroleptic Action

I n d u c t i o n o f C a t a t o n i a

2 g r o u p s o f 1 0 m i c e e a c h r e c e i v e d , r e s p e c t i v e l y , 5

m g / k g o f a h a l o p e r i d o l d r u g ( i .p .) , a n d 6 8 5 m g / k g o f t h e

e x t r a c t o f D i o c l e a g r a n d i f l o r a ( i .p .) . T h e a n i m a l s w e r e t h e n

p l a c e d w i t h t h e i r f r o n t p a w s s u p p o r t e d b y a h o r i z o n t a l b a r

a n d o b s e r v e d f o r t o n i c i m o b i l i t y a n d p a l p e b r a l p t o s i s ( T u f i k

e t . c o l s ., 1 9 7 9 )

4. Evaluation of Anxiolytic Action

A n t i - p e n t y l e n e t e t r a z o l E f f e c t

2 g r o u p s o f 1 0 m i c e e a c h r e c e i v e d , r e s p e c t i v e l y ,

s a l i n e s o l u t i o n a n d 6 8 5 m g / k g o f t h e e x t r a c t o f D i o c l e a

g r a n d i f l o r a . A f t e r 6 0 m i n u t e s t h e a n i m a l s r e c e i v e d 1 0 0

m g / k g o f a n t i c a r d i a z o l e f f e c t ( s .c .) , a f t e r w h i c h t h e l a t e n c y

t i m e f o r c l o n i c c o n v u l s i o n s w a s o b s e r v e d a n d r e c o r d e d .

P u n i s h e d R e s p o n s e T e s t

1 0 r a t s p r e v i o u s l y d e p r i v e d o f w a t e r w e r e

c o n d i t i o n e d , r e i n f o r c i n g t h e b e h a v i o r o f p r e s s i n g a b a r o n

a S k i n n e r b o x w i t h w a t e r . T h e a n i m a l s w e r e t h e n s u b j e c t e d

t o t h e G e l l e r a n d S e i f t e r c o n f l i c t t e s t ( 1 9 6 0 ) , m o d i f i e d i n

a c c o r d a n c e w i t h A l m e i d a a n d L e i t e ( 1 9 9 0 ) . T h e a n i m a l s

w e r e t r a i n e d , a f t e r b e i n g d e p r i v e d o f w a t e r f o r 2 0 h o u r s ,

t o p e r f o r m b a r - p r e s s i n g b e h a v i o r a t a f i x e d r a t i o ( F R - I 0 )

r e i n f o r c e m e n t s c h e m e . W h e n t h e a n i m a l s a t t a i n e d a s t a b l e

l e v e l o f r e s p o n s e s , o b t a i n i n g c o n t i n u o u s l y t h e

r e i n f o r c e m e n t o r r e w a r d , a l u m i n o u s s t i m u l u s w a s

'!< li:% W il""""""",= m z.= .'= '.< e :W ilu = m z~ = " = ( ,« ,« = ,'W il,W il"~ = '~ W < '= _ W il~ = ""'= '~ '= $ .= ,..W il"= + f= ~ '(= A ~ W il.h W ilN :.m m :~ ~ = = = lliIl. =.. = = = = = *= m $ lliIli$ = *'"= ' = = = m z# lliIl4 = = ~ = = = ..:= . ~ g. ' i h ~ ..~ ~ ," r"'t ~

in tr o d u c e d , T h is w a y e a c h tim e th e a n im a l p r e s s e d th e b a r

it r e c e iv e d th e r e w a r d a n d th e lu m in o u s s ig n a l w a s

a c tiv a te d . A f te r 5 s e s s io n s , a s h o c k o f 0 .7 r n A w a s r e le a s e d

if th e a n im a l p r e s s e d th e b a r d u r in g th e lu m in o u s s ig n a l.

T h e b e h a v io r o f p r e s s in g th e b a r w a s th u s s u p p r e s s e d . T h e

a n im a ls r e c e iv e d , a t th r e e d a y in te r v a ls , s a lin e s o lu tio n ,

2 .0 m g lk g o f d ia z e p a m o r 6 8 5 m g lk g o f th e e x tr a c t o f

D io c le a g r a n d if lo r a ( i.p .) o n e h o u r b e f o r e b e in g s u b je c te d

to th e te s t.

Evaluation of Hypnotic Action

P o te n tia tio n o f P e n to b a r b ito l~ in d u c e d S le e p

4 g r o u p s o f 1 0 m ic e e a c h , r e c e iv e d , r e s p e c tiv e ly ,

d o s e s o f 1 5 0 ,3 4 2 , a n d 6 8 5 m g lk g ( i.p .) o f th e e x tr a c t o f

D io c le a g r a n d if lo r a . T h e c o n tr o l g r o u p w a s tr e a te d b y th e

s a m e v ia o f a d m in is tr a tio n . A f te r 6 0 m in u te s , th e a n im a ls

r e c e iv e d a d o s e o f 3 5 m g lk g o f s o d iu m p e n to b a r b ito l, a n d

th e n th e tim e b e tw e e n lo s s a n d r e c o v e r y o f b a la n c e r e f le x e s

w a s d e te r m in e d . T h is in te r v a l w a s c o n s id e r e d to b e th e

s le e p tim e ( S a v a k i e t c o ls ., 1 9 7 6 , M a s u r a n d B o e r n g e n ,

1 9 8 0 ) .

S ta tis tic a l A n a ly s is

T h e d a ta w e r e e v a lu a te d .th r o u g h v a r ia n c e a n a ly s is

( A N O V A ) f o llo w e d b y th e S tu d e n t's t- te s t.

6 0 0

> 5 0 0

I

-:> i= 4 0 0 ( )

< I I :

3 0 0

0 I -0

::E _{2 0 0}

1 0 0

0

1 5 0 3 4 2 5 2 0 6 8 5

D O S A G E

F ig u r e 1 - L o c o m o t o r a c t iv it y o f c o n t r o l m ic e _ o r t h o s e t r e a t e d w it h e x t r a c t o f D io c le a g r a n d if lo r a _ _ in d o s e s o f 1 5 0 , 3 4 2 , 5 2 0 , a n d 6 8 5 m g / k g .

*S t a t is t ic a lly d if f e r e n t f r o m t h e c o n t r o l g r o u p ( p < 0 . 0 5 ) ( S t u d e n t 's t - T e s t ) .

T a b le I

A v e r a g e t im e s o f m ic e r e m a in in g o n a s p in n in g b a r

d u r in g t h e r o t a - r o d a p p a r a t u s t e s t , a f t e r b e in g

t r e a t e d w it h d ia z e p a m o r e x t r a c t o f D io c le a

g r a n d if lo r a .

G r o u p D o s a g e m g / k g t im e o n b a r

( s e c o n d s )

R E S U L T S

1. Preliminary tests

S a lin e s o l.

D ia z e p a m

D io c le a g r a n d .

2 .5

685

60

28

60

M e a s u r e m e n t o f M o to r A c tiv ity

T h e r e s u lts p r e s e n te d in f ig u r ~ 1 s h o w th a t th e e x tr a c t

o f D io c le a g r a n d if lo r a in d o s e s o f 1 5 0 , 3 4 2 , 5 2 0 , a n d 6 8 5

m g /k g a lte r e d th e lo c o m o to r y a c tiv ity in a m a n n e r

p r o p o r tio n a l to th e d o s e .

M e a s u r e m e n t o f M o to r C o o r d in a tio n

T h e r e s u lts p r e s e n te d in ta b le I s h o w th a t th e e x tr a c t

o f D io c le a g r a n d if lo r a in a d o s e o f 6 8 5 m g lk g d o e s n o t

p r o d u c e a n a lte r a tio n in th e p e r f o r m a n c e o f th e a n im a ls

a f te r 6 0 , 1 2 0 , a n d 1 8 0 m in u te s .

2. Evaluation of Anticonvulsivant

Action

P r e v e n tio n o f E le c tr o s h o c k - in d u c e d C o n v u ls io n s

T a b le I I s h o w s th a t th e e x tr a c t o f D io c le a g r a n d if lo r a

in a d o s e o f 6 8 5 m g lk g d o e s n o t e x e r c is e a p r o te c tiv e a c tio n

w ith r e g a r d to to n ic c o n v u ls io n s . T h e r e is h o w e v e r a

s ig n if ic a n t p r o te c tio n w ith r e g a r d to th e p e r c e n ta g e o f

d e a th s in r e la tio n to th e c o n tr o l g r o u p .

Table II

The effect of Dioclea grandiflora

on transcorneal

electroshock-induced

convulsions

in mice (Average

of 10 animals). *(p<0.05)(Student's

t-Test).

Saline sol.

Dioclea grand.

685

Group

Dosage . Tonic convulsions

g/kg

.

%

1 0 0

1 0 0

Deaths

%

4 0

0*.

4. Evaluation of Anxiolyolytic

Action

A n ti-p e n ty le n e te tra z o l E ffe c t

T h e re s u lts o b ta in e d in d ic a te th a t th e e x tra c t o f

D io c le a g ra n d iflo ra d o e s n o t p ro te c t th e a n im a is fro m

c lo n ic c o n v u ls io n in d u c e d b y c a rd ia z o l.

P u n is h e d R e s p o n s e T e s t

T h e d a ta in ta b le III (to ta l s u p re s s io n o f re s p o n s e )

in d ic a te th a t th e e x tra c t o f D io c le a g ra n d iflo ra in a d o s e

o f 6 8 5 m g /k g d o e s n o t e x h ib it a n tip u n is h m e n t a c tio n .

Table III

Average number of punished

and non-punished

responses

in rats treated with diazepam

or extract of

Dioclea grandiflora,

when subject

to the conflict

test.

Non-punished

Punished

responses

responses

30 CLONIC CONVULSION

25

en

w ₂₀ I-::I Z

:E

15

~

> 10 U z W I-5

«

. J 0

342 520 685

TONIC CONVULSION

*

342 520 685

Group

Saline sol.

Diazepam

Dioclea grand.

Dosage

mg/kg

20

685

2 6 1

251

14

32

DOSAGE

Figur'e 2 - The effects of different dosages (342, 520, or 685 mgt kg) of the extract of Dioclea grandiflora on pentylenetetrazol-induced convulsions. In the graph are shown the latency times

for the beginning of clonic _ and tonic __ convulsions in treated

mice and in control groups _'_ (Average of 10 mice).

*Statistically different from control group (p<0.05) (Student's

t-Test)

P re v e n tio n o f P e n ty le n e te tra z o l-in d u c e d C o n v u ls io n s

F ig u re 2 s h o w s th a t th e e x tra c t o fD io c le a g ra n d ifl~ ra

in a d o s e o f 3 4 2 m g /k g d o e s n o t a lte r th e la te n c y fo r th e

m a n ife s ta tio n o f c lo n ic o r to n ic c o n v u ls io n s . F o r d o s e s o f

5 2 0 a n d 6 8 5 m g /k g th e re is a s ig n ific a n t in c re a s e . in th e

la te n c y fo r th e m a n ife s ta tio n o f th e tw o ty p e s o f

c o n v u ls io n s .

3. Evaluation of Neuroleptic Action

120 100

en

w I-::I 80 z

:E

~

60 w

~

i= 40 D. W w 20 . J

en

0 150 342 DOSAGE 685

*

In d u c tio n o f C a ta to n ia

T h e d a ta o b ta in e d s h o w th a t th e e x tra c t o f D io c le a

g ra n d iflo ra d o e s n o t in d u c e c a ta to n ia e v e n a fte r fo u r h o u rs

o f tre a tm e n t.

Figure 3 - Pentylenetetrazol-induced sleep in mice in a control

group _ or in mice treated with extract of Dioclei grandiflora _

_: in doses of 150, 342 and 685 mg/kg (Average of 10 mice).

*Statistical!y different from control group (p<0.05) (Student's

t-Test).

5. Evaluation of Hypnotic Action

P o te n tia tio n

o f P e n to b a rb ito l-in d u c e d

S le e p

T h e re su lts p re se n te d in fig u re 3 in d ic a te th a t th e

e x tra c t o f D io c le a g ra n d iflo ra in a d o se o f 1 5 0 m g /k g d o e s

n o t a lte r th e tim e o f sle e p in d u c e d b y p e n to b a rb ito l.

H o w e v e r, in d o se s o f 3 4 2 a n d 6 8 5 m g /k g th e sle e p tim e is

p o te n tia te d b y th is h y p n o tic su b sta n c e .

CONCLUSIONS

T h e in itia l stu d ie s o f th e a c tio n m e c h a n ism s o f

D io c le a g ra n d iflo ra M a rt. e x B e n t in d ic a te a p ro b a b le

d e p re ssa n t e ffe c t o n th e le v e l o f th e c e n tra l n e rv o u s sy ste m ,

w ith m a jo r o r m in o r p o te n c y , w h ic h c o u ld b e re la te d to

th e q u a n tity o f th e a c tiv e p rin c ip le o r in g re d ie n t p re se n t.

in th e p re p a ra tio n s u se d . In d e te rm in in g th e p o ssib le

p sy c h o p h a rm a c o lo g ic a c tio n s o f th e p la n t, w ith re g a rd to

fo lk u se (In v e n ta rio , 1 9 7 9 ), w e o b se rv e d th a t th e

th e ra p e u tic e ffe c ts a ttrib u te d to it w e re n o t c o n firm e d

th ro u g h e x p e rim e n t. A n a n tic o n v u lsiv a n t a c tio n , w h ic h

w o u ld ju stify its u se a s a n d a n tie p ile p tic , w a s n o t o b se rv e d ,

a lth o u g h it sh o u ld b e n o te d th a t th e re w a s a sig n ific a n t

p ro te c tio n w ith re g a rd to th e la te n c y tim e o f th e

m a n ife sta tio n o f c o n v u lsio n , a s w e ll a s th e p ro te c tio n

sh o w n w ith re g a rd to th e n u m b e r o f d e a th s in th e a n im a ls

te ste d . T h is fa c t, h o w e v e r, d o e s n o t ju stify its u se a s a n .

a n tic o n v u lsiv a n t. In v e rify in g th e p o ssib le n e u ro le p tic

e ffe c t, w e d id n 't o b ta in a p o sitiv e re sp o n se in th e a n im a ls

w ith re g a rd to c a ta to n ia , a ty p ic a l e ffe c t o f n e u ro le p tic

su b sta n c e s. T h e se o b se rv a tio n s w e re fu rth e r c o n firm e d in

stu d y in g th e a n x io ly tic e ffe c t, w h e re a g a in n o e v id e n c e

w a s fo u n d o f a p ro te c tiv e a c tio n w ith re g a rd to c lo n ic

c o n v u lsio n . W e k n o w th a t a d ru g w ith a n x io ly tic p ro p e rtie s

in d u c e s c e ssa tio n o f th .is ty p e o f c o n v u lsio n in c e rta in

c irc u m sta n c e s, a s w e ll a s a n in c re a se in th e n u m b e r o f

re sp o n se s to th e c o n flic t te st. O n th e o th e r h a n d , w e sa w

th a t D io c le a g ra n d iflo ra in c re a se d th e sle e p tim e in sp e c ific

te sts, th e tim e o b ta in e d b e in g p ro p o rtio n a l to th e

c o n c e n tra tio n u se d . It is n o t p o ssib le to c o n c lu d e , h o w e v e r,

th a t su c h a re sp o n se is re la te d to a h y p n o tic e ffe c t. O n th e

o th e r h a n d , th is o b se rv a tio n su g g e sts a p ro b a b le in d u c tio n

o f a h e p a to to x ic e ffe c t. T h e p o ssib le to x ic ity o f D io c le a

g ra n d iflo ra M a rt. e x B e n t. is fu rth e r su g g e ste d b y th e to ta l

su p re ssio n o f re sp o n se s in th e c o n flic t te st. D a ta in th e

lite ra tu re sh o w th a t a d v e rse re a c tio n s lik e d e rm a titis,

p a lp ita tio n s, h e a d a c h e a n d h a llu c in a tio n s w e re o b se rv e d

in h u m a n s, a fte r c o n su m in g se e d s o f N lu c u n a P ru rie n s

(B u ll. W H O , 1 9 8 4 , a n d M M R W R , 1 9 8 5 ). '

O u r re su lts in d ic a te a p o ssib le m e d ic a l w a rn in g o r

a le rt in re g a rd to th e th e ra p e ~ tic u se o f D io c le a g ra n d iflo ra

M a rt. e x B e n t., w ith fu rth e r, m o re sp e c ific te sts o f to x ic ity

b e in g in d ic a te d in o rd e r fo r its u se to b e ju stifie d .

ACKNOWLEDGEMENTS

T h e a u th o rs a re g ra te fu l to P ro f. L u c ia n o P a g a n u c c i

d e Q u e iro z , c u ra to r o f th e H e rb a riu m o f th e U n iv e rsid a d e

E sta d u a l d e F e ira d e S a n ta n a fo r th e v a lu a b le c o lla b o ra tio n

o n th e id e n tific a tio n o f th e se e d s o f D io c le a g ra n d iflo ra

M a rt. e x B e n t., a n d to M r. S e v e rin o F e rre ira d e L im a fo r

th e te c h n ic a l a ssiste n c e .

T h is stu d y is d e d ic a te d to D r. A rm a n d o S ilv a R a m o s

F ilh o (in m e m o ria m ).

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