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Review of Ethnomedical, Phytochemical and Pharmacological Studies of

Zanthoxylum Zanthoxyloides

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Review of Studies Onzanthoxylum Zanthoxyloids (Lam):

Availability and Ethnomedical, Phytochemical,
Pharmacological Uses
F. Guendéhou1*, B. A. Djossa2 C. Kènou1 et C. A. E. Assogbadjo1
1
Laboratoire d’Ecologie Appliquée (LEA), Faculté des Sciences Agronomiques (FSA)/ Université d’Abomey-Calavi
(UAC), 01 BP 526 Recette Principale, Cotonou 01, République du Bénin.
2
Laboratoire de Foresterie et de Conservation des Bioressources (LaFCBio), École de Foresterie Tropicale (EForT),
Université Nationale d’Agriculture (UNA), BP 43, Kétou, BP 910 Abomey-Calavi, République du Bénin.
*Auteur correspondant : gferdi4@yahoo.fr

Abstract
The conservation, the availability and exploitation of multiple use plants mainly medicinal
ones are always of high concern of natural resources and biodiversity managers.
Zanthoxylum zanthoxyloides (Rutaceae) is a multipurpose plant widely distributed in a
variety of habitat and stations throughout its distribution range. It was reported be
recalcitrant and low natural regeneration in its habitats. Local communitiesuse it to heal
many diseases in tropical areas including digestive disorders, toothache, abdominal pain,
sickle cell disease, snake bites, etc. This article reviews previous works conducted on the
phytochemical, pharmacological and toxicological studies of this plant. Many traditional
uses of this plant have been validated with nowadays researches. To date, several
bioactive compounds, including tannins, saponins, sterols, glycosides, polyterpenes,
polyphenols, flavonoids and alkaloids have been isolated from its extracts. These various
compounds possess anti-inflammatory and analgesic, antibacterial, anti-sickle cell,
antihypertensive, anti-plasmodic, anthelmintic, and insecticidal effects. However, further
studies are needed to document the mechanisms of action of these different compounds
and their clinical effects. Although all these recognized values, the plant’s propagation and
domestication is poorly mastered and much need to be done to make it available for
present and future needs. Apart from this weak point, it is also necessary to assess this
plant’s availability and distribution as well as the use pressures in Benin. Then, the
conservation status will be analysed accordingly.
Keywords: Traditional medicinal uses; Chemical compounds; Pharmacology, Benin.
1. Introduction
With nearly 200 species distributed in the warm and tropical regions of the world, mainly in Africa, North and South
America, Asia and Australia, Zanthoxylum is the most abundant genus in the Rutaceae family (Groppoet al., 2012). It is
represented by trees, monoecious or dioecious shrubs, the trunk, twigs and leaves are often thorny. The bark of the wood
is yellow, fragrant and sometimes spicy.
The genus Zanthoxylum is of great ethnobotanical importance and is used as a source of pharmaceutical and cosmetic
raw materials (Patiñoet al., 2008; Negi et al., 2011). Several species of Zanthoxylum are used in different parts of the
world mainly in Africa and Asia to treat a number of diseases in humans and animals (Diéguez-Hurtadoet al., 2003;

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Adesina, 2005; Rochfort et al., 2008; Pereira et al., 2010). It has also been shown that some of its species possess
pharmacological properties of interest including anti-tumor, anti-leukemic, antimicrobial (de Mouraet al., 1997;
Nissankaet al., 2001), antibacterial (de Abreu et al., 2003), anti-HIV (Chenget al., 2005), antimalarial (Jullianet al.,
2006), trypanocides (Ferreiraet al., 2007). Extracts of these plants of the genus Zanthoxylum are used commercially as
dyes for tissues (Cucaet al., 1998) and as piquant spices in some cooking recipes (Xionget al., 1995).
In Africa, this plant is used especially in the treatment of sickle cell disease (Ouattaraet al., 2004), inflammatory and
painful pathology (Larsenet al., 2015).With a study in Burkina Faso it has been reported that many species of great
socioeconomic importance including Z. zanthoxyloïdes are difficult to conserve and to promote because of the short
lifespan of their seeds (Ouédraogo et al. 1996). Moreover, there is little information about their propagation, germination
and storage, making it difficult to grow and plant these species. Low germination of Z. zanthoxyloides seeds might be
because of seed immaturity or dormancy problems. Improvements (2 to 37%) in seed germination of Z. zanthoxyloides
under various storage conditions (moisture content and temperature) suggest that removal of dormancy may have
occurred. All these results indicate that there is a need to investigate in detail the stages of maturity and optimum
conditions for germination and storage of these seeds.
Unfortunately, up to now different attempts to propagate the plant by classical approaches have been poorly successful
and natural regeneration through seed has been shown to be difficult (De La Mensbruge, 1966; Couillerot, 1994). Several
micropropagation techniques such as somatic embryogenesis, organogenesis and axillary shoot proliferation have been
applied for in vitro propagation of woody plants.
Due to the pharmacological value of Z. zanthoxyloïdes highlighted by several pharmacological, phytochemical and
toxicological studies, it is necessary to better understand the growing interest of Z. zanthoxyloïdes for a better
valorisation of this species. In this context, the literature review presented in this article intends to report currently
available data on Z. zanthoxyloïdeswith regard to its conservation. The objectives of this work were to make the state of
knowledge through researches conducted on Z. zanthoxyloïdes in ethnomedical, phytochemical, pharmacological,
toxicological, genetic fields but also the conservation status and domestication possibilities, and to highlight the
unexplored potential of this plant species.
2 Materials and Method
To report scientific knowledge on Z. zanthoxyloïdes, a literature review was conducted. Scientific articles, dissertations
and theses dealing with targeted species have been exploited and synthesized. A total of 43 articles published from 2001
to 2013 were selected. From these, 21 were published in Benin and 22 in other countries such as Cameroon (3), Nigeria
(6), Togo (2), Ghana (6), Côte d'Ivoire (1) and Mali (2) and Burkina Faso (2). These exploited materials were obtained
via free searching engines (www.google scholar; www.google.com; www.academicjournals.org;
www.aginternetwork.net) and some directly from their authors via internet or directly. The research was done using
keywords such as: Z. zanthoxyloïdes, indigenous knowledge, ethnobotany, ethnopharmacology and ecology, Benin, West
Africa, Central Africa, etc.
3. Results
3.1 Botanical Description
Z. zanthoxyloïdes (Lam.) Zepernick and Timlerm (1981) (Synonyms Fagara zanthoxyloïdes Lam., Zanthoxylum
senegalense DC, Zanthoxylum polyganum Schum.) (Rutaceae) is a tree 6 to 12 m tall. The gray-beige bark has a rough
surface with large, sharply curved, sharp, claw-shaped prickles. The spines are located everywhere on the stem, the
branches at regular intervals. The spine and sometimes the midrib bear large curved spines. The leaves are alternate,
compound and imparipinnate with a petiole of 2 to 5 cm rachis more or less cylindrical or flattened, canaliculate,
garnished with prickles. They include 5 to 9 pairs of opposite, sub-opposite or alternate glabrous leaflets up to 6 cm; an
acute limb at the base, of a leathery consistency with margin edged above; median vein depressed above, strongly
protruding below, very often garnished with prickles on both sides. The white or green flowers are 5-6 mm in diameter,
and are stamens with five petals that are barely open. The fruits, which are usually between 5-6 mm in diameter, are
capsules that open with two valves and contain a single seed of a beautiful shiny black. The stems are in the form of
cylindrical fragments 3 to 5 cm in diameter. The wood is light yellow and very hard.
3.2 Habitat, Diversity and Geographical Distribution
Zanthoxylum is pantropical and comprises about 200 species, with tropical America being richest in species. Mainland
Africa harbours about 35 species, whereas about 5 species are endemic to Madagascar. Several other Zanthoxylum
species are medicinally used in West Africa. Zanthoxylum atchoum (Aké Assi) P.G.Waterman is endemic to Côte
d’Ivoire. Zanthoxylum chevalieri P.G.Waterman (synonym: Fagara pubescens A.Chev.) occurs from Guinea east to
Ghana.
Zanthoxylum viride (A.Chev.) P.G.Waterman occurs from Guinea east to Cameroon.

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Z.zanthoxyloïdes is a woody plant present in the savannah of West Africa and in coastal areas from Senegal to Nigeria
and Cameroon (Adjanohounet al., 1979; Hawthorneet al., 2006). The plant is present on well-drained soils and is
generally found at low altitude (Matu, 2011). Based on these distribution habitats and soil conditions, this woody plant is
expected to be quiet well distributed in Benin. As its uses are widely reported in Benin, it will be pertinent to evaluate its
availability in Benin and also the use intensity in order to infer on its conservation status in Benin.
3.3 Natural Regeneration and Propagation
Traditionally, Zanthoxylum species are propagated through seeds, stems and root cuttings. Seeds of many species of
Zanthoxylum have been found to have low germination rates. The successful micro-propagation of Z. zanthoxyloïdes has
also been reported by Etsèet al. (2011). Z. zanthoxyloïdes is considered an endangered species, due to uncontrolled
harvesting methods and growing interest in the plant's pharmacological properties (Etsèet al., 2011).
Unfortunately, up to now different attempts to propagate the plant by classical approaches have been poorly successful
and natural regeneration through seed has been shown to be difficult (De La Mensbruge, 1966; Couillerot, 1994). Several
micropropagation techniques such as somatic embryogenesis, organogenesis and axillary shoot proliferation have been
applied for in vitro propagation of woody plants. Among these methods, axillary shoot proliferation is the most widely
used (Jain & Häggman, 2007). Adventitious root formation is essential for successful vegetative propagation of many
woody plants. However, in several tree species, rooting is a major limiting factor. There are very limited reports on
micropropagation of plants of Zanthoxylum genus. Hwang (2005) reported on multiplication of Z. piperitum through
shoot-tip explant cultures using 0.5 mg/L 6-benzylaminopurine (BA) for shoot proliferation. The author achieved root
induction by transferring the shoots to the same basal medium containing 2 mg/L indole butyric acid (IBA). Due to
insufficiency of Z. zanthoxyloides in the wild and the ever-increasing demand, vitro culture techniques have even been
developed to overcome propagation problems.
All these quiet sophisticate techniques are not usable by rural peoples who are more attached to this plant uses for many
different needs including the healing of so many diseases. With the current needs and demand of Z. zanthoxyloidesand
the well documented difficult regeneration problems, it is worthy to research on other propagation techniques that could
be more usable in rural communities of developing countries like Benin so that the domestication and long term
conservation of this multipurpose plant will be conserved for current and future uses.
3.4 Ethnomedical Uses
Z. zanthoxyloïdes is widely known in Africa for its various uses in traditional medicinal practices. It is widely used in
many ailments such as deworming, toothache, sexual weakness (Chaaib et al., 2003; Adesina, 2005; Queiroz et al.,
2006). A decoction of bark of Z. zanthoxyloïdes is used in Mali to control hypertension, this effect is attributable to the
presence of flavonoids in the extracts of this plant species (Malgras, 1992; Andersson et al., 1996). The water extracts of
the plant have also shown significant activities against bacteria related to periodontal diseases (Rotimiet al., 1988;
Taiwoet al., 1999). Root bark extract is used in the treatment of elephantiasis, toothache, sexual impotence, gonorrhea,
malaria, dysmenorrhea and abdominal pain and snake bites (Adjanohoun et al., 1989; Anokbonggoet al., 1990;
Adjanohounet al., 1993). Similarly, the root bark of Z. zanthoxyloïdes is traditionally used in the treatment and
prevention of sickle cell disease (Sofowora et al., 1974; Kouri, 2004) and is known for its antiflammatory properties
(Ouattara et al., 2004). An anti-sickle cell phytomedicine called FACA® was developed from the root bark of Z.
zanthoxyloïdes in association with that of Calotropis procera (Asclepiadaceae) with numerous pharmacological and
toxicological studies.
In Mali, the roots of Z. zanthoxyloïdes are also used against dysmenorrhoea (Sanogo, 2011). In addition, the roots of Z.
zanthoxyloïdes are used for the treatment of chest pain, pain and heart palpitations (Hodouto, 1990).
In Côte d’Ivoire a leaf decoction as used as a mouth-wash to soothe toothache, or leaves are chewed. Pulped leaves are
also applied to leprous sores, and a bark decoction is taken orally. Crushed root bark is applied as an enema to treat
gonorrhoea. Pulped roots are used in embrocation to treat head-ache, rheumatic, lumbar and intercostal pain. Bark
macerated in wine or a bark decoction is drunk as an aphrodisiac and to treat venereal diseases. A bark decoction is also
taken to treat intestinal worms and dysentery. Crushed bark is applied to scabies. It is a good bee-plant as the flowers
produce large quantities of nectar. The wood can be used in cabinet work, although the pieces are usually small. The
strong-smelling roots are sniffed as an emmenagogue. It is a good bee-plant as the flowers produce large quantities of
nectar.
In western Côte d’Ivoire powdered leaves are used as a snuff to treat migraine.
In Nigeria, Z. zanthoxyloïdes stem bark porridge is used as a contraceptive prior to coitus by Igede women (Igoliet al.,
2005). The leaves of Z. zanthoxyloïdes have shown a real efficacy on inflammation and pain (Diattaet al., 2014). The
fruit pulp is used in traditional medicine against rheumatism (Bouquet and Debray, 1974). More recently, the work of
(Denloyeet al., 2010) demonstrates the potential of Z. zanthoxyloïdes to protect cowpea and maize grains against storage
insects such as Callosobruchus maculatus F., Sitophilus zeamais M. and Tribolium castaneum. In addition, the potential

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of Z. zanthoxyloïdes leaf, bark and root extracts as biopesticides for the protection of stored food was revealed by Udo
(2011). The plant is also used as a religious means to protect against evil spirits (Matu, 2011).
In Benin, the plant is used as teeth brush (Akpona et al., 2009; Yedomonhan et al., 2017). Z. zanthoxyloidesis declared
by local peoples to have antimicrobial properties and positive effect on oral pathogens such as Candida albicans, C.
krusei and C. tropicalis (Osho et al., 2012). These uses strongly vary from one ethnic group to anotherdepending on the
floristic landscape. This is due to the great variability of the selection criteria used, even for a given species.
3.5 Phytochemistry
The first phytochemical studies on Z. zanthoxyloïdes were conducted in the 1950s and gave rise to the identification and
determination of the structure of several components of essential oils, root, and bark of the root, bark of stem, leaves and
fruits. Several biological effects have been documented. Indeed, Z. zanthoxyloïdes is a plant rich in various natural
compounds, including alkaloids (Messmer et al., 1972; Couillerot et al., 1994; Adesina, 2005), flavonoids (Bowden and
Ross, 1963; Adesina, 1986; Azandoet al., 2011b), lignans, amides (Bowden and Ross, 1963; Adesina, 1986, Adesina,
2003). Other phytochemical studies on Z. zanthoxyloïdes have revealed the presence of essential oils (Menutet al., 2000;
Ngassoumet al., 2003; Dongmoet al., 2008; Foganget al., 2012).
Phytochemical analysis of the aqueous root bark extract of Z. zanthoxyloïdes reveals the presence of tannins, saponins,
sterols, glycosides, polyterpenes, polyphenols, flavonoids, quinones and alkaloids (Chaaib et al., 2003; Adesina, 2005;
Queirozet al., 2006; Zahouiet al., 2010). Its chemical composition is almost similar to that of macerated, infused and
decocted dried barks of the same plant (Zahouiet al., 2010).
The stem bark and root bark contain alkaloids of the benzophenanthridine, furoquinoline and aporphine types. From the
stem bark fagaronine and chelerythrine (Torto et al., 1966; Chaaib et al., 2003). Root bark was isolated from fagaronine,
dihydroavicin, chelerythrin, oxychelerythrin (benzophenanthridines), skimmianin and 8-methoxydictamine
(furoquinolines), as well as magnoflorine, berberine, tembetarin and N-methyl-corydine (aporphines). The root bark also
contains the following aromatic amides: arnottianamide, fagaramide, piperlonguminine, rubemamine and N-isopentyl
cinnamamide (Chaaib et al., 2003; Queirozet al., 2006). The root contains isomeric divaniloylquinic acids (3,4-O-
divanilloylquinic acid or burkinabin A, 3,5-O-divanilloylquinic acid or Burkinabine B and 4,5-O-divanilloylquinic acid
or Burkinabine C) (Ouattara et al., 2009). Burkinabine is a type of hydrolysable tannin (Ouattara et al., 2004).
Roots, fruits and stem bark, several aliphatic amides have been isolated, including N-isobutyldeca-2,4-dienamide and N-
isobutylocta-2,4-dienamide, which are the main constituents of the pellitorin. From the stem bark, many coumarins have
been isolated: umbelliferone, scopoletin, scoparone, xanthotoxin, impertorin, bergaptenin, marmesin and pimpinellin; the
root bark and stem bark contain sesamin, a lignan, while the root bark also contains its C-7 epimer, asarinin (Ogunbolude
et al., 2014). From aerial biomass of the plant have been extracted Zanthoxylol, diosmin, fagarol and hesperidin (sterols),
but also triterpenes such as lupeol, β-sitosterol, stigmasterol, campesterol and β- amyrin. From roots have been isolated a
series of acids: vanillic acid, hydroxybenzoic acid, parahydroxybenzoic acid, 2-hydroxymethyl benzoic acid and
parafluorobenzoic acid, but also Burkinabines A, B and C (divanilloylquinic acids) (Adesina, 1986; Dupontet al., 2005).

Figure 1: Structure of faragonine Figure 2: Structure of burkinabine C

The diversity of these phytochemicals induces the many traditional uses of this medicinal plant. Chemical investigations
of the whole root, stem and aerial parts of all Z. zanthoxyloïdes species revealed the presence of single coumarins.
Biologically, coumarins are very useful and many of them have antibacterial, antitumor, vasodilator (in the coronary
vessels) and anticoagulant activities (Lau-Cam and Chu-Fong, 1972). Furocoumarins have also been detected in this
plant species (Adesina, 2005). In addition, two xanthotoxins and bergaptenes have been reported in fruits (Paris and
Moyse-Mignon, 1947). Subsequently, three single coumarins (umbelliferone, 6,7-dimethylsculin and scopoletine) and
five furocoumarins (imperatorin, xanthotoxin, bergaptene, marmesine and psoralen) were identified and quantified in
dried fruit extracts of the species (Adesina, 1986).

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Menut et al. (2000) revealed that leaf oil contained only monoterpene hydrocarbons (98.2%). Among the latter, α-pinene
(26.5%), myrcene (30.0%) and trans-β-ocimene (31.9%) were the most predominant. The composition of fruit oil is more
diversified, with 85.5% of monoterpenoids and a fairly high proportion of oxygenates including linalool (11.3%) and
geranial (9.5%). These results are similar to those obtained by the other works on the composition of the essential oils of
Z. zanthoxyloïdes.
3.6 Toxicology
Z. zanthoxyloïdes is a plant used in traditional medicine in the treatment of many diseases. Several studies report that the
bark of the root of the plant is the organ most affected by toxicity. Reference (Ogwal-Okenget al., 2003) evaluated the
acute toxicity of the methanoid extract of the root bark of Z. zanthoxyloïdes. Zahouiet al. (2010) demonstrated that the
value of the median lethal concentration (LC50) of the aqueous extracts of the bark of the root of Z. zanthoxyloïdes was
4168 ± 462 mg / kg body weight (CP) and 5500 ± 875mg / kg of PC, respectively by the graphical method of Miller and
Tainter and by the calculation method of Dragsted and Lang. This work indicates that the species can be classified as
slightly toxic, since the median lethal concentration (LC50) value was found to be between 0.5 - 5.0 g / kg. It has been
observed that the overdose of Z. zanthoxyloïdes extract is usually nonfatal. Victims tend to suffer from gastrointestinal
disorders (Anokbonggo et al., 1990).
Extracts of the root bark of Z. zanthoxyloïdes appear to be cytotoxic and genotoxic to leukocytes at a high concentration,
thus confirming the need to be cautious with use of the plant (Ogunbolude et al., 2014).
3.7 Pharmacology
3.7.1- Antibacterial Activity
In vitro studies have shown that essential oils of fruits and leaves, and fruit extracts and bark root have an antimicrobial
effect against a variety of bacteria. The essential oils of leaves and / or fruits of the species have shown an inhibitory
effect on bacteria such as Salmonella enteritidis, Salmonella typhimurium, Bacillus subtilis, Listeria monocytogenes,
Staphylococcus aureus (Ngassoumet al., 2003; Gardini et al., 2009; Misraet al., 2013a; Kamdemet al., 2015). Similarly,
the antibacterial activity of the essential oils of Z. zanthoxyloïdes has been shown by Misraet al., (2013b). It is suggested
that the high concentration of geraniol in the essential oil of the plant correlates with antimicrobial activity (Kamdemet
al., 2015). In addition, the methanoid extract of the root powder of Z. zanthoxyloïdes contains flavonoids, chelerythrine,
berberine and phenol canthine-6-one, which have revealed antimicrobial activity (Odebiyi and Sofowora, 1979). A
substance isolated from fruit, 3,4,5,7-tetrahydroxy-1-methoxy-10-methyl-9-acridone, gave a moderate antibacterial
activity against the bacteria Micrococcus luteus and Pseudomonas aeruginosa (Misraet al., 2013b; Wouatsa et al.,
2013b). In addition, recent work has demonstrated the antiseptic and anti-infectious properties of certain compounds
isolated from the stem bark of this plant (Magassoubaet al., 2007). These studies may indicate the action of traditional
use against intestinal disorders.
3.7.2 Deworming Activity
The use of Z. zanthoxyloïdes extracts has been identified as one of the best treatments for Ascaris diseases, suggesting
their use as a complementary treatment option for ascariasis. Azandoet al. (2011b) showed that the powder from extracts
of Z. zanthoxyloïdes significantly reduced egg excretion of strongyles, thereby validating the in vivo anthelmintic activity
of the species on the gastrointestinal strongyles that are dominant parasites of the young ruminants in Benin.
3.7.3 Anti-Sickle Cell Activity
Several studies have shown that the active ingredients in root bark of Z. zanthoxyloïdes against sickle cell disease are
drifts of vanillic acid (Adesina, 2005; Ouattara et al., 2009). Various molecules possessing anti-sickle cell properties such
as divaniloylquinic acids, vanillic acid, p-hydroxy benzoic acid, p-fluoro benzoic acid, 2-dihydroxymethylbenzoic acid
have been isolated from Z. zanthoxyloïdes. In addition, an anti-inflammatory property due to ortho-
hydroxymethylbenzoic acid makes Z. zanthoxyloïdes useful in the treatment of pain in the crisis of sickle cell disease
(Folashade and Omoregie, 2013).
3.7.4 Anti-Oxidant Activity
The presence of antioxidants has been shown in the methanolic extract of Z. zanthoxyloïdes by Chaaibet al. (2003).
Queiroz et al. (2006) have shown that this methanolic extract also has an acetylcholinesterase inhibitory activity.
3.7.5 Anti-Plasmodial Activity
Malaria, caused by parasites of the genus Plasmodium, is one of the major infectious diseases in many tropical regions.
Many plants have scientifically proven efficacy including Z. zanthoxyloïdes (Kassim et al., 2005; Adebayo and Krettli,
2011; Muganga et al., 2010). Fagaronine, another benzo [c] phenanthridine, active compound isolated from Z.
zanthoxyloïdes has been described as one of the major antimalarial compounds found in several traditional remedies and

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plants from different parts of the world (Kassim et al., 2005; Nyanguluet al., 2005). Kassim et al. (2005) demonstrated,
in vitro, an anti-plasmodial activity of Z. zanthoxyloïdes, by its inhibitory action on the growth and development of the
erythrocytic phase of Plasmodium falciparum. Same authors reported antimalarial activity attributed to the
benzophenanthridine alkaloid, fagaronime from extracts of Z. zanthoxyloïdes roots. Reference Gansaneet al. (2010) also
reported in a study using Z. zanthoxyloïdes trunk bark extracts, the antimalarial activity of the species.
3.7.6 Anti-Inflammatory Activity
Z. zanthoxyloïdes is used in the treatment of many conditions such as inflammatory diseases and pain. The
hydroalcoholic extracts of the roots of Z. zanthoxyloïdes have been shown to possess anti-inflammatory properties. In
fact, they significantly inhibit at 300 mg / kg the inflammatory process of acute edema of the rat paw induced by
carrageenan. In addition, the hydroalcoholic extract of Z. zanthoxyloïdes leaves at 300 mg / kg significantly prevents the
appearance of pain, in the same way as acetylsalicyclic acid, administered at a dose of 100 mg / kg per os (Diatta et al.,
2014). For a sustainable conservation of the species, Diatta et al. (2014) has demonstrated the possibility of substituting
the roots of Z. zanthoxyloïdes by its leaves in the care of several pathologies. Root extract at a concentration of 0.1 μg / L
showed in vitro with inhibitory activity of COX-1 inhibition of more than 90% (Larsenet al., 2015). This supports the
traditional use of the species against inflammatory disorders, pain, fever and infections.
3.7.7 Anthelmintic Activity
The ethanolic extracts of the bark of the roots of Z. zanthoxyloïdes showed their anthelmintic property especially against
Ascaris suum, a pork parasite that is very close to the A. lumbricoides species of humans (Ogwal-Okeng, 1990; Williams
et al., 2016). In vitro studies with Z. zanthoxyloïdes demonstrated anthelmintic effects of the crude leaf extracts of this
plant against Haemonchus contortus and Trichostrongylus colubriformis, sheep parasites (Hounzangbe-Adoteet al.,
2005; Azandoet al., 2011b). In addition, the distillate essential oils of Z. zanthoxyloïdes showed in vitro anthelmintic
effects against rat parasites, Strongyloides ratti (Olounladéet al., 2012) and in vivo against gastrointestinal nematode
parasites of Djallonke sheep (Azandoet al., 2017). The anthelmintic properties of Z. zanthoxyloïdes partially depend on
the flavonoids and related polymeric tannins contained in the species, inhibit the development of the life cycle of larvae,
but also other bioactive compounds such as terpenes derived from its essential oil (Prempeh and Mensah-Attipoe, 2008;
Olounladéet al., 2012).These studies need to be continued in collaboration with specialist of pharmacy to make
medicines that can be used to cure identified diseases on which Z. Zanthoxyloïdes active compounds were identified. So,
in-depth studies are needed to identify the bioactive compounds responsible of these different activities and to determine
their mechanisms of action. One more time this show the need of maturing good and efficient propagation techniques for
this plants.
3.7.8 Antihypertensive Activity
Extracts of the root bark of Z. zanthoxyloïdes showed anti-hypertensive activity at a dose of 2.7 × 10-4 to 5.5 × 10-1 g /
kg body weight (Zahoui et al., 2010); and confirms its use in traditional medicine. Indeed, Zahoui et al. (2010) reported
the inhibitory actions of the active compounds present in the extracts of the plant on cholinergic muscarinic receptors,
resulting in a decrease in blood pressure.
3.7.9 Analgesic Activity
Some alkaloids isolated and purified from the root bark of Z. zanthoxyloïdes show analgesic activities on pain models
(Prempeh and Mensah-Attipoe, 2008). An investigation into the chemical composition of the leaves may support the
perspective of using leaves instead of roots in pathologies of inflammation and pain (Diatta et al., 2014).
3.7.10 Cytotoxic Activity
Fruit extracts of Z. zanthoxyloïdes have shown in vitro cytotoxic activity in breast cancer, liver cancer, colon cancer and
prostate cancer [59] [64]. Compounds isolated from fruit showed cytotoxic activity against breast cancer and 3-hydroxy-
1,5,6-trimethoxy-9-acridone showed a moderate cytotoxic effect against liver cancer (Wouatsa et al., 2013a; Wouatsa et
al., 2013b). In addition, the remarkable cytotoxic effects of Z. zanthoxyloïdes are probably related to the presence of
geraniol and citronellol, which exhibited strong antiproliferative activity against all of the human tumor cell lines tested,
and favored the traditional local use of this plant for the treatment of various cancers (Foganget al., 2012a). In the same
sense, Patel et al., (2010) mentioned nitidine as the active compound of Z. zanthoxyloïdes with anticancer properties.
Fagaronin isolated from Z. zanthoxyloïdes also has anticancer potential with various mechanisms. Several studies
confirm the traditional use of Z. zanthoxyloïdes against cancer. Indeed, fagaronine has been shown to inhibit
topoisomerases I and II of DNA and acts as a DNA intercalator (Messmeret al., 1972; Larsen et al., 1993). Previous
pharmacological studies have shown that the aqueous Z. zanthoxyloïdes inhibit growth and differentiation of human K
562 and L 1210 leukemia cells (Barret and Sauvaire, 1992; Kassim et al., 2015). It also inhibits the growth of HeLa S3
cells (Kassim et al., 2015). Similarly, Kassim et al. 2015) have shown that Z. zanthoxyloïdes extracts may serve as
potential chemopreventive agents in the treatment of prostate cancer.

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3.7.11 Insecticide Activity

Several studies have shown that the root, bark of roots and leaves of Z. zanthoxyloïdes have insecticidal activity,
including pests Prostephanus truncatus and Tribolium castaneumEziah et al., 2013) and Acanthosecelides obtectus
(Foganget al., 2012b). Root extracts have been shown to be toxic and repellent to houseflies, Musca domestica, the main
vector for many pathogenic organisms (Bisseleuaet al., 2008). Adesina (1986) has shown that there are substances such
as pellitorine, fagaramide, which would be the root cause of the insecticidal activity of the species.
4. Discussion and Outlook
This multipurpose plant is widely distributed in many different regions and habitats in tropics in general and in Africa in
particular. It is everywhere in use for different reasons. Its demand is growing due to the fact that the majority of rural
and low income communities in its distribution areas rely on herbal healing as first recourse for health problems. Van
Andel et al. (2012) stated with their study in Ghana on herbal market that the diversity of flora and uses on these markets
show plant diversity but also health problems of the country. In another hand Vodouhe et al. (2008) reported that
collectors gain so small money from Z. Zanthoxylum collection in contrary to wholesalers that they intend to collect more
to increase their incomes. Uncontrolled and destructive harvesting methods used by pulling up roots provoke a highly
significant decline of Z. zanthoxyloides populations in their native locations. Thus, the plant has been identified as an
endangered species (Apkagana et al., 1999; Ouro Djeri et al., 2001). In this context it is necessary to propagate and
domesticate the plant to support its demand in order to conserve it for present and future uses. But so far not many
natural regeneration or propagation techniques were reported to be really efficient. Micro-propagation techniques were
reported to produce more success. There is then place of more research to find out more local and context efficient
propagation techniques applicable for localcommunities that exploit most the plant for their personal needs but also for
marketing. The need of new knowledge to propagate and domesticate the plant is so pertinent nowadays because the
increasing pharmacological value of Z. zanthoxyloides showed by recent phytochemical studies (Dupont et al., 2005;
Ouattara et al., 2009), assume a greater demand for this plant in the future.It is also necessary to study the
pharmacological mechanism of Z. zanthoxyloïdes in combination with other plants used in traditional medicine. And
emphasize on substitutive studies to propose to users which part can be used with same efficiency like roots.
Despite several pharmacological, toxicological and phytochemical studies conducted on Z. zanthoxyloïdes, there are still
many unresolved issues concerning domestication, genetics, and commercialization. Indeed, there is a lack of data on the
genetic structure of the population of the species. Z. zanthoxyloïdes is classified as vulnerable in many African countries
and is subject to multiple human pressures, so it is essential to study the population genetics of the species to guide the
best conservation strategies. In addition, there is little information on the population structure of the species in relation to
climate change and the geographic distribution of the species' populations. Finally, few studies have addressed the
commercialization of different parts of the species or ethno botanical information and uses of the plant in Benin, as
indirect measure of use pressure on its populations.
In summary, several studies are still needed on Z. zanthoxyloïdes in the following areas: (i) improvement of the
propagation and growth capacity of the species, (ii) knowledge on genetic diversity, (iii) knowledge on the mechanism of
action of bioactive molecules responsible for biological activities, (iv) research on plant organs that can replace roots in
order to reduce the risk of extinction in areas of heavy root utilization, (v) better knowledge of the value chains of
products of the species.
5 Conclusion
Z. zanthoxyloïdes is a plant well known in traditional medicine for its multiple pharmacological actions. In this review,
the state of knowledge on the ethnomedical uses, phytochemistry, pharmacology, toxicology of the species has been
made descriptively. All parts of the plant are used, resulting in multiple pressures on the populations of the plant.
Currently, studies on the actual state of conservation and genetic variation are very limited. In addition, genetic and
environmental factors affecting traits of interest are poorly documented. To promote the sustainable use of Z.
zanthoxyloïdes, it is necessary to deepen knowledge about propagation practices, knowledge on the substitution of roots
with other parts of the plant, the value chain of the parts used and bioactive compounds useful in cosmetics and
pharmaceutical industries and to ensure the conservation of case.
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