Introduction

The genus Ehretia P.Browne was described by Browne in 1756 as a taxon within the Boraginaceae family consisting of approximately 40 species (Gottschling et al., 2016). Recent molecular and phylogenetic studies based on nuclear (ITS) and plastid loci (rps16, trnL-trnF and trnS-trnG) supported the segregation of the family Ehretiaceae from Boraginaceae sensu lato (Gottschling et al., 2016). The plant species belonging to the genus Ehretia have been recorded in the Old and New World tropics with a few species in tropical America and the West Indies, with centres of diversity in tropical Africa and East Asia (Gottschling et al., 2016). Ehretia cymosa Thonn. occurs naturally from Sierra Leone in West Africa to Eritrea and Kenya in East Africa, and Zimbabwe in southern Africa (Martins, Brummitt, Boraginaceae, Launert, & Pope, 1990; Miller, 2002). Ehretia cymosa is divided into three varieties distinguished by flower size, hairiness of the inflorescence and geographical distribution. Ehretia cymosa var. cymosa is confined to the evergreen forests of Uganda (Verdcourt, Boraginaceae, Polhill, Balkema, & Rotterdam, 1991). Ehretia cymosa var. divaricata (Bak.) Brenan is widespread, recorded in evergreen forest, grassland and bushland in DRC, Ethiopia, Kenya, Malawi, Mozambique, Tanzania, Uganda, Zambia and Zimbabwe (Verdcourt et al., 1991). Ehretia cymosa var. silvatica (Gürke) Brenan has been recorded in the rain forest, riverine forest, bushland and grassland in Ethiopia, Kenya, Tanzania and Uganda (Verdcourt et al., 1991). The genus name Ehretia is in honour of a German botanical artist and entomologist of the 18^th century known as Georg Dionysius Ehret (1708-1770). The species name cymosa is derived from the Latin word “cymosus", meaning “flowers in a cyme”, that is, flowers forming clusters with flowers opening from the centre first, then in succession outward towards the periphery. Synonyms of E. cymosa include E. abyssinica R.Br. ex Fresen., E. breviflora De Wild., E. corymbosa Bojer ex A.DC., E. diffusa Vahl ex A.DC., E. divaricata Baker, E. inamoena Standley, E. laevis Sieber ex A.DC., E. silvatica Gürke and E. thonningiana Exell (Miller, 2002; Verdcourt et al., 1991).

Ehretia cymosa is a deciduous medium-sized to large tree growing up to a height of 20 metres. Ehretia cymosa has been recorded in the understory or at edges of evergreen forest, riverine forest, forest margins, wooded savanna and bushland on steep mountain slopes. The bark of E. cymosa grey to dark grey in colour, ranging from smooth to rough and scaly. The leaves are simple and entire, arranged spirally, broadly ovate to elliptic in shape, papery to leathery, glossy dark green above and paler dull green below. Flowers of E. cymosa are white in colour, sweetly scented, occurring in large terminal heads. The fruit is a drupe, ovoid to globose in shape, fleshy, orange to red and turning black when ripe.

The fruits of E. cymosa are edible and the leaves are also consumed in Benin as leafy vegetables (Achigan-Dako et al., 2010). The fresh leaves of E. cymosa are sold in local markets in Benin as leafy vegetables (Achigan-Dako et al., 2010). But the fruits of E. cymosa are known to cause gastrointestinal disorders and the leaves and roots are also known to be poisonous (Dharani, 2019; Wickens & Burkill, 1986). It is, therefore, within this context that the current study was undertaken aimed at documenting the medicinal uses, phytochemistry and biological activities of E. cymosa.

Materials and Methods

Results of the current study are based on a literature search on the ecological, biological and medicinal properties of E. cymosa throughout its distributional range using information from internet databases. The databases used 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 scientific articles obtained from the university library.

Results and Discussion

Medicinal uses of Ehretia cymosa

The herbal concoctions prepared from the bark, leaf juice, leaves, roots, seeds, stems, twigs and whole plant parts of E. cymosa are used to treat and manage at least 38 human and animal diseases and ailments (Table 1). The major diseases and ailments treated by E. cymosa extracts include gastro-intestinal problems recorded in five countries based on eight literature records (Figure 1), followed by wounds (four countries, eight literature records), malaria (three countries, five literature records), fever and typhoid (three countries, four literature records), convulsions and epilepsy (three countries, four literature records), ethnoveterinary medicine (three countries, three literature records), aphrodisiac (two countries, five literature records), toothache (two countries, four literature records), respiratory infections (two countries, four literature records) and laxative (two countries, two literature records).

Phytochemical composition of Ehretia cymosa

Researchers identified several phytochemical compounds from the leaves, roots and whole plant parts of E. cymosa (Table 2). The phytochemical compounds identified from the species include alkaloids, anthraquinones, essential oils, fatty acids, flavonoids, glycosides, phenolics, proanthocyanidins, pseudotannins, reducing sugars, saponins, steroids, tannins and terpenes (Table 2). Some of these phytochemical compounds may be responsible for the biological activities exhibited by the species.

Biological activities of Ehretia cymosa

The following biological activities have been documented from the leaf and whole plant parts of E. cymosa as well as phytochemical compounds isolated from the species, antibacterial, antidiabetic, antihyperglycaemic and antioxidant activities.

Antibacterial activities

(Sarkodie et al., 2015) evaluated the antibacterial activities of 70% ethanolic extract of the whole plant of E. cymosa against Bacillus subtilis, Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli using agar diffusion assay with gentamicin (10.0 μg/mL) as a positive control. The extract exhibited activities against tested pathogens. (Bagaje, Melaku, & Dessalegn, 2017) evaluated the antibacterial activities of the

methanol extract of E. cymosa leaves against seudomonas aeruginosa, Escherichia coli, Staphylococcus aureus and Proteus mirabilis using well diffusion method with gentamicin and vancomycin as positive controls. The extract exhibited activities against Escherichia coli and Staphylococcus aureus with a zone of inhibition of 12.0 mm and 9 mm, respectively (Bagaje et al., 2017). Similarly, (Sori et al., 2018) evaluated the antibacterial activities of n-hexane, methanol and ethyl acetate extracts and the triterpenoid compound isolated from E. cymosa leaves against Pseudomonas aeruginosa and Staphylococcus aureus using disc diffusion assay with gentamicin as a positive control. The extracts and the compound exhibited activities with inhibition zones ranging from 9.0 mm to 30.0 mm in comparison to the inhibition zone of 22.0 exhibited by the positive control (Sori et al., 2018).

Antidiabetic activities

(Ogundajo et al., 2017; Ogundajo et al., 2017) evaluated the antidiabetic activities of ethanol, methanol and ethyl acetate extracts of E. cymosa leaves using α-amylase and α-glucosidase inhibitory assays. The extracts exhibited activities against α-glucosidase (0.6 mg/mL) and α-amylase (2.1 mg/mL), respectively (Ogundajo et al., 2017; Ogundajo et al., 2017).

Antihyperglycaemic activities

(Sarkodie et al., 2015) evaluated the in vivo antihyperglycaemic activities of 70% ethanolic extract of the whole plant of E. cymosa using Sprague Dawley rats. The extract exhibited dose independent decrease of blood glucose (Sarkodie et al., 2015).

Antioxidant activities

(Sarkodie et al., 2015) evaluated the antioxidant activities of 70% ethanolic extract of the whole plant of E. cymosa using 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging assay with ascorbic acid and butylated hydroxytoluene (BHT) as positive controls. The extract exhibited activities with a half maximal inhibitory concentration (IC₅₀) value of 0.5 μg/ml, comparable to IC₅₀ values of 03 μg/ml and 0.4 μg/ml exhibited by ascorbic acid and BHT, respectively (Sarkodie et al., 2015). (Bagaje et al., 2017) evaluated the antioxidant activities of the methanol extract of E. cymosa leaves using DPPH free radical scavenging assay with ascorbic acid as a positive control. The extract exhibited low inhibition of DPPH in comparison to high activities exhibited by the positive control (Bagaje et al., 2017). (Ogundajo et al., 2017; Ogundajo et al., 2017) evaluated the antioxidant activities of methanol, ethanol and ethyl acetate extracts of E. cymosa leaves using DPPH, 2,2‑azino‑bis (3‑ethylbenzothiazoline)‑6‑sulfonic (ABTS), hydroxyl radical, metal chelating and superoxide anion scavenging assays. The extracts showed activities exhibiting IC₅₀ values ranging from 0.5 mg/mL to 1.7 mg/mL (Ogundajo et al., 2017; Ogundajo et al., 2017).

Conclusions

Ehretia cymosa 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 E. cymosa as a 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 E. cymosa as food and the treatment of human diseases and ailments should be treated with caution and rigorous toxicological and clinical studies of the bark, fruits, leaves, roots, seeds, tubers and compounds isolated from the species are necessary.