Moroccan J. Biol. 2-3 (2006) 21-30 Toxic effects of some medicinal plants used in Moroccan traditional medicine

Mohamed Bnouham1*, Fatima Zahra Merhfour1, Mostafa Elachoui1, Abdelkhaleq Legssyer1, Hassane Mekhfi1, Driss Lamnaouer2 & Abderrahim Ziyyat1 1Laboratoire de Physiologie et Ethnopharmacologie. Département de Biologie. Faculté des Sciences. Université Mohamed Ier. B.P. 717 - Oujda, Morocco. Tel: ++21267627496. Fax: ++2123650 06 03 2Institut Agronomique et Veterinaire Hassan II, Departement de Pharmacie Toxicologie et Biochimie, Rabat- Instituts, Maroc.

Abstract Phytoremedies are becoming mainstream worldwide; the increasing of these medicinal approaches is due to the recognition of the value of traditional medicine and indigenous pharmacopoeia. Although medicinal plants are often promoted as natural and therefore harmless, they are not free from adverse effects. The potential toxicity of herbal medicine is not new. In several countries, where herbal medicines are commonly used, it is well known that some plants must used with caution because the adverse reaction can be caused inherently by toxic herbs, by herbs overdoses, or by drug-drug interaction, thus, especially other adverse reaction can be due to quality problems such as adulteration caused by manufacturing, misidentification, substitution of one herbs for an others, improper processing of preparation and use, etc… The present study reviews the cases of some plants commonly used by Moroccan people in traditional medicine and reported as highly toxic. Twenty eight plants are selected dangerous for health; these toxic species belonging to 16 families have been repertoried. The families reported to be most representative of these kinds of plants are Solanaceae (7 species). All physiological functions can be affected by the toxicity of plants. However, the highly toxic plants reviewed are those which produce irreversible health injury, serious aftermath, and irreversible damage such as renal failure, liver damage, hemiplegia, blindness…etc and sometimes they can produce the death. The plants that have been reported to produce the sever damages are: Aconitum vulparia Rchb., Anagyris foetida L., Atractylis gummifera L., Bryonia dioica Jacq, Chenopodium album L., Colchicum autumnale L., Conium maculatum L., Daphne gnidium L., Daphne laureola L., Ferula communis L, Hyosciamus niger L., Mandragora autumnalis Bertol, Nerium oleander L., Ricinus communis L., Solanum nigrum L., Tamus communis L. and Thapsia garganica L. The review indicates the scientific name of the plant (family and specie), the vernacular name, the part used, the LD50 (lethal dose 50) and summarized the most relevant toxicological investigations. The products carrying the toxicity of the plants and the acute toxicity have been mentioned. The great part of these toxic drugs belongs to the alkaloid class. Key words: Toxic plants, Active components, Toxicity, Traditional medicine.

Introduction The use of herbal medicines has increased herbal remedies are innocuous in contrast to considerably over the last decade over the conventional drugs; 3) The idea that what is world. Widespread reliance on traditional natural can only be good; 4) The medicine can attributed to 1) High cost of development of new diseases with severe conventional medicine; 2) The belief that complications, for which there is still no appropriate treatment and 5) The belief that * Corresponding author: Pr. Mohamed Bnouham herbal medicines are natural and safe. E-mail address: [email protected] M. Bnouham et al. / Moroccan J. Biol. 2-3 (2006) 21-30 22

Although phytotherapy continues to be a The colchicine, which is a highly toxic drug, main strategy of remedies in several obtained from Colchicum autumnale was very countries, few plants received scientific or useful against congestive heart failure. The medical scrutinity (Gray and Flatt, 1998). digitalin obtained from digital known for its Moreover, a high number of the medicinal high toxicity was very useful for the treatment plants possess a degree of toxicity. For of cardiac insufficiencies. In the same way we example, it was reported that about one third know very well the diverse important medical of medicinal plants used in the treatment of applications of the narcotics obtained from diabetes are considered to be toxic (Marles very toxic plants. These sorts of applications and Fransworth, 1988). concern for example the belladonna that has a This review is based on the literature such as remarkable importance in pharmaceutical using Medline and other reference sources industry. Indeed, it intervenes in the materials including the books, the Moroccan manufacture of 86 drugs; that is to say, 10.42 thesis, the papers and reviews published in % of pharmaceutical product in Morocco scientific journals and websites (such as FDA (Choulli et al. 1999). Although the seeds of database and Cornell Poisonous plants) Citrullus colocynthis are highly toxic, they giving database on ethnobotanic, were used for the treatment of diabetes. phytotherapy and toxicology. The Medline Recently, it has been shown that this plant search included the following key words: contains insulinotropic compound (Abdel- herbs, herbal, traditional medicines, Hassan et al. 2000. Nmila et al. 2000). The phytoremedies, toxicity, adverse effects, toxicity (acute toxicity) of some of these plants adverse reaction, drug-drug herbs interaction, was largely highlighted. In Morocco, it was overdose. In order to clarify this field for the noted that a great number of intoxication cases scientific researchers as well as for the in the Moroccan Poison Center (CAPM) are herbalists and users, we focused our searches due to ingestion of the plants and products of only on the highly toxic plants commonly traditional pharmacopoeia (2.5 % of the used by Moroccan people in traditional declared cases of intoxications) (CAPM). The medicine in order to better highlight this field most fatal toxic products in Morocco are the and to provide guideline for plant medicines plants and the products of the traditional users as for the herbalists, practitioners and pharmacopoeia whose lethality reached 17 %. consumers. CAPM has registered 100 cases of intoxication by Atractylis gummifera between 1992 and In this view we listed twenty seven plants 2000; that is to say 87.7 % of the total number more dangerous if they don’t used carefully. of the registered cases (CAPM). These plants are those which produce Since intoxications by Atractylis gummifera L. irreversible health injury, serious aftermath, frequently happens in Morocco, this plant was and irreversible damage such as renal failure, relatively well studied in Morocco. Several liver damage, hemiplegia, blindness…etc and tens of case of accidents due to the sometimes they can produce the death. intoxication by Atractylis gummifera were Indeed, the list is best used only as a studied and published (Berrada 1979, Sandali preliminary screening of potentially 1970). These studies made it possible to draw poisonous plants, not as a definitive a clinical table related to the ingestion of conclusion of toxicity and a complete list of Atractylis gummifera. This table includes a toxic plants. phase of latency of 24 H to 48 H before the appearance of the first signs of the Discussion intoxication. There is initially appearance of the digestive disorders then respiratory, Several toxic plants (used with adequate cardiovascular disorders, and hepato-renal amounts in traditional medicine) were useful function disorders. for humanity during many centuries for the treatment of certain serious illnesses. M. Bnouham et al. / Moroccan J. Biol. 2-3 (2006) 21-30 23

Table 1. Presentation of some plants used in Moroccan traditional medicine, their scientific names, the family, the vernacular name, the used parts, and information about medicinal uses, toxic components and toxicological signs Scientific names Local vernacular Used Medicinal uses Toxics compounds Toxicological signs DL50 References Species names names part (mg/kg) Family names Aconitum vulparia - Igantar or Ijantar Root Analgesic; Antirheumatic; - Aconitine Vertigo; Diarrhea; Iv cat 0,07-0,13 9,12,19 Renonculacae -Quatel ed-dib Anticongestif; Against Hypertension; Shivering Iv rat 0,08-0,14 - Hanq ed-dib sciatic and teeth pain Tachycardia; Respiratory Or rat 1 paralysis Iv mouse 0,12 Sc mouse 0,27 Ip mouse 0,38 Or mouse 1,8 Adonis oestivalis - Ayn el hajla Leaves Sedative; Diuretic; - Aconitic acid Colic; Convulsion; Ip rat >100 4, 8, 20, 26, Renonculaceae - Benaaman saghir Steams Antirheumatic; Against - Adonitol (ribitol) Dyspnea; Hypertension Iv mouse 180 31 - Dem elatrouss asthma; Against epilepsy; - Vernadin (coumarin) - Tit ntaceknout Emenagogue Anagyris foetida - Rharoub lkhenzir Seeds Against eczema; - Anagyrine (alkaloid) Tachycardia; 4, 20 Legumineuse - Ful lkleb Purgative; Against renal Hypertension; Vomiting; - Ufni ufen disease; Emetic Diarrhea - Kharaya - Tizzat Aristolochia longa - Breztom Roots Against intestinal pain; Aristolochic acid Nephrotoxicity; Or rat 184-203 4, 8, 12, 25 Aristolochiacoe - Chajrat rustom Diuretic; Cutaneous Carcinogenic effects; Iv mouse 22,4 - Qitte lehmir lberi diseases; Cataplasm Alteration of liver and Or mouse 49-106 - Aarifi against snake kidney enzymes; Damage - Ajrachi liver and kidney Atractylis gummifera - Addad Roots Emetic Diterpenic heterosides : Death - Iv rat 431 6, 12, 20 Compositae - Ahfyun atractylosides, -Ip mouse 580 - Ishis carboxyatractylosides, parquine, carboxiparquine M. Bnouham et al. / Moroccan J. Biol. 2-3 (2006) 21-30 24

Scientific names Local vernacular Used Medicinal uses Toxics compounds Toxicological signs DL50 References Species names names part (mg/kg) Family names Atropa belladona - Zbib elkhidus Roots Narcotic; Diuretic; - Troponic acid ester Nervous system Or rat 750 6, 12, 18, Solanaceae - Tidilla Leaves Antispasmodic; Treatment - Tropanol (scopariol) intoxication Sc rat 3800 20, 34 - Aadil wussen of eye diseases; Antidote - Atropine Iv rat 170 - Buquinin of opium; As lotion; - Hyosciamine (alkaloid) Iv mouse 153 Rheumatism and sciatic; - Scaplomine Sc mouse 590-1700 Giving in collapse of - Starch Ip mouse 400 pneumonia; Typhoid fever - Belladonine Iv rabbet (apoatropine) Bryonia dioica - Luwaya Roots Against dysentery; - Cucurbitacin Titanic convulsion; Or mouse 340 4, 12, 20 23 Cucurbitacae - Fasir Fruits Purgative; Against ulcer (tetracyclic diterpen) Hypothermia; Cramp; - Kerma elbayda - Brydiofin Coma - Herbuna Chenopodium album - Blis Roots Against colic - Oxalic acid Trouble of CNS; LDlo, Or human 700 3, 12, 20, Chenopodiacae - Remrem, Cephalia; Vertigo; - 30,000 ppm 29, 35 beremrem Paralysis; Nausea; - Blitu Vomiting; Hypotension with meningitis Citrulus colocynthis - Hantal Fruits Antidiabetic; Against - Elatermidine Gastrointestinal pain; 2500 8, 11, 20, 27 Cucurbutacae - Lehdej Seeds blenorrhagia - Glycosides Diarrhea; Vomiting; - Umheddijit - Resin Hypothermia; Cardiac - Alkad - Dihydric alcohol disorder; Cerebral - Aaknet -Heltiacontane congestion; Necrosis of - Lemnun serqui - Citrullin liver and renal cells - Citrullinic acid Colchicum autumnal - Bukbuka Seeds For rheumatism; Arthritis; Colchicine Vomiting; Diarrhea; 18, 19 Liliaceae - Elbsila Capsule Sedative; Act upon all (alcaline substances) Antimitotic; General - Tirket secreting organs paralysis; Respiratory particularly the bowels paralysis and kidneys Conium maculatum - Sikran Whole Narcotic; Sedative; - Coniine (alkaloid) Asphyxia; Death Or mouse 100 8, 18, 20 Compositae - Barbus plant Antispasmodic; Antidote - Conhydrine Sc mouse 80 - Ziyyata of strychnine; Tetanus; - Methyl coniine Iv rabbit LDlo 15 M. Bnouham et al. / Moroccan J. Biol. 2-3 (2006) 21-30 25

Scientific names Local vernacular Used Medicinal uses Toxics compounds Toxicological signs DL50 References Species names names part (mg/kg) Family names - Banj Hydrophobia; Spasm of - Pseudoconhydrine Sc rabbit LDlo 80 larynx; Gullet; Asthma; - Ethyl piperidine Cure tumors; Swilling and - Mucilage pains of the joints and skin - Fixed oils Daphne gnidum L - Lezzar leaves Hair care; Against tinea - Tannin Headache, Shivering, Or UnK 0,25 4, 6, 8, 12, Thymelaceae - Metnan - Vesicant resin Paleness; Pupil dilation; 20, 27 -Inif - Daphnetoxin Diarrhea; Convulsion; - Mezerin Pulmonary disorder; Difficulty of deglutition; Death; Daphne laureola - Ad-dufayla leaves Laxative; Strong purgative Berries Paleness; Pupil dilation; 4 Thmeleaceae - Talidrar Mouth and lips swilling; - Walidrar Diarrhea; Convulsion; Pulmonary disorder; Difficulty of deglutition; Death Datura stramnium - Chdeq ejjmel leaves Antispasmodic; Emollient; -Hyosciamine(alkaloide) Serious neuralgic; 18, 20 Solanaceae - Taburzigt Narcotic; Against asthma; - Atropine Hallucination - Tidila Palliate the pain; Muscle - Hyoscine (scoplamine) - Ghayata rheumatism; Neuralgia; - Malic acid - Elmurquid Hemorrhoid; Fistula; - Daturin (mixture of - Jawzat elmurquid Abscesses; Inflammation hyosciamine and atropine) - almuswika Diditalis purpura Leaves Diuretic; Cardiotonic; For - Digitalis Cardiovascular, 18, 19 Scrofulariaceae cardiac arrhythmias - Glycosides neurological and digestive oedema; Oliguria - Digitoxin troubles; Hallucination; - Digitalin Photophobia; - Digitalein Exophthalmia - Digitonin Ferula communis Ikelha; Ufful, Resine Antidiabetic; Sedative 4 hydroxy coumarinic: Hypoprothrombinuria; Or rat 1650 4, 13, 15, Apiaceae tuffat; Anbi, auli; ferulinol, Hemorrhage (internal and Or mice 2g/kg 16, 20, 33 Tagult; I-bubal hydroxyfelunirol, external); Anti vitamin K; M. Bnouham et al. / Moroccan J. Biol. 2-3 (2006) 21-30 26

Scientific names Local vernacular Used Medicinal uses Toxics compounds Toxicological signs DL50 References Species names names part (mg/kg) Family names ferprenine and Anorexia; Diarrhea; isoferprenine Hypothermia; Weakness Hyosciamus niger Sikran; Bunarjuf; Resine Against spinal column - Alkaloids, hyociamine, Convulsion; Dyspnea; Iv mouse 95 20 Solanaceae Benj; Lebtina, atropine, scopolamine Digestive disorder; Gengit; Afelhelhe; Vegetative nervous Falezlez; Barbar disorder; Tachycardia; Dryness of mucus membrane; Cardiac depression; Coma and death Iris pseudoacorus - Ud alambar Rhizome Emetic; Purgative; - Irisin Abdominal pain; Nausea- 20 Iridacae - Ambar Rubefacient - Iridin Vomiting; Diarrhea; - Sif ed-dib Against sneezing Spasm; Staggering; - Sekkin eddib Paralysis - Busrika Mandragora - Bid elghoul Roots Against asthma and cold; - Atropine Death 4, 27 automnalis - Taryala Leaves Narcotic; Anestesic; - Hyosciamine - Luffah Apetizine - Scopolamine Solanaceae - Ybruh - Luffah eljenn Nerium oleander - Ddefla Leaves Hypoglycemiant; Against - Oleandrin Vomiting; Shivering; Iv cat 0,3 4, 6, 8, 12, Apocinaceae - Elel headache - Neriine (neroside) Gastroenteritis; Neriin LDlo sc 19, 20, 37 - lili - Oleandroside Respiratory disorder; mouse 95 - Ouabain Death by asphyxia; - Cardiotoxics Weakness; Bradycardia; - Digitoxine Convulsion; Hyperthermia; Heart failure Ricinus communis - Kherwaa Seeds Against sterility; For hair - Ricin Death Ip rat 500 ng/kg 4, 20 Euphorbiaceae - Krank Parenteral rat 326 - Tmazzit ng/kg - Awriys Or rat Ldlo 30 M. Bnouham et al. / Moroccan J. Biol. 2-3 (2006) 21-30 27

Scientific names Local vernacular Used Medicinal uses Toxics compounds Toxicological signs DL50 References Species names names part (mg/kg) Family names Sc mouse 22,1 If mouse 2 µg/kg Iv mouse 2,2 µg/kg Or man 300 µg/kg Sc man Ldlo 43 µg/kg Or man Ldlo 900 µg/kg Solanum nigrum - Ineb eddib Leaves Emolient; Antinevralgic; - Solanine Narcotic properties; Mice 42 4, 18, 22 Solanaceae - Ineb ettaaleb Sedative; Strong sudorific; - Solanidine Vomiting; Cephalia - Buqnina Promotes sleep for infant; mental confusion; - Adilwussen Cutaneous disorders; Tachycardia; Burns; Ulcers; Gout Hallucination; Coma; Death; Potential CNS depressant action Solanum - lim nsara Leaves For eye cleaning; - Glucoalkaloids ( 4, 20, 27 sodomaeum - Hedja Stopping the menses; heterosides of solasodine) - Mtisat lehmir Aphrodisiac; Against - Saponosides Solanaceae insomnia Tamus communis - Tamier Leaves - Against skin diseases - Campestrol Irritation of the mucous Ip mouse 3 12, 18, 20 Dioscraceae - Belmimoune Stem - Against rheumatism and - Stigmastrol membrane; Trouble of Inj rat LDlo 10 lumbago; Rubifacient; - ß sistrol respiration Diuretic; For asthma complaints; Stimulating plaster Taxus baccata - Dahs Leaves Treatment of rheumatism -Cyclitols; -Fatty acid; - Paralysis of cardiac and 4, 19, 20, 27 Taxaceae - Igen Stérols pulmonary functions; -Adgan - bisflavonoids Hypotension; Respiration - Imerwel - ProanthoCyanidols depression; Vomiting; - Lignanes Nausea; Diarrhea; -Cyanogenetic Abdominal pain; Heterosides;-Terpens Convulsion; Coma M. Bnouham et al. / Moroccan J. Biol. 2-3 (2006) 21-30 28

Scientific names Local vernacular Used Medicinal uses Toxics compounds Toxicological signs DL50 References Species names names part (mg/kg) Family names Thapsia garganica - Deryas Roots Against rheumatism; Resin Vomiting; Violent Compositae - Bu-neffaa Bronchitis; Feminine diarrhea; Digestive 4, 8, 20 - Tufflet sterility mucous inflammation; - Alauu Salivary secretion; - Usbat anissa Nervous disorder; Violent colic; Gastroenteritis; Death Urginea maritima - Bsal alfar Bulb Against sterility; For Bitter and corrosive juice 20 Liliaceae - Bsal elkhenzir mouth care - Dsal elferawn - Ferruma - Azalim u wussen - Ikfil - Isquil Withania somnifera - Hab al lahw Seeds Narcotic; Sedative; Alkaloids Vomiting; Tetanic 4, 27 Solanaceae - Sikran Roots Antiepileptic; Diuretic; convulsion; Mydriasis - Ineb eddib Light laxative; Abortive - Sem elfar

Abbreviations: iv: intra venous; sc.: sub cutanous; im: intra muscular; or: oral; LD50: lethal dose 50; LDLo: Lethal dose low; the lowest dose in an animal study at which lethality occurs. FDA: U. S Food and drug administration; ip: intraperitoneal; WHO: World Health Organization; CAPM: Anti-Poisonous Moroccan Center. Unk: unknown.

References: 1. Abadome, 1988; 2. Abdel-Hassan et al. 2000; 3. Bellakhdar, 1978; 4. Bellakhdar, 1997; 5. Berrada; 1979; 6. Bruneton, 1996; 7. CAPM: Centre AntiPoison Maroc; 8. Charnot; 1945; 9. Choulli et al. 1999; 10. Cornell Poisonous plants; 11. Diwan et al. 2000; 12. Duke, 1992; 13. El Alouani, 1986; 14. FDA; U. S Food and drug administration; 15. Fraigui et al. 2001; 16. Fraigui et al. 2002; 17. Gray &, Flatt; 1998; 18. Grieve; 1971; 19. Hmamouchi, 1999; 20. Kahouaji; 1995; 21. Marles & Fransworth 1988; 22. Merck Index 12th edition. Merck and Co INC. 1996; 23. Munoz et al. 1992; 24. Nmila et al. 2000; 25. Pakrashi & Shaha, 1979; 26. Palevitch, 1982; 27. Paris & Moyse, 1976-1981; 28. Perez et al. 1998; 29. Rahmani, 1979; 30. Sandali, 1970; 31. Sharma et al. 1978; 32. Skalli et al. 2002; 33. Tligui et al. 1994; 34. Trabattoni et al. 1984; 35. Whitehead & Moxon, 1952; 36. World Health Organization Expert Committee on Diabetes Mellitus; 1980; 37. Ziyyat et al., 1997 M. Bnouham et al. / Moroccan J. Biol. 2-3 (2006) 21-30 29

Finally a hepatic coma and death occurs 4 (Abadome, 1988). Moreover, a trial to 6 days after ingestion of Atractylis. In conducted with wild rats using 0.1 % order to take stock of this intoxication of "Fessoukh" extract baits demonstrated which diagnosis is clinical and treatment "Fessoukh" rodenticide effects (Fraigui et symptomatic, Skalli et al. in 2000 have al. 2001). suggested analyzing one clinical case of the The most toxic plants listed in this review intoxication by Atractylis gummifera L. on are 28 species belonging to 16 families. a 12 year old child who accidentally The familie that have been reported to be ingested this plant. In fact, the sweetened most representative of the highly toxic taste of the root of this plant especially plants used in the traditional medicine in facilitates the intoxication in the child Morocco is Solanaceae (7 species). (Bellakhdar, 1997). A great part of the poisonous substances of The intoxication by seeds of Ricinus the plants listed in this review belongs to communis can be accidental. The seeds of the class of alkaloids. It is the case of the the fruits of Ricinus communis are following plants: Aconitum vulparia, frequently confused with edible seeds. The Anagysis foetida, Atropa belladona, intoxication can occur by therapeutic Conium maculatum, Datura stramonium, overdose or following their use as abortive. Digitalis purpurea, Hyosciamus niger, Bellakhdar in 1997 reported that Mandragora autumnalis, Withania intoxication has been produced in somnifera. Goulimine (southern of Morocco) In conclusion, the families most following a traditional treatment against representative of these plants are the female sterility consisting of the Ricinus family of Solanaceae (7 species). The communis seed ingestion associated with a intoxication by these plants is not only vaginal rectal injection with a solute of seed related to the fact that they are used in decoction. The castor seeds are often used traditional herbal medicine but more like abortive (Bellakhdar, 1997). especially because of some factors such as: The intoxications by another toxic plant: the overdose, bad methods of use as well Ferula communis are well known in as confusion with other edible plants. The Morocco as well for the animals as for the children are touched the most by these Man. It is a plant which was much studied. intoxications. The majority class of the The toxic principle of this plant is toxic principles of these plants belongs to concentrated in secretions which give a alkaloids. Moreover, strong efforts are product locally called "Fessoukh". This wished to inform populations that continue product is not water soluble and hexane but to use traditional medicine in order to it is soluble in the acetone, the chloroform avoid the bad practices due to the and solution of NaOH (3 %) (El Alouani, ignorance of the good uses of the 1986). It has been tried to profit to prepare traditional medicine. rodenticide from Ferula communis

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