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Ethnomedicinal uses, biological activities, and toxicity of Voacanga africana

Stapf Ex Scott-Elliot

Article in Advances in Traditional Medicine · October 2023

DOI: 10.1007/s13596-023-00709-y

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Advances in Traditional Medicine
https://doi.org/10.1007/s13596-023-00709-y

REVIEW

Ethnomedicinal uses, biological activities, and toxicity of Voacanga

africana Stapf Ex Scott‑Elliot
Emelia Oppong Bekoe1 · Jochebed A. Amene Opare1 · Michael Lartey2 · Patrick Amoateng3

Received: 10 October 2022 / Accepted: 8 September 2023

© The Author(s), under exclusive licence to Institute of Korean Medicine, Kyung Hee University 2023

Abstract
Voacanga africana, is a medicinal plant widely used in many African countries. Various parts of this plant are used, but
more especially the seeds are held in high esteem for it’s their additional economic value due to the presence of the alkaloids
ibogaine, tabersonine, and voacangine. These alkaloids have peculiar medicinal uses in the treatment of psychotic ailments,
drug addiction, and also serve as precursors for drug synthesis. V. africana is traditionally used to treat a myriad of diseases
including malaria, worm infestation, amoebiasis, ulcers, pain, cardiovascular conditions, depression, fatigue, shortness of
breath, diarrhoea, gynaecological conditions, delayed labour, kidney conditions, malaria, asthma and convulsions, how-
ever not all these have been investigated. Studies have demonstrate possible efficacy in the treatment of worm infestation,
amoebiasis, ulcer, pain and inflammation, cardiovascular condition, depression, diarrhoea, onchocerciasis, mental disorder,
and microbial infections. The plant also has CNS, neuro-protective, sedative, anti-microbial, anti-tumor and anti-oxidant
activities. Further studies is however needed to verify its activity in the treatment of malaria, fatigue, gynaecological and,
labour conditions, respiratory conditions and carious teeth. With respect to safety, the ethanolic leaf extract is reported to be
relatively non-toxic with an estimated L­ D50 of ≥ 5000 mg while the aqueous leaf extract had no significant alteration on the
blood biochemistry or histopathology of essential organs in murine models. Some isolated alkaloids from this plant: vobtu-
sine, voacangine and voacamine are however known to exhibit toxicity in the form of cardiac depressor activity, asphyxia and
convulsions, hypertension and CNS depressant activities. In addition to alkaloids, the plant is also rich in saponins, tannins,
terpenes, steroids, flavonoids, phenols, anthranoids, glycosides, and oils. This review therefore suggests the need for further
robust and detailed investigations on the activity of the extracts and compounds of this plant and their potential toxicities.

Keywords Voacanga africana · Ethnomedicinal · Pharmacology · Toxicity · Phytochemistry

Abbreviations Introduction
ALP Alkaline phosphatase
CNS Central nervous system Voacanga africana is a tropical evergreen shrub (Hussain
DPPH 1, 1-Diphenyl- 2- picryl-hydrazyl et al. 2012) which is prevalent in the landmasses of tropical
HDL High-density lipoproteins Africa beginning from Senegal to Sudan, Nigeria, Angola,
LDL Low-density lipoproteins Democratic Republic of the Congo (formerly Zaire), Kenya,
Angola, Zimbabwe, and Mozambique within the Africa
region (Schmelzer GH and Gurib-Fakim 2008; Olaleye
* Emelia Oppong Bekoe
eoppongbekoe@ug.edu.gh et al. 2004). In Ghana, V. africana is distributed over the
middle and southern belts of the country (Brako–Danquah
* Patrick Amoateng
PAmoateng@ug.edu.gh 2012). It is known as ‘small- fruit wild frangipani’ in Eng-
lish, “kakapempe or ofruma” in Akan, a local Ghanaian
1
Department of Pharmacognosy and Herbal Medicine, School language (Leeuwenberg 1985), and Voacanga d’ African in
of Pharmacy, University of Ghana, Legon, P.O Box LG 43, French. The accepted name of this plant is V. africana Stapf
Accra, Ghana
Ex Scott-Elliot (Plantlist 2013) with recognized synonyms
2
Department of Pharmaceutical Chemistry, University being V. magnifolia Wernham, V. eketensis Wernham, V.
of Ghana, Legon, P.O Box LG 43, Accra, Ghana
glabra K. Schum, V. glaberrina Wernham and V. talbotti
3
Department of Pharmacology and Toxicology, University Wernham (Maurice 2014).
of Ghana, Legon, P.O Box LG 43, Accra, Ghana

13
Vol.:(0123456789)

V. africana belongs to the family Apocynaceae, and the
genus Voacanga which has about 12 different species. Fam-
ily Apocynaceae is made up of trees, shrubs, vines, and
herbs, and it is characterized by the production of a milky
sap (Wong et al. 2013). Though it is a tropical plant, it exhib-
its both evergreen and deciduous characteristics. V. africana
contains saponins, tannins, alkaloids, terpenes, steroids, fla-
vonoids, phenols, and oils (Agbor et al. 2007; Ayoola et al.
2008; Duru and Onyedineke 2010; Tona et al. 1998). The
plant has a total alkaloidal content of about 9.2% in the root
bark, and 3.9% in the stem bark, with voacamine, voabasine,
voacangine, voacristine, vobtusine, and ibogaine being the
major indole alkaloids (Hedberg et al. 1982).
Since the 1980s, there has been a steady market for
V. africana seeds, and several hundred tons of these are
exported from Ghana and Cote D’Ivoire to pharmaceuti-
cal companies in France and Germany. V. africana seeds
gained recognition due to the high tabersonine content (Igbe
and Edike 2015). Tabersonine is used as a precursor for the
synthesis of vindoline, an anticancer agent (Kulagina et al.
2021; Lemos Cruz, Kulagina et al. 2021; Li et al. 2021).
The iboga alkaloid, ibogaine, has CNS activity (Kombian
et al. 1997), and is used in the treatment of drug addiction
(Jenks 2002). However, its isolation from the root bark of
Tabernanthe iboga (Jenks 2002) is fraught with difficulty
due to the low content of ibogaine as against increasing
demand. V. africana was therefore identified as an alterna-
tive source, because of its larger scale of cultivation, and
higher content of voacangine in the root and stem bark,
from which ibogaine can be semi- synthesized (González
et al. 2021). Over the last years, there have been few sum-
marized reviews on the biological activities, toxicity and
phytochemistry of V. africana, hence the relevance of this
review. Despite the widespread use of this plant, there still
exist gaps in the justification and validation of the relation-
ship between some of the ethnomedicinal uses and phar-
macological activities, as well as the bioactive compounds
responsible for some pharmacological activities, and the tox-
icity of the plant. Moreover in recent years, there has been
few summarized studies on the activities of this plant. This
review therefore covers the phytochemistry, ethnomedicinal
uses, pharmacological and, toxicity studies of V. Africana.
Plant description
V. africana is a small tree reaching up to 6 m in height
(Maurice 2014). It possesses opposite leaves which are
acuminate,obovate and up to 30 cm in length (Burkill 1985).
The leaves are often stalkless, and have a glossy dark green
color above, and green beneath. Its fruits are mottled green,
spherical and usually occur in pairs with seeds enveloped
in a yellow pulp (Maurice 2014). Seeds are numerous, dark
brown in colour, approximately 7–10 × 3.5–5 × 3–4 mm,
13
E. O. Bekoe et al.
obliquely ellipsoid, 4–5 grooves to its side, uneven and
microscopically tuberculate (Leeuwenberg 1985). Flowers
are white or pale yellow, and borne in axillary or loosely
branched glabrous inflorescences (Maurice 2014). It primar-
ily produces flowers at the end of the dry season (Leeuwen-
berg 1985), that is in the month of May, and starts bearing
fruit in July in Ghana (Brako–Danquah 2012). The bark of
the plant is smooth, and either pale or grey-brown and con-
tains a white latex. This plant is propagated by vegetative
cuttings and by seeds. The seeds are not viable because they
are desiccation sensitive and damaged by drying or freezing
(Kontoh 2008) after harvesting. Figure 1 displays images of
the various parts of V. Africana.
Phytochemistry
The medicinal properties of plants result from the presence
of different phytochemicals which are found as either pri-
mary or secondary plant metabolites in one or more parts of
the plant. V. africana is reported to contain flavonoids, alka-
loids, saponins, tannins, terpenes, steroids, phenols, and oils
which are important phytotherapeutic agents (Agbor et al.
2007; Tona et al. 1998). This plant is a reservoir of several
alkaloids, from which several pharmaceutically important
compounds can be synthesized (Adu et al. 2015). Ibogaine
can be semi-synthesized from voacangine sourced from the
bark of V. africana (Jenks 2002). Also through a precursor
directed synthesis, tabersonine from the seeds can be fed to
engineered yeast to also synthesize vindoline, a compound
found in Catharanthus roseus which has anti-cancer activity
(Kulagina et al. 2021; Lemos Cruz et al. 2021). The indole
alkaloids in this plant are known for their medicinal impor-
tance because they possess a wide range of biological activi-
ties (Koroch et al. 2009). These alkaloids have been sub-
categorized as monoterpenoid indole alkaloids, bisindole
alkaloids, iboga alkaloids and apidosperma-type alkaloids.
Quantitatively, the total amount of alkaloids in the leaves
of V. africana is estimated at 0.3–0.4%, trunk bark is 4–5%,
root bark is 5–10% and seeds are 1.5–3.5% (Brako–Danquah
2012; Maroyi 2008). Each part of the plant contains a variety
of these alkaloids and other secondary metabolites of which
some have shown significant biological activity.
The seeds contain: O-methyl-16-epi- Δ14-vincanol,
subsessiline, subsessiline lactone (Pegnyemb et al. 1999;
Rolland et al. 1976) vincamol, vincamone, ibogaine (Kom-
bian et al. 1997), 14- vincamone, 14- vincanol (Pegny-
emb et al. 1999), tabersonine (Stöckigt et al. 1982), voaf-
rine A and B, 3-oxotabersonine, 3α-acetonyltabersonine,
3α-acetonylvoafrine B, 3-oxovoafrine B, melodinine S
(Koroch et al. 2009; Zhao, Zhu, Ding et al. 2021), anthra-
noids, anthraquinone, cardiac glycosides, phenols, phlo-
batannins, starch and tannins (Duru and Onyedineke 2010).
The leaves contain vobtusine, voafolidine, voafoline,
Ethnomedicinal uses, biological activities, and toxicity of Voacanga africana Stapf Ex…
Fig. 1  Voacanga africana a. Fruit b. Lower leaf surface c. Flowers d. Upper leaf surface e. Stem bark
vobasine, vobtusine-lactone, deoxyvobtusine, vobtusine
3-lactam ­Nb'-oxide,, voaphylline, voacorine, voalfolidine,
voacanidine (Koroch et al. 2009; Maurice 2014), saponins,
cardiac glycosides, phlobatannins, terpenes, tannins, fla-
vonoids, and anthraquinone (Ayoola et al. 2008). The bark
contains: voacangine, voacristine, vobasine, voacamine, voa-
cangine 7-hydroxyindolenine, voacristine 7- hydroxyindo-
lenine, vobtusine (Diavara et al. 1984; Rao and John 1958),
voacafricine, ibogaine, voacafrine, voacamine, 20’hydroxyl-
voacamine, vacorine, voacamidine, voacryptine (Chen et al.
2016; Kombian et al. 1997; Koroch et al. 2009; Maurice
2014), anthraquinone, cardiac glycosides, saponins, tannins,
flavonoids and terpenes (Ayoola et al. 2008). Both the stem
bark and root bark contain iso-voacangine, ibogaine, vobas-
ine and traces of ibogamine and coronaridine (Krengel et al.
2020). Figure 2 displays the chemical structures of some
alkaloids known to be present in V. Africana.
Ethnomedicinal uses
In African traditional medicine, the seeds, roots, and bark
of V. africana have been used to manage a variety of both
infectious and non-infectious ailments. In Cote D’Ivoire for
example, V. africana is used to treat CNS-related conditions
such as convulsions in infants, psychosis and gastrointestinal
ailments such as diarrhoea, topical ailments, inflammatory
conditions (Bouquet and Debray 1974; Burkill 1985); Mau-
rice (2014).
Treatment of worm infestation
The bark of V. africana has been used to treat worm infesta-
tions in Congo, as well as for onchocerciasis in the northwest
region of Cameroon. Traditionally decoctions are prepared
from the bark for administration. Studies have highlighted
the effectiveness of this preparation in addressing both worm
13
 E. O. Bekoe et al.

Fig. 2  Chemical structures of alkaloids present in V. Africana

13
Ethnomedicinal uses, biological activities, and toxicity of Voacanga africana Stapf Ex…

Fig. 2  (continued)

13

Fig. 2  (continued)
infestations (Maroyi 2008; Tona et al. 1998). This same
preparation is also used to treat onchocerciasis in the north-
west region of Cameroon (Borakaeyabe et al. 2015). These
findings explore the potential role of V. africana in tradi-
tional medicine for managing parasitic infections and show
the need for further research of its therapeutic properties.
Treatment of Amoebiasis
In tropical regions, intestinal amoebiasis is one of the causes
of diarrhoea. In Congo, macerations of the root bark is
reported as used to treat amoebiasis (Tona et al. 1998). The
traditional usage of V. africana as an anti-amoebial treat-
ment against intestinal amoebiasis highlights its potential
as a valuable natural remedy in combatting amoebiasis and
managing diarrhoea.
Treatment of Ulcer
Cold water infusions of the seeds and fruits are taken to
treat internal sores and peptic ulcer in the West Africa
Countries of Cote d’Ivoire, Senegal, and Cameroon (Bis-
set 1985; Hedberg et al. 1982). Also, V. africana has been
shown to possess an anti-ulcer compound with histamine H2
receptor blocking activity (Tan and Nyasse 2000). Previous
studies have shown that the aqueous and methanol extracts
of V. africana bark possess anti-ulcer properties (Tan et al.
1997). Moreover, the plant's fruit aqueous extract demon-
strated cytoprotective characteristics in that it possessed
gastric anti-secretory properties similar to histamine recep-
tor blockers. Moreover, it exhibited cytoprotective and ulcer
healing effects by enhancing the gastric mucosal defenses,
leading to increased production of gastric mucus (Tan and
Nyasse 2000).
13
E. O. Bekoe et al.
Treatment of wounds
Traditional use of the plant's latex in wound management
further validates its efficacy in promoting wound healing
in regions such as Senegal and Nigeria (Igbe et al. 2015;
Olaleye et al. 2004). The flavonoid fraction of the meth-
anol extract of the leaves is reported to have remarkable
antioxidant and anti-inflammatory properties. Studies have
demonstrated its ability to scavenge free radicals and inhibit
carrageenan-induced edema in rats, emphasizing its poten-
tial in wound healing (Olaleye et al. 2004).These natural
polyphenolic compounds found in V. africana play a crucial
role in improving the healing process, managing inflamma-
tion, accelerating wound closure, and enhancing the appear-
ance of scars (Diagne et al. 2023). In Senegal and Nigeria,
the latex of the plant is used in the management of wounds
(Igbe et al. 2015; Olaleye et al. 2004).
Treatment of pain
In Senegal and Cote d’Ivoire, the locals use a decoction
made from the root and bark of V. africana to address vari-
ous types of pain. This traditional remedy is specifically
employed for painful hernias, providing relief for those suf-
fering from this condition (Bisset 1985; Houndjo et al. 2022;
Ighodaro et al. 2015; Joshua et al. 2017). Furthermore, the
decoction of V. africana is also consumed to alleviate pain-
ful menstruation and postpartum pain (Ighodaro et al. 2015).
Research has demonstrated that extracts from V. africana
can effectively reduce the inflammatory phases of pain, sug-
gesting that it has a beneficial impact on modulating inflam-
matory mechanisms (Olaleye et al. 2004). This potential for
pain modulation makes V. africana a valuable traditional
remedy for pain management in these regions.
Ethnomedicinal uses, biological activities, and toxicity of Voacanga africana Stapf Ex…
Treatment of cardiovascular conditions
In Tanzania, V. africana plays a significant role in man-
aging cardiovascular conditions. The use of its seeds is
reported for treating high blood pressure (Hedberg et al.
1982; Lovett et al. 2006), and a decoction of the bark or
root bark is administered orally to treat heart conditions
including cardiac spasms (Burkill 1985; Neuwinger 2000).
This plant is reported to he also used in combination with
other sister specie such as V. thouarsii (Babiaka et al.
2021). Furthermore, the bark decoction is consumed to
alleviate cardiac spasms (Neuwinger 2000). These diverse
traditional practices highlight the potential of V. africana
as an effective natural remedy for managing various car-
diovascular conditions.
Treatment of mental disorders
V. africana is used as a remedy for mental disorders. Its
root bark has been used in African traditional medicine to
address depression, psychiatric disorders, and potentially
neurodegenerative diseases (Akunne 2017; Houndjo et al.
2022; Joshua et al. 2017). Research has reported its thera-
peutic potential, with active components displaying neuro-
protective properties that may alleviate depressive symptoms
and modulate the pathological mechanisms associated with
mental disorders (Houndjo et al. 2022). However, further
research is needed to explore its direct effects on neurode-
generative diseases as it emerges as a fascinating natural
resource that needs extensive investigation to elucidate its
full therapeutic potential.
Treatment of diarrhoea
V. africana has been traditionally used to treat diarrhea
(Hussain et al. 2012). A decoction of the leaves is applied
as a wash to treat diarrhoea in Cote d’Ivoire (Maroyi 2008).
In Congo, Coast, Ghana, and Cameroon an aqueous extract
of the root bark is used against diarrhoea (Babiaka et al.
2020; Joshua et al. 2017; Tona et al. 1999). These findings
suggest the potential of V. africana as an effective treatment
for diarrhea and warrant further research.
Treatment of malaria
Decoctions derived from the plant's stem and leaves have
been traditionally employed to combat malaria (Ameyaw
and Duker-Eshun 2009; Burkill 1985; Joshua et al. 2017).
Additionally, the decoction of its seeds, leaves and roots has
been implicated in folk medicine as a remedy for malaria (Li
et al. 2021; Niu et al. 2016). These findings underscore the
potential of V. africana in fighting against malaria.
Treatment of fatigue
In Senegal and Cote D’Ivoire, V. africana is utilized as a
remedy for fatigue. A decoction of the leaves is consumed
as a tonic to alleviate fatigue (Bisset 1985; Ighodaro et al.
2015). The seeds are also reported as used for stimulating
nerves and reducing fatigue (Lovett et al. 2006). These tra-
ditional applications demonstrate the potential of V. africana
as a natural solution for combating fatigue and enhancing
overall energy levels. Further research is needed to fully
understand its mechanisms of action and validate its efficacy
as a fatigue-relieving agent.
Treatment of gynaecological conditions
V. africana demonstrates significant relevance in managing
gynaecological conditions, as evidenced by its traditional
uses in various regions. In Congo, the inner bark is skill-
fully prepared and mixed with porridge to address menstrual
problems (Maroyi 2008). Also, in Tanzania, a decoction of
the root is administered orally to treat dysmenorrhea (Burkill
1985). These observations lend support to the traditional
use of V. africana and underscore its promising role in the
management of gynaecological conditions.
Treatment of gonorrhea
V. africana fruits, bark and leaf extracts have been used in
Cameroonian ethnomedicine for the treatment of gonorrhea
(Babiaka et al. 2021; Joshua et al. 2017). Recent research
further supports its potential in managing this sexually
transmitted infection (Li et al. 2021). These findings pro-
vide insights into the potential role of V. africana as a natu-
ral remedy for gonorrhea, emphasizing the need for further
studies to explore its potential contributions to the treatment
of this infection.
Treatment of preterm and delayed labour
Preterm birth is a leading cause of neonatal mortality world-
wide, with Sub-Saharan Africa facing a significant burden
of related complications (Alamneh et al. 2021). In Senegal,
traditional medicine offers hope, utilizing a decoction from
the root of V. africana to combat the incidence of preterm
labour (Olaleye et al. 2004). Notably, women in Nigeria
employ a decoction of V. africana leaves as a local rem-
edy for birth control and other fecundity issues, highlight-
ing its potential fertility properties, which were found to
be comparable to the standard estradiol valerate (Li et al.
2021).Exploring this natural remedy could hold promise in
13

addressing preterm birth challenges and improving neonatal
health outcomes. In Eastern Cote D’Ivoire also, a decoction
of the leaves is administered as an enema or orally to stimu-
late labour when the pregnancy has lasted over nine months
(Malan and Neuba 2011).
Treatment of bronchitis
V. africana is a treatment option for bronchitis, with its
twigs being reported utilized in an infusion to combat the
condition effectively (Maroyi 2008). This natural approach
manages bronchitis and offers an alternative remedy. Further
research is needed to understand its therapeutic properties in
enhancing respiratory health.
Treatment of kidney conditions
In both Cote D’Ivoire and Cameroon, V. africana as tra-
ditional medicine to treat kidney conditions. The method
involves preparing a decoction from the plant's root in Cote
D’Ivoire and from the bark in Cameroon, which is then
orally administered for the treatment of kidney-related ail-
ments. Numerous studies have documented the use of V.
africana in these regions for managing kidney conditions
(Brako–Danquah 2012; Maroyi 2008; Neuwinger 2000).
The traditional use of this plant highlights its potential as
a medicinal resource for kidney-related issues and empha-
sizes the importance of further scientific investigation to
determine its efficacy and safety in treating such health
conditions.
Treatment of carious teeth
In Nigeria, the abundant latex of V. africana is applied to
remedy carious teeth (Joshua et al. 2017; Neuwinger 2000;
Olaleye et al. 2004). This traditional practice reflects the
potential use of V. africana in managing carious teeth and
highlights its relevance in traditional oral healthcare prac-
tices. Further investigation may shed light on the effective-
ness and potential benefits of this natural remedy for dental
health.
Treatment of asthma
A decoction from the leaves is reported as used for asthma
in children (Joshua et al. 2017; Neuwinger 2000). Further
13
E. O. Bekoe et al.
research is needed, however this preliminary finding sug-
gests possible therapeutic benefits for managing asthma
symptoms.
Convulsions
Empirical reports have indicated that V. Africana is
used in Cameroon to treat diseases related to the brain:
epilepsy, pains, anxiety, sleep, dizziness, headaches,
and migraine (Bum et al. 2009b; Ighodaro et al. 2015).
The extract obtained from the leaves or stem bark of V.
Africana is utilized to alleviate convulsions in children
(Ighodaro et al. 2015). Research has shown that V. afri-
cana extracts, demonstrated anticonvulsant effects in ani-
mal models by prolonging the time it took for convulsions
to occur (Bum et al. 2009a) This indicates its protective
effects against convulsions and delays it. Empirical
reports have indicated that V. Africana is used in Came-
roon to treat diseases related to the brain: epilepsy, pains,
anxiety, sleep, dizziness, headaches, and migraine (Bum
et al. 2009a; Ighodaro et al. 2015). These findings make
V. africana a valuable candidate for further investigation
as a natural remedy for managing convulsions. Thus,
additional research, including clinical trials is needed to
explore its safety and efficacy in treating convulsive dis-
orders and to better understand the mechanisms underly-
ing their anticonvulsant effects.
Oedema
Oedema is a symptom of several disorders, including can-
cer, heart failure, cirrhosis, and nephrotic syndrome. Con-
ventional methods of treatment include limiting dietary
salt intake, employing diuretics and anti-inflammatory,
while adding specific therapies for each clinical disorder
(O’Brien 2005). Among these, V. Africana, has shown
promise in potentially treating oedema. The methanol
extract of the V. Africana leaves have been shown to
inhibit inflammation by reducing the synthesis of muco-
polysaccharide and collagen, as well as the number of
fibroblasts and vascular permeability which could play a
significant role in reducing oedema (Olaleye et al. 2004).
The stem bark has been used in combination with the
sister species V. thouarsii in the treatment of generalized
oedema in Ivory Coast, Cameroon, Ghana and Congo
(Babiaka et al. 2021).
Ethnomedicinal uses, biological activities, and toxicity of Voacanga africana Stapf Ex…
Biological activities
In-vivo and in-vitro studies conducted on the plant extracts,
and some of its isolated alkaloids have exhibited the follow-
ing activities: anthelmintic (Adu et al. 2015), anti-amoebic
(Koroch et al. 2009), anti-ulcerogenic (Tan and Nyasse
2000; Tan et al. 2000), anti-diarrhoeal (Lo et al. 2011), anti-
microbial (Duru and Onyedineke 2010), anti-inflammatory
(Olaleye et al. 2004), analgesic (Olaleye et al. 2004) (Igbe
and Edike 2015), cardiovascular (Omodamiro and Nwankwo
2013), CNS (Kombian et al. 1997), sedative (Omotayo et al.
2019), anti-depressant (Owolabi, Ezenwa, Amodu et al.
2019), anti-oxidant (Ayoola et al. 2008), anti- onchocercal
(Babiaka et al. 2021) and anti-filarial (Borakaeyabe et al.
2015) activities of which some have scientifically validated
their corresponding ethnomedicinal uses. The plant parts
mostly investigated were the leaves, stem bark, root bark,
and seeds which were extracted with either water, ethanol,
or methanol to obtain crude extracts. From the information
obtained, the bark was the plant part mostly used in the
studies, followed by the leaves and the seeds. The bioac-
tive phytoconstituents responsible for the anti-helminthic,
anti-amoebic, anti-ulcerogenic, analgesic, cardiovascular,
anti-depressant, anti-microbial, sedative, anti-inflammatory,
and anti-oxidant activities have not yet been identified. The
anti-helminthic, anti-amoebic, anti-ulcerogenic, analge-
sic, cardiovascular, anti-depressant, anti-diarrhoeal, anti-
onchocercal, CNS and anti-microbial investigations go some
way to validate their corresponding ethnomedicinal uses as
detailed in Table 1. Voacangine, voacamine and tabersonien
were also as identified bioactive compounds responsible for
the antifilarial, anti-diarrhoeal, anti-tumor and anti-filarial
activities respectively of V. africana (Borakaeyabe et al.
2015). Table 1 displays a summary of investigated biological
activities of V. africana extracts and other identified bioac-
tive compounds.
Toxicological studies
The aqueous and ethanolic leaf extracts, as well as the meth-
anol root extract have been investigated for toxicity. The
sub-acute toxicity of the aqueous leaf extract administered
at 800 mg/kg per os in rats showed no observable toxic-
ity. The ethanolic leaf extract was also reported to be non-
toxic orally with no mortality recorded at the highest dose
of 5000 mg/kg (Omotayo et al. 2019). Cytotoxic activity is
also reported against several tumour cell lines (Table 2). The
LD50 of the methanolic root bark extract was estimated as
1250 mg/kg (Akunne et al. 2017). Table 3 displays details of
toxicity studies of V. africana extracts and some associated
bioactive compounds such as vobtusin, voacangine and voa-
camine which have been reported to have cardiac depressor,
asphyxia and cardiac toxicity.
Conclusion
The various parts of V. africana, root, bark, stem, leaves,
seeds, and fruits are used in the treatment of a myriad of
diseases. The methanolic, hydro-ethanolic and ethanolic
extracts of the t extracts of V. africana have shown some
experimental biological activities which supports the folk-
loric use of the plant in the treatment of worm infestation,
amoebiasis, ulcer, depression, diarrhoea, onchocerciasis,
cardiovascular conditions, mental disorders, pain, and
microbial infection. However these as yet have not been
linked to specific bioactive constituents. Studies aimed at
isolating bioactive compounds from this plant, have mainly
focused on the alkaloidal components. To the best of our
knowledge, there are few biological studies on this plant to
validate the ethnomedicinal uses in the treatment of fatigue,
shortness of breath, gynaecological conditions, delayed
labour, kidney conditions, convulsion, carious teeth, malaria,
asthma, and bronchitis, hence additional studies are needed
in that respect. Sub-acute toxicity studies on leaf extracts
showed no toxicity in Albino Wistar rats. In the acute toxic-
ity studies, ­LD50 of the methanolic and ethanolic extracts in
animal models were 1250 mg/kg and ≥ 5000 mg/kg respec-
tively indicating that the ethanolic extract is relatively non-
toxic as compared to the methanol extract. Individual alka-
loids from this plant have also shown been reported to have
toxic effects; vobtusine exhibits cardiac depressor activity
and induces peripheral vasodilation resulting in hypoten-
sion with the possibility of convulsion and death by large
doses of vobtusine. Asphyxia and convulsions are known to
be caused by high doses of voacangine. Voacamine showed
toxicity of about one third of digitalin. High doses of voa-
camine can cause hypertension and depress the CNS, hence
caution need to be exercised in the use of this plant and its
constituents. Additional studies are needed on the mecha-
nism of action of the bioactive compounds and toxicity and
the relationship that exist between them to produce more
information on their potential therapeutic activity and their
use as precursors for drug synthesis.
13
 Table 1  Biological activities of V. africana extracts
Bioactivity Plant part /Solvent Method Results Bioactive compound(s) Reference

13
Anti-helminthic Leaves, Bark/Methanol Anti-helminthic activity against The bark demonstrated a con- not determined (n.d) (Adu et al. 2015)
Pheretima posthuma centration dependent effect
with decreasing paralytic and
death times. The paralytic and
death times at concentrations
of 30, 40 and 50 mg/mL with
reference to albendazole was
significant (p < 0.001)
Anti-amoebic Root-bark/Water Anti-amoebic activity against E. Extract showed MIC at 62.5 µg/ n.d (Tona et al. 1998)
histolytica mL, but less active in compari-
son to metronidazole
Anti-ulcerogenic Fruit/Alkaloidal extract Pylorus ligated-rat model The extract insignificantly n.d (Tan and Nyasse 2000)
reduced gastric juice acidity
but prevented gastric mucosal
damage
Fruit/Alkaloidal extract Male Wistar rats model Oral administration of the extract n.d (Tan and Nyasse 2000) (Tan et al.
to male Wistar rats significantly 2000)
improved healing of chronic
ulcers induced caused by
acetic acid, and prevented the
formation of gastric injuries
induced by absolute-ethanol,
indomethacin-HCl, HCl-
ethanol, ethanol, cold restraint
stress, and pylorus ligation. The
alkaloidal extract had gastric
anti-secretory effects similar to
histamine receptor blockers
Analgesic Leaves/Methanol Hot plate test in mice Oral administration of vary- n.d (Olaleye et al. 2004)
ing doses of leaf extract from n.d (Igbe and Edike 2015)
50-150 mg/kg increased in n.d
reaction time
Leaves/Methanol Acetic acid-induced writhing in Oral administration of leaf
mice extract reduced the frequency
of writhing and stretching
movement. This anti nocicep-
tive effect of the extracts was
most pronounced at dose of
150 mg/kg
E. O. Bekoe et al.
 Table 1  (continued)
Bioactivity Plant part /Solvent Method Results Bioactive compound(s) Reference

Leaves/Methanol Formalin-induced paw licking Leaf extract caused dose-

in mice dependent inhibition of both
the neurogenic phase and the
inflammatory response phase
of formalin-induced pain. The
inhibitory effect was significant
at 150 mg/kg dose
Leaves/water Acetic acid induced writhing in The leaf extract showed a notable
Swiss albino mice dose-dependent reduction in
writhing at 100 mg/kg, 200 mg/
kg and 400 mg/kg
Leaves/Water Hot plate test in Swiss albino rats The leaf extract increased latency (Igbe and Edike 2015)
time at 200 mg/kg and 400 mg/
kg
Cardiovascular Leaves/Water Albino Wistar rats 75 mg/kg body weight decreased n.d (Omodamiro and Nwankwo 2013)
LDL cholesterol and 125 mg/
kg increased HDL cholesterol
levels
Anti-depressant Stem bark/Water Tail suspension test The extract showed significant n.d (Owolabi et al. 2019)
anti-depressant effect after
oral administration at doses
of 50 mg/kg, 100 mg/kg and
200 mg/kg compared to the
Ethnomedicinal uses, biological activities, and toxicity of Voacanga africana Stapf Ex…

control
Root- bark/ Methanol Forced Swimming test Extract showed abolition of n.d (Akunne et al. 2017)
depressive-like behavior in a
dose-dependent manner. Extract
400 mg/kg and amitriptyline
15 mg/kg showed the highest
reduction in immobility time
Anti-diarrhoeal Rootbark/Methanol Capsaicin-induced contractions The extract showed a significant n.d (Lo et al. 2011)
in isolated mouse rectum inhibitory effect in a concen-
tration-dependent manner at
30–300 µg/mL
Root bark/Alkaloidal extract Capsaicin-induced contractions The isolated alkaloids showed Voacangine, Voacristine, 3-Oxo- (Lo et al. 2011)
in isolated mouse rectum a more significant inhibitory voacangine, 7α-Voacangine (Hussain et al. 2012)
effect in the capsaicin-induced Hydroxyindolenine
contraction in a dose-dependent
manner at 3–100 μM
Ibogaine (Kombian et al. 1997)

13
 Table 1  (continued)
Bioactivity Plant part /Solvent Method
13
Anti-onchocercal Stem-bark/Isolated alkaloids Isolated cattle derived O. ochengi At 30 µM drug concentration, the Voacangine, Voacamine,
worms
CNS activity Leaves, Stem /Methanol Cell-based screening assay
relevant to Alzheimer’s disease
[in-vitro ischemia, oxytosis,
intracellular amyloid toxicity,
inhibition of microglial activa-
tion and PC12 cells differentia-
tion
Seeds/Methanol Spraque-Dawley rat coronal pon- The extract showed a postsynap-
tine slices using the nystatin-
perforated patch whole-cell
technique
Root bark/Methanol Phenobarbitone induced sleeping The extract also significantly
time in mice
Results Bioactive compound(s) Reference
(Babiaka et al. 2021)
isolated compounds were active Voacamine A, Voacorine, (Borakaeyabe et al. 2015)
against O. ochengi microfilae Iboxygaine, Voacristine And
and adult male worms in a con- Coronaridine
centration-dependent manner,
but were only averagely active
on the adult female worms. The
­IC50 values of the isolates are
2.49–5.49 µM for microfilariae
and 3.45–17.87 µM for adult
males
The leaves and stem extracts Voacamine (Currais et al. 2014)
showed the highest EC50 in the
following phenotypic screen-
ing assays: in-vitro ischemia,
oxytosis, intracellular amyloid
toxicity, and inhibition of
microglial activation in com-
parison with the bark extract
but it did not induce PC12
activation
tic effect, depolarizing parabra-
chial neurons and enhancing
excitability and firing rate by
depressing the non-NMDA
receptor- mediator for rapid
excitatory synaptic transmis-
sion in the parabrachial nucleus
(Akunne et al. 2017)
(p < 0.05) and dose depend-
ently, potentiated the onset of
sleep and duration of sleep
in phenobarbitone induced
sleeping time. At 400 mg/
kg the extract almost doubled
the duration of sleep while
diazepam (3 mg/kg), a standard
agent, tripled the same param-
eter
E. O. Bekoe et al.
 Table 1  (continued)
Bioactivity Plant part /Solvent Method Results Bioactive compound(s) Reference

Leaves/50% Ethanol Ketamine-induced sedation in
mice
Phenobarbitone-induced sedation The extract decreased the onset
in mice model
Anti-microbial Seeds/70% Ethanol Disc diffusion technique
Seeds/Hot Ethanol Disc diffusion technique
Extract significantly increased n.d (Omotayo et al. 2019)
both onsets of sleep and sleep-
ing time in a dose-dependent
manner at 100–800 mg/kg.
Duration of sleep was short as
compared to phenobarbitone-
induced sedation. Extract
showed rapid action of sedative
effect in mice
n.d (Omotayo et al. 2019)
of sleep and caused a signifi-
cant increase in sleeping time,
implying the extract possesses
good CNS depressing activity
E. coli, P. aeruginosa, S. marc- n.d (Duru and Onyedineke 2010)
escens and S. aureus were less
sensitive at 100 and 200 µg/mL
compared to gentamicin
C. albicans, A. flavus, A. niger, A. n.d
solani, and R. stolonifer were n.d
less sensitive to extract at 100
and 200 µg/mL compared to
clotrimazole
Ethnomedicinal uses, biological activities, and toxicity of Voacanga africana Stapf Ex…

E. coli, P. aeruginosa, S. marc-

escens and S. aureus were less
sensitive to extract at 100 g/
mL and 200 g/mL compared to
gentamicin
Seeds/Cold Ethanol Disc diffusion technique C. albicans, A. flavus, A. solani, n.d
and R. stolonifer were less
sensitive to extract and at 100
and 200 µg/mL compared to
clotrimazole
Bark/Cold ethanol Disc diffusion technique E. coli, S. marcescens, and P. n.d (Christopher, Uchechukwu and
notatum were sensitive to n.d Ernest 2009)
extract
Bark/Hot Water E. coli, S. marcescens, S. aureus,
A. niger and P. notatum were
sensitive to extract
Anti-inflammatory Leaves/Methanol Carrageenan-induced paw Significant inhibition of oedema n.d (Olaleye et al. 2004)
oedema in rats was observed with oral pretreat-
ment of l0-150 mg/kg of extract

13
 Table 1  (continued)
Bioactivity Plant part /Solvent Method Results Bioactive compound(s) Reference

13
Cotton pellet granuloma The extract reduced granuloma n.d
tissue formation in rats in a
dose-related manner at all doses
from 50 to 150 mg/kg
Leaves/Methanol Acetic acid-induced vascular At 50 -150 mg/kg, the extract n.d (Olaleye et al. 2004)
permeability reduced the degree of perito-
neal inflammation resulting in
a significant reduction in dye
leakage indicating anti-inflam-
matory activity, more especially
at the highest dose
Anti-tumor Seeds/Methanol MTT assay Amongst 6 compounds isolated Tabersonine (Li et al. 2021)
from the plant, tabersonine
exhibited remarkable cytotoxic
activity with an ­IC50 value
on 10 types of human cancer
cell lines range from 0.4 mg/
mL to 22.5 ± 1.4 µmg/mL. The
cytotoxicity of tabersonine is
thought to be through apoptosis
induction
Anti-filarial Stem bark/Methanol Motility and viability assay of O. Voacangine and voacamine iso- Voacamine, Voacangine (Borakaeyabe et al. 2015)
ochengi and Loa loa worms lated from the stem bark were
found to inhibit the motility of
both the microfilariae (Mfs) and
adult male worms of O. ochengi
in a concentration-dependent
manner, but were only mod-
erately active on the adult
female worms at 30 µM drug
concentration. The ­IC50s for
voacangine were 5.49 µM for
Mfs and 9.07 µM for adult male
worms; while for voacamine
the values were 2.49 µM for
Mfs and 3.45 µM for adult
males. At 10 µM, voacamine
showed 100% inhibition of Loa
loa Mfs motility after 24 h
E. O. Bekoe et al.
Ethnomedicinal uses, biological activities, and toxicity of Voacanga africana Stapf Ex…
Table 2  Summary of toxicity studies on V. africana extracts
Test Model
1. Sub-acute toxicity Albino Wistar rats
2. Acute toxicity Murine
Swiss male albino rates
3. Cytotoxicity Bioassay against HEPG-2, A375,
MDA-MB-231, SH-SY5Y, and
CT26 tumor cell lines
Plant part/ Solvent Effect Reference
Leaves/ Water All doses [100 mg/kg, 400 mg/kg, (Ighodaro et al. 2015)
and 800 mg/kg] of the extract did
not significantly alter the blood
biochemistry after oral administra-
tion. The extract had no harmful
effect on liver function. Also, no
noticeable alterations occurred
on liver enzymes and proteins
except ALP which revealed a
drastic decrease at 100 mg/kg,
and 800 mg/kg. Compared to the
control, there was a decrease in
the pattern of weight gain in the
female albino rats at all concentra-
tions. No pathological change was
shown on the histological studies
with the liver, spleen, heart, and
lungs
Root bark/ Methanol LD50 of the extract was estimated as (Akunne et al. 2017)
1250 mg/kg per oral in mice
Leaves /Ethanol No mortality was recorded, LD50 of (Omotayo et al. 2019)
the extract was estimated to be ≥
5000 mg/kg
Bark/ Ethyl acetate Voacamine displayed noticeable (Chen et al. 2016)
cytotoxic effect on all tumor cell
lines. Vobasine showed average
cytotoxicity effect on all tumor
cell lines: HEPG-2, A375, MDA-
MB-231, SH-SY5Y, and CT26
[ IC50 = 19.3 µg/mL, 19.5 µg/mL,
25 µg/mL, 19 µg/mL and 20 µg/
mL] respectively. Voacristine
showed average cytotoxic effect
on all tumor cell lines with IC50 =
20 µg/mL. Voacangine displayed
average cytotoxic effect against
A375 and CT26 with IC50 =
14 µg/mL and 11 µg/mL] respec-
tively and noticeable cytotoxic
effect against HEPG-2, MDA-
MB-231, and SH-SY5Y with
IC50 = 10 µg/mL, 8.0 µg/mL and
7.6 µg/mL] respectively
13
 E. O. Bekoe et al.

Table 3  Toxicological studies on isolated alkaloids from V. Africana

Alkaloid Plant part Model Effect References

1. Vobtusine Leaves Mice Vobtusine exhibited cardiac depressor activity and induced peripheral (Hussain et al. 2012)
vasodilation resulting in hypotension. The intravenous LD50 of vob- (Rolland et al. 1976)
tusine for mice was approximately 34 mg/kg. Convulsion and death
was also reported with large doses of vobtusine
2. Voacangine Bark Mice Asphyxia and convulsions are reported to be caused by high doses (Maurice 2014)
of voacangine. The LD50 of voacangine by intravenous injection in (Koroch et al. 2009)
mice was 41– 42 mg/kg
Guinea pig The lethal dose of the salt of voacangine sulphate given by direct (Maurice 2014)
infusion into the jugular vein was reported as 348 mg/kg
Roots Isolated rabbit auricle Voacamine showed toxicity of about one third of digitalin (Macabeo, Alejandro,
Hallare et al. 2009)
3. Voacamine Bark Guinea pig High doses of voacamine reportedly caused hypertension due to (Maurice 2014)
peripheral vasoconstriction and CNS depression (Koroch et al. 2009)
Roots Isolated rabbit auricle Voacamine showed toxicity of about one third of digitalin on the (Macabeo et al. 2009)
cardiac system
Roots Mice The camphor sulfonate derivative of voacamine was compared to (Macabeo et al. 2009)
voacamine sulfate salt and the intravenous LD50 of the respective
alkaloidal salts in mice was 46.2 mg/kg and 21.5 mg/kg respec-
tively

Acknowledgements The authors declare that they did not receive any
financial support for this work.
Authors’ contributions All authors contributed to the study conception
and design. Data collection, analysis and the first draft of the manu-
script was were performed by OJAA and EOB. EOB, PA and ML were
responsible for the biological, toxicity and the phytochemical sections
respectively and did the final editing. All authors read and approved
the final manuscript.
Funding The authors declare that this study has no funding.
Declarations
Ethical approval This article does not contain any studies involving
animals performed by any of the authors. This article does not con-
tain any studies involving human participants performed by any of
the authors.
Competing interests Emelia Oppong Bekoe has no conflict of interest.
Jochebed A. Amene Opare has no conflict of interest. Michael Lartey
has no conflict of interest. Patrick Amoateng has no conflict of interest.
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