Food and Chemical Toxicology 62 (2013) 609–621 Contents lists available at ScienceDirect Food and Chemical Toxicology journal homepage: www.elsevier.com/locate/foodchemtox Invited Review Toxicology of some important medicinal plants in southern Africa Ashwell R. Ndhlala, Bhekumthetho Ncube, Ambrose Okem, Rofhiwa B. Mulaudzi, Johannes Van Staden ⇑ Research Centre for Plant Growth and Development, School of Life Sciences, University of KwaZulu-Natal Pietermaritzburg, Private Bag X01, Scottsville 3201, South Africa a r t i c l e i n f o Article history: Received 21 June 2013 Accepted 19 September 2013 Available online 27 September 2013 Keywords: Alkaloids Cancer remedies Cardiac glycosides Phytotherapy Traditional natural medicines Toxic plants a b s t r a c t Africa is home to two major floral kingdoms: the Paleotropical kingdom of central Africa and the Capensis kingdom of the Western Cape province of South Africa, the latter of which consists of approximately 10,000 species, representing about 20% of Africa’s floral ‘gold mine’, better known as the Cape herbal medicine. Needless to say, such rich flora comes with numerous plants with a potential to cause poisoning to humans. This review document reports important toxic medicinal plants and their toxic ingredients for plant species resident in the southern African region. These include important medicinal uses and pharmacological properties ranging from antimicrobial, antiviral, anticancer, anti-inflammatory as well as those that are used as aphrodisiacs and for maternal health care. Ó 2013 Elsevier Ltd. All rights reserved. Contents 1. 2. 3. 4. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Important toxic plants of southern Africa with ethnopharmacological uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1. Toxic plants used against bacterial and fungal infections . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2. Important toxic plants used for viral treatments in southern Africa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3. Important toxic plants used for treatment of CNS-related conditions in southern Africa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4. Important toxic plants used as aphrodisiacs and for maternal health care in southern Africa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.5. Important toxic plants used to treat miscellaneous conditions such as cancer, arthritis and heart conditions in southern Africa . . . . . . Toxicity through contaminations – a case of heavy metal poisoning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conclusions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Conflict of Interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1. Introduction Southern Africa has a rich flora that includes several biodiversity hotspots (Botha and Penrith, 2008). Most of the populations in rural and urban southern African communities rely on the rich Abbreviations: CNS, central nervous system; DNA, deoxyribonucleic acid; GAP, Good Agricultural Practice; GABA, gamma-aminobutyric acid; GI, gastrointestinal; HIV, human immune deficiency virus; HIV 1 RDDP, HIV-1 RNA-dependent DNA polymerase; ISO/TC249, International Organization for Standardization of Traditional Medicine; LD, lethal dose; RNA, ribonucleic acid; SABS, South African Bureau of Standards; WHO, World Health Organization. ⇑ Corresponding author. Tel.: +27 33 2605130. E-mail address: rcpgd@ukzn.ac.za (J. Van Staden). 0278-6915/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.fct.2013.09.027 609 610 610 610 614 616 618 618 618 619 619 619 flora as herbal medicines for their health care needs and food security (Fennell et al., 2004). Needless to say, such a rich flora comes with numerous plants with the potential to cause poisoning to humans. This is because all plants produce a plethora of compounds as defense against invasion by microorganisms and viruses as well as herbivores (Wink and Van Wyk, 2008). The complex substances include several groups of compounds, some of which are deadly to humans even when consumed in smaller quantities. There are approximately 750 known poisonous substances occurring out of a pool of 150,000 plant secondary metabolites that exists in about 1000 plant species (Wink and Van Wyk, 2008). Poisonous plants can cause superficial irritation or discomfort through contact with the skin or serious poisoning when ingested 610 A.R. Ndhlala et al. / Food and Chemical Toxicology 62 (2013) 609–621 (Van Wyk et al., 2002). Toxic substances from plants can affect the entire spectrum of vital human organs while some may affect key functional body systems like the central nervous system (CNS) thereby interfering with the coordination of nerve functions of the body. The most dominant toxins are neurotoxins that affect the brain and CNS, followed by cytotoxins and metabolic toxins that affect organs such as kidneys, the liver, heart and lungs. The severity of a toxic effect may depend on the route of administration, growth stage or part of the plant, the amount consumed, the species and susceptibility of the victim (Botha and Penrith, 2008). Other factors that may influence the severity of toxins include the solubility of the toxin in body fluids, frequency of intoxication as well as the age of the victim. The toxicity of plants has been known for a long time, and humans learnt how to cope with them for their benefit. Humans developed skills to use poisonous plants for hunting, war, rituals, murder, executions, suicide, abortions and euthanasia. Toxic plants that act on the CNS, inducing paralysis when injected were used by hunters as arrow poisons for hunting and warfare. Examples are Taxus alkaloids, atropine and toxiferine together with various cardiac glycosides. In southern Africa, the San hunters used fast-acting cardiac glycosides from genera such as Acokanthera, Boophone, Strophanthus and Adenium (Wink and Van Wyk, 2008). Most substances that act as poisonous defense chemicals tend to have medicinal properties at lower concentrations. Some of the groups of such compounds include alkaloids, cardiac glycosides, phorbol esters, lectins and cyanogenic glycosides which are classified as extremely toxic. In early civilizations, plants rich in alkaloids and other toxins such as Conium maculatum were used for murder, abortions, executions and suicide. These included the infamous coniine, aconitine, atropine, strychnine, colchicine and several cardiac glycosides. Extracts from Bryonia dioica, Helleborus viridis and Petroselium crispum are rich in cytotoxic alkaloids, sesqui- and triterpenes (cucurbitacins) used as abortifacides (Van Wyk et al., 2002). Unfortunately, very few of the African toxic plants from these early times have been recorded. In southern Africa, the scales of the poisonous Boophane bulbs were used to preserve the bodies of the Khoisan. Boophane bulbs were also associated with the traditional trance dance which forms part of ancient healing and divination traditions (Wink and Van Wyk, 2008). This review documents some important toxic medicinal plants that are either introduced or indigenous to southern Africa and used for different therapeutic purposes. 2. Important toxic plants of southern Africa with ethnopharmacological uses 15.8% cases of poisoning from traditional medicines of which 15.3% resulted in death (Popat et al., 2001). Table 1 represents toxic plants that are used ethnobotanically for the treatment of bacterial and fungal infections in humans. Most of the active principles in the plants are highly poisonous e.g. cardiac glycosides. Plants containing cardiac glycosides have been used traditionally since ancient times as arrow poisons and as heart tonic agents (Botha and Penrith, 2008). To date cardiac glycosides such as digoxin from the genus Digitalis are still prescribed by western doctors for the treatment of congestive heart failure (Botha and Penrith, 2008). Most of the poisonous plants highlighted in Table 1 induce diarrhoea when consumed, however, the mode of action for most toxins differ considerately. Active principles that are mostly reported to affect the gastrointestinal tracts are the lectins. Lectins cause necrosis of the cell linings of the gastrointestinal tracts (Gonzalo, 2011). Examples of medicinal plants reported to contain lectins affecting humans are Abrus precatorus and Jatropha curcas. However, these plants continue to be used in traditional medicine as treatment for bacterial and fungal infections. It is, however, speculated that the antibacterial and antifungal activity of these species could not be from the lectins. Yadava and Reddy (2002) reported flavonol glycoside 7,3’,5’-trimethoxy-4’-hydroxy flavone-3-O-b-Dgalactosyl-(1?4)-a-L-xyloside to be the biologically active compound from A. precatorius. It is also interesting to note that some of the plant species such as Catharanthus roseus are reported to be used as antibacterial medicines yet they contain cardiac glycosides. It is thus important to regulate the dosages to be administered to a patient in order to prevent lethal side effects. In some cases, plants used for treating wounds also contain skin irritants. Skin irritation by some compounds can cause mechanical damage resulting in skin problems and sometimes allergic dermatitis, pruritic in sensitive individuals as well as blindness (Botha and Penrith, 2008). Such plants include C. roseus and Solanum incanum (Table 1). The plants presented in Table 1 are regarded as ‘important medicinal plants of southern Africa’ and are highly utilised by at least 80% of the southern African population on a yearly basis. One of these highly utilised plants is Callilepis laureola which is a highly reported toxic plant commonly used by the Zulu people to treat stomach problems, tape worm infections, impotence, cough and to induce fertility. The plant is administered to pregnant women to ensure the health of the mother and child as well as to facilitate birth labour (Popat et al., 2001). The value of this plant among people is great (Steenkamp et al., 1999; Bye and Dutton, 1991) yet approximately 1500 deaths per annum have been reported to be caused by C. laureola in KwaZulu-Natal province of South Africa alone (Obatomi and Bach, 1998). Despite its highly reported toxicity, C. loureola continues to be used due to its traditional value among South African populations. 2.1. Toxic plants used against bacterial and fungal infections Poisoning in humans from plants usually arises either from the misidentification and unintentional use of toxic plants for medicinal purposes (Van Wyk et al., 2002). This type of poisoning is higher in societies where plant-based traditional medicines are common practices (Botha and Penrith, 2008). A study by Joubert and Mathibe (1989) revealed that traditional medicine poisoning is the second most common cause of acute poisoning representing 12.1% in South Africa. Previously, Joubert and Sebata (1982) had reported 277 cases of acute poisoning cases of patients admitted to Ga-Rankuwa hospital (Gauteng Province, South Africa) between 1981 and 1982, of which 18% were due to ingestion of toxic traditional medicines, 26% of these resulted in death. Six years later, Venter and Joubert (1988) reported an increase in these incidents amounting to 1306 cases at the same hospital, this time with 2.2. Important toxic plants used for viral treatments in southern Africa Unlike bacterial and fungal cells, which exist as living entities, viruses are parasitic entities containing little more than wads of genetic material in either ribonucleic acid (RNA) or deoxyribonucleic acid (DNA) form. Viral infections thus present a challenge to both human and animal health due to the difficulty associated with their treatment. With the ever increasing incidents in human immune deficiency virus (HIV) infection rates and other associated viral infections in the world, most societies in Africa continue to seek treatment options from the indigenous flora. As a result, several medicinal plants have been found to be useful as drug agents targeted on the different stages of the viral life cycle. To date, varying degrees of efficacies have been recorded in each case. Time and 611 A.R. Ndhlala et al. / Food and Chemical Toxicology 62 (2013) 609–621 Table 1 Important toxic medicinal plants used to treat bacterial and fungal infections in southern Africa. Scientific name and family Toxic plant part Traditional uses Biological activities Type of toxic or Active principle Symptoms Reference Abrus precatorius L. Fabaceae Seeds Eye infections, ulcers and intestinal wounds Antibacterial, antifungal Lectin abrin Wink and Van Wyk (2008), Adelowotan et al. (2008), Zore et al. (2007) Acokanthera oppositifolia (Lam.) Codd Apocynaceae Leaves, roots or wood Abdominal pain, headache Antifungal Cardiac glycoside Adenia digitata (Harv.) Engl. Passifloraceae Tuberous base, roots, fruits Whole plants Leprosy, malaria Modeccin, cyanogenic glycosides Loss appetite, bloody diarrhoea, vomiting intestinal inflammation, haemorrhage, diabetes due to pancreas damage, delirium, chills, convulsion and coma. Death due to heart failure Nausea, salivation, retching, purging and exhaustion and cardiac abnormalities associated with heart glycosides Nausea, vomiting, diarrhoea and fits. It can damage kidneys and liver. Moustafa et al. (2013), Reyes et al. (2011), Abdel-Sattar (2008), Van wyk et al. (2002), Wink and Van Wyk (2008) Van Wyk et al. (2002), Ndhlala et al. (2011) Van Wyk et al. (2002), Cheesman et al. (2012) Eczema, itch and other skin disorder Antifungal, antibacterial Sanguinarine, berberine, protopine and isoquinoline alkaloid Vomiting, diarrhoea, blurred vision in chronic cases swollen legs and other serious symptom Leaves and roots Bulbs Headache and tuberculosis Antibacterial, antifungal Antibacterial Cardiac glycoside (cardenolide) Isoquinoline alkaloid Bowiea volubilis Harv. Ex Hook.f. subsp volubilis Hyacinthaceae Callilepis laureola DC. Asteraceae Bulbs Various ailments Antibacterial, antifungal Cardiac glycoside Fever, paralysis, respiratory problem and weak heartbeat Dizziness, restlessness, impaired vision, unsteady gait, visual hallucinations, final coma and death Vomiting, purging,excessive salivation and irregular heart palpitations Woody tubers Cough for adults in very specific way Catharanthus roseus (L.) G.Don Apocynaceae Whole plant Antibacterial Indole alkaloid Chironia baccifera L. Gentianaceae Whole plant Antibacterial Clivia miniata [Lindl.] Regel Amaryllidaceae Conium maculatum L. Apiaceae Cotyledon orbiculata var. orbiculata Amaryllidaceae Crinum bulbispermum (Burm.f.) Milne-Redh. & Schweick. Crassulaceae Leaves Haemorrhoids (piles), stomach ulcers, syphilis, leprosy, diabetes and kidney and bladder infections, Hodgkin’s disease, lymphomas, cancer Haemorrhoids (piles), stomach ulcers, syphilis, leprosy, diabetes and kidney and bladder infections Fever, snakebite and pain Traditional medicine Antifungal Piperidine alkaloid Remove warts, to treat epilepsy, internal parasites, earache and toothache Antibacterial, antifungal Bufadienolide Datura stramonium L. Solanaceae Drimia elata Jacq. Hyacinthaceae Drimia robusta Baker Hyacinthaceae Seeds and leaves Argemone ochroleuca subsp. ochroleuca Papaveraceae Asclepias fruticosa L. Asclepiadaceae Boophane disticha (L.f.) Herb. Amaryllidaceae Roots, leaves fruits Leave Whole plant Bulbs and leaves Bulbs Wounds Cold, rheumatism, varicose veins, reduction of swelling and the treatment of septic sores; urinary tract infections and swelling of the body; treat rheumatism, aching joints, septic sores, varicose veins and kidney and bladder infections Atractyloside Wink and Van Wyk (2008) Van Wyk et al. (2002), Masondo et al. (2013), Stafford et al. (2005a) Wink and Van Wyk (2008) Vomiting, abdominal pain, headache, strong convulsions and rapid progression into coma and death. Irritant of the skin, respiratory tract and damage to the cornea of the eye Van Wyk et al. (2002), Govindasamy and Srinivasan (2012) Gentiopicroside and chironiocide Slightly loose stools and sleepiness Van Wyk et al. (2009), Thring et al. (2007) Isoquinoline alkaloid Salivation, vomiting and diarrhoea, leading to paralysis and collapse Drowsiness, nausea, vomiting, breathing difficulty and finally asphyxia, paralysis and death Convulsions, paralysis, finally death Van Wyk et al. (2002) Isoquinoline alkaloid Nausea, vomiting, dizziness, diarrhoea, kidney trouble and respiratory arrest. Van Wyk et al. (2002), Watt and BreyerBrandwijk (1962). Wink and Van Wyk (2008) Antibacterial and antifungal Tropane alkaloid Blurred vision, suppressed salivation, vasodilation and delirium Blister the skin; rash Antibacterial and antifungal 12bhydroxyscillirosidin and other bufadienolides Rash, nausea, vomiting, diarrhoea, colic, haematuria, death by cardiac arrest. Van Wyk et al. (2002), Sharma and Sharma (2010) Hutchings et al. (1996), Van wyk et al. (2009) Van Wyk et al. (2002), Hutchings et al. (1996), Van wyk et al. (2009), Ncube et al. (2011a), Wink and Van Wyk (2008) Asthma, pain Uterus; blood purification; stomach ailments Van Wyk et al. (2002), Aremu et al. (2010) Van Wyk et al. (2002), Al-Barwani and Eltayeb (2004) Wink and Van Wyk (2008), Aremu et al. (2010) (continued on next page) 612 A.R. Ndhlala et al. / Food and Chemical Toxicology 62 (2013) 609–621 Table 1 (continued) Scientific name and family Toxic plant part Traditional uses Biological activities Elaeodendron transvaalense (Burtt Davy) Celastraceae Erythrina caffra Thunb. Fabaceae Bark Bulbs used to treat urinary infections, diseases of the uterus Antibacterial Whole plant bark and stem Stomach cleanser, stomach ache, fever, intestinal cramps, coughs, herpes and Antibacterial Erythraline, erysotrine and Isoquinoline alkaloid Erythrophleum lasianthum Corbishley Fabaceae Bark, seeds and aerial parts Sexually associated diseases Antibacterial Diterpenoid alkaloid, cassaine, erthrophleine Galenia africana L. Aizoaceae Leaves Sores, wounds and arthritis, earache, tooache Antibacterial Geigeria ornativa, G. aspera, G. filifolia Asteraceae Gnidia kraussiana Meisn. var. kraussiana Aerial parts Antibacterial Sesquiterpene lactones Stomach and kidney disturbance Whole plant Fever, headache and other pains; heart problem, dermatitis, wounds, rheumatism, Syphilis, gonorrhoea, leprosy, tuberculosis, Antibacterial, antifungal Irritation of the nose and throat, coughing, sneezing, headache and nausea Wink and Van Wyk (2008), Ndhlala et al. (2011),; Saadabi and Moglad (2011), Hutchings et al. (1996) Gomphocarpus fruticosus (L.) Aiton f. Apocynaceae Hyaenanche globosa (Gaertn.) Lamb. & Vahl Euphorbiaceae Hypericum perforatum L. Hypericaceae Whole plant Bronchitis, angina, ordeal and hunting poison Antibacterial Gnidicin, kraussianin, gnidilatin, gnidilatidin, gnididin and gniditrin Cardiac glycosides Diarrhoea; cardiac arrest Fruits, seeds Toothache, inflammation wound and lesions Tutin, mellitoxin, urushiol III and isodihydrohyaenanchine Convulsion, delirium, coma even death Wink and Van Wyk (2008), Madureira et al. (2012), Van Wyk et al. (2009) Wink and Van Wyk (2008) Whole plant Choking, respiratory paralysis, exhaustion from vomiting, purgation, heart failure. Antifunagal, antibacterial Hyperforin, naphthodianthrone Jatropha curcas L. Euphorbiaceae Leaves, seeds and bark Treatment of burns, snake bites, stomach complaints, used to ensure easy birth Antibacterial, antifungal Lectin Erythema, sores, necrosis, leathery and parchment-like. Lip and eye lids become immobilised Dairrhoea, abdominal pain and vomiting Melianthus comosus Vahl Melianthaceae Roots Used medicinally to treat headaches, stomach pain, tuberculosis Antibacterial and antifungal Bufadienolides, melianthugenin, melianthusigenin and hellebrigenin-3acetate. Nicotiana glauca Graham Solanaceae Whole plant Emetic Antifungal Anabasine, nornicotine and other piperidine alkaloids Scadoxus puniceus (Baker) Friis & Nordal Amaryllidaceae Solanum incanum Willd. Solanaceae Spirostachys africana Sond. Euphorbiaceae Whole plant Oil used for Wounds and burns, vermifuge inflammation of the GI tract. Antibacterial and antifungal Whole plant Purgative Antifungal, antibacterial Haemanthamine, haemanthidine and other isoquinoline alkaloids Steroid alkaloid Stem bark, root bark and latex Sores, ulcers, bruises, swellings or wounds that are slow to heal, including venereal sores; a leaf paste may be applied as a local dressing to the affected area. Antibacterial, antifungal Thymelaeaceae Type of toxic or Active principle Symptoms Reference Van wyk et al. (2009) Paralysis effect on skeletal muscles,cardiac glycoside poisonind with disturbance of gastrointestinal (GI) tract and CNS; trembling, unrest, spasm, dyspnoea, cardiac arrest. Vomiting, diarrhoea, hypertension, positive inotropic, heart effects, death through respiratory and cardiac arrest. Heart failure and liver damage, blistering of mouth Nausea, salivation, foaming vomit, colic, gastrointestinal disturbance, purging, exhaustion, respiration and cardiac symptoms associated with heart glycoside poisoning Salivation, perspiration, spasms of eyelids and lips, dyspnoea, cyanosis, mydriasis, bleeding in most internal organs, respiratory arrest. Disturbance of GI tract and CNS, hypotensive, convulsive Skin irritation, headache, salivation, nausea, vomiting, diarrhoea, fever, and coma Death, irritant latex cause inflammation and blister. Destruction of mucous membranes. Blindness if contact with eyes Van Wyk et al. (2002), York et al. (2012), Chukwujekwu et al. (2011), Olajuyigbe and Afolayan (2012), Wink and Van Wyk (2008) Van Wyk et al. (2002), Nielsen et al. (2012), Wink and Van Wyk (2008) Van Wyk et al. (2002), Mativandlela et al. (2008) Wink and Van Wyk (2008) Wink and Van Wyk (2008), Mašković et al. (2011), Reichling et al. (2001) Van Wyk et al. (2002), Igbinosa et al. (2009), Arekemase et al. (2011), Saetae and Suntornsuk (2010) Wink and Van Wyk (2008), Kelmanson et al. (2000) Wink and Van Wyk (2008), Mdee et al. (2009) Wink and Van Wyk (2008), Ndhlala et al. (2011) Van Wyk et al. (2002) Van Wyk et al. (2002), Al-Fatimi et al. (2007), Konaté et al. (2011) Wink and Van Wyk (2008), Mulaudzi et al. (2012) (continued on next page) 613 A.R. Ndhlala et al. / Food and Chemical Toxicology 62 (2013) 609–621 Table 1 (continued) Scientific name and family Toxic plant part Traditional uses Biological activities Type of toxic or Active principle Symptoms Reference Synadenium cupulare (Boiss.) L.C.Wheeler Euphorbiaceae Whole plant To treat septic wounds, sores, bruises, backache and rheumatic joints, sores, ulcers, bruises, swellings or wounds that are slow to heal, including venereal sores; a leaf paste may be applied as a local dressing to the affected area Antibacterial and antifungal Diterpene Inflammation, oedema and blistering of the skin Van Wyk et al. (2002) Urginea maritime (L.) Baker Hyacinthaceae Urginea sanguinea (Schinz) Jessop Hyacinthaceae Zantedeschia aethiopica (L.) Spreng. Araceae Whole plant Antibacterial Scillaren A and other bufadienolides Antibacterial Cardiac glycoside Nausea, vomiting, diarrhoea, colic, haematuria, death by cardic arrest, blister Gastrointestinal, nausea and vomiting Wink and Van Wyk (2008), Majinda and Motswaledi (1998) Van Wyk et al. (2002) Burning sensation in mouth and throat, nausea, vomiting Wink and Van Wyk (2008), Watt and Breyer-Brandwijk (1962) Bulbs Whole plant Stomach ulcers – soak a piece of root in lukewarm water and drink the bitter infusion Coughs and gastro-intestinal problems. Used to ensure easy birth Ca2+-Oxalates Table 2 Important toxic medicinal plants used to treat viral infections in southern Africa. Scientific name and family Toxic plant part Traditional uses Biological activities Type of toxic or Active principle Symptoms Reference Adenia gummifera (Harv.) Harms Passifloraceae Root Antiviral Modeccin, cyanogenic glycosides Nausea, diarrhoea, vomiting and fits. Damage to liver and kidney Bryant (1966), Gelfand et al. (1985), Wink and Van Wyk (2008) Aloe ferox Mill Leaf Infusions administered as emetic tonics or stimulants for seediness or depression and to treat madness, malaria, colds and epilepsy Used as a laxative, emetic, relief of arthritis, sinusitis, conjunctivitis and opthalmia, skin and wound healing, treatment of infectionrelated ailments including sexually transmitted infections Treatment of colds, influenza, cough, sore throat, asthma, pneumonia, blocked nose, stomach ailments, colic, flatulence, constipation, gastritis Treatment of venereal discharges, dysentery, diarrhoea, asthma, bronchitis, hay fever, cough and cold Antiviral Aloin Intestinal bleeding, enhanced menstrual and uterus bleeding, kidney disturbance, hypertrophy of intestinal tissues Kambizi et al. (2007), Wink and Van Wyk (2008); Antiviral Thujone Wink and Van Wyk (2008), Van Wyk et al. (2009) Antiviral Phorbol esters, latex Tannins, punicalagin Vomiting, strong diarrhoea, dizziness, headache, cramps, hallucinations, comma, deliriums and seizures Inflammation, oedema, blister formation, swollen eye lids, conjunctivitis, lesions in mouth and throat, abdominal pain and kidney inflammation Gastrointestinal tract and kidney problems Asphodelaceae Artemisia afra Jacq. ex Willd Asteraceae Leaf Euphorbia hirta Linn. Aerial parts Euphorbiaceae Terminalia sericea Burch. ex. DC. Combretaceae Leaf, root, fruit Treatment of colds, fever and sexually transmitted diseases Antiviral Tulbaghia violacea Harv. Alliaceae Leaf, bulb Antiviral Vernonia colorata Drake Asteraceae Leaf, root Treatment of gastrointestinal ailments, asthma, tuberculosis, colds and fever, protection from evil spirits before ritual dancing by diviners. Leaves are rubbed on the head of restless young children Fevers, coughs, diarrhoea, boils, general tonic, Abdominal pain, colic, rheumatism, dysentery, epilepsy, venereal diseases Antiviral again, medicinal plants are commonly used with the assumption that they are safe. This notion or belief is based on their long term usage in the treatment of diseases based on knowledge accumulated over centuries. Table 2 represents some of the important medicinal plants used to treat viral ailments but have been found to have some toxic effects. Terminalia sericea, for example, demonstrates very strong activity against the HIV-1 RNA-dependent DNA polymerase and HIV-1 RNase enzymes with 98% and 99.3% inhibi- Vomiting and dizzines Glaucolide B, alkaloids Continuous decrease in cardiac contraction, central toxic vagal stimulation, complete motor paralysis Wink and Van Wyk (2008), Gyuris et al. (2009) Bessong et al. (2004), Eldeen et al. (2006), Wink and Van Wyk (2008) Hutchings et al. (1996), Fennell et al. (2004), Van Wyk et al. (2009), Ncube et al. (2011b) Neuwinger (1996), Rabe et al. (2002), Clarkson et al. (2004), Bruschi et al. (2011) tion, respectively (Bessong et al., 2004) but the same plant contains high levels of toxic tannins (Wink and Van Wyk, 2008). Although a lot of medicinal plants are being used as antiviral agents, there is still, not only a gross lack of information on the antiviral activity of isolated compounds from such promising medicinal plants but more so regarding their toxicity. A case to reiterate this view are the devastating symptoms from the excessive use of Vernonia colorata and Aloe ferox despite the two plant species being exten- 614 A.R. Ndhlala et al. / Food and Chemical Toxicology 62 (2013) 609–621 Table 3 Important toxic medicinal plants used for the treatment of CNS-related conditions in southern Africa. Scientific name and family Plant part Traditional uses Biological activities Type of toxic or Active principle Symptoms Reference Abrus precatorius L. Fabaceae Leaf, seed, root Used as sedatives and anticonvulsants Abrin Root Modeccin, cyanogenic glycosides Agapanthus africanus Whole plant Infusions administered as emetic tonics or stimulants for seediness or depression and to treat madness, malaria, colds and epilepsy Used by the Southern Sotho diviners to develop memory and make initiates mentally fit for their work Used in the initiation of traditional healers. treat people with a type of mental illness and for inducing visions Loss of appetite, bloody diarrhoea, vomiting, diabetes, intestinal inflammation, haemorrhage, deliriums, chills, convulsions, coma and heart failure Nausea, diarrhoea, vomiting and fits. Damage to liver and kidney Adesina (1982), Hutchings et al. (1996) Adenia gummifera (Harv.) Harms Passifloraceae Haemagglutinating properties, analgesic potential, antiinflammatory activity, bronchodilator activity Antioxidant activity Agonist activity on uterine muscarinic receptors, antiinflammatory activity Antidepressant activity (serotonin, noradrenalin and dopamine transporters inhibitor) analgesic and antiinflammatory activities, acetylcholinestarase inhibitory activity Acetylcholinestarase inhibitory activity, GABA activity, postnatal stress activity (cardiovascular) Antinociceptive activity, acetylcholinestarase inhibitory activity, Yuccagenin, agapanthagenin Gastrointestinal tract and kidney problems Yuccagenin, agapanthagenin Gastrointestinal tract and kidney problems Steroidal saponins (spirostanol, furostanol glycosides) Isoquinoline alkaloid Gastrointestinal disturbances Walker (1996), Veale et al. (1999), Wink and Van Wyk (2008) Laydevant (1932), Hutchings et al. (1996), Sobiecki (2002), Pedersen et al. (2008) Kokwaro (1976), Debella et al. (2000) Dizziness, restlessness, impaired vision, unsteady gait, visual hallucinations, final coma and death Van Wyk and Gericke (2000), Sobiecki (2002) Isoquinoline alkaloid Nausea, dizziness, diarrhoea, respiratory arrest and kidney problems Sobiecki (2002), Van Wyk et al. (2002), Ratnasooriya et al. (2005), Wink and Van Wyk (2008) Van Wyk et al. (2002), Wink and Van Wyk (2008), Devi et al. (2011) Agapanthaceae Agapanthus campanulatus F.M.Leigh Agapanthaceae Asparagus africanus Lam. Asparagaceae Rhizome Bryant (1966), Gelfand et al. (1985), Wink and Van Wyk (2008) Whole plant Whole plant infusions used to relieve problems of mental disturbance Bulb Weak decoctions given to sedate violent, psychotic patient, bulb infusions used to induce hallucinations for divinatory purpose and mental illness Bulb Infusions used to induce hallucinations and to treat mental illness Datura stramonium L. Solanaceae Seed, leaf Acetylcholinestarase inhibitory activity, antiasthmatic activity, analgesic effect Hyosyamine, scopolamine, atropine Blurred vision, suppressed salivation, vasodilation, hallucinations and delirium Ipomoea batatas (L.) Lam Seed Leaves used to sedate hysterical and psychotic patients, and to treat insomnia. Also used as a hypnotic drug against hysteria and as a‘diviner’s aid Treatment of madness Hyperglycemic activity Ergometrine Nausea, giving away secrets, vomiting, respiratory arrest and weakness Gelfand et al. (1985), Wink and Van Wyk (2008) Boophone disticha (L.f.) Herb. Amaryllidaceae Crinum bulbispermum Amaryllidaceae Convolvulaceae Ipomoea tricolor Cav. Seed Hallucinogenic, vivid dreams and treatment of convulsions Psychoactive effect Ergometrine, chanoclavine, elynoclavine Nausea, giving away secrets, vomiting, respiratory arrest and weakness Gelfand et al. (1985), Wink and Van Wyk (2008) Convolvulaceae Ruta graveolens L. Rutaceae All parts Leaf juice used for convulsions and fits in infants and children and treatment of hysteria Analgesic activity, anti-inflammatory activity, spasmolytic activity Causes CNS excitation or depression and visual disturbances Acetylcholinestarase inhibitory activity, GABA activity Strong skin and mucosal irritant, blister formation, internal itching, visual distortions, salivation and haematuria Hypotension and convulsion Watt and BreyerBrandwijk (1962), Wink and Van Wyk (2008) Bulb Bergapten, psolralen, skimmianine, rutamine, dictamine Isoquinoline alkaloid (Montanine) Leaf, bulb Protection from evil spirits before ritual dancing by diviners. Leaves are rubbed on the head of restless young children Hypertensive effect, Anti-inflammatory activity Vomiting and dizziness Batten and Bokelmann (1966), Hutchings et al. (1996) Scadoxus puniceus (L.) Friis & Nordal Amaryllidaceae Tulbaghia violaceae Harv Alliaceae sively used for the treatment of diverse ailments. With V. colorata, therapeutically potent alkaloids are also thought to be responsible for the toxic properties of this plant (Wink and Van Wyk, 2008). Datura stramonium on the other hand contains some extremely poisonous compounds leading to blurred vision in affected individuals. Veale et al. (1992), Stafford et al. (2005b), Wink and Van Wyk (2008) 2.3. Important toxic plants used for treatment of CNS-related conditions in southern Africa Table 3 shows some important toxic medicinal plants used for CNS and related conditions in southern Africa. A number of alkaloid-producing plants have been reported to possess stimulating 615 A.R. Ndhlala et al. / Food and Chemical Toxicology 62 (2013) 609–621 Table 4 Important toxic plants used as aphrodisiacs and for maternal health care in southern Africa. Scientific name and family Poisonous plant part Traditional uses Biological activities Type of toxic or Active principle Symptoms Reference Bersama lucens (Hochst.) Szyszyl.; Bersama abyssinica Melianthaceae Leaf and root Decoction for barrenness and impotence, to treat menstrual pain and leprosy Antimicrobial, cytotoxic Berberine, magnoflorine and other isoquinoline alkaloids Bowiea volubilis Herv. Ex Hook. f. Hyacinthaceae Bulb Infusion are taken during pregnancy to facilitate delivery, to procure abortions and to treat venereal diseases Antimicrobial, antiinflammatory Cardiotoxic glycosides of the bufodienolide group Hutchings et al. (1996), Wink and Van Wyk (2008), Buwa and Van Staden (2006), Abdillahi and Van Staden (2012) Stafford et al. (2005a), Iwalewa et al. (2007), Wink and Van Wyk (2008) Callilepis laureola DC. Asteraceae Root Cytotoxic Atractyloside Capparis tomentosa Lam. Capparaceae All parts including fruits Weak decoctions are taken during pregnancy to ensure an easy childbirth, to induce fertility and treat impotency Infertility and impotency, illnesses resulting from miscarriage Nausea, vomiting, kidney inflammation. High doses cause respiratory arrest, haemorrhagic nephritis, fatal cases of poisoning and death Vomiting purging, irregular heart palpitations and numerous fatalities in humans and animals within few minutes Liver and kidney damage with high fatalities resulting in human death within 5 days Antimicrobial, antioxidant Isothiocyanates, stachydrine, Sulphur oil Gastrointestinal tract disturbance, several cases of fatality in human poisoning and livestock lose Catunaregam spinosa (Thunb.) Tirvengaum subsp. Spinosa Rubiaceae Cissampelos mucronata A. Rich. Bark and root Used as aphrodisiac, gynecological ailments, febrile complains, fever, epilepsy and arthritis Antimicrobial Hutchings et al. (1996), Steenkamp et al. (2004), Wink and Van Wyk (2008), Abdillahi and Van Staden (2012) Hutchings et al. (1996), Abdillahi and Van Staden (2012) Rhizomes and aerial parts Decoctions as aphrodisiac, used during pregnancy and as emmenagogues and gynaecoological purposes, as abortifacient Infusion as uterotonic to facilitate or induce child birth, for infertility fever and snake bite Antimicrobial, enzyme inhibitory Cissampareine, glaziovine and insularine Neuromuscular blocking effects Hutchings et al. (1996), Tshibangu et al. (2002), Wink and Van Wyk (2008) Uterotonic effects, inhibitor of protein biosynthesis, cytotoxic, virustatic properties and diuretic Lycorine, cliviamin, clivonine and cliviamaritine Vomiting, diarrhoea, salivation and depression of CNS leading to paralysis and collapse Women have died after vaginal insertion of powdered roots, abdominal pain, vomiting and confusion Nausea, vomiting, dizziness, diarrhoea and kidney problem, and respiratory arrest and livestock loss has been reported Hutchings et al. (1996), Wink and Van Wyk (2008) Menispermaceae Vomiting and purging and even death within a day Wink and Van Wyk (2008), Steenkamp et al. (2005) Clivia miniata (Lindl.) Regel Amaryllidaceae Bulb Combretum erythrophyllum (Burch.) Sond.; Combretum molle R. Br. ex G. Don Combretaceae Crinum bulbispermum (Burm. f.) MilneRedh. & Schweick; Crinum macowanii Bak. Amaryllidaceae Dioscorea dregeana (Kunth) Dur. & Schinz Dioscoreaceae Seed, root Decoction taken during pregnancy to facilitate delivery Ant-inflammatory, Antimicrobial Bulb To simulate breast milk, unspecified part are taken regularly during pregnancy to ensure easy delivery Antinociceptive crinamine, powelline, bulbispermine and crinalbine Tuber Highly cytotoxic,haemolytic Dioscorine, diosgenin, dioscin, deltonin, dltoside, hircinol and demethylbetatstin Mydriatic activity and paralytic effect on the CNS and caused human death Wink and Van Wyk (2008), Stafford et al. (2005b) Eucomis autumnalis (Mill.) Chitt. subsp. Autmnalis Hyacinthaceae Bulb Infusion are taken regularly during pregnancy to ensure an easy childbirth, as oral contraceptives, nervous spasms and cramps Decoctions taken during pregnancy to facilitate delivery, for urinary diseases and abdominal pain Antiinflammatory,antimicrobial Punctatin, autumnalin and ecomin Abdominal pain, diarrhoea, renal failure and sometimes death Flueggea virosa (Roxb. ex Willd.) Voigt. Euphorbiaceae Root Securinine and hordenine Gloriosa superba Corm, Fatal case of poisoning from aqueous extracts, facial paralysis and neurasthenia, and CNS effects Numbness of the lips, Hutchings et al. (1996), Rabe and Van Staden (1997), Taylor and Van Staden (2001), Iwalewa et al. (2007) Hutchings et al. (1996) Decoctions as contraceptives, for treating sterility, syphilis, gonorrhoea, mental illness and pneumonia Infusion taken as Antimicrobial, anti- Colchicine and Hutchings et al. (1996), Schwikkard et al. (2000), Brookes and Smith (2003), Martini et al. (2004) Hutchings et al. (1996), Abd el Hafiz et al. (1991), Ratnasooriya et al. (2005), Wink and Van Wyk (2008) Hutchings et al. (continued on next page) 616 A.R. Ndhlala et al. / Food and Chemical Toxicology 62 (2013) 609–621 Table 4 (continued) Scientific name and family Poisonous plant part Traditional uses Biological activities Type of toxic or Active principle Symptoms Reference Linn.), Gloriosa virescens Lindl. Colchicaceae leaves, stems and flowers aphrodisiacs, for impotency, bareness and abortion inflammatory colchamine Punica granatum L. Lythraceae Seed Fertility Acetylcholine receptors,antiinflammatory Pelletieine, Nmethylisopelletierine and pseudopelletierine (1996), Aleem (1992), Mendis (1989), Joshi et al. (2010), Khan et al. (2008), Abdillahi and Van Staden (2012) Wink and Van Wyk (2008), Lee et al. (2010) Scadoxus puniceus (L.) Friis & Nordal Amaryllidaceae Merwilla plumbea (Lindl.) Speta Hyacinthaceae Root For safe delivery during pregnancy Antimicrobial,antiinflammatory a Lycorine, montanine and haemanthine Bulb Infusion taken during pregnancy to facilitate delivery. Antimicrobial Proscillaridine A, saponins and other bufadienolides vomiting and diarrhoea, abdominal pain, convulsions, respiratory failure and caused numerous death CNS, hypertension, disturbance of vision, spasms, nausea, vomiting, gastroenteritis, convulsions and even death (by respiratory failure) Dizziness, visual disturbances, CNS depression and sometimes death Gastrointestinal disturbance, neurotoxic, cytotoxic Senecio jacobaea L.; Senecio oxyriifolius DC. Asteraceae Leave Alkylate proteins and DNA, mutagenic, teratogenica, carcinogenic and neuroreceptors and CNS activity Senecionine, seneciphyllin, jacobine and sceleratin Acute and chronic poisoning of humans and animals, damage the liver, kidneys, pancrease and gastrointestinal tract Withania somnifera (L.) Dun. Solanaceae Root Decoctions for treating capillary and arterial bleeding, especially in gynecological conditions, to induce menstruation and manage pain and inflammation Aphrodisiac, ointments as uterine tonic after miscarriage. Leave infusions as sexual stimulant to treat syphilis, haemorrhoids Antibiotic, antitumour, anti-inflammatory, cytotoxic,cholesterollowering activities, and rejuvenating properties Withaferin A, withasomninie Sedative and hypnotic effects effects and hallucinogenic properties. Most groups of alkaloids are known to affect signal transduction in neurons of the brain either by modulating the receptors of neurotransmitters or hormones or their reuptake into the presynaptic neuron (Wink and Van Wyk, 2008). For this reason, many of the alkaloid-producing plants, particularly those from the Amaryllidaceae family, are used traditionally in the treatment of such disorders. A comprehensive review of the Amaryllidaceae alkaloids covering their ethnopharmacology and toxicology has been published (Nair and Van Staden, 2013). On the contrary, similar groups of alkaloids are also implicated to have some toxic effects on humans (Table 3). Among the toxic plants listed in Table 3, three species (Boophone disticha, Crinum bulbispermum and Scadoxus puniceus) all have the isoquinoline alkaloids as the toxic compound with characteristic symptoms of dizziness. Among these, B. distica presents some acute symptoms of impaired vision, coma and death (Sobiecki, 2002). The lack of prescribed dosage on the use of these traditional herbal remedies imply that most of the users are at risk of being intoxicated each time this form of medicine is taken. In Abrus precatorius, the compound abrin, a therapeutically potent agent, is also implicated in such acute symptoms as bloody diarrhoea, haemorrhage, convulsions, coma and heart failure. 2.4. Important toxic plants used as aphrodisiacs and for maternal health care in southern Africa Table 4 highlights some of the important medicinal plants used in southern Africa as aphrodisiac and maternal purposes. Plants for this purpose are highly popular and their safety is of great concern. Recently, a review was conducted to document South African Veale et al. (1992), Wink and Van Wyk (2008), Ndhlala et al. (2011) Van wyk et al. (2002), Sparg et al. (2002), Taylor et al. (2003) Wink and Van Wyk (2008) Wink and Van Wyk (2008), Sing et al. (2010) plants used for male reproductive healthcare (Abdillahi and Van Staden, 2012). There is, however, a great concern raised due to several cases of poisoning/or intoxication associated with the use of aphrodisiac and maternal health care plants. For instance, C. laureola, mentioned earlier in Section 2.1, is one of the most toxic medicinal plants in South Africa, with the ingestion of a small quantity of the rootstock being fatal (Hutchings and Terblanche, 1989). The toxic compound isolated from the plant is atractyloside and was found to induce renal necrosis, mitochondrial toxicity and hepatocyte death (Popat et al., 2001). In Zimbabwe, root decoction of Combretum erythrophyllum administered to reduce the size of the vaginal orifice has caused numerous deaths to women (Rogers and Verotta, 1996). Among the plant species described in Table 4, Crinum macowanii and Merwilla plumbea were reported to exhibit high mutagenic effects in Salmonella/microsome assay (Elgorashi et al., 2003), Bersama lucens was reported to induce genotoxicity in the micronucleus test in the form of structural and numerical chromosome aberrations in the comet assay (Taylor et al., 2003), and Catunaregam spinosa was considered to be highly toxic because it caused both DNA damage and chromosomal aberrations (Taylor et al., 2003). These plant species are considered to be extremely hazardous and can induce cytotoxicity (Wink and Van Wyk, 2008). The major toxic compounds, crinamine and lycorine from Crinum macowanii are highly lethal with an oral lethal dose (LD)50 at a concentration of 10 mg/kg in dogs (Wink and Van Wyk, 2008). Cardiac glycosides are found in the following plant species; M. plumbea, Bersama abyssinica and Bowiea volubilis. Toxic effects of cardiac glycosides range from gastro-intestinal and nervous system disorders to respiratory effects resulting 617 A.R. Ndhlala et al. / Food and Chemical Toxicology 62 (2013) 609–621 Table 5 Important toxic medicinal plants used to treat miscellaneous conditions such as cancer, arthritis and heart conditions in southern Africa. Scientific name and family Toxic plant part Traditional uses Biological activities Type of toxic or active principle Symptoms Reference Aconitum napellus L. Ranunculaceae Leaf Cancer treatment Anticancer activities Aconitine Burning, tingling and numbness of mouth and throat followed insensitivity of fingers and toes. Severe diarrhoea Asclepias fruticosa L. Leaf Used as a purgative. Dried powdered leaf is inhaled as a snuff for the relief of headache and coryza Once used as an arrow poison by the Khoisan. Used to treat pain Cardiac glycosidesasclepiadin, gomphoside, afroside Weakness, spasms, seizures Buphanidrine has analgesic properties Buphanidrine Catharanthine has antihypogycemic properties, vincristine and vinblastine have anticancer properties Vinca alkaloids-norharman, indole alkaloids, catharanthine, leurosine, vindolinine, vincristine and vinblastine Restlessness, dyspnoea, dizziness, distorted vision, loss of coordination, dry mouth, blood and water accumulation in the lungs, bleeding of the intestinal mucosa, hallucinations and coma, leading to death Vinca alkaloids are irritants of the skin and respiratory tract. They also cause damange to the cornea of the eye. Vincristine and vinblastine cause gastrointestinal and neurological disorders characterised by nausea, vomiting, disturbance of vision and hearing. They also cause hair loss. Nausea, vomiting, dizziness, diarrhoea, kidney problems and respiratory arrest Bruneton (1999), Harbone et al. (1997), Van Wyk et al. (2002) Warashina and Noro (1994), Wink and Van Wyk (2008) Pooley (1998), Wink and Van Wyk (2008) Asclepiadaceae Boophone disticha (L.f.) Herb. Bulb Amaryllidaceae Catharanthus roseus (L.) G.Don Apocynaceae Whole plant Used in the treatment of diabetes and cancer (leukaemia) Crinum bulbispermum (Burm.f.) Milne-Redh. & Schweick. Bulb Used to treat colds, flu symptoms, fever, kidney and bladder problems, glandular swelling and skin ailments Alkaloids- crinine, powelline, lycorine and crinamine Fruit, leaf or root used as an emetic, purgative or enema for various ailments Triterpenoids-cucurbitacin Vomiting, bloody diarrhoea, kidney damage, spasms, respiratory arrest and death. Datura stramonium L. Solanaceae Leaf, seed, root Used to relieve asthmasymptoms and as an analgesic during surgery Tropane alkaloids atropine, hyoscyamine and scopolamine Dioscorea dregeana (Kunth) T.Durand & Schinz Dioscoreaceae Encephalartos longifolius (Jacq.) Lehm. Zamiaceae Erythrina caffra Thunb. Fabaceae Rootstock Used in the treatment of epilepsy, hysteria, insomnia and acute psychosis. Stems and fruit pulp Used as traditional emetics Bark, stem, rarely leaf and root Bulb Used in the treatment of arthritis, earache and toothache Piperidine alkaloiddioscorineSteroidal saponinsdiosgenin. Other compounds include dioscin, deltonin, deltoside, hircinol and demthylbatatstin Alkaloidal glycosides- cycasin and macrozamin. Neurotoxin amino acids- 3-methylaminoL-alanine Tetracyclic alkaloidserythraline, erysotrine Depressant and sedative effect, hallucinations, reddening of the face, dry mouth, confusion, insomnia, respiratory arrest and death Hallucinogenic Amaryllidaceae Cucumis africanus L.f. Cucurbitaceae Scadoxus puniceus (L.) Friis & Nordal Whole plant Bulb Watt and BreyerBrandwijk (1962) Preissel and Preissel (2002) Zukulu et al. (2012), Van Wyk et al. (2002 Wink and Van Wyk (2008) Hypotention, paralysis of motoric nerves, euphoria, drunkenness, enhanced lobido, deep sleep and death from respiratory arrest Hutchings et al. (1996), Wink and Van Wyk (2008) Du Plessis and Duncan (1989), Hutchings et al. (1996); Wink and Van Wyk (2008) Roberts (1990) Used traditionally as an antiseptic and diuretic Isoquinoline alkaloidshaemanthamine, haemanthidine Hypotensive and convulsive properties Used as a cure for cancer and immune booster in the treatment of HIV/AIDS Used as emetic, diuretic and heart tonic Canavanine Inhibits uptake systems for amino acids in the gut and inhibits enzymes responsible for amino acid biosynthesis Gastrointestinal symptoms followed by nausea and vomiting and death by cardiac arrest Cardiac glocosidebufadienolide mainly scillaren A Du Plessis and Duncan (1989), Van Wyk et al. (2002) Bloody diarrhoea, vomiting, liver damage, neuronal disturbances Amaryllidaceae Sutherlandia frutescens (L.) R.Br. Fabaceae Urginea sanguinea Shinz Hyacinthaceae Bruneton (1999), Van Wyk et al. (2002), Wink and Van Wyk (2008) Van Wyk et al. (2002) 618 A.R. Ndhlala et al. / Food and Chemical Toxicology 62 (2013) 609–621 from neuromuscular disorder and death is usually due to cardiotoxic effects (Kellerman et al., 2005). A decoction of Dioscorea dregeana is reported to make a person ‘‘mad drunk’’ and is also hallucinogenic. The toxic compound dioscorine isolated from D. dregeana is highly toxic to humans and an LD50 of 60 mg/kg in mice has been recorded (Wink and Van Wyk, 2008). The clinical features of colchicine toxicity in a patient was reported following the ingestion of Gloriosa superba tubers which induced gastroenteritis, acute renal failure, cardiotoxicity and haematological abnormalities, bone marrow depression and acute brain injury (Aleem, 1992). Colchicine exhibited cytotoxicity and capillary poisoning by its high affinity for tubulin as well as blocking the polymerisation and deplolymerisation of microtubules (Wink and Van Wyk, 2008). 2.5. Important toxic plants used to treat miscellaneous conditions such as cancer, arthritis and heart conditions in southern Africa Researchers and pharmaceutical companies with a vested interest in finding new drugs have scoured the world seeking for new sources of plant material used by indigenous people or as remedies in the treatment of cancer, heart conditions and arthritis. There are hundreds of indigenous plants used in traditional therapies in various regions of the world. Some of them have been tested and are still undergoing trials in current efforts to find a way of curing cancer, heart conditions and arthritis. Through the search for cures, a long list of plants used to treat these conditions can be produced. However, most of these medicinal herbs and plants are extremely toxic as they contain toxic alkaloids and glycosides as their main active constituents. Table 5 lists some of southern Africa’s most important medicinal plants that are toxic yet they are used to treat cancer, heart problems, arthritis among many other miscellaneous conditions. Some examples of well documented alkaloids such as hyoscyamine and atropines have been shown to have an effect on the autonomic nervous system by increasing the heart rate. Vincristine and vinblastine from Catharanthus roseus have reported activity against lymphocytic leukaemia in mice. Their semi synthetic analogues, vinorelbine and vindesine are made from the templates of the two active compounds. They showed potential activity against leukaemia’s, lymphomas, advanced testicular cancer, breast cancer, lung cancer and Kaposi’s sarcoma (Cragg and Newman, 2005; Nirmala et al., 2011). Cardenolides (cardiac glycosides) such as bufadienolide have been used for the treatment of cancer for years but due to their toxicity, which affect gastro-intestinal, respiratory and nervous systems, these compounds were abandoned (Hartwell and Abbott, 1969), until Stenkvist (1999) reported the beneficial anticancer effect of the cardiac glycoside and some researchers and oncologists came to the conclusion that certain concentrations could be used with negligible toxicity to humans (Haux, 1999; Haux et al., 1999). Most natural products used in the anticancer chemotherapy are generally toxic and non-selective/restrictive to cancer cells (Sowemimo et al., 2007). 3. Toxicity through contaminations – a case of heavy metal poisoning Heavy metals are not the usual composition of traditional medicine but are contaminants or adulterants due to alleged increase in therapeutic properties they are purported to cause in traditional remedies (Ernst, 2002; Haider et al., 2004; Okem et al., 2012). Metal contamination in herbal remedies can occur through plant mineral and water uptake, during transportation and storage. During storage or transportation, plant materials can be exposed to environmental pollutions due to unhygienic handling conditions thereby making the plant materials toxic (Hina et al., 2011). Numerous medicinal plants have the ability to accumulate heavy metals when grown under natural conditions. For instance, Punica granatum leaves have demonstrated to have a good biosorption system for Ni (II), copper (Cu) (II) and lead (Pb) (II). The plant has been recommended for its notable application in remediation of Pb from the environment (Salehi et al., 2010). In-depth studies are needed to elucidate the translocation of heavy metals in P. granatum so as to safeguard the public health. Street et al. (2008) reported accumulated arsenic (As) and cadmium (Cd) levels that exceeded the legal limits recommended by the World Health Organization (WHO) (1998) in B. volubilis, Eucomis autumnalis and D. dregeana samples obtained from a street herbal market in Pietermaritzburg, South Africa. High levels of manganese (Mn) were found in C. laureola (Steenkamp et al., 2006). High levels of various toxic metals have been reported in W. somnifera (Khan et al., 2008). Elevated levels of As and chromium (Cr) have been reported in C. tomentosa (Okatch et al., 2012). The concentration of toxic heavy metals in medicinal plants is of great concern to safeguard the public health. According to WHO (2007), the concentration of trace elements must be controlled in medicinal plants in order to meet and improve the quality assurance and safety of herbal medicinal standards. A case study of heavy metal contamination in Ayurvedic medicines used by the Indian community in South Africa was reported as the major source of metal poisoning (Keen et al., 1994). Nriagu et al. (1997) investigated the high rate of lead poisoning among children in KwaZulu-Natal and the leading causes were linked to food and traditional medicine contaminated with Pb. Steenkamp et al. (2002) reported a severe case of multiple heavy metal poisoning in children treated with a South Africa traditional remedy to have several clinical manifestations of gastrointestinal and neurological disorders. 4. Conclusions In addition to China and India, the African continent is universally recognized as the epicentre for the use, practice and trade in traditional medicine. This status is drawn out of several contributing factors, which include an abundant floral biodiversity platform with two resident floral kingdoms, affordability, a fragmented conventional health care sector, and extensive traditional knowledge and expertise within local communities. However, the toxicity of medicinal plants in southern Africa is poorly documented. This puts enormous pressure on the legislation, control of use of traditional medicine, regulation standards and public education. There is a lack of education amongst traditional healers, vendors and the public about the safety of medicinal plants. If this matter is not considered seriously, the rate of death due to toxicity resulting from medicinal plants will continue. Recently, there has been a positive move from the South African Bureau of Standards (SABS), carrying out consultations and working towards the standardisation of African Traditional Medicines by the introduction of ISO/TC249. In southern Africa, many cases of poisoning from the use of traditional medicine are thought to remain unreported due to the fact that patients residing in rural areas may die before reaching a hospital (Steenkamp et al., 1999). More so, people are generally reluctant to admit using traditional medicine because of the cultural secrecy surrounding their uses as well as the negative view orthodox practitioners have toward traditional medicines (Bhat and Jacobs, 1995; Steenkamp et al., 1999). Toxicity of herbal medicine in some cases may result from misidentification, inadvertent or A.R. Ndhlala et al. / Food and Chemical Toxicology 62 (2013) 609–621 deliberate substitution of herbal materials, incorrect preparation or inappropriate administration and unregulated dosages (Stewart et al., 1998). The toxicity of herbal medicine, if not properly assessed, can result in adverse effects such as drug-drug interactions (Mosihuzzaman and Choudhary, 2008). The source and quality of raw materials, Good Agricultural Practices (GAP) and manufacturing processes are essential steps for quality control of herbal medicines. These will play a pivotal role in guaranteeing the quality and stability of herbal products (WHO, 1998). Based on the available literature, it was possible to list, in five tables, important toxic medicinal plants resident in the southern African region with pharmacological properties ranging from antimicrobial, antiviral, anticancer, anti-inflammatory as well as those that are used as aphrodisiacs and maternal health care. Conflict of Interest The authors declare that there are no conflicts of interest. Acknowledgements This work was supported by the Claude Leon Foundation and the University of KwaZulu-Natal, South Africa in the form of fellowships. References Abd el Hafiz, M.A., Ramadan, M.A., Jung, M.L., Beck, J.P., Anton, R., 1991. 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