Introduction

The genus Cussonia Thunb. is one of the most important sources of herbal medicines among the Araliaceae genera. The Araliaceae family consists of approximately 55 genera and 1500 species, which are mainly woody plants with a few herbaceous plants (Frodin, Smith, Mori, Henderson, & Stevenson, 2004; Kim et al., 2017). Research by (Brussell, 2004) revealed that many Araliaceae species such as Acanthopanax sciadophylloide Franch. & Sav., A. seiboldianum Makino, Acer mono Maxim., Aralia cordata Thunb., A. elata (Miq.) Seem., A. spinosa L., Eleutherococcus spinosus (L. f.) S.Y. Hu, Fatsia japonica (Thunb.) Decne. & Planch., Gamblea innovans (Siebold & Zucc.) C.B. Shang, Lowry & Frodin, Hedera helix L., H. rhombea (Miq.) Siebold ex Bean, Oplopanax japonicus Nakai, Panax ginseng C.A. Mey., P. japonicus (T. Nees) C.A. Mey. and Schefflera heptaphylla (L.) Frodin are noteworthy culinary and medicinal plants. Some members of the Araliaceae family have demonstrated pharmacological properties such as neuroprotective, anti-aging, immunostimulant, antiapoptotic, immunomodulatory, anticancer, antiviral, antidiabetic, antibacterial, antidiabetes, antipsoriasis, antiarthritis, antifungal, anticonvulsant, antioxidant, antiobesity and anti-inflammatory (Kim, Tabassum, Uddin, & Park, 2016). Phytochemical studies on species belonging to the Araliaceae family revealed the presence of flavonoids, triterpenes, volatile oils, triterpenoid glycosides, saponins and tannins (Kim et al., 2016)

The genus Cussonia Thunb. comprises about 22 species which are mainly trees or shrubs or occasionally subshrubs recorded in grasslands, woodlands, and forests of sub-Saharan Africa, the Arabian Peninsula (Yemen) and the Comoro Islands (Reyneke, 1984; Villiers, Plunkett, Tilney, & Wyk, 2009). Cussonia natalensis Sond. and C. zuluensis Strey are among the species widely used as herbal medicines in southern Africa. Other Cussonia species regarded as important medicinal plants in tropical Africa include C. arborea Hochst. ex A. Rich., C. bancoensis Aubrév. & Pellegr., C. holstii Harms ex Engl., C. nicholsonii Strey, C. ostinii Chiov., C. paniculata Eckl. & Zeyh., S. spicata Thunb., C. transvaalensis Reyneke and C. zimmermannii Harms (Kokwaro, 2009; Watt & Breyer-Brandwijk, 1962). Apart from used as herbal medicines for similar medicinal conditions, C. natalensis and C. zuluensis have been recorded in overlapping geographical areas in southern Africa (Figure 1). It is therefore, within this context that the current review was undertaken aimed at providing a comparative analysis of the botanical, medicinal, chemical and biological activities of C. natalensis and C. zuluensis.

Materials and Methods

Results of the current study are based on literature search on the botanical, medicinal, chemical and biological activities of C. natalensis and C. zuluensis 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 scientific articles obtained from the University library.

Results and Discussion

Botanical description of Cussonia natalensis and C. zuluensis

The genus name “Cussonia” is in honour of Pierre Cusson (1727-1783), a French Professor of botany at the University of Montpellier who specialized in Apiaceae family (Palmer & Pitman, 1972). The specific name “natalensis” means “of Natal”, part of KwaZulu-Natal province in South Africa where the type specimen of the species was collected (Bayton, 2019). Cussonia natalensis is commonly referred to as “rock cabbage tree”, “simple-leaved cabbage tree” and “Natal cabbage tree”. Cussonia natalensis is a sturdy, small to medium-sized deciduous tree with a rounded crown which can grow up to a height of 11 metres (Schmidt, Lotter, & Mccleland, 2017). The bark of C. natalensis is dark grey to brown in colour, deeply rectangularly fissured and corky. The leaves of C. natalensis are simple, deeply lobed, leathery, glossy green, hairless, apex tapering to a point, base lobed with bluntly toothed leaf margins. The flowers are greenish yellow in colour, occurring in terminal heads of radiating cylindrical spikes. The fruit is a cone-shaped drupe, fleshy and purple in colour when ripe and closely crowded along the spikes. Cussonia natalensis has been recorded in Eswatini, South Africa and Zimbabwe at an altitude ranging from 100 m to 1640 m above sea level (Germishuizen & Meyer, 2003). Cussonia natalensis has been recorded in bushveld, usually in rocky places, hills, hillsides and mountain sides.

The specific name “zuluensis” refers to Zululand (part of KwaZulu-Natal province in South Africa) from where the type specimen of the species was collected (Glen, 2004). Cussonia zuluensis is commonly referred to as “Zulu cabbage tree”. Cussonia zuluensis is a small, multi-stemmed, sparsely branched tree with a spindly shape, growing to a height of six metres (Germishuizen et al., 2003). The bark is grey-green in colour, smooth to flaking. The leaves of C. zuluensis are multi-digitate, clustered near ends of branches or arranged spirally at the ends of branches. The leaves are leathery, glossy dark green above, dull green below, apex tapering with a hair-like tip, base tapering with sparsely to distinctly toothed leaf margins. Flowers occur in terminal simple umbels and are greenish yellow in colour. The fruit is a goblet-shaped drupe, fleshy and mauve in colour when ripe and closely crowded along the axes. Cussonia zuluensis has been recorded in Eswatini, Mozambique and South Africa at an altitude ranging from 10 m to 1000 m above sea level (Germishuizen et al., 2003). Cussonia zuluensis has been recorded in sandy soils and river valleys in bushveld, dry coastal scrub and forest.

Medicinal uses of Cussonia natalensis and C. zuluensis

In Eswatini and Zimbabwe, the bark, fruits and roots of C. natalensis are used as emetic, purgative and protective charm, and traditional medicine against diarrhoea and stomach ache (Table 1). In Eswatini, the stem bark of C. natalensis is mixed with that of Gardenia volkensii K. Schum. subsp. spatulifolia (Stapf. & Hutch.) Verdc. as herbal medicine for gastro-intestinal problems (Amusan, 2010). In Eswatini and South Africa, the root infusion of C. zuluensis is used as emetic and purgative, and herbal medicine for fever and swellings (Amusan et al., 2007; Long, 2005).

Phytochemical and biological activities of Cussonia natalensis and C. zuluensis

There is very little information available concerning the phytochemistry of the crude extracts of C. natalensis and C. zuluensis. However, Fourie, Matthee, and Snyckers (1989) identified pentacyclic triterpene acids, 23-hydroxy-3-oxo-urs-12-en-28-oic acid and oleanolic acid from the leaves and twigs of C. natalensis. Preliminary research by Fourie et al. (1989) showed that the triterpene acid, 23-hydroxy-3-oxo-urs-12-en-28-oic acid isolated from the leaves and twigs of C. natalensis has anti-ulcer properties. Similarly, Amusan et al. (2007) identified cardiac glycosides, flavonoids, polyphenols, saponins and steroids from the roots of C. zuluensis. Some of these chemical compounds may be responsible for the pharmacological properties of the species. The phytochemical compounds like triterpenes are associated with antioxidant, antimicrobial, antimalarial, anti-inflammatory, anticancer, α-glucosidase inhibitors and antidiabetic properties (Tan et al., 2008; Zhang et al., 2016). Many flavonoids, polyphenols, saponins and steroids have anti-inflammatory, anticancer, antioxidant, antiparasitic, antiphlogistic, antiallergic, immunomodulating, antihepatotoxic, antiviral, hypoglycemic, antifungal and molluscicidal activities (Rasouli, Farzaei, & Khodarahmi, 2017; Sülsen, Lizarraga, Mamadalieva, & Lago, 2017).

Villiers, Vuuren, Zyl, and Wyk (2010) evaluated the antibacterial activities of methanol and water extracts of C. natalensis leaves against Pseudomonas aeruginosa, Neisseria gonorrhoeae, Enterococcus faecalis, Staphylococcus aureus and Escherichia coli using the microdilution method with ciprofloxacin (0.01 mg/mL) as positive control. Both extracts exhibited activities against all the tested pathogens with the minimum inhibitory concentrations (MIC) values ranging from 0.3 mg/mL to 8.0 mg/mL. Similarly, Villiers et al. (2010) evaluated the antibacterial activities of methanol and water extracts of C. zuluensis leaves against Pseudomonas aeruginosa, Neisseria gonorrhoeae, Enterococcus faecalis, Staphylococcus aureus and Escherichia coli using the microdilution method with ciprofloxacin (0.01 mg/mL) as positive control. Both extracts exhibited activities against all the tested pathogens with the MIC values ranging from 0.2 mg/mL to 9.3 mg/mL (Villiers et al., 2010). Shai (2007); Shai, McGaw, Masoko, and Eloff (2008) evaluated the antibacterial activities of acetone, dichloromethane and n-hexane extracts of C. zuluensis leaves against Enterococcus faecalis, Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus using the microdilution method with gentamicin as a positive control. The extracts exhibited activities against the tested pathogens with MIC values ranging from 0.3 mg/ml to 2.5 mg/ml and total activity ranging from 8.0 ml to 267.0 ml (Shai, 2007; Shai et al., 2008).

Mangoyi and Mukanganyama (2011) evaluated the antifungal activities of ethanol extracts of C. natalensis leaves against Candida krusei and Candida albicans using the agar disc diffusion and broth dilution methods with miconazole as positive control. The extract exhibited activities against Candida albicans with zone of inhibition value of 16.0 mm, MIC and minimum fungicidal concentration (MFC) values of 0.3 mg/ml and 1.3 mg/ml, respectively. The zone of inhibition exhibited by miconazole, the control ranged from 20.0 mm to 22.6 mm, and the MIC and MFC values ranged from 0.3 mg/ml to 0.6 mg/ml (Mangoyi et al., 2011). Shai (2007); Shai et al. (2008) evaluated the antifungal activities of acetone, dichloromethane and n-hexane extracts of C. zuluensis leaves against Cryptococcus neoformans, Aspergillus fumigatus, Candida albicans, Micrococcus canis and Sporothrix schenckii using the microdilution method with amphotericin B as positive control. The extracts exhibited activities against tested pathogens with MIC values ranging from 0.06 mg/ml to 2.5 mg/ml and total activity ranging from 8.0 ml to 133.0 ml (Shai, 2007; Shai et al., 2008). Mokoka (2007); Mokoka, McGaw, and Eloff (2010) evaluated the antifungal activities of hexane, dichloromethane, acetone and methanol leaf extracts of C. zuluensis against Cryptococcus neoformans using the two-fold serial dilution microplate and microdilution methods. The extracts exhibited activities against the tested pathogen with MIC values ranging from 0.02 mg/mL to 0.6 mg/mL and total activity ranging from 9.0 mL/g to 496.0 mL/g (Mokoka, 2007; Mokoka et al., 2010).

Villiers et al. (2010) evaluated the antiprotozoal activities of methanol and water extracts of C. natalensis against the protozoan pathogen associated with urogenital or sexually transmitted infections, Trichomonas vaginalis using the microdilution method with ciprofloxacin (0.01 mg/mL) as positive control. The methanol extract exhibited activities against the tested pathogen with MIC value of 1.0 mg/mL which was higher than the MIC value of 0.001 mg/mL exhibited by the positive control. Villiers et al. (2010) evaluated the antiprotozoal activities of methanol and water extracts of C. zuluensis leaves against the protozoan pathogen associated with urogenital or sexually transmitted infections, Trichomonas vaginalis using the microdilution method with ciprofloxacin (0.01 mg/mL) as positive control. The methanol extract exhibited activities against the tested pathogen with MIC value of 0.8 mg/mL which was higher than the MIC value of 0.001 mg/mL exhibited by the positive control (Villiers et al., 2010).

Villiers et al. (2010) evaluated the antimalarial activities of methanol and water extracts of C. natalensis leaves using the [G-³H] hypoxanthine incorporation assay using chloroquine-sensitive (3D7) strain of Plasmodium falciparum as the test organism. The extracts exhibited weak activities with half maximal inhibitory concentration (IC₅₀) values >50.0 μg/mL. (Villiers et al., 2010) also evaluated the antimalarial activities of methanol and water extracts of C. zuluensis leaves using the [G-³H] hypoxanthine incorporation assay using chloroquine-sensitive (3D7) strain of Plasmodium falciparum as the test organism. The extracts exhibited weak activities with IC₅₀ values >50.0 μg/mL (Villiers et al., 2010).

De Villiers et al. (2010) evaluated the cytotoxicity activities of methanol and water extracts of C. natalensis against the human T-cell leukemia (Jurkat) cell line using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) calorimetric assay with (S)-(+)- camptothecin as a positive control. The extracts exhibited weak cytotoxicity activities with IC₅₀ values >50.0 µg/mL in comparison to IC₅₀ value of 0.07 µg/mL exhibited by the positive control. Corrigan et al. (2011) also evaluated the cytotoxicity activities of methanol and water extracts of C. zuluensis leaves against the human T-cell leukemia (Jurkat) cell line using the MTT calorimetric assay with (S)-(+)- camptothecin as a positive control. The methanol and water extracts exhibited moderate cytotoxicity activities with IC₅₀ values of 37.0 µg/mL and >50.0 µg/mL, respectively in comparison to IC₅₀ value of 0.07 µg/mL exhibited by the positive control (Villiers et al., 2009).

Conclusions

The present review summarizes the botanical, medicinal, chemical and biological activities of C. natalensis and C. zuluensis. Based on the presented information, these two species are closely related and deemed as potent traditional medicines for treating and managing fever, heart problems, headache, earache, skin disorders, fatigue and respiratory problems. Cussonia natalensis and C. zuluensis should be subjected to detailed phytochemical, pharmacological and toxicological evaluations aimed at correlating their medicinal uses with their phytochemistry and pharmacological properties.

Acknowledgement

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

Conflict of Interest

The authors declare that they have no conflict of interest for this study.

Funding Support

The authors declare that they have no funding support for this study.