Maerua edulis (Gilg & Gilg-Ben.) DeWolf: A review of its ethnomedicinal uses, phytochemistry and pharmacological properties

Maerua edulis (Gilg & Gilg-Ben.) DeWolf is collected from the wild for its edible fruits and also used as traditional medicine. This study is aimed at evaluating the ethnomedicinal uses, phytochemistry and pharmacological properties of M. edulis. Results of the current study are based on data derived from several online databases such as Scopus, Google Scholar, PubMed and Science Direct, and pre-electronic sources such as scienti ic publications, books, dissertations, book chapters and journal articles. This study revealed that the bark, fruit, leaf, root and tuber infusion and decoction of M. edulis are mainly used as a thirst quencher and ethnoveterinary medicine, and traditionalmedicine for eye infections, stomach ache, infertility inwomen,wounds, fungal infections, rheumatic swellings, cough and tuberculosis and sexually transmitted diseases. Phytochemical compounds identi ied from the species include agmatine, betaines, cardiac glycosides, fatty acids, lavonoids and quaternary ammonium compounds. Ethnopharmacological research revealed that M. edulis extracts and compounds isolated from the species have acaricidal, anthelmintic, antibacterial, antimycobacterial, antifungal, antiproliferative and insecticidal activities. Future research on M. edulis should focus on the possible biochemicalmechanisms of both the crude extracts and identi ied phytochemical compounds including toxicological, in vivo and clinical studies to corroborate the traditional medicinal applications of the species.


INTRODUCTION
Maerua edulis (Gilg & Gilg-Ben.) DeWolf is a small shrub belonging to the Capparaceae or caper family. The Capparaceae family is a tropical and subtropical taxon of trees, shrubs, herbs and lianas consisting of approximately 417 species (Kers, 2003;Iltis et al., 2011). The genus Maerua Forssk has been recorded in tropical and southern Africa, and tropical Asia with about 60 species recorded from the African continent (Hall, 2008;Abreu et al., 2014).
The English common name of M. edulis is a blueleaved bush berry, and the species has been recorded in the Democratic Republic of Congo, Kenya, Malawi, Mozambique, South Africa, Tanza (Wild, 1960;Elfers et al., 1964). Maerua edulis is an evergreen shrub reaching three metres in height with thick, perennial and swollen tuber-ous rootstock. The main stem is multi-stemmed with stiff and spreading branches from near the base with young branches covered in a bluish wax layer. The leaves are alternate, simple, leshy, hairless and entire, broadly lanceolate to ovate in shape and bluish-green in colour.
The leaves have a rounded apex with a bristle-tip and a rounded base. The lowers are bisexual, yellow-green in colour, borne singly in the upper leaf axils. The fruit is a globose or oval capsule, bluishgreen at irst, turning yellow-orange when ripe. The seeds are discoid, smooth and pale brown. Maerua edulis has been recorded in sandy areas, light clay soils and in rocky areas in the riverine thicket in Acacia bushland and woodland, Acacia desert grassland, deciduous or semi-evergreen bushland, bushed grassland, wooded grassland, Colophospermum mopane (Benth.) Leonard woodland, often near seasonal rivers or lakes and burnt grassland at an altitude ranging from sea level to 1,850 m above sea level (Dharani, 2019).
The fruits and leaves of M. edulis are considered edible throughout the distributional range of the species (Johns and Kokwaro, 1991;Bosch, 2013). The ripe yellow fruits are sweet and widely eaten by children herding livestock, and the fruits are also regarded as a famine food. The fruits are usually eaten fresh, and in some areas, the fruits are boiled irst, and the water is thrown away before eating (Bosch, 2013).
The roots of M. edulis are eaten during food shortages in Tanzania, but death often occurs when the roots are eaten in excess. The roots of M. edulis are widely used in Kenya to purify and reduce the turbidity of water. This evergreen shrub is used as an ornamental plant, live fence, hedge, bee forage and fodder for livestock (Bosch, 2013). Maerua edulis is regarded as poisonous, and in Tanzania and Zimbabwe, the leaves, roots and whole plant parts of the species are used as a ish poison. In Tanzania, root powder of M. edulis is applied to the funnel of maize (Zea mays L.) as a control for stalk borer and to control pests on stored maize (Bosch, 2013).
In Zimbabwe, the leaf extract of M. edulis is used as an insecticide. The leaves and roots of M. edulis are sold as traditional medicines in the informal herbal medicine markets in the Limpopo province in South Africa. Thus, this review aims to provide an integrated and detailed appraisal of the existing knowledge on the ethnomedicinal uses, phytochemistry and pharmacological properties of M. edulis in an attempt to explore the therapeutic and functional potential of this species.

METHODS
Results of the current study are based on a literature search on the phytochemistry, pharmacological properties and medicinal uses of M. edulis using information derived from several internet databases. The databases included Scopus, Google Scholar, PubMed and Science Direct. Other sources of information used included pre-electronic sources such as journal articles, theses, books, book chapters and other scienti ic articles obtained from the university library.

Medicinal uses of Maerua edulis
The bark, fruit, leaf, root and tuber infusion and decoction of M. edulis are mainly used as a thirst quencher and ethnoveterinary medicine, and traditional medicine for eye infections, stomach ache, infertility in women, wounds, fungal infections, rheumatic swellings, cough and tuberculosis and sexually transmitted diseases (Table 1, Figure 1). Other medicinal applications supported by at two literature reports include the use of bark, fruit, leaf, root and tuber infusion and decoction as an insecticide, pesticide and stimulant, and traditional medicine against allergies, pain and sore joints (Table 1). In Tanzania, the roots of M. edulis are mixed with leaves of Boscia mossambicensis Klotzsch (family Capparaceae) as ethnoveterinary medicine against poultry diseases (Komwihangilo et al., 1995). In Zimbabwe, the roots of M. edulis are mixed with fruits of Solanum incanum L. (family Solanaceae) as ethnoveterinary medicine against ticks (Nyahangare et al., 2015).

Nutritional and phytochemistry of Maerua edulis
Some researchers identi ied nutritional elements and phytochemical compounds from the fruits, leaves and roots of M. edulis include agmatine, betaines, cardiac glycosides, lavonoids, nutritional compounds, quaternary ammonium compounds Tanzania (Komwihangilo et al., 1995) Ticks Roots mixed with fruits of Solanum incanum L.
Zimbabwe (Nyahangare et al., 2015)  Fruits, leaves and roots (Njue et al., 2016) and trace elements (Table 2). Luo et al. (2011a) identi ied linear chain unsaturated fatty acids from the roots of M. edulis. Some of these phytochemical compounds may be responsible for the biological activities of the species.

Pharmacological properties of Maerua edulis
The following pharmacological activities have been documented from the leaves, roots and tubers of M. edulis and compound isolated from the species: acaricidal, anthelmintic, antibacterial, antimycobacterial, antifungal, antiproliferative and insecticidal activities.
Acaricidal activities Kaposhi (1992) and Kaposi et al. (1995) evaluated the acaricidal activities of aqueous extracts of M. edulis leaves against Rhipicephalus appendiculatus cattle tick larvae. The extracts exhibited activities demonstrating the ef icacy of 51.0% against the tested tick larvae (Kaposhi, 1992;Kaposi et al., 1995). Nyahangare et al. (2016) evaluated the acaricidal activities of aqueous, hexane and methanol extracts of M. edulis leaves against Rhipicephalus (Boophilus) decoloratus tick larvae with commercial amitraz-based acaricide (Tickbuster) as a positive control. The highest activity (98.0%) was observed in methanol extract, causing larvae mortality which was comparable to the activities of the positive control (Nyahangare et al., 2016). Nyahangare et al. (2017) evaluated the in vivo acaricidal activities of crude aqueous extracts of M. edulis leaves and tubers at concentrations of 10.0% w/v against cattle ticks with commercial amitrazbased acaricide (Tickbuster) as a positive control. The tuber extract exhibited activities which were comparable to activities exhibited by the amitrazbased acaricide positive control (Nyahangare et al., 2017). Nyahangare et al. (2019) evaluated the acaricidal activities of acetone, and crude water extracts of M. edulis leaves and tubers with or without liquid soap against Rhipicephalus (Boophilus) decoloratus ticks using the Shaw larval immersion test method with commercial amitraz-based acaricide as a positive control. The non-polar fractions of the acetone extract of leaf and tuber caused up to 100.0% mortality of the ticks (Nyahangare et al., 2019). Gakuya et al. (2000) evaluated the anthelmintic activities of the water extract of M. edulis tuber against gastro-intestinal nematodes in sheep. The extract demonstrated a 49.0% reduction of worm egg count (Gakuya et al., 2000). Gakuya (2001) and Gakuya et al. (2005) evaluated the anthelmintic activities of the water extract of M. edulis root using mice that had been experimentally infected with the intestinal nematode Heligmosomoides polygyrus. The mice were administered with extract at a dosage of 5.0 gm/kg, 10.0 gm/kg and 20.0 gm/kg body weight and faecal worm egg count reduction determined after seven days of treatment. The results showed a percentage of faecal Heligmosomoides polygyrus egg count reduction of 69.0% to 16.0% (Gakuya, 2001;Gakuya et al., 2005). Maregesi et al. (2008) evaluated the antibacterial activities of aqueous, n-hexane and methanol extracts of M. edulis roots against Bacillus cereus, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae and Salmonella typhimurium using a liquid dilution method with ampicillin and rifampicin as positive controls. The n-hexane extract exhibited activities against Bacillus cereus, Staphylococcus aureus and Klebsiella pneumoniae with the minimum inhibitory concentration (MIC) values ranging from 500.0 µg/ml to 1000.0 µg/ml against MIC values of 0.1 µg/ml to 0.6 µg/ml exhibited by the positive control (Maregesi et al., 2008). Kowero et al. (2016) evaluated the antibacterial activities of chloroform, ethyl acetate and methanol extracts of M. edulis leaves against Salmonella kisarawe, Klebsiella oxytoca, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, Escherichia coli and Salmonella typhi using microdilution methods with gentamycin as a positive control. The chloroform and ethyl acetate extracts exhibited activities with MIC values ranging from 1.6 mg/mL to 25.0 mg/mL (Kowero et al., 2016). Luo et al. (2011b,a) evaluated the in vitro antimycobacterial activities of n-hexane, dichloromethane, ethyl acetate and 70% ethanol extracts of M. edulis roots against Mycobacterium smegmatis, Mycobacterium tuberculosis, Mycobacterium avium and Mycobacterium Bovis using the broth microdilution method with isoniazid, kanamycin, puromycin and rifampicin as positive controls. Only n-hexane extract exhibited activities with MIC values ranging from 31.2 µg/mL to 250.0 µg/mL (Luo et al., 2011b,a). Maregesi et al. (2008) evaluated antifungal activities of aqueous, n-hexane and methanol extracts of M. edulis roots against Aspergillus niger and Candida albicans using a liquid dilution method with lucytosine as a positive control. The aqueous extract exhibited activities against Candida albicans with the MIC value of 1000.0 µg/ml against MIC value of 0.06 µg/ml exhibited by the positive control (Maregesi et al., 2008). Samie et al. (2010) evaluated the antifungal activities of acetone and hexane root extracts of M. edulis against Cryptococcus neoformans, Candida krusei and Candida albicans isolated from acquired immunode iciency syndrome (AIDs) patients using agar diffusion and the microdilution methods with nystatin (10.0 µl) and lourocystosine (10.0 µl) as positive controls. The extracts exhibited activities against tested pathogens with MIC values ranging from 1.0 mg/ml to 7.5 mg/ml in comparison to MIC values of 0.2 µg/ml to 1.9 µg/ml exhibited by the positive controls (Samie et al., 2010). Kiswii (2014) evaluated the antifungal activities of crude extracts of M. edulis leaves against Aspergillus lavus using agar well diffusion method with miconazole (10.0 mg/ml) as the positive control. The extract exhibited weak activities with a zone of inhibition of 7.0 mm against the zone of inhibition of 19.4 mm exhibited by the positive control (Kiswii, 2014).

Antiproliferative activities
Sithole and Mukanganyama (2017) evaluated the antiproliferative activities of aqueous, acetone, hexane and methanol extracts of M. edulis roots against human leukemic Jurkat-T cell line using 1,3-bis (2chloroethyl)-1-nitrosourea (BCNU) as a reference drug. The methanol extract inhibited the growth of Jurkat-T cells in a dose-dependent manner with half-maximal growth inhibition cell proliferation (GI 50 ) value of 18.5 µg/ml (Sithole and Mukanganyama, 2017).

Insecticidal activities
Mazhawidza and Mvumi (2017) evaluated the insecticidal activities of crude aqueous extracts of M. edulis leave against pests of cabbage (Brassica oleracea L.), Plutella xylostella and rape (Brassica namus L.), Brevicoryne brassicae with commercial synthetic pesticides used as positive controls. The extracts exhibited activities at a concentration of 5.0% to 20.0% w/v (Mazhawidza and Mvumi, 2017). Stevenson et al. (2018) evaluated the insecticidal activities of the crude M. edulis leaf extracts and the compounds 4hydroxy-Z-cinnamoyl-4-aminobutylguanidine, 4-hydroxy-E-cinnamoyl-4-aminobutylguanidine, E-cinnamoyl-4-aminobutylguanidine and Zcinnamoyl-4-aminobutylguanidine isolated from the species against the cowpea (Vigna unguiculata (L.) Walp.) bruchid Callosobruchus maculatus at concentrations equivalent to those present in extracts used by smallholder farmers with rotenone as the positive control. The extracts and the compounds exhibited activities against the tested insect (Stevenson et al., 2018).

CONCLUSION
Maerua edulis is known to be poisonous, and there is a need for detailed clinical and toxicological evaluations of crude extracts and compounds isolated from the species. Therefore, the widespread use of M. edulis as food plant and source of traditional medicines throughout its distributional range suggest that the species is not taken at toxic dosages. But the use of M. edulis as food and for the treatment of human diseases and ailments should be treated with caution and rigorous toxicological and clinical studies of the bark, fruits, leaves, roots and tubers, and compounds isolated from the species are necessary.