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
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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
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(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
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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)
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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)
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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-
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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
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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)
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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
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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. Cytotoxic
activity of Amaryllidaceae alkaloids from Crinum augustum and Crinum
bulbispermum. Planta Med. 57, 437–439.
Abdel-Sattar, E., 2008. Antimicrobial activity of extracts of some plants collected
from the Kingdom of Saudi Arabia JKAU. Med. Sci. 15, 25–33.
Abdillahi, H.S., Van Staden, J., 2012. South African plants and male reproductive
healthcare: conception and contraception. J. Ethnopharmacol. 143, 475–480.
Adelowotan, O., Aibinu, I., Adenipekun, E., Odugbemi, T., 2008. The in vitro
antimicrobial activity of Abrus precatorius (L.) fabaceae extract on some clinical
pathogens. Niger. Postgrad. Med. J. 15, 32–37.
Adesina, S.K., 1982. Studies on some plants used as anticonvulsants in Amerindian
and African traditional medicine. Fitoterapia 5–6, 147–162.
Al-Barwani, F.M., Eltayeb, E.A., 2004. Antifungal compounds from induced Conium
maculatum L. plants. Biochem. Sys. Ecol. 32, 1097–1108.
Aleem, H.M., 1992. Gloriosa superba poisoning. J. Assoc. Physicians India 40, 541–
542.
Al-Fatimi, M., Wurster, M., Schröder, G., Lindequist, U., 2007. Antioxidant,
antimicrobial and cytotoxic activities of selected medicinal plants from
Yemen. J. Ethnopharmacol. 111, 657–666.
Arekemase, M.O., Kayode, R.M.O., Ajiboye, A.E., 2011. Antimicrobial activity and
phytochemical analysis of Jatropha curcas plant against some selected
microorganisms. Int. J. Biol. 3 (3).
Aremu, A.O., Ndhlala, A.R., Fawole, O.A., Light, M.E., Van Finnie, J.F., Staden, J., 2010.
In vitro pharmacological evaluation and phenolic content of ten South African
medicinal plants used as anthelmintics S. Afr. J. Bot. 76, 558–566.
Batten, A., Bokelmann, H., 1966. Wild flowers of the Eastern Cape Province. Cape
and Transvaal Printers Ltd., Cape Town.
Bessong, P.O., Obi, C.L., Igumbor, E., Andréola, M-L., Litvak, S., 2004. In vitro activity
of three selected South African medicinal plants against human
immunodeficiency virus type 1 reverse transcriptase. Afr. J. Biotechnol. 3,
555–559.
Bhat, R.B., Jacobs, T.V., 1995. Traditional herbal medicine in Transkei. J.
Ethnopharmacol. 48, 7–12.
Botha, C.J., Penrith, M.-L., 2008. Poisonous plants of veterinary and human
importance in southern Africa. J. Ethnopharmacol. 119, 549–558.
Brookes, B.K., Smith, A.N., 2003. Cytotoxicity of pregnancy-related traditional
medicines. Scientific Letters. S. Afr. Med. J. 93, 359–361.
Bruneton, J., 1999. Toxic plants dangerous to humans and Animals. Intercept,
Hampshire.
Bruschi, P., Morganti, M., Mancini, M., Signorini, M.A., 2011. Traditional healers and
lay people: a qualitative and quantitative approach to local knowledge on
medicinal plants in Muda (Mozambique). J. Ethnopharmacol. 138, 543–563.
Bryant, A.T., 1966. Zulu Medicine and Medicine-Men. Struik, Cape Town.
Buwa, L.V., Van Staden, J., 2006. Antibacterial and antifungal activity of traditional
medicinal plants used against venereal diseases in South Africa. J.
Ethnopharmacol. 103, 139–142.
Bye, S.N., Dutton, M.F., 1991. The inappropriate use of traditional medicines in
South Africa. J. Ethnopharmacol. 34, 253–259.
Cheesman, L., Nair, J.J., Van Staden, J., 2012. Antibacterial activity of crinane
alkaloids from Boophone disticha (Amaryllidaceae). J. Ethnopharmacol. 140,
405–408.
619
Chukwujekwu, J.C., Van Heerden, F.R., Van Staden, J., 2011. Antibacterial activity of
flavonoids from the stem bark of Erythrina caffra thumb. Phytother. Res. 25, 46–
48.
Clarkson, C., Maharaj, V.J., Crouch, N.R., Grace, O.M., Pillay, P., Matsabisa, M.G.,
Bhagwandin, N., Smith, P.J., Folb, P.I., 2004. In vitro antiplasmodial activity of
medicinal plants native to or naturalised in South Africa. J. Ethnopharmacol. 92,
177–191.
Cragg, G.M., Newman, D.J., 2005. Plants as a source of anti-cancer agents. J.
Ethnopharmacol. 100, 72–79.
Debella, A., Kunert, O., Schmid, M.G., Michl, G., Bucar, F., Abebe, D., Haslinger, E.,
2000. A diterpene, a flavonol glycoside, and a phytosterol glycoside from
Securidaca longipedunculata and Entada abyssinica. Monatsh. Chem. 131, 401–
408.
Devi, M.R., Bawari, M., Paul, S.B., Sharma, G.D., 2011. Neurotoxic and medicinal
properties of Datura stramonium L. – review. Assam Univ. J. Sci. Technol.: Biol.
Environ. Sci. 7, 139–144.
Du plessis, N., Duncan, G., 1989. Bulbous Plants of Southern Africa. Tafelberg,
Capetown.
Eldeen, I.M.S., Elgorashi, E.E., Mulholland, D.A., Van Staden, J., Anolignan, B., 2006. A
bioactive compound from the roots of Terminalia sericea. J. Ethnopharmacol.
103, 135–138.
Elgorashi, E.E., Taylor, J.L.S., Verschaeve, L., Maes, A., Van Staden, J., De Kimpe, N.,
2003. Screening of medicinal plants used in South African traditional medicine
for genotoxic effects. Toxicol. Lett. 143, 195–207.
Ernst, E., 2002. Toxic heavy metals and undeclared drugs in Asian herbal medicines.
Trends Pharmacol. Sci. 23, 136–139.
Fennell, C.W., Lindsey, K.L., McGaw, L.J., Sparg, S.G., Stafford, G.I., Elgorashi, E.E.,
Grace, O.M., Van Staden, J., 2004. Assessing African medicinal plants for efficacy
and safety: pharmacological screening and toxicology. J. Ethnopharmacol. 94,
205–217.
Gelfand, M., Mavi, S., Drummond, R.B., Ndemera, B., 1985. The Traditional Medical
Practitioner in Zimbabwe. Mambo Press, Gweru.
Gonzalo, J.D., 2011. Toxic plants of veterinary and agricultural interest in colombia.
Int. J. Poisonous Plant Res. 1, 1–15.
Govindasamy, C., Srinivasan, R., 2012. In vitro antibacterial activity and
phytochemical analysis of Catharanthus roseus (Linn.). G. Don. Asian Pac. J.
Trop. Biomed., 155–158.
Gyuris, A., Szlaviki, L., Minarovitsi, J., Vasa, A., Molnar, J., Hohmann, J., 2009.
Antiviral activities of extracts of Euphorbia hirta L. against HIV-1, HIV-2 and
SIVmac251. In vivo 23, 429–432.
Haider, S., Naithani, V., Barthwal, J., Kakkar, P., 2004. Heavy metal content in some
therapeutically important medicinal plants. Bull. Environ. Contam. Toxicol. 72,
119–127.
Harbone, J.B., Baxter, H., Moss, G.P., 1997. Dictionary of Plant Toxins. John Wiley and
Sons, Chichester.
Hartwell, J.L., Abbott, B.J., 1969. Antineoplastic principles in plants: recent
developments in the field. Adv. Pharmacol. 7, 117–209.
Haux, J., 1999. Digitoxin is a potential anticancer agent for several types of cancer.
Med. Hypotheses 53, 543–548.
Haux, J., Lam, J., Marthinsen, A.B.L., Strickert, T., Lundgren, S., 1999. Digitoxin, in
non-toxic concentrations induces cell death in Jurkat T cells in vitro. Z.
Krebsforsch. Klin. Onkol. 31, 14–20.
Hina, B., Rizwani, G.H., Naseem, S., 2011. Determination of toxic metals in some
herbal drugs through atomic absorption spectroscopy. Pak. J. Pharm. Sci. 24,
353–358.
Hutchings, A., Terblanche, S.E., 1989. Observations on the use of some known and
suspected toxic Liliiflorae in Zulu and Xhosa medicine. S. Afr. Med. J. 75, 62–69.
Hutchings, A., Scott, A.H., Lewis, G., Cunningham, A.B., 1996. Zulu Medicinal Plants:
An Inventory. University of Natal Press, Pietermaritzburg.
Igbinosa, O.O., Igbinosa, E.O., Aiyegoro, O.A., 2009. Antimicrobial activity and
phytochemical screening of stem bark extracts from Jatropha curcas (Linn.). Afr.
J. Pharm. Pharacol. 3, 058–062.
Iwalewa, E.O., McGaw, L.J., Naidoo, V., Eloff, J.N., 2007. Inflammation: the foundation
of diseases and disorders. A review of phytomedicines of South African origin
used to treat pain and inflammatory conditions. Afr. J. Biotechnol. 6, 2868–
2885.
Joshi, C.S., Priya, E.S., Mathela, C.S., 2010. Isolation and anti-inflammatory activity of
colchicinoids from Gloriosa superba seeds. Pharm. Biol., 206–209.
Joubert, P.H., Mathibe, L., 1989. Acute poisoning in developing countries. Adverse
Drug React. Acute Poisoning Rev. 8, 165–178.
Joubert, P., Sebata, B., 1982. The role of prospective epidemiology in the
establishment of a toxicology service for a developing community. S. Afr.
Med. J. 62, 853–854.
Kambizi, K., Goosen, B.M., Taylor, M.B., Afolayan, A.J., 2007. Anti-viral effects of
aqueous extracts of Aloe ferox and Withania somnifera on herpes simplex virus
type 1 in cell culture. S. Afr. J. Sci. 103, 359.
Keen, R.W., Deacon, A.C., Delves, H.T., Moreton, J.A., Frost, P.G., 1994. Indian herbal
remedies for diabetes as a cause of lead poisoning. Postgrad. Med. J. 70, 113–
114.
Kellerman, T.S., Coetzer, J.A.W., Naudé, T.W., Botha, C.J., 2005. Plant Poisonings and
Mycotoxicoses of Livestock in Southern Africa, second ed. Oxford University
Press, Cape Town.
Kelmanson, J.E., Jäger, A.K., Van Staden, J., 2000. Zulu medicinal plants with
antibacterial activity. J. Ethnopharmacol. 69, 241–246.
Khan, H., Khan, M.A., Mahmood, T., Choudhary, M.I., 2008. Antimicrobial activity of
Gloriosa superba Linn (Colchicaceas) extracts. J. Enzyme Inhib. Med. Chem. 23,
855–859.
620
A.R. Ndhlala et al. / Food and Chemical Toxicology 62 (2013) 609–621
Kokwaro, J.O., 1976. Medicinal Plants of East Africa. East African Literature Bureau,
Nairobi.
Konaté, K., Kiendrébéogo, M., Ouattara, M.B., Souza, A., Lamien-Meda, A., Nongasida,
Y., Barro, N., Millogo-Rasolodimby, J., Nacoulma, O.G., 2011. Antibacterial
potential of aqueous acetone extracts from five medicinal plants used
traditionally to treat infectious diseases in Burkina Faso. Curr. Res. J. Biol. Sci.
3, 435–442.
Laydevant, F., 1932. Religious or sacred plants of Basutoland. Bantu Stud. 6, 65–69.
Lee, C.-J., Chen, L.-G., Liang, W.-L., Wang, C.-C., 2010. Anti-inflammatory effects of
Punica granatum Linne in vitro and In vivo. Food Chem. 118, 315–322.
Madureira, A.M., Ramalhete, C., Mulhovo, S., Duarte, A., Ferreira, M.J., 2012.
Antibacterial activity of some African medicinal plants used traditionally
against infectious diseases. Pharm. Biol. 50, 481–489.
Majinda, R.R.T., Motswaledi, M.S., 1998. Antibiotic activity of selected Botswana
Medicinal plants. Botsw. Notes Rec. 30, 157–161.
Martini, N.D., Katerere, D.R., Eloff, J.N., 2004. Biological activity of five antibacterial
flavonoids from Combretum erythropyllum (Combretaceae). J. Ethnopharmacol.
93, 207–212.
Mašković, P.Z., Mladenović, J.D., Cvijović, M.S., Aćamović-Ðoković, G., Solujić, S.R.,
Radojković, M.M., 2011. Phenolic content, antioxidant and antifungal activities
of acetonic, ethanolic and petroleum ether extracts of Hypericum perforatum L..
Hemijska Industrija 65, 159–164.
Masondo, N.A., Ndhlala, A.R., Aremu, A.O., Van Staden, J., Finnie, J.F., 2013. A
comparison of the pharmacological properties of garden cultivated and muthi
market-sold Bowiea volubilis. S. Afr. J. Bot. 86, 135–138.
Mativandlela, S.P., Meyer, J.J., Hussein, A.A., Houghton, P.J., Hamilton, C.J., Lall, N.,
2008. Activity against Mycobacterium smegmatis and M. tuberculosis by extract
of South African medicinal plants. Phytother. Res. 22, 841–845.
Mdee, L.K., Masoko, P., Eloff, J.N., 2009. The activity of extracts of seven common
invasive plant species on fungal phytopathogens. S. Afr. J. Bot. 75, 375–379.
Mendis, S., 1989. Colchicine cardiotoxicity following ingestion of Gloriosa superba
tubers. Postgrad. Med. J. 65, 752–755.
Mosihuzzaman, M., Choudhary, M.I., 2008. Protocols on safety, efficacy,
standardization, and documentation of herbal medicine. Int. Union Pure Appl.
Chem. 80, 2195–2230.
Moustafa, M.F.M., Alamri, S.A., Taha, T.H., Alrumman, S.A., 2013. In vitro antifungal
activity of Argemone ochroleuca Sweet latex against some pathogenic fungi. Afr.
J. Biotechnol. 12, 1132–1137.
Mulaudzi, R.B., Ndhlala, A.R., Kulkarni, M.G., Van Staden, J., 2012. Pharmacological
properties and protein binding capacity of phenolic extracts of some Venda
medicinal plants used against cough and fever. J. Ethnopharmacol. 143, 185–
193.
Nair, J.J., Van Staden, J., 2013. Pharmacological and toxicological insights to the
South African Amaryllidaceae. Food Chem. Toxicol., 18 August 2013 (in press).
Ncube, B., Finnie, J.F., Van Staden, J., 2011a. Seasonal variation in antimicrobial and
phytochemical properties of frequently used medicinal bulbous plants from
South Africa S. Afr. J. Bot. 77, 387–396.
Ncube, B., Ngunge, V.N.P., Finnie, J.F., Van Staden, J., 2011b. A comparative study of
the antimicrobial and phytochemical properties between outdoor grown and
micropropagated Tulbaghia violacea Harv. plants. J. Ethnopharmacol. 134, 775–
780.
Ndhlala, A.R., Finnie, J.F., Van Staden, J., 2011. Plant composition, pharmacological
properties and mutagenic evaluation of a commercial Zulu herbal mixture:
Imbiza ephuzwato. J. Ethnopharmacol. 133, 663–674.
Neuwinger, H.D., 1996. African Ethnobotany: Poisons and Drugs: Chemistry,
Pharmacology, Toxicology. Medpharm Scientific Publishers, Stuttgart.
Nielsen., T.R.H., Kuete., V., Jäger, A.K., Meyer, J.J.M., Lall, N., 2012. Antimicrobial
activity of selected South African medicinal plants. BMC Complement. Alt. Med.
12, 1–6.
Nirmala, M.J., Samundeeswari, A., Sankar, P.D., 2011. Natural plant resources in
anti-cancer therapy – a review. Res. Plant Biol. 1, 1–14.
Nriagu, J., Jinabhai, C.C., Naidoo, R., Coutsoudis, A., 1997. Lead poisoning of children
in Africa, KwaZulu/Natal, South Africa. Sci. Total Environ. 197, 1–11.
Obatomi, D.K., Bach, P.H., 1998. Biochemistry and toxicology of the diterpenoid
glycoside atractyloside. Food Chem. Toxicol. 36, 335–346.
Okatch, H., Nqwenya, B., Raletamo, K.M., Andrea-Marobela, K., 2012. Determination
of potential toxic heavy metals in traditionally used medicinal plants for HIV/
AIDS opportunistic infections in Ngamiland District in Northern Botswana.
Anal. Chim. Acta 730, 42–48.
Okem, A., Ndhlala, A.R., Southway, C., Van Staden, J., 2012. Determination of total
and bioavailable heavy and trace metals in South African commercial herbal
concoctions using ICP-OES. S. Afr. J. Bot. 82, 75–82.
Olajuyigbe, O.O., Afolayan, A.J., 2012. In vitro antibacterial and time-kill evaluation
of the Erythrina caffra Thunb. extract against bacteria associated with diarrhoea.
Sci. World J. 2012, 1–8.
Pedersen, M.E., Szewczyk, B., Stachowicz, K., Wieronska, J., Andersen, J., Stafford,
G.I., Van Staden, J., Pilc, A., Jäger, A.K., 2008. Effects of South African traditional
medicine in animal models for depression. J. Ethnopharmacol. 119, 542–548.
Pooley, E., 1998. Field Guide To Wild Flowers of KwaZulu-Natal and The Eastern
Region. Natal Flora Publications Trust, Durban.
Popat, A., Sheara, N.H., Malkiewicz, I., Stewart, M.J., Steenkamp, V., Thomson, S.,
Neuman, M.G., 2001. The toxicity of Callilepis laureola, A South African
traditional herbal medicine. Clin. Biochem. 34, 229–236.
Preissel, U., Preissel, H.G., 2002. Brugmansia and Datura: Angel’s Trumpets and
Thorn Apples. Firefly Books, Toronto.
Rabe, T., Van Staden, J., 1997. Antibacterial activity of South African plants used for
medicinal purposes. J. Ethnopharmacol. 56, 81–87.
Rabe, T., Mullholland, D., Van Staden, J., 2002. Isolation and identification of
antibacterial compounds from Vernonia colorata leaves. J. Ethnopharmacol. 80,
91–94.
Ratnasooriya, W.D., Deraniyagada, S.A., Bathiqe, S.D., Hettiarachchi, H.D., 2005. Leaf
extract of Crinum bulbispermum has antinociceptive activity in rats. J.
Ethnopharmacol. 97, 123–128.
Reichling, J., Weseler, A., Saller, R., 2001. A current review of the antimicrobial
activity of Hypericum perforatum L.. Pharmacopsychiatry 34, 116–118.
Reyes, F.D., Peña, C.J., Canales, M., Jiménez, M., Meráz, S., Hernandez, T., 2011.
Antimicrobial activity of Argemone ochroleuca Sweet (Chicalote). Latin American
and Caribbean Bulletin of Medicinal and Aromatic Plants. 10, 139–146.
Roberts, M., 1990. Indigenous Healing Plants. Southern Book Publishers, Halfway
House, Pretoria.
Rogers, C.B., Verotta, L., 1996. Chemistry and biological properties of the African
Combretaceae. In: Proceedings of the first international organisation of
chemical development symposium: Victoria Falls, Zimbabwe; 25–28
February, 1996. p. 121–42.
Saadabi, A.M.A., Moglad, E.H., 2011. Experimental evaluation of crtain Sudanese
plants used in folkloric medicine for their antibacterial activity (In vitro tests). J.
Appl. Sci. Res. 7, 253–256.
Saetae, D., Suntornsuk, W., 2010. Antifungal activities of ethanolic extract from
Jatropha curcas seed cake. J. Microbiol. Biotechnol. 20, 319–324.
Salehi, P., Asghari, B., Mohammadi, F., 2010. Biosorption of Ni(II), Cu(II) and Pb(II) by
Punica granatum from aqueous solutions. J. Water Resour. Prot. 2, 701–705.
Schwikkard, S., Zhou, B.N., Glass, T.E., Sharp, J.L., Mattern, M.R., Johnson, R.K.,
Kinqston, D.G., 2000. Bioactive compounds from Combretum erythrophyllum. J.
Nat. Prod. 63, 457–460.
Sharma, M.C., Sharma, S., 2010. Phytochemical, preliminary pharmacognostical and
antimicrobial evaluation of combined crude aqueous extract. Int. J. Microbiol.
Res. 1, 166–170.
Sing, G., Sharma, P.K., Dudhe, R., Sing, S., 2010. Biological activities of Withania
somnifera. Ann. Biol. Res. 1, 56–63.
Sobiecki, J.F., 2002. A preliminary inventory of plants used for psychoactive
purposes in southern Africa healing traditions. Trans. Roy. Soc. S. Afr. 57, 1–24.
Sowemimo, A.A., Fakoya, F.A., Awopetu, I., Omobuwajo, O.R., Adesanya, S.A., 2007.
Toxicity and mutagenic activity of some selected Nigerian plants. J.
Ethnopharmacol. 113, 427–432.
Sparg, S.G., Van Staden, J., Jager, A.K., 2002. Pharmacological and phytochemical
screening of two Hyacinthaceas species: Scilla natalensis and Ledebouria
ovatifolia. J. Ethnopharmacol. 80, 95–101.
Stafford, G.I., Jäger, A.K., Van Staden, J., 2005a. Effect of storage on the chemical
composition and biological activity of several popular South African medicinal
plants. J. Ethnopharmacol. 97, 107–115.
Stafford, G.I., Jäger, A.K., Van Staden, J., 2005b. Activity of traditional South African
sedative and potentially CNS-acting plants in the GABA-benzodiazepine
receptor assay. S. Afr. J. Bot. 100, 210–215.
Steenkamp, V., Stewart, M.J., Zuckerman, M., 1999. Detection of poisoning by Impila
(Callilepis laureola) in a mother and child. Hum. Exp. Toxicol. 18, 594–597.
Steenkamp, V., Stewart, M., Curowska, E., Zuckerman, M., 2002. A severe case of
multiple metal poisoning in a child treated with a traditional medicine. Forensic
Sci. Intern. 128, 123–126.
Steenkamp, V., Mathivha, E., Gouws, M.C., Van Rensburg, C.E.J., 2004. Studies on
antibacterial, antioxidant and fibroblast growth stimulation of wound healing
remedies from South Africa. J. Ethnopharmacol. 95, 353–357.
Steenkamp, V., Grimmer, H., Semano, M., Gulumian, M., 2005. Antioxidant and
genotoxic properties of South African herbal extracts. Mutat. Res. 581, 35–42.
Steenkamp, V., Cukrowska, E., Stewart, M.J., 2006. Metal concentrations in South
African traditional herbal remedies. S. Afr. J. Sci. 102, 256–258.
Stenkvist, B., 1999. Is digitalis a therapy for breast cancer? Oncolologyogy 6, 493–
496.
Stewart, M.J., Steenkamp, V., Zuckerman, M., 1998. The toxicology of African herbal
remedies. Ther. Drug Monit. 20, 510–516.
Street, R.A., Kulkarni, M.G., Stirk, W.A., Southway, C., Van Staden, J., 2008. Variation
in heavy metals and microelements in South African medicinal plants obtained
from street markets. Food Add. Contam. 25, 953–960.
Taylor, J.L.S., Van Staden, J., 2001. The effect of age season and growth conditions on
anti-inflammatory activity in Eucomis autumnalis (Mill.) Chitt. Plant extracts. J.
Plant Growth Regul. 34, 39–47.
Taylor, J.L.S., Elgorashi, E.E., Maes, A., Van Gorp, U., De Kimpe, N., Van Staden, J.,
Veschave, L., 2003. Investigating the safety of plants used in South African
traditional medicine. Environ. Mol. Mutagen. 42, 144–154.
Thring, T.S.A., Springfield, E.P., Weitz, F.M., 2007. Antimicrobial activities of four
plant species from the southern Overberg region of South Africa. Afr. J.
Biotechnol. 6, 1779–1784.
Tshibangu, J.N., Chifundera, K., Kaminsky, R., Wright, A.D., König, G.M., 2002.
Screening of African medicinal plants for antimicrobial and enzyme inhibitory
activity. J. Ethnopharmacol. 80, 25–35.
Van Wyk, B.-E., Gericke, N., 2000. People’s Plants. A Guide to Useful Plants of
Southern Africa. Briza Publications, Pretoria.
Van Wyk, B.-E., Van Heerden, F.R., Van Oudtshoorn, B., 2002. Poisonous Plants of
South Africa. Briza Publications, Pretoria.
Van Wyk, B.-E., Van Oudtshoorn, B., Gericke, N., 2009. Medicinal Plants of South
Africa. Briza Publications, Pretoria.
A.R. Ndhlala et al. / Food and Chemical Toxicology 62 (2013) 609–621
Veale, D.J.H., Furman, K.I., Oliver, D.W., 1992. South African traditional herbal
medicines used during pregnancy and childbirth. J. Ethnopharmacol. 27, 341–
346.
Veale, D.J., Havlik, I., Oliver, D.W., Dekker, T.G., 1999. Pharmacological effects of
Agapanthus africanus on the isolated rat uterus. J. Ethnopharmacol. 66, 257–262.
Venter, C.P., Joubert, P.H., 1988. Aspects of poisoning with traditional medicines in
southern Africa. Biomed. Environ. Sci. 1, 388–391.
Walker, J., 1996. Wild Flowers of KwaZulu-Natal. W.R. Walker family Trust,
Pinetown.
Warashina, T., Noro, T., 1994. Steroidal and cardenolide glycosides from Asclepias
fruticosa. Phytochemistry 37, 217–226.
Watt, J.M., Breyer-Brandwijk, M.G., 1962. The Medicinal and Poisonous Plants of
Southern and Eastern Africa. Livingstone, London.
Wink, M., Van Wyk, B.-E., 2008. Mind-Altering and Poisonous Plants of the World.
Briza Publications, Pretoria.
621
World Health Organization, 1998. Quality Control Methods for Medicinal Plants
Materials, Geneva.
World Health Organization, 2007. WHO Guidelines for Assessing Quality of Herbal
Medicines with Reference to Contaminants and Residues, Geneva.
Yadava, R.N., Reddy, V.M.S., 2002. A new biologically active flavonol glycoside from
the seeds of Abrus precatorius Linn.. J. Asian Nat. Prod. Res. 4, 103–107.
York, T., Van Vuuren, S.F., de Wet, H., 2012. An antimicrobial evaluation of plants
used for the treatment of respiratory infections in rural Maputaland, KwaZuluNatal, South Africa. J. Ethnopharmacol. 144, 118–127.
Zore, G.B., Awad, V., Thakre, A.D., Halde, U.K., Meshram, N.S., Surwase, B.S.,
Karuppayil, S.M., 2007. Activity-directed fractionation and isolation of four
antibacterial compounds from Abrus precatorius L. roots. Nat. Prod. Res. 21, 933–
940.
Zukulu, S., Dold, T., Abbott, T., Raimondo, D., 2012. Medicinal and Charm Plants of
Pondoland. South African National Biodiversity Institute, Pretoria.