Abstract
Context: Warburgia (Canellaceae) species have a long history of ethnomedicinal uses in east, central and southern Africa. Due to the popularity of Warburgia as a source of ethnomedicines; all the species are severely over-harvested throughout their distributional ranges.
Objective: This review documents fragmented information on traditional uses and pharmacological evidence of the genus Warburgia.
Methods: Information on Warburgia species was collected from scientific journals, books, theses and reports via library and electronic search using Medline, Pubmed, Google Scholar, ScienceDirect and Web of Science.
Results: Ethnomedicinal uses of Warburgia species have been recorded from east, central and southern Africa for 30 human and 7 animal ailments. Warburgia species are used to treat gastro-intestinal disorders, cold, cough and sore throat; fever or malaria, respiratory and odontological ailments. Warburgia species are rich in drimane and colorotane sesquiterpenoides, and other compounds. The extracts of Warburgia, particularly those from stem bark and leaves, exhibited a wide range of pharmacological effects, including antibacterial, antifungal, antimycobacterial, antioxidant, anti-inflammatory, antifeedant, antiplasmodial, antileishmanial, anthelmintic, cytotoxic and molluscicidal activities.
Conclusion: Pharmacological results have validated the use of this genus in traditional medicine. Further investigations are needed to explore the bioactive compounds responsible for the in vitro and in vivo pharmacological effects and their mode of action.
Introduction
The genus Warburgia Engl. is a member of Canellaceae Martius, a dicot family that contains 16 species grouped in 6 genera (Kubitzki, Citation1993). Genus Warburgia was named after Dr. Otto Warburg (1859–1938), who was born in Hamburg, Germany. He was a lecturer in botany at the University of Berlin and author of several botanical papers. In southern Mozambique and South Africa, Warburgia is commonly referred to as Chibaha (Xibaha) and hence Bertolini’s original generic name Chibaca Bertol. f. The genus Warburgia with 4 plant species is the only genus of family Canellaceae that extends into the African mainland (Verdcourt, Citation1956, Citation1990). Warburgia is distributed in Democratic Republic of Congo (DRC), Ethiopia, Kenya, Malawi, Mozambique, South Africa, Swaziland, Tanzania, Uganda, Zambia and Zimbabwe.
Warburgia elongata Verdc. is a small evergreen tree or shrub endemic to the lowland coastal riverine and swamp forests of Uzaramo district, Tanzania (Verdcourt, Citation1954, Citation1956). Warburgia elongata is endangered mainly due to its small area of occupancy, extent of occurrence and the small number of mature individual plants (Lovett & Clarke, Citation1998a). It is also potentially threatened by harvesting for firewood, charcoal, building poles, tool handles, carvings and medicinal purposes (Lovett & Clarke, Citation1998a). Warburgia salutaris (Bertol. f.) Chiov. is known from a few localities in the north-eastern parts of South Africa, Swaziland, south-eastern Zimbabwe, southern Mozambique, Malawi and Zambia (Palgrave, Citation2000). It is found in evergreen montane forests including wooded ravines and along the coasts (Palgrave, Citation2000; Venter & Venter, Citation2002). Warburgia salutaris is categorized as endangered on the IUCN Red List (IUCN, Citation2012), primarily because of reduction in population size based on decline in area of occupancy, extent of occurrence and/or quality of habitat; and actual or potential levels of exploitation. It is categorized as vulnerable in Mozambique (Izidine & Bandeira, Citation2002), endangered in Malawi (Msekandiana & Mlangeni, Citation2002) and South Africa (Williams et al., Citation2008), critically endangered in Swaziland (Dlamini & Dlamini, Citation2002) and extinct in the wild in Zimbabwe (Maroyi, Citation2008, Citation2013). The species is generally slow growing in the wild; and its limited distribution and low abundance makes it vulnerable to human-induced habitat degradation and over-exploitation as a medicinal plant. Warburgia stuhlmannii Engl. is confined to dry lowland forests of Kenya and Tanzania (Verdcourt, Citation1954, Citation1956). Warburgia stuhlmannii is vulnerable mainly due to its small area of occupancy, extent of occurrence and the small number of mature individual plants (Lovett & Clarke, Citation1998b). It is also potentially threatened by harvesting for timber, firewood, building poles, carvings and medicinal purposes (Lovett & Clarke, Citation1998b). Warburgia ugandensis Sprague ssp. longifolia Verdc. is endemic to southern Tanzania (Verdcourt, Citation1956), while W. ugandensis Sprague ssp. ugandensis is more widespread, recorded in lowland rainforest, evergreen and swamp forest of DRC, Ethiopia, Kenya, Malawi, Tanzania, Uganda (Verdcourt, Citation1956, Citation1990). Both taxa are used for timber, firewood, building poles, charcoal, carvings and medicinal purposes (Lovett & Clarke, Citation1998b).
Warburgia species are characterized by aromatic and pungent bark, which is used medicinally. Warburgia salutaris, W. stuhlmannii and W. ugandensis have yielded a series of drimane sesquiterpenoids such as isopolygodial, muzigadial, polygodial, salutarisolide, ugandensidial and warburganal (Brooks & Draffan, Citation1969; Jansen & de Groot, Citation1991; Kioy et al., Citation1990; Kubo et al., Citation1977, Citation1983; Manguro et al., Citation2003; Mashimbye et al., Citation1999a; Rabe & van Staden, Citation2000; Wube et al., Citation2005; Xu et al., Citation2009). The genus certainly has a high use value. The present review compiles the fragmented information on the traditional uses and pharmacology of the Warburgia species. I hope that this information will highlight the importance of the genus and will provide baseline information for future researchers intending to do further work on genus Warburgia.
Vernacular names and traditional uses
Warburgia species are known by various vernacular names in different geographical areas in eastern, central and southern Africa (). Insight into the societal value of Warburgia species in east, central and southern Africa can be gained by examining these vernacular names. People rarely name plant species that they do not use. For example, a Swahili vernacular name of W. stuhlmannii “Pilipili mwitu” translates to “wood pepper” (Verdcourt, Citation1954), is in reference to the peppery taste of the stem bark, wood, leaves, etc; a diagnostic feature of all Warburgia species. Warburgia salutaris, W. stuhlmannii and W. ugandensis are often referred to as the “Pepperbark tree” alluding to the stem bark’s aromatic and peppery smell. The near-panaceal qualities of W. salutaris, for example, was also early recognized, not only by the traditional users but by the taxonomist who awarded it the epithet “salutaris” meaning “health giving” or “wholesome” (Hollmann & Van der Schijff, Citation1996).
Table 1. Vernacular names of Warburgia species.
A survey of literature shows no fewer than 2 vernacular names for W. elongata, 16 for W. salutaris, 5 for W. stuhlmannii, 3 for W. ugandensis ssp. longifolia and 34 for W. ugandensis ssp. ugandensis (). South Africa and Kenya have the highest number of vernacular names for W. salutaris and W. ugandensis ssp. ugandensis, respectively (). This long list of names indicates that local people in these countries have an active interest in Warburgia species. With the exception of W. elongata, all Warburgia species are well-known medicinal plants that have long been in regular demand among local communities and practitioners of traditional medicines in east, central and southern Africa. Warburgia species have been over-exploited by collectors in the wild as ethnomedicines, with the stem bark as the most sought after and traded plant part.
The traditional uses of Warburgia species are referred to in many folkloric and ethnobotanical studies done in east, central and southern Africa, where the species are still used as primary sources of traditional medicine. A total of 30 human and 7 animal ailments are treated with Warburgia species (). Gastro-intestinal disorders, cold, cough and sore throat; fever or malaria, respiratory and odontological () are the most commonly treated human ailments. Gastro-intestinal disorders, particularly cholera, diarrhea and dysentery are a major concern in Africa (Mathabe et al., Citation2006; Semenya & Maroyi, Citation2012), where dysentery and cholera usually result in high mortality rate if not treated promptly (Ribeiro et al., Citation2010). Many similarities can be recognized when the ethnomedicinal uses of Warburgia species are considered in totality over their distributional range in east, central and southern Africa (). This may be ascribed to shared cultural heritage about Warburgia species through exchange of its ethnobotanical information. The relations of people to their indigenous plants and that of other regions near or further away aids in measuring their cultural status and their contacts with each other (Gilmore, Citation1932).
Table 2. Medicinal uses of Warburgia species.
Table 3. Major ailment categories and uses reported.
The most frequently used plant parts are bark (79%), leaves (11%), roots (7.5%) and stalks (2.1%) (). It is well recognized by conservationists that medicinal plants primarily valued for their root parts and those which are intensively harvested for their bark often tend to be the most threatened by over-exploitation (Flatie et al., Citation2009). This is the case with all Warburgia species, with its users targeting mainly stem bark as source of ethnomedicine. Warburgia remedies are often utilized in the form of decoction or infusion (54.5%), bark chewed and juice swallowed (27.3%) and ointments or paste (10.4%) (). Other preparation methods include smoking, use of bark fungus, application of bark powder on incision, chewing of bark after it has been boiled and bark powder blown into patient’s anus (). Most (89.9%) of the preparations are prescribed orally (). The majority of the Warburgia remedies (91.3%) are used as monotherapies (). Multitherapies are mostly used in herbal medicines involving W. salutaris in South Africa (). A mixture of W. salutaris bark powder and Erythrophleum lasianthum Corbishley (Fabaceae) is taken as snuff as a remedy for headache (Hutchings et al., Citation1996). Powdered bark of W. salutaris and leaves of Cannabis sativa L. (Cannabaceae) are smoked as herbal remedy for cough (Hutchings et al., Citation1996). Ointments made from a mixture of powdered bark of W. salutaris, leaves of Hibiscus surrattensis L. (Malvaceae) and fat are applied on inflammation of the urethra, irritation and sores on the penis (Hutchings et al., Citation1996). The use of multiple therapies in traditional medicine based on combining plants has recently been shown to increase the efficacy of the herbal medicine (Zonyane et al., Citation2012). Research by Bussmann and Sharon (Citation2006) showed that the use of more than one plant species to prepare a remedy for ailments is attributed to the additive or synergistic effects that they could have during ailment treatment.
Figure 1. Characteristics of Warburgia herbal medicines in east, central and southern Africa. (A) Plant parts used, and (B) herbal preparations. Other herbal preparations in B include smoking, use of bark fungus, application of bark powder on incision and chewing of bark after it has been boiled.
In addition to the medicinal uses, all Warburgia species are used as timber. Warburgia elongata is cultivated for shade and ornamental purposes (Lovett et al., Citation2006). Warburgia salutaris can also be grown around boundaries of homesteads as a barrier, hedge; and ornamental and shade tree (Venter & Venter, Citation2002). Fresh or dried leaves of W. salutaris are used in various dishes to add an aroma and peppery taste (Venter & Venter, Citation2002). Research done by Nichols (Citation2005) in South Africa showed that the leaves of W. salutaris are browsed by hippos. Warburgia stuhlmannii is used in east Africa as a spice or curry and oil from the tree is used as a perfume (Orwa et al., Citation2009). Warburgia ugandensis is used for fodder, food seasoning, insecticide, mulch for soil conservation, ornamental, resin, shade and toothbrush (Maundu & Tengnas, Citation2005; Verdcourt, Citation1954).
Phytochemistry
Warburgia species have high pharmaceutical value, both for humans and livestock, this is due to the abundance of drimane and colorotane sesquiterpenoides (Frum et al., Citation2005; Frum & Viljoen, Citation2006; Jansen & de Groot, Citation1991; Kioy et al., Citation1990), tannins and mannitol (Van Wyk & Gericke, Citation2000; Watt & Breyer-Brandwijk, Citation1962). Drimane sesquiterpenes that have been isolated from W. salutaris include: 11α-hydroxycinnamosmolide (1) () (Madikane et al., Citation2007), isopolygodial (isotadeonal) (2), warburganal (3) (Mashimbye et al., Citation1992), polygodial (4) (Mashimbye, Citation1993), salutarisolide (5) (Frum & Viljoen, Citation2006; Frum et al., Citation2005; Mashimbye et al., Citation1999a), muzigadial (cannelal) (6) (Rabe & van Staden, Citation2000), ugandensidial (cinnamodial) (7), isopolygodial (8) (Mashimbye et al., Citation1999a), and mukaadial (9) (Mashimbye et al., Citation1999b). Other drimane type sesquiterpenes isolated from W. salutaris include isodrimenol (10), drimenol (11), confertifolin (12) and a non-sesquiterpene monoaldehyde, polygodial (13) (Mashimbye et al., Citation1999b). Mohanlall & Odhav (Citation2009) isolated a sesquiterpenoid 5, 10-dihydro-6, 7-dimethyl-4H-benzo [5,6] cyclohepta [1, 2-b]-furan (14) from W. salutaris bark.
Figure 2. Drimane, colorotane sesquiterpenoides and other compounds isolated from Wurburgia species.
Phytochemical investigations of W. stuhlmannii leaves showed the presence of mukaadial 6-O-β-d-glucopyranoside (15), mukaadial 6-O-α-l-rhamnopyranoside (16) together with a novel flavonol glycosides 3′,5′-O-dimethylmyricetin 3-O-β-d-2″,3″-diacetylglucopyranoside (17)and 3′-O-methylquercetin 3-O-β-d-2″,3″,4″-triacetylglucopyranoside (18) (Manguro et al., Citation2003). Other compounds isolated from W. stuhlmannii include mukaadial (9), deacetylugandensolide (19), quercetin (20), kaempferol (21), kaempferol 3-O-α-l-rhamnopyranoside (22), quercetin 3-O-β-d-glucopyranoside (23), kaempferol 7-O-β-d-glucopyranoside (24), myricetin 3-O-α-l-rhamnopyranoside (25), quercetin 3-O-α-l-rhamnopyranoside (26), quercetin 3-O-sophoroside (27) and isorhamnetin 3-O-β-d-glucopyranoside (28) (Kioy et al., Citation1990; Manguro et al., Citation2003).
Phytochemical investigations of W. ugandensis showed the presence of ugandensolide (29), ugandesidial (cinnamodial) (7), warburgin (30) and warburgiadione (31) from the heartwood (Brooks & Draffan, Citation1969), cinnamolide (32), cinnamolide-3β-acetate (33), 11α-hydroxymuzigadiolide (34), 7α-hydroxy-8-drimen-11,12-olide (35), deacetylugandensolide (19), linoleic acid (36), mukaadial (9), muzigadiolide (37), ugandensolide (29), ugandensidial (cinnamodial) (7), muzigadial (cannelal) (6), pereniporin B (38), polygodial (4) and waburganal (3) from the stem bark (Kioy et al., Citation1990; Kubo et al., Citation1976; Wube et al., Citation2005); and monoterpenes (Kioy et al., Citation1990) from the leaves. Wube et al. (Citation2005) isolated coloratane sesquiterpenes 6α,9α-dihydroxy-4(13),7-coloratadien-11,12-dial (39), 4(13),7-coloratadien-12,11-olide (40), and 7β-hydroxy-4(13),8-coloratadien-11,12-olide (41) from the stem bark of W. ugandensis.
Pharmacological reports
Antibacterial activity
In a preliminary antibacterial screening of South African medicinal plants used for treating wounds, sores and boils, W. salutaris stem bark methanol extract inhibited the growth of Escherichia coli (Rabe & van Staden, Citation1997). The leaves and bark of W. salutaris have also demonstrated similar antibacterial properties (Zschocke et al., Citation2000). In addition, Zschocke et al. (Citation2000) reported that the TLC-fingerprints of the leaf and bark extracts of W. salutaris were very similar. In further studies on W. salutaris by Rabe & van Staden (Citation2000), fractionation of the ethyl acetate extract of the stem bark by chromatographic techniques yielded muzigadial which was found to be the main antibacterial agent with an MIC of 12.5 μg/ml against both Staphylococcus aureus and Bacillus subtilis; and 50 μg/ml against Micrococcus luteus. In another experiment by Mohanlall and Odhav (Citation2009), W. salutaris heartwood extract in methanol/ethyl acetate and stem bark in methanol/hexane showed activity against Staphylococcus aureus and Bacillus subtilus. Leaf extract in ethyl acetate/dichloromethane showed activity against Escherichia coli, Staphylococcus aureus and Bacillus subtilus (Mohanlall & Odhav, Citation2009). Mbwambo et al. (Citation2009) demonstrated that ethanol extract from the dried leaves of W. ugandensis exhibited antibacterial activity against Staphylococcus aureus, Escherichia coli, Vibrio cholerae, and Bacillus cereus. In another experiment by Kuglerova et al. (Citation2011), W. ugandensis stem bark exhibited antibacterial activity with an MIC of 256 μg/ml against Staphylococcus aureus and 512 μg/ml against Enterococcus faecalis.
Antifungal activity
Experiments by Mohanlall and Odhav (Citation2009) demonstrated that W. salutaris heartwood extract in methanol/ethyl acetate and stem bark in methanol/hexane have antifungal activity against Fusarium moniliforme. Leaf extract of W. salutaris in dichloromethane showed antifungal activity against Fusarium moniliforme (Mohanlall & Odhav, Citation2009). Taniguchi et al. (Citation1983) demonstrated using a two-fold dilution method that warburganal in W. ugandensis exhibited a broad antifungal activity against yeasts and filamentous fungi; and it was highly active against Saccharomyces cerevisiae, Candida utilis and Sclerotinia libertiana. Olila et al. (Citation2001) demonstrated that W. ugandensis ethanol extract of stem bark had antifungal activity against Candida albicans. Mbwambo et al. (Citation2009) demonstrated that ethanolic extract from the dried leaves of W. ugandensis exhibited antifungal activity against Candida albicans and Cryptococcus neoformans. In another experiment by Kuglerova et al. (Citation2011), W. ugandensis stem bark exhibited antifungal activity with an MIC of 256 μg/ml against Candida albicans. Warburgia ugandensis was also found to exhibit antifungal activity against Candida utilis (Kubo, Citation1995; Taniguchi et al., Citation1978).
Antimycobacterial activity
Madikane et al. (Citation2007) show that crude extracts and drimane sesquiterpenoid lactone, 11α-Hydroxycinnamosmolide obtained from W. salutaris exhibited anti-mycobacterial activity against Mycobacterium tuberculosis H37Rv and Mycobacterium bovis BCG Pasteur. The crude extract and purified compound inhibited pure recombinant arylamine N-acetyltransferase (NAT), an enzyme involved in mycobacterial cell wall lipid synthesis (Madikane et al., Citation2007). Dichloromethane extract of the stem bark of W. ugandensis demonstrated antimycobacterial activity against Mycobacterium aurum, Mycobacterium fortuitum, Mycobacterium phlei and Mycobacterium smegmatis (Wube et al., Citation2005). The active constituents showed MIC values ranging from 4 to 128 μg/ml compared to the antibiotic drugs ethambutol with MIC ranging from 0.5 to 8 μg/ml and isoniazid with MIC ranging from 1 to 4 μg/ml (Wube et al., Citation2005). Therefore, the use of W. ugandensis stem bark to treat tuberculosis in traditional medicine can be attributed to the presence of linoleic acid and the drimane sesquiterpenoids.
Anti-inflammatory and antioxidant properties
The leaves and bark of W. salutaris have been shown to display equipotent activity against the cyclooxygenase-1 enzyme (Zschocke et al., Citation2000). Methanol extracts of W. salutaris leaves displayed 5-lipoxygenase inhibitory activity with an IC50 of approximately 32.11 ppm (Frum, Citation2006). In the same study, warburganal and mukaadial displayed 5-lipoxygenase inhibitory activities with IC50 values of 61.86 ppm and >100 ppm respectively (Frum, Citation2006). These results serve as evidence that both mukaadial and warburganal are contributing to the 5-lipoxygenase inhibitory activity of W. salutaris. In another experiment, Frum (Citation2006), demonstrated that W. salutaris bark has anti-inflammatory activity; and mukadiaal and warburganal were partially responsible for displayed anti-inflammatory activity of the plant species. Due to its antioxidant properties, extracts of W. salutaris showed protective effects against crystalline silica induced inflammatory cytokine expression, activation of nuclear transcription factor-κB, DNA strand breakage and lipid peroxidation (Leshwedi et al., Citation2008). Hence, W. salutaris may be a potential therapeutic agent against the fibrogenic and carcinogenic effects of crystalline silica (Leshwedi et al., Citation2008). Antioxidant activity of the methanol extract of W. salutaris could possibly be due to the presence of flavonoid compounds (Frum, Citation2006). Warburgia ugandensis showed antioxidative properties with IC50 = 6.59 μg/ml, which was very close to the inhibitory effect achieved by reference compound Trolox (IC50 = 3 μg/ml), suggesting strong potent antioxidative properties (Kuglerova et al., Citation2011).
Molluscicidal activity
Aqueous extracts of dried leaf samples of W. salutaris were assessed for in vitro molluscicidal activity against Bulinus africanus and found to be active (IC50 = 2.483 mg/ml) (Clarke & Appleton, Citation1997). Warburganal has shown effective molluscicidal activity (Appleton et al., Citation1992; Nakanishi & Kubo, Citation1978). Warburgia stuhlmannii and W. ugandensis demonstrated molluscicidal activity (Kubo et al., Citation1983), making them potential in the control of schistosomiasis. Drimane sesquiterpenoids are known to have molluscicidal activity (Frum, Citation2006; Fukuyama et al., Citation1982; Taniguchi & Kubo, Citation1993).
Antifeedant activity
The methanol extract of the bark of W. ugandensis was found to exhibit potent insect antifeedant activity against the African armyworm Spodoptera exempta (Kubo, Citation1991, Citation1995). Based on fractionation guided by the assay, three antifeedants were isolated from the bark, leaves and fruit of W. ugandensis (Kubo & Nakanishi, Citation1977; Kubo, Citation1993, Citation1995). Warburganal and muzigadial inhibited the feeding of larvae of two species of African armyworm, the monophagous Spodoptera exempta and the polyphagous Spodoptera littoralis at a concentration of 0.1 ppm in a regular leaf disk method (Kubo & Nakanishi, Citation1977). In another experiment, Kubo et al. (Citation1977) found that polygodial and ugandensidial were also antifeedants for Spodoptera but less active. Antifeedant activity was also observed against Spodoptera frugiperda, Heliothis armigera and Heliothis virescens (Meinwald et al., Citation1978). Sesquiterpene dialdehyde present in W. stuhlmannii and W. ugandensis demonstrated insect antifeedant against the African armyworm Spodoptera exempta (Kubo et al., Citation1977). Drimane sesquiterpenoids are known to have insect-antifeedant activity (Frum, Citation2006; Fukuyama et al., Citation1982; Taniguchi & Kubo, Citation1993).
Antiplasmodial activity
Muthaura et al. (Citation2007b) investigated antiplasmodial activity of W. stuhlmannii showing that the methanol extract was highly active against Plasmodium falciparum clones. The activity of W. stuhlmannii could presumably be ascribed to the presence of the drimane sesquiterpenes in addition to flavonols, which collectively may be involved in the antiplasmodial activity. Anti-plasmodial activity of stem bark of W. ugandensis has also been demonstrated against Plasmodium knowlesi and P. berghei (Were et al., Citation2010). Methanol extracts from various parts of W. ugandensis have shown antiplasmodial activity with an IC50 value of less than 5 mg/ml against both chloroquine-sensitive (D6) and chloroquine resistant (W2) strains of Plasmodium falciparum (Nanyingi et al., Citation2010). Extract of W. ugandensis also showed moderate in vivo antiplasmodial activity in mice infected with P. burghei (Nanyingi et al., Citation2010). The plant extracts offer the potential for the isolation of lead antimalarial compounds, or for the characterization of some active compounds that could be used as markers for standardization of the extracts for use as antimalarials.
Cytotoxic, anthelmintic and antileishmanial activities
Mbwambo et al. (Citation2009) demonstrated that ethanolic leaf extracts of W. ugandensis exhibited cytotoxic activity (95% CI), against brine shrimp larvae with reference to cyclophosphamide, a standard anticancer drug. Research by Xu et al. (Citation2009), showed that the ethyl acetate extract of W. ugandensis bark exhibited potent cytotoxic activity on KB cell line (99% and 64% inhibition at 10 and 1 μg/ml, respectively. Drimane sesquiterpenoids are known to have cytotoxic activities (Frum, Citation2006; Fukuyama et al., Citation1982; Taniguchi & Kubo, Citation1993). Ethanol, dichloromethane and water extracts at 2.5, 5, 10 and 30% concentrations of W. salutaris exhibited anthelmintic effects against Haemonchus contortus (Ahmed et al., Citation2012).
Ngure et al. (Citation2009) demonstrated in vitro antileishmanial activity of W. ugandensis hexane extract against Leishmania major and Leishmania donovani. The hexane extract had the best activity against L. major promastigotes and amastigotes with IC50 value of 9.95 for promastigotes and 8.65 for amastigotes and MIC of 62.5 μg/ml (Ngure et al., Citation2009). The activity of the hexane extract on amastigotes was comparable to that of pentostam and amphotericin B. Similar results were obtained for L. donovani with IC50 values of 8.67 for promastigotes and 100-fold reduction of amastigotes in macrophage cultures (Ngure et al., Citation2009). The water and methanol extracts of the stem bark of W. ugandensis showed anti-leishmanial activity (with IC50 of 1.114 mg/ml against Leishmania major) and immunomodulative effects (Githinji et al., Citation2010). These results confirm that natural products from Warburgia species are potential sources of new and selective agents for the treatment of important tropical diseases caused by protozoans.
Other activities
A sesquiterpene characterized as muzigadial, isolated from W. ugandensis showed trypanocidal activity against Trypanosoma brucei in vitro (Olila et al., Citation2001). A cytotoxic sesquiterpine (characterized as muzigadial) has been isolated from W. ugandensis and used to treat trypanosomiasis (Olila et al., Citation2002) and other parasitic diseases (Kioy et al., Citation1990) in animals. In another experiment by Rugutt et al. (Citation2006) in Kenya, W. ugandensis showed its activity against soil pathogens namely Fusarium oxysporum, Alternaria passiflorae and Aspergillus niger.
Conclusion
Data collected in the present review illustrates that drimane and colorotane sesquiterpenoides are the major constituents in Warburgia genus as they have been detected in three out of four species of the genus. Despite the presence of this phytochemical compound and other phytochemical metabolites, Warburgia species have not been fully explored. Previous research by Heinrich et al. (Citation2005) has shown that phytomedicines are complex mixtures of compounds and they have a more pronounced effect than individual compounds. The role of such complex mixtures and the “ideal” composition of an active extract needs to be investigated first using a combination of in vitro (or in vivo animal) techniques in combination with phytochemical or metabolomic techniques (Jagtap & Bapat, Citation2010; Verpoorte et al., Citation2005). There is need therefore to validate the traditional medicinal applications of Warburgia species through tests in vitro and in vivo as well as clinical trials. Further investigations on phytochemical constituents and subsequent screening are needed for opening new opportunities to develop pharmaceuticals based on Warburgia constituents.
Reports of the uses of Warburgia species for the same ailments in east, central and southern Africa indicate that the species are valuable sources of ethnomedicine. Pharmacological studies carried out on crude extracts and purified compounds of Warburgia species provided support for the documented traditional uses, and have revealed this genus to be a valuable source for medicinally important molecules. With further research, Warburgia species may also prove to be suitable for product development. Significant advances in the utilization of W. salutaris in southern Africa has been made over the years, and also an increasing number of commercial products of the species have appeared in the market (Maroyi, Citation2013). Warburgia salutaris is sold in South Africa in tablet form to treat bronchitis, chest infections and ulcers (Botha et al., Citation2004). Tablets made from the leaves are also used as a natural antibiotic, thought to be effective against oral and esophageal thrush (Botha et al., Citation2004; Van Wyk et al., Citation2009).
Warburgia species are used as fresh and dried plant material. The stem bark is widely used; and leaves and roots are used as well. As all Warburgia species are undergoing considerable decline throughout their natural habitats in east, central and southern Africa due to over-exploitation for medicinal purposes, the presence of biologically active drimane sesquiterpenoides in the leaves provides rational basis for their substitution in ethnomedicine (Drewes et al., Citation2001; Frum, Citation2006; Zschocke et al., Citation2000). Expansion of research materials would provide more chances for discovery of new bioactive principle from the genus Warburgia. Validating the correlations of the ethnomedicinal uses, bioactive substances and pharmacological effects is of special importance, and is still the primary task for future research. Efforts are also needed to investigate the physiological and biochemical functions demonstrated by these species, identify the individual bioactive natural products, and illustrate their mechanism of action. The current results are largely limited to in vitro bioassay, and in vivo studies using laboratory animals. Furthermore, the promising results confirmed by animal models should be further investigated by clinical trials. The pharmacological study of Warburgia species is still in its infancy and a great deal of work needs to be done. For example, with our present knowledge of chemistry, phytochemistry and pharmacological activities of Warburgia species, it is not yet known whether there are significant qualitative and quantitative phytochemical differences between the various plant material forms used in ethnomedicine. Such phytochemical analysis will highlight the chemical constituents in Warburgia plant material and how the limited population numbers of the plant group can be utilized.
Declaration of interest
The author reports no conflicts of interest. The author alone is responsible for the content and writing of the paper.
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