Rev. Soc. Bras. Med. Trop. vol.37 suppl.2

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Would Sacaca,

Croton caju cara

Benth ( Euphor biaceae) be an hepatotoxic

plant like Ger mander,

Teu criu m cham aedrys

L. ( Labiatae) ?

Será a Sacaca,

Cro to n ca juca ra

Benth ( Euphorbiaceae

)

uma planta hepatotóxica

semelhante à Germander,

Te ucrium cha m a e drys

L. ( Labiatae) ?

Manoel do Car mo Per eir a Soar es

1

ABSTRACT

Cli n i c a l a n d e x p e ri m e n ta l stu d i e s h a ve c o n si ste n tly i n c ri m i n a te d th e m e d i c i n a l p la n t ge rm a n d e r (Te uc r ium c hamae dr ys

L.) i n e p i d e m i c a n d sp o ra d i c c a se s o f li ve r d i se a se s. Th e sa c a c a (Cr o to n c aj uc ar a Be n th ) , a c o m m o n p la n t i n Bra zi li a n Am a zo n re gi o n a lso c o m e s b e ing incrim ina te d in sim ila r clinica l ca se s. Of b o th pla nts we re iso la te d dite rpe no id co um po unds with sim ila r che m ica l structure s.

Ke y-words: Sa c a c a . Cr o to n c aj uc ar a. Ge rm a n d e r.

RESUMO

Estu d o s c lí n i c o s e e x p e ri m e n ta i s te m i n c ri m i n a d o , d e f o rm a c o n si ste n te , n a Fra n ç a , a p la n ta m e d i c i n a l ge rm a n d e r (Te uc r ium c hamae dr ys L.) e m c a so s e sp o rá d i c o s o u e p i d ê m i c o s d e h e p a to p a ti a s. A Sa c a c a (Cr o to n c aj uc ar a Be n th ) , u m a p la n ta c o m u m n a Am a zô n i a b ra si le i ra , ta m b é m ve m se n d o i n c ri m i n a d a e m c a so s c lí n i c o s se m e lh a n te s. De a m b a s a s p la n ta s, f o ra m i so la d o s d i te rp e n ó i d e s c o m e stru tu ra s q u í m i c a s se m e lh a n te s.

Pal avr as-chave s: Sa c a c a . Cr o to n c aj uc ar a. Ge rm a n d e r.

1 . Instituto Evandr o Chagas da Se c r e tar ia de Vigilânc ia e m Saúde do Ministé r io da saúde .

En de r e ço par a cor r e spon dê n ci a: Dr. Mano e l do Car mo Pe r e ir a So ar e s. Av. Almir ante B ar r o so 4 9 2 , 6 6 0 9 0 - 0 0 0 . B e lé m, PA B r azil. Fax: 9 1 2 4 1 - 4 4 1 8 , 9 1 2 2 6 - 1 2 8 4

e - mail: mso ar e s@ ie c . pa. go v. b r

Clin ic a l a n d e x pe r im e n ta l s tudie s h a ve c o n s is te n tly in c r im in a te d th e m e dic in a l pla n t ge r m a n de r (Te u c ri u m cha m a e drys L.) in epidemic and sporadic cases of acute hepatitis as we ll as in fulminant, c hr o nic he patitis and c ir r ho sis5 8_.

Germander has been used in Europe since ancient times as a folk medicine. Aerial parts of the plant in bloom were used to prepare

herbal teas used in the assumption of having c holeretic and

antiseptic pro perties. The plant was in general regarded as

harmless. Nevertheless, in 1 9 8 6 , when was marketed in France as an adjuvant to slimming diets resulted in an epidemic of hepatitis

in that c ountry5 8_{. Germander c ontains furano}_{ne o}_{-c lerodane}

diterpenoids which has been shown to induce hepatotoxicity5 7_.

Sac ac a (Cro to n c a ju c a ra B enth) is a c ommon shrub in the B razilian Amazo n regio n that gro ws in mainland. Rural c ommunities use its bark and leaf in the preparation of a tea to

treat diar r he a, diab e te s, live r and k idne y distur b s9_{. B e c ause}

o f its pr o pe r tie s in de c r e asing c ho le ste r o le mia and we ight

c o ntr o l its use has inc r e se ad amo ng ur b an po pulatio ns. It has been used under vario us presentatio ns suc h as teas o r

capsules containing sacaca powder. Recent reports have attributed

to s a c a c a c o um po unds b o th a ntiulc e r a tive a nd

hypoglycemiantproperties1 3_{. On the other hand, in 1 9 9 1 Kubo et al}4

ha ve pub lis he d the is o la tio n o f a ne w dite r pe no id (c is -dehydrocrotonin) together with the known no r-diterpene tra

ns-dehydrocrotonin, both extracted from the bark of sacaca came from

B razilian Amazon and, these authors, aware its popular use, performed an in vitro assay to evaluate the extract antihepatotoxic activity. Paradoxically, however, it showed potent hepatotoxic activity4_.

Exe mplar c he mic al str uc tur e s o f dite r pe no ids iso late d

fr o m b o th Te u c ri u m c h a m a e d rys and Cro to n c a ju c a ra ar e sho wn in Figur e 1 . B o th plant spe c ie s c o ntain o the r s fur ano

dite r pe no id c o umpo unds4 7_.

Some published and unpublished observations have recently

implicated sacaca in cases of liver injury in Amazon region2_{, mainly}

after it was marketed as an adjuvant for weight c ontrol and

cholesterolemia level decrease. It has been incriminated in acute, fulminant and c hronic hepatitis. In a rec ent 3 6 month study,

Cartágenes et al2_{reported 2 5 cases of liver disease attributed to}

sacaca hepatotoxicity: 2 1 patients had acute hepatitis, three had

chronic hepatitis and one developed fulminant hepatitis2_.

Revista da Sociedade Br asileir a de Medicina Tr opical 3 7 ( Suplemento II) , 2 0 0 4

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1A

1B

Teucrin A

Crotonin

4 . Kub o I, Asak a Y, Shib ata K. Inse c t gr o wth inhib ito r y no r-dite r pe ne s, c is-de h ydr o c r o to n in a n d tr a n s - is-de h ydr o c r o to n in , fr o m Cro to n c a ju c a ra. Phyto c he mistr y 3 0 : 2 5 4 5 -2 5 4 6 , 1 9 9 1 .

5 . La r r e y D. He p a to to x i c i ty o f h e r b a l r e m e di e s . J o u r n a l o f He p a to l o gy 2 6 ( supl 1 ) : 4 7 - 5 1 , 1 9 9 7 .

6 . La r r e y D, Via l T, Pa uwe ls A, Ca s to t A, B io ur M, Da vid M, Mic h e l H. He pa titis a fte r ge r m a n de r (Te u c r i u m c h a m a e d r ys) a dm in is tr a tio n : a no the r insta nc e o f he r b a l m e dic ine he pa to to xic ity. Anna ls I nte r na tio na l Me dic a ls 1 1 7 : 1 2 9 - 1 3 2 , 1 9 9 2 .

7 . Le k e h a l M , P e s s a yr e D , Le r e a u J M , M o u l i s C, Fo u r a s t F, Fa u D . He pato to xic ity o f the he r b al me dic ine ge r mande r. Me tab o lic ac tivatio n o f its fur ano dite r pe no ids b y c yto c hr o m e P4 5 0 3 A de ple te s c yto sk e le to n-a s s o c in-a te d pr o te in th io ls n-a n d fo r m s pln-a s m n-a m e m b r n-a n e b le b s in r n-a t he pato c yte s. He pato lo gy 2 4 : 2 1 2 - 2 1 8 , 1 9 9 6 .

8 . Mo ste fa- Kar a N, Pauwe ls A, Pe ne s E, B io ur M, Le vy VG. Fatal he patitis afte r he r b al te a. Lanc e t 3 4 0 : 6 7 4 , 1 9 9 2 .

9 . Vi e i r a LS . Fi to te r a p i a da Am a zô n i a : Ma n u a l da s P l a n ta s Me di c i n a i s , 2 ª e diç ão , Agr o nô mic a Ce r e s, São Paulo , 1 9 9 2 .

Fi gu re 1 - Ch e m i c a l stru c tu re o f th e Te u c ri n A a n d Cre to n i n , f u ra n o d i te rp e n o i d s i so la te d f ro m b o th Te uc r ium c hamae dr ys ( 1 A) a n d Cr o to n c aj uc ar a ( 1 B) .

Sac ac a and ge r mande r have similar c he mic al str uc tur e s

fo r th e ir fur a n o dite r pe n o ids . Sin c e Am a zo n ia n h e r b a l

m e dic ine s have o b taine d gr o wing inte r e st thr o ugho ut the

wo r ld, c a utio n s s h o uld b e e xe r c is e d in r e ga r ds to th e ir po te ntial to xic e ffe c ts.

REFERENCES

1 . B r i t o AR , R o d r í g u e z J A, Hi r u m a Li m a CA, Ha u n M , Nu n e s D S . Antiulc e r o ge nic ac tivity o f tr ans- de hydr o c r o to nin fr o m Cro to n c a ju c a ra. Planta Me dic ine 6 4 : 1 2 6 - 1 2 9 , 1 9 9 8 .

2 . Cartágenes PRB, Moreira CC, Teixeira AC, Silveira FAA, Dias-Junior LB, Bichara CDA. Hepatite por sacaca (Cro to n ca juca ra Benth) : Epidemiologia clínica em 2 5 casos [ resumo] . Gastroenterologia Endoscopia Digestiva 1 8 ( supl 1 ) : 2 4 , 1 9 9 9 .

3 . Far ias RA, Rao VS, Viana GS, Silveir a FR, Mac iel MA, Pinto AC. Hypo glyc emic e ffe c t o f tr ans-de hydr o c r o to nin, a no r-c le r o dane dite r pe ne fr o m Cro to n c a ju c a ra. Planta Me dic ine 6 3 : 5 5 8 - 5 6 0 , 1 9 9 7 .

Revista da Sociedade Br asileir a de Medicina Tr opical 3 7 ( Suplemento II) , 2 0 0 4