A synthesis and review of medicinal uses, phytochemistry and pharmacological properties of Schef lera umbellifera (Sond.) Baill. (Ar

Schef lera umbellifera (Sond.) Baill. is an evergreen tree widely used as traditional medicine throughout its distributional range in southern Africa. Schef lera umbellifera is indigenous to Eswatini, Malawi, Mozambique, South Africa and Zimbabwe. This study was aimed at providing a critical review of medicinal uses, phytochemical and pharmacological properties of S. umbellifera. Documented information on medicinal uses, phytochemical and pharmacological properties of S. umbellifera was collected from several online sources such as Scopus, Google Scholar, PubMed, Francis and Taylor and Science Direct, and pre-electronic sources such as book chapters, books, journal articles and scienti ic publications obtained from the University library. This study revealed that the bark, leaf and root decoction or infusion of S. umbellifera are mainly used as diuretic, laxative, colic and protective charm, and traditional medicine for stomach ulcers, weaning infants, insanity, in lammation, rheumatism and malaria. Phytochemical compounds identi ied from the species include 3-hydroxy-20(29)-lupen-28ol, 7-hydroxy-6-methoxycoumarin, betulin, ent-kaur-16-en-19-oic acid and oleanolic acid. Pharmacological research revealed that S. umbellifera extracts and compounds isolated from the species have antibacterial, anti-HIV, antiin lammatory, antimalarial, antiprotozoal, larvicidal and cytotoxicity activities. Schef lera umbellifera should be subjected to detailed phytochemical, pharmacological and toxicological evaluations aimed at correlating its medicinal uses with its phytochemistry and pharmacological activities.


INTRODUCTION
Schef lera umbellifera (Sond.) Baill. is an evergreen tree belonging to the Araliaceae family. The Arali-aceae family consists of approximately 55 genera and 1500 species, which are mainly woody plants with a few herbaceous plants (Kim et al., 2017). The genus name Schef lera J.R. Forst. & G. Forst. is in honour of Johann Peter Ernst Von Schef ler, an 18 th century German physician and botanist (Palmer and Pitman, 1972). Schef lera is a genus of between 600 to 900 species, mainly trees, shrubs and lianas with several species grown as garden ornamental and house plants (Plunkett et al., 2005;Fiaschi and Plunkett, 2011). The speci ic name "umbellifera" refers to the umbellate arrangement of the lowers in which the lower stalks spring from the same point like the ribs of an umbrella (Palmer and Pitman, 1972). The English common name of S. umbellifera is "false-cabbage tree" and "for-est cabbage tree". The synonyms associated with the name S. umbellifera include Cussonia chartacea Schinz, C. umbellifera Sond. and Neocussonia umbellifera (Sond.) Hutch (Strey, 1973). Schef lera umbellifera is a medium to large evergreen tree with a tall trunk and much-branched and rounded crown, reaching a height of 20 metres (Strey, 1973;Venter and Venter, 2015). The bark on young stems is smooth with raised cork dots, resinous and rough to longitudinally issured on older branches and stems. The leaves of S. umbellifera are clustered at ends of branches, alternate, compound and handshaped. The leaves are glossy dark green above, paler below with toothed and waxy margins in the upper half of the leaf. The lowers are large, branched and terminal and pale yellow to white in colour. The fruit is a cone-shaped drupe, leshy and dark red in colour when ripe. Schef lera umbellifera is widely distributed in Eswatini, Malawi, Mozambique and Zimbabwe as well as in South Africa at an altitude ranging from 60 m to 1980 m above sea level (Strey, 1973;Venter and Venter, 2015). Schef lera umbellifera has been recorded in welldrained and humus-rich soil in coastal forest, evergreen forest, afromontane forest and forest margins. Schef lera umbellifera is widely used as traditional medicine throughout its distributional range in southern Africa (Watt and Breyer-Brandwijk, 1962;Long, 2005). It is therefore, within this context that this review was undertaken aimed at reviewing the medicinal uses, phytochemical and pharmacological properties of S. umbellifera so as to provide baseline data required in evaluating the therapeutic potential of the species.

MATERIALS AND METHODS
Results of the current study are based on literature search on the phytochemistry, pharmacological properties and medicinal uses of S. umbellifera 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.

Pharmacological properties of Schef lera umbellifera
The following pharmacological activities have been documented from the bark, leaves, roots, stems and twigs of S. umbellifera and compounds isolated from the species: antibacterial, anti-HIV, antiin lammatory, antimalarial, antiprotozoal, larvicidal and cytotoxicity activities.

Antibacterial activities
Similarly, De Villiers et al.
(2010) evaluated the antibacterial activities of methanol and water extracts of S. umbellifera against Pseudomonas aeruginosa, Neisseria gonorrhoeae, Enterococcus faecalis, Staphylococcus aureus and Escherichia coli using the microdilution method with cipro loxacin (0.01 mg/mL) as positive control. The methanol extract exhibited activities against all the tested pathogens with the exception of Enterococcus faecalis with the minimum inhibitory concentrations (MIC) values ranging from 1.5 mg/mL to 6.7 mg/mL while both extracts exhibited activities against Neisseria gonorrhoeae with MIC values ranging from 0.2  mg/mL to 6.7 mg/mL (Villiers et al., 2010).

Anti-HIV activities
Nthambeleni et al. (2010) evaluated the anti-HIV activities of aqueous extract of S. umbellifera leaves using EMF and InPheno bioassay screening against the cellular co-receptor types for human immunode iciency virus (HIV), CCR5 and CXCR4 viruses. The extract exhibited moderate activities shown by inhibition of 50% viral replication (IC 50 ) and concentration of extract provoking 50% of cell death after a 4day time-window (CD 50 ) (Nthambeleni et al., 2010).

Antiprotozoal activities
De Villiers et al. (2010) evaluated the antiprotozoal activities of methanol and water extracts of S. umbellifera leaves against the protozoan pathogen associated with urogenital or sexually transmitted infections, Trichomonas vaginalis using the microdilution method with cipro loxacin (0.01 mg/mL) as positive control. The methanol and water extracts exhibited activities with MIC values of 1.5 mg/mL and 4.5 mg/mL, respectively which were higher than the MIC value of 0.001 mg/mL exhibited by the positive control (Villiers et al., 2010). Mokoka (2013) and Mokoka et al. (2011) evaluated the antiprotozoal activities of dichloromethane and dichloromethane: methanol (1:1) extracts of S. umbellifera roots against Trypanosoma cruzi, Trypanosoma brucei rhodesiense and Leishmania donovani with benznidazole (IC 50 = 0.5 µg/mL), melarsoprol (IC 50 = 0.03 µM) and miltfosine (IC 50 = 0.2 µg/mL) as reference drugs. Determination of the activities of the extracts against these pathogens was done using Almar Blue and resazurin assays. The extracts exhibited activities with IC 50 values ranging from 5.0 µg/mL to 99.5 µg/mL (Mokoka, 2013;Mokoka et al., 2011). Maharaj et al. (2006) evaluated the larvicidal activities of water, dichloromethane, methanol and dichloromethane: methanol (1:1) extracts of S. umbellifera leaves against the 3rd instar larvae of Anopheles arabiensis using Temephos (Mostop; Agrivo) as positive control. The extract exhibited mortality between 40.0% and 59.0%, indicating limited toxicity (Maharaj et al., 2006).

CONCLUSIONS
The present review summarizes the medicinal uses, phytochemistry and pharmacological properties of S. umbellifera. Detailed studies on the pharmacokinetics, in vivo and clinical research involving both extracts and compounds isolated from the species are required. Therefore, future research should focus on the molecular modes or mechanisms of action, pharmacokinetics and physiological pathways for speci ic extracts of the species including identi ication of the bioactive compounds of the species and their associated pharmacological activities.

ACKNOWLEDGEMENT
I am grateful to the reviewers who kindly commented on my manuscript.