Introduction

Southern Africa contains over 30,000 plant species, many of which have potential as economically useful plants that are relatively unknown to Western civilization due to past trade embargoes. In fact, only 50 of these species are currently traded to any significant degree.¹ A few hundred of these species are already known in preliminary research to have potentially beneficial biological activities. The scale of a potential marketing opportunity is large. With new ethnic ingredients in cosmetics and so-called cosmeceuticals being launched into the Western market, it is only a matter of time before African botanicals are targeted as potential sources of new drugs, cosmetics, and cosmeceuticals by members of industry.

One native African plant with great marketing potential is the sausage tree (Kigelia africana; syn. K. pinnata*). Kigelia is now generally considered to be a highly variable monospecific genus of the family Bignoniaceae. Although several species have been reported in the past, they are also synonomous with Bignonia africana, K. abyssinica, K. acutifolia, K. aethiopum, K. africana, K. ellioti, K. elliptica, K. impressa, and K. spragueana. The aim of this article is to review the ethnobotanical uses and scientific research regarding this useful plant.

Nomenclature and Botanical Description

The adult sausage tree has spectacular fruits; these can weigh several kilograms and resemble large sausages, hence the tree’s common English name. In Afrikaans, it is known as worsboom, kalabasboom, and komkommerboom; it is also known as umfongothi (Zulu), muvevha (Venda), and mvunguti (Chichewa-Malawi). It is a semi-deciduous-to-deciduous tree that grows up to 25 meters tall. It can be found all over sub-Saharan Africa, but its native range extends from Tanzania in the north to KwaZulu–Natal in South Africa in the south. Its habitat includes open woodlands and moist places such as riverbanks on alluvial soils, but is widespread throughout the savannah areas of tropical Africa. (See map 1)

The tree’s bark is grey and smooth and flakes in older specimens. Leaves are crowded near the tips of branches, and young leaves are brownish red. Flowers bloom in long, loose, pendulous sprays of 5-12 flowers. Petals are a deep, velvety red with yellow veining on the outside. The cylindrical fruit is pendulous on a long fruit stalk. The fruit can grow up to 1 meter long and 20 cm wide and is grey and rounded at the apex.

The tree flowers from August to October and fruits from December to June. Depending on the climate, the sausage tree is remarkably fast-growing and can mature in 4 to 5 years. Ripe fruits can weigh up to 12 kg and can cause considerable damage when they drop. With its fast growth rate, spreading canopy, and interesting flowers and fruit, Kigelia is a popular street tree in South Africa and is grown to provide shade in Australia. It can also be used successfully for bonsai; the thick stem makes for an attractive feature.²

Harvesting

Kigelia begin to flower from the age of 6 years. Mature fruits can be found on trees year-round, but fruit collected from the ground is often of poor quality as it is quickly infested with insects or consumed by animals and therefore not used by humans. Fresh fruit from the trees are used to produce dried fruit pulp which has a range of applications. Seed germination improves after 1 year of storage, which could be due to physiological dormancy or simply because the fruits are shed before the seeds are fully mature and continue their development on the ground naturally. Soaking the seeds in boiling water for 1 minute aids germination—an 80% success rate has been noted. Cuttings can also be used for propagation. Truncheons cut from the tree can be planted directly into soil and root readily. Kigelia pinnata is pollinated by bats, but insects are also attracted to the flowers’ color and fragrance.

The trees are normally found on flatlands which have a high water content (alluvial soils), and are periodically flooded, thereby often rendering them unsuitable for farming other crops. This benefits the Kigelia trees because it prevents large losses of the higher diameter fruit, as harvesting from flooded plains can become difficult. This flooding rescues trees from damage by herbivores (e.g., baboons, elephants) and allows for regeneration.

Collection

In Malawi, the fruit is collected by a company called TreeCrops with support from the local community. Only fruit from trees within the forest areas are collected to avoid contamination, as TreeCrops regards farmlands as areas not suitable for sustainable collection and tries to preserve the organic agricultural status of the wild-harvested Kigelia fruit. The forest areas are established by the local community and mapped and monitored by TreeCrops. The land use is contracted for a period of at least 3 years to maintain the vegetation status and the forest ecology dynamics.

Harvestable Yields

During trials, TreeCrops established an average weight per fruit of 4.5 kg. Counts of the fruit per tree gave large variations between those not bearing fruit and those with over 200 fruits per tree. The average number was 41 fruits, meaning approximately 185 kg of fruit can be harvested per tree

Sustainability

Annual assessments are carried out on the sustainable harvestable yield per tree. The average figure is multiplied with the number of trees per registered forest area and compared with the market demand. The real threat to sustainability is not over-harvesting from the tree, but the influence of humans—particularly grazing of wildstock, wildfires, and woodland destruction, as farming poses a threat to the natural vegetation. It is hoped that via TreeCrops and the local community, establishment of woodland areas shall reduce the threat of forest destruction from local slash-and-burn agriculture methods and ensure not only the sustainability of the Kigelia resource, but the entire ecosystem and its delicate relationships among K. pinnata and other interdependent species.

Traditional Medicinal Uses

There are many anecdotal uses of the sausage tree.^3,4,5 The powdered mature fruit is applied as a dressing in the treatment of wounds, abscesses, and ulcers. The green fruit is used as a poultice for syphilis and rheumatism, and a poultice made from leaves is used as a treatment for backache. An infusion is made from the ground bark and fruits to treat stomach problems in children, and an infusion from the roots and bark is taken to treat pneumonia.² In Zimbabwe, a decoction made from the bark is gargled to relieve toothache. The whole head is also washed with an infusion made from the bark to treat epilepsy.⁶ Fruit is used as a snakebite antidote, to fatten babies, and also as a purge for stock animals. In Ghana, fruit and roots are boiled with the “tassels” of plantain flowers as a “woman’s remedy,” while fruit is rubbed on the breasts of young girls in Cape Verde to enhance their development.⁷ Fruit is also used by the Vhavenda men of the Limpopo province of South Africa to increase penis size.⁸ This local use was thought explainable by the Doctrine of Signatures (a theory that the use of a plant for treating disease was indicated by its color and/or appearance, e.g. the shape of the fruits of K. pinnata resemble a penis and was seen as an aphrodisiac). Bark and leaf decoctions are taken as abortifacients, and fruit is commonly added to beer as an aphrodisiac in Kenya.⁹ In West Africa, leaves are used for dysentery, stomach and kidney ailments, snakebite, and wounds, while stems and twigs are used to restore taste and for sores, wounds, snakebite, rheumatism, and dysentery, as well as other stomach and kidney ailments. Fruit is used for sores, to restore taste, and for constipation, gynecological disorders, hemorrhoids, lumbago, dysentery, and as a purgative and galactagogue. Roots are used for gynecological complaints, constipation, and tapeworm. Notably, there are several anecdotal reports of the use of crude creams of the Kigelia fruit extract in South Africa for the treatment of solar keratosis (a pre-cursor to skin cancer) and malignant melanoma.^3,10

The fruit is reported to have strong purgative properties, and unripe fruit is reputed to be highly poisonous if taken orally.² Fruit sometimes causes blistering of the tongue and skin.^11,12

The seeds of K. aethiopum (synonymous with K. pinnata) are partly roasted and placed in beer, but if left too long render it poisonous. It has also been alleged that a woman died 36 hours after vomiting when this plant was used as an abortifacient. Additionally, Kigelia is used in beer to enlarge the sexual organs and reports exist of use for criminal poisoning.¹²

Non-Medicinal Uses

While baboons are known to eat the fruits, the pulp of unripe fruits are said to be posionous to humans. However, slices of mature baked fruits are used to ferment and flavor traditional African beer.¹³ The seeds of ripe fruits can also be roasted in warm ash and consumed and are reported to be energy-rich, with significant amounts of phosphorous, protein, and lipids. In turn, the seed oil is rich in oleic acid and essential fatty acids, and has potential to be an important nutritional resource.¹⁴ Additionally, the leaves of K. pinnata have been positioned as an important nutritional resource, comparable to other green leafy vegetables such as spinach.¹⁵ They are consumed by lactating women in various parts of sub-Saharan Africa as they are thought to enhance the volume and quality of breastmilk. The dried leaves contain levels of essential amino acids that may provide beneficial health benefits as well as other minerals and nutrients including calcium, magnesium, and iron.¹⁵

The flowers are eaten by domestic stock and game, kudu, nyala, impala, and grey duiker. Leaves are consumed by elephants and kudu. The tree produces good quality timber and the wood is reported to be easy to work with. People living along large rivers, especially the Chobe and Zambezi, make their dugout canoes from the tree.¹⁶

The boiled fruits are also used to produce a red dye and the roots are reported to produce a yellow dye.⁵ Much of the traditional use of K. pinnata surrounds topical application to the skin. It is reported that the Tonga women of the Zambezi Valley regularly apply cosmetic preparations of the fruits to their faces to maintain a blemish-free complexion.⁵ Although not fully identified, this traditional use, like many others, is linked to the bioactive components of K. pinnata.

Chemical Constituents

It is always important to understand what secondary metabolites are found in a plant as they may form the basis for its traditional use, particularly if they are the same as, or similar to, compounds from other species. The family Bignoniaceae, of which K. pinnata is a member, is noted for the occurence of many secondary metabolites including iridoids, naphthoquinones,¹⁷ saponins, tannins, flavonoids, coumarins, and several others, and is said to be an important source of bioactive compounds.¹⁸ The roots and bark of K. pinnata have the naphthoquinone lapachol and the dihydroisocoumarin kigelin as major compounds.^19,20 Several other compounds, including the naphthaquinoids kigelinone, pinnatal, and isopinnatal, and the sterols stigmasterol and beta-sitosterol have been isolated from the bark.²⁰ The flavonoids 6-hydroxyluteolin-7-alpha-glucoside and luteolin have been isolated from the fruits and the leaves 21 while the roots have also yielded dihydroisocoumarins, lapachol, and sterols, and the presence of iridoid glycosides also has been reported.^19,22,23 Additionally, a study of the heartwood identified the presence of lapachol, dehydro-alpha-lapachone, tecomaquinone-I, D-sesamin, paulownin, kigeliol, kigelinone, β-sitosterol, and stigmasterol.²⁴

Iridoids

The iridoids found in Kigelia correspond to the 9-carbon skeleton type, e.g., catalpol, found in other members of the Bignoniaceae family. The major iridoids found in the root bark and stem bark of K. pinnata are specioside, verminoside, and minecoside.²⁵ These iridoids, specifically verminoside, have had the most scientific literature published on their unique anti-inflammatory properties. In vitro assays showed that verminoside had significant anti-inflammatory effects and inhibited both iNOS (nitric oxide synthase) expression and NO (nitric oxide) release in macrophage cell lines.^26,27,28 Further research also was undertaken in vitro on the cytotoxicity and cutaneous irritation of Kigelia fruit crude extract on skin cells grown in monolayers (ML) and in reconstituted human epidermis (RHE, 3D). These tests found that neither the iridoids verminoside nor verbascoside extracted from the fruit of the plant caused any release of pro-inflammatory mediators, and no histomorphological changes were noted of the RHE,²⁹ further suggesting anti-inflammatory activity

Antiamoebic properties of iridoids also have been reported.³⁰ Extracts from the stem bark of K. pinnata were tested in vitro against Entamoeba histolytica. Butanol extracts from the K. pinnata stem bark showed in vitro antiamoebic activity. Three known iridoids—specioside, verminoside and minecoside—were isolated from stem bark and tested in isolation, and verminoside was shown to have a 2-fold antiamoebic activity as compared to a standard drug (metronidazole).³⁰

Further analysis of the fruits by scientists in Egypt has identified 4 new iridoid compounds and 7 compounds already known.³¹ A new furanone derivative formulated as 3-(2’-hydroxyethyl)-5-(2”-hydroxypropyl)-dihydrofuran-2(3H)-one, and 4 new iridoids named 7-hydroxy viteoid II, 7-hydroxy eucommic acid, 7-hydroxy-10-deoxyeucommiol, and 10-deoxyeucommiol have been isolated together with 7 known iridoids, jiofuran, jioglutolide, 1-dehydroxy-3,4-dihydroaucubigenin, des-p-hydroxybenzoyl kisasagenol B, ajugol, verminoside, and 6-trans-caffeoyl ajugol.

Phenylpropanoid and Phenylethanoid Derivatives

Further phytochemical investigation of the fruits of K. pinnata has yielded a new phenylpropanoid derivative identified as 6-p-coumaroyl-sucrose together with 10 known phenylpropanoid and phenylethanoid derivatives and a flavonoid glycoside. Compounds identified were 6-O-caffeoyl-β-D-fructofuranosyl-(2-1)-α-D-glucopyranoside 2-(3-hydroxy-4-methoxyphenyl) ethyl O-α-L-rhamnopyranosyl-(1-3)-[β-D-gluco-pyranosyl-(1-6)]-(4- O-feruloyl)-β-D-glucopyranoside, decaffeoylacteoside, acteoside, isoacteoside, jionoside D, echinacoside, 6-caffeoylglucose, and 6-feruloylsucrose while a flavonoid glycoside was identified as isoschaftoside.³²

Naphthoquinones

In some South American species of Bignoniaceae, naphthoquinones are present in quite large amounts and influence the color of the wood. Lapachol was identified within root and bark extracts.¹⁹ The characteristic compound of several species of Tabebuia, a related genus of the Bignoniaceae in the Western Hemisphere (mainly South America), lapachol is known to be cytotoxic and at one time was investigated as a potential treatment for cancer by the National Institutes of Health in the United States. Lapachol has been reported as present in small amounts in the wood and roots of K. pinnata by several investigators.¹⁷ Two pairs of monoterpenoid-naphthaquinoid compounds—named pinnatal and isopinnatal—and kigelinol and isokigelinol, unique to K. pinnata, have been isolated from the roots and fruit of the plant.³³

Coumarins

Researchers in India^17,19 identified and isolated from the root and the bark of K. pinnata 2 new dihydroisocoumarins: kigelin, and O-methylkigelin.

Flavonoids

The flavonoids 6-hydroxyluteolin-7-alpha-glucoside and luteolin have been isolated from the fruits and the leaves.²¹ The flavonol quercetin and 4 flavonones, luteolin, its 6-OH analogue, and corresponding 7-O glucosides, were isolated from the leaves and fruits of K. pinnata.

Fatty Acids

Palmitic acid, already known to possess antibacterial activity, was identified in the fruit extract of Kigelia.³⁴

Lignans

The lignan kigeliol was isolated from the wood and was the only lignan reported until 1999, when the neolignan balanophonin was isolated from the stembark.¹⁷

Steroids

The common steroids β-sitosterol and stigmasterol have been isolated by various workers from the bark and the root.¹⁷

Biological Activities

Most, if not all, of the experimentally demonstrated biological activity of K. pinnata has been connected in some way to its traditional uses.

Cytotoxic Activity

Anecdotal reports allege that applications of ethanolic extracts from the fruit have shown remarkable effects on solar hyperkeratoses and simple warts. The napthaquinoids norviburtinal and isopinnatal have been shown to inhibit cancer cell growth in culture.³⁵

Based on the anecdotal reports of anti-melanoma activity, crude dichloromethane extracts of K. pinnata stem bark and fruit were tested and showed cytotoxic activity in vitro against cultured melanoma and other cancer cell lines.^4,10,35,36

The dichloromethane extract of stem bark had been tested previously and found to give IC50 values between 2 and 5 µg/ml and, in this study, a similar extract also gave IC₅₀ values between 1 and 4 µg/ml.³⁵ (See Table 1E online^†)

The US National Cancer Institute (NCI) has recommended that if the IC₅₀ value is less than 4 mcg/ml, then the extract/compound can be considered as having a cytotoxic effect. It is therefore apparent that these extracts possess such activity and that the activity of some of the fractions makes them candidates for further investigation. It appears that the extracts contain more than one active compound since activity of less than 4 mcg/ml was displayed by several fractions.³⁵ (See Tables 1E and 2E online^†). Furthermore, work published by the Centre for Cancer Research and Cell Biology at Queen’s University, Belfast, Ireland, reports that of the compounds identified and linked to cytotoxicity against human melanoma cells, furo-naphthoquinones were found to be the most potent. These compounds also demonstrated a cytotoxic effect in 2 human breast cancer cell lines; the authors suggest follow-up research into the impact of further modifications of the isocoumarin and furo-naphthoquinone moieties.³⁷

The fractions B4 and F4 (See Table 1E^†) were selected for further investigation and isolation of constituents since they showed the greatest and most consistent cytotoxic activity in all the melanoma cell lines tested. Thin-layer chromatography (TLC) examination of fractions of both stem bark and fruits contained the same 2 prominent zones, isolated and characterized as norviburtinal, isopinnatal, and beta-sitosterol.

Beta-sitosterol was shown by TLC to be present in all the active fractions, but it displayed little activity when tested and thus is unlikely to be responsible for the activity shown. Norviburtinal showed a much greater cytotoxic effect but showed little selectivity toward melanoma cell lines. Isopinnatal displayed slightly greater cytotoxic activity against the melanoma cell lines,³⁵ but its high cytotoxicity against the non-cancer fibroblasts indicates that it probably has a general cytotoxic effect that precludes it from being considered as a lead molecule for novel anticancer agents (see Tables 1E and 2E^†).

If norviburtinal is the major cytotoxic compound present in the fractions, then its concentration should approximate to the IC₅₀ value of the fraction or extract. The calculated concentration of norviburtinal shows that its concentration in the active fractions is well below its IC₅₀ value; so although it probably contributes to the overall cytotoxic effects observed, it is likely that other active substances are present that eluded isolation due to their small amounts or because of decomposition during the fractionation and isolation procedures (see Table 3E online†). The presence of other napthaquinoids has been reported from the stem bark, but they were not detected in this investigation. The discrepancy between content of norviburtinal and cytotoxicity might also be explained by the possibility that other substances present in the bark or fruits work in synergy with norviburtinal.³⁵ As shown in Table 1E^†, the crude extract of Kigelia had a lower IC₅₀ value than isolated compounds alone, perhaps giving credence to several compounds’ working together synergistically to give an overall anti-neoplastic effect.

These results provide further evidence for the possible efficacy of preparations made from this traditional remedy in the treatment of skin cancers, although the general cytotoxicity implies that there could be some hazards with its use.

Further work undertaken on the ethanolic extract of the K. pinnata fruit extracts in vivo and in vitro showed anti-cancer properties.³⁸ The ethanolic fruit extract showed moderate cytotoxic activity in the brine shrimp (Artemia salina) nauplii bioassay with an LC₅₀ of 7500 mcg/ml. The in vivo studies in Swiss mice showed an LD₅₀ of 1.3 g/kg i.p. (intraperitoneally). Oral administration of the extract to mice resulted in a significant inhibition in the tumor incidence and burden by 67% and 76%, respectively, in the benzo (a)pyrene-induced forestomach tumorgenesis model. It would seem that these results are starting to affirm the validity of the ethnopharmacological uses of the fruits of K. pinnata for the treatment of cancer and edema in the traditional system of medicine in Nigeria.

The University of Illinois at Chicago’s NAPRALERT database contains references to K. pinnata’s, stem, fruit, and roots’ use for the treatment of cancer of the uterus in Malawi.³⁹

Anti-inflammatory

In vivo studies in India⁴⁰ have shown antinociceptive and anti-inflammatory activites of K. pinnata fruit. A methanolic extract of K. pinnata fruit exhibited significant, dose-dependent activity on the tested experimental animal models. The extract produced a significant decrease in mouse writhing induced by acetic acid, an elevation of the pain threshold in the hot-plate method, and inhibition of both phases of the formalin pain test in mice. The methanolic extract of the K. pinnata fruit also produced a significant inhibition of carrageenan-induced paw edema in rats. These results further confirm the traditional use of K. pinnata for the treatment of painful inflammatory conditions. It is also apparent that the anti-inflammatory compounds are not restricted to the fruits as a methanolic extract of the flower has also shown significant acitivites.⁴¹

The extract also displayed marked anti-inflammatory effects in female Wistar rats as reflected by a significant inhibition of the increase in rat paw circumference of 72% and 54%, which was caused by a subplantar injection of fresh agg albumen.

Recent studies also have investigated the link between inflammatory disorders and male infertility, where application of K. pinnata fruit extract was found to decrease testicular and seminal fluid oxidative stress, suggesting Kigelia’s potential to increase fertility.⁴² To fully understand the mechanisms involved, further research is required, but the studies, once again, provide a scientific basis for traditional use of this species.

Wound Healing

There is a long history of use surrounding K. pinnata and wound healing, particularly in relation to burns and bacterial infections. Aqueous stem bark extract applied to wound models supported this traditional use by showing an increased rate of wound contraction compared to the control.⁴³ The activity is presumably due to the free radical scavenging properties of the stem bark including the presence of β-sitosterol, an active compound in K. pinnata.^43,44

Antimicrobial Activity

Traditionally, the use of the K. pinnata bark in many parts of Africa is for the treatment of sexually transmitted diseases, so it is of great interest that crude aqueous extracts from the stem bark have shown significant antimicrobial activity against Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Candida albicans.^45,46 This activity was partially accounted for by the presence of pure iridoids, minecoside 1, and specioside 2. Further work at the University of Natal, in Durban, South Africa, also has shown antibacterial activity against gram-negative and gram-positive bacteria.³⁴ A mixture of 3 fatty acids exhibiting antibacterial effects was isolated from the ethyl acetate extract of the fruits using bioassay-guided fractionation. Palmitic acid, already known to possess antibacterial activity, was the major compound in this mixture. Among the various other studies on this topic, a recent publication demonstrated that all K. pinnata extracts tested showed mild antibacterial activity, and the highest inhibition was displayed by the chloroform-soluble extract against Shigella boydii and Pseudomonas aeruginosa.⁴⁷ The identification of the compounds involved in the activity is crucial if medicinal uses of K. pinnata are to be further developed.

The antibacterial activity of K. pinnata stem bark on Salmonella species was investigated and demonstrated 100% inhibition of the test organism at an extract concentration of 10% to 20% (v/v).⁴⁸ The anti-nutrients which may be reponsible for the inhibition include alkaloids, tannins, saponins, phenols, and flavonoids, all of which are present in K. pinnata.⁴⁸ The results of this particular study indicate the potential of K. pinnata extracts to be used in the treatment of infections caused by antibiotic-resistant Salmonella species.

Antidiarrheal Activity

Antidiarrheal activity has also been exhibited in experimental in vivo models. Aqueous leaf extracts were tested on mice. Evidence for antidiarrheal activity was provided by the reduced fecal output and protection from castor oil-induced diarrhea in the extract-treated animals. The extract remarkably decreased the propulsive movement of the gastrointestinal contents. On the isolated guinea pig ileum, the extract did not appreciably affect acetycholine- and histamine-induced contractions, but significantly reduced nicotine-evoked contractions. The intraperitoneal LD₅₀ of the extract in mice was estimated at 78.65±24 mg/kg.²⁶

Antimalarial Activity

The World Health Organization has estimated that about 80% of the world’s population in developing countries use herbal remedies to treat various ailments, and one of the world’s biggest issues is treatment of malaria.⁴⁹ It is no surprise that the local populations in Africa use a concoction of several plant species, one being K. pinnata.⁵⁰ Researchers in Tanzania investigated the management of malaria with traditional herbal remedies, including the use, preparation, and administration by traditional healers in Tanzania. The results showed that all traditional healers treat malaria with herbal remedies consisting of 1-5 different plants, one of those being K. pinnata. Further work undertaken at the University of California-Berkeley has shown that the naphthoquinones extracted from the root extract of K. pinnata were highly effective against the malaria-causing protozoa, Plasmodium falciparum.³³ The search for new antimalarial drugs is becoming increasingly important as malarial parasites become more resistant to conventional treatments. Due to the positive results of K. pinnata preliminary trials, compounds from this species represent an interesting lead in the development of drugs and combination therapies against malaria.^33,51 One compound of particular interest in this field is specioside which has shown high activity as an antiplasmodial ingredient. Further work is required in this area to investigate drugs and compounds in combination and their potential toxicity.⁵¹ Although specioside and p-hydroxycinnamic acid were found to be non-cytotoxic, 2 compounds present in an n-hexane extract, atranorin and 2β, 3β, 19α-trihydroxy-urs-12-en-28-oic acid, did show cytotoxity at high concentrations.

Hepatoprotective Activity

Recent studies have been undertaken on K. pinnata and its potential hepatoprotective properties. Paracetamol (acetaminophen) is a widely used over-the-counter analgesic and antipyretic drug, and large doses can result in liver damage (hepatic necrosis). Studies performed in vivo on the protective effects of administration of extracts of K. pinnata on induced liver damage in mice showed that it was able to act as a hepatoprotective against paracetamol toxicity and that the mechanism by which it does this is by acting as an antioxidant.^53,54

African Trypanosomiasis (Sleeping Sickness)

Human African trypanosomiasis, otherwise known as sleeping sickness, is a parasitic disease of people and animals caused by protozoa of the species Trypanosoma brucei and transmitted by the tsetse fly. It is a huge medical problem in Africa; research undertaken has shown that extracts from the root and stem bark of K. pinnata were active against T. brucei. Further activity-guided fractionation led to the isolation of 4 napthaquinoids, namely isopinnatal, kigelinol, isokigelinol, and 2-(1-hydroxyethyl)-naptho[2,3-b]furan-4,9-quinone, the most active compound being the furano-naphthoquinone structure.

Sustainability

One organization dedicated to the sustainability and scaleability of African botanicals is PhytoTrade Africa (www.phytotradeafrica.com). This nonprofit trade organization, which represents various natural products producers in the southern Africa region, states that the global natural products industry—including the key sub-sectors of food and beverages, cosmetics, herbal medicine, and pharmaceuticals—is currently valued at $65 billion USD per annum and is booming with a 15-20% annual growth rate in the last few years.⁵⁵ The current (as of October 2010) formal natural products trade in the southern Africa region is estimated at only $12 million USD per annum, although it may have the potential to grow to $3.5 billion USD per annum (data are based on author’s presentation at the United Nations Food and Agricultural Organization in October 2010, in Harare, Zimbabwe). The market appears to be set for steady long-term growth, and tapping into this market is attractive for several reasons, particularly in the number of beneficiaries and their location in areas of low agricultural and economic productivity. The sausage tree is only one such example of a raw natural African botanical that could unleash a whole range of useful extracts, chemicals, and drugs for use in numerous markets.

PhytoTrade Africa, along with its members and partner organizations, works to develop sustainable, ethical, and traceable supply chains for key indigenous African plant products. The introduction of the PhytoTrade Africa Ethical Biotrade Charter enables members to embark on a path of continuous improvement with regards to environmental and social practices, and highlights PhytoTrade’s commitment to fair and ethical trade, while simultaneously promoting biodiversity conservation. Important aspects of the Charter include sustainable resource use and harvesting practices, benefit-sharing agreements, and compliance with national and international legislation. Building capacity of harvesters is fundamental and is supported through a process of good-harvesting practices, including the development of transparent and sustainable business relationships between harvesters, manufacturers, and consumers of natural plant ingredients.

Two member organizations that work under the PhytoTrade Africa charter and supply extracts of Kigelia are Afriplex (Pty)Ltd (www.afriplex.co.za) and Blue Sky Botanics (www.blueskybotanics.com).

Conclusion

There are many anecdotal medicinal claims for the sausage tree,^{2,3,6,16,46,56} and scientific research has identified several interesting compounds, many of which are known to have anti-microbial,³⁰ anti-inflammatory,^29,40 anti-fungal, antibacterial,²⁷ and cytotoxic activity.^35,36,57 Obviously, additional research is required to determine the modes of action and disease states upon which these compounds show activity. Nevertheless, K. pinnata remains an interesting plant for further research into novel agents for the dietary supplement, pharmaceutical, cosmetics, and so-called “cosmeceutical” industries.

Commercial Kigelia preparations for treating the skin are marketed in South Africa, but no medical claims are made. However, it is widely believed that these creams reduce pigmentation in freckles and help sores to heal, the latter effect possibly being related to traditional wound-healing and antibacterial components. In Europe and Asia, the traditional claims for bust-firming and skin-tightening have been used in many commercial applications and skin-care products are available in these markets.

However, from a commercial standpoint, it would seem that efforts to address the twin goals of environmental sustainability and economic development in southern Africa regarding African botanicals have only just begun.⁵⁵ Work performed in Uganda has highlighted that prioritization and domestication of key medicinal plant species must be undertaken, and a survey in 2004 nominated K. pinnata as a key species for domestication for future use as a medicinal crop.⁵⁸

It is the aim of this article and all the cited references to provide an overview of the potential, current, and future contributions that Kigelia, and eventually other African plants, can make both internal to Africa and on the global stage. This is a message mirrored recently in the first chapter of a new book on African medicinal plants, African Natural Plant Products: Discoveries and Challenges in Chemistry and Quality.⁵⁹

Simon Jackson, PhD, is a pharmacognosist who earned his MPhil and PhD at Kings College, in Chelsea, London. His studies centered on African medicinal plants in the treatment of malignant melanoma and solar keratosis, and he worked alongside the melanoma unit at Charing Cross Hospital, Fulham, London. He performed his post-doctorate research at the Royal Botanic Gardens, Kew.

Among his many career accomplishments, Dr. Jackson has served as a pharmacognosy lecturer at University of Zimbabwe School of Pharmacy, and, in 2011, he worked on an African indeginous plants project sponsored by the Food and Agriculture Organization of the United Nations. He currently acts as a pharmacognosy consultant for a UK-based herb company. (Disclosure: Dr. Jackson has formulated a Kigelia product that will launch this year through his own company, Dr. Jackson’s Natural Products.)

Katie Beckett received her First Class Honours Degree in Environmental Biology from Newcastle University, where she was also awarded for achievements in plant science. She was one of a team of three to undertake an expedition to the southern rainforests of Cameroon to map and record cultural and resource-based reliance on the forest by indigenous groups. Additionally, Beckett has co-authored several publications on natural plant products from Africa, including cosmetic, food, and herbal medicinal ingredients.

Beckett currently sits on the membership committee for the Union of Ethical BioTrade. She is employed as a research associate at PhytoTrade Africa, the natural products trade association for southern Africa. Her research focus ranges from the supply chain of natural plant products to plant chemistry to regulatory issues and market trends.

Acknowledgement

The authors wish to acknowledge Emeritus Professor Peter Houghton, whose example and expansive body of Kigelia research inspired this article.

*As with most botanical nomenclature, there are several scientific names for the same plant. In the American Herbal Products Association’s Herbs of Commerce, 2nd edition—the primary reference HerbalGram uses for Latin binomials—the preferred binomial for sausage tree is Kigelia africana. The same is true in other taxonomic resources, The Plant List and the United States Department of Agriculture’s (USDA) Germplasm Resource Information Network (GRIN), with Kigelia pinnata listed as a synonym. The author of this article has preferred to use K. pinnata.

References

1. Welford L, Le Breton G. Bridging the Gap: Phytotrade Africa’s experience of the certification of natural products. Forests, Trees and Livelihoods. 2008;18:69-79.
2. Watt JM, Breyer-Brandwijk MG. The Medicinal and Poisonous Plants of Southern and Eastern Africa. 2nd ed. London, UK: Livingstone; 1962.
3. Jackson SJ, Houghton PJ, Photiou A, Retsas S. The isolation of a novel antineoplastic compound from a bioassay guided fractionation of stem bark and fruit extracts of Kigelia pinnata (Bignoniaceae). Br J Cancer. 1996;73(170):68.
4. Jackson SJ. Enlisting tree sausage in the war on cancer. National Geographic. 1995;188(2).
5. Saini S, H Kaur, et al. Kigelia africana (Lam.) Benth—An overview. Natural Products Radiance. 2009;8(2):190-197.
6. Gelfand M, Mavi S, Drummond RB, Ndemera B. The Traditional Medical Practitioner in Zimbabwe. Gweru, Zimbabwe: Mambo Press; 1985.
7. Oliver–Bever B. Medicinal Plants in Tropical West Africa. London, UK: Cambridge University Press; 1986.
8. Mabogo DEN. The ethnobotany of the Vhavenda. [Unpublished Master of Science thesis: University of Pretoria; 1990.]
9. Kokwaro JO. Medicinal Plants of East Africa. 3rd ed. Nairobi, Kenya: University of Nairobi Press; 2009.
10. Houghton PJ, Photiou A, Uddin S, et. al. Activity of extracts of Kigelia pinnata against melanoma and renal carcinoma cell lines. Planta Med. 1994;60:430-433.
11. Roberts M. Indigenous Healing Plants. Southern Book Publishers, Halfway House; 1990.
12. Vercourt B, Trump EC. Common Poisonous Plants of East Africa. London, UK: HarperCollins; 1969:210
13. Laswai H, Wendelin A, et al. The under-exploited indigenous alcoholic beverages of Tanzania: Production, consumption and quality of the undocumented “Denge.” African Study Monographs.1997;18(1):29-44.
14. Chivandi E, Davidson B, et al. Kigelia africana seed: proximate, mineral, vitamin E, fibre, amino acid and fatty acid composition. Int J Food Sci Technol. 2011;46:2153-2158.
15. Glew R, Amoako-Atta B, et al. An indigenous plant food used by lactating mothers in West Africa: The nutrient composition of the leaves of Kigelia africana in Ghana. Ecol Food Nutr. 2010;49:72-83.
16. Venter F, Venter JA. Making the Most of Indiginous Trees. 2nd ed. Pretoria, South Africa: Briza Publications; 2007.
17. Houghton PJ. The sausage tree (Kigelia pinnata): ethnobotany and recent scientific work. S Afr J Bot. 2002;68:14-20.
18. Choudhury, S, Datta S, et al. Phytochemistry of the Family Bignoniaceae - A review. Assam University Journal of Science & Technology: Biological and Environmental Sciences. 2011;7(1):145-150.
19. Govindachari TR, Patankar SJ, Viswanathan N. Isolation and structure of two new dihydroisocoumarins from Kigelia pinnata. Phytochem. 1971;10:1603-1606. Cited by Oliver-Bever B, in Medicinal plants in Tropical West Africa. Cambridge, UK: Cambridge University Press; 1986.
20. Dictionary of natural products on CD-ROM, release 4:2 (1996) Chapman & Hall, London.
21. El Sayyad SM. Flavonoids of the leaves and fruits of Kigelia pinnata. Fitoterapia. 1982;42:189-191.
22. Alamelu I, Bhuwan CJ. An iridoid glycoside from Kigelia pinnata. Herba Pol. 1974;20:319. Cited by Oliver-Bever B, in Medicinal plants in Tropical West Africa. Cambridge, UK: Cambridge University Press; 1986.
23. Lino von Poer G, Schripsema J, Henriques A, Jensen S. The distribution of iridoids in Bignoniacea. Biochem Syst Ecol. 2000;28:351-366.
24. Singh P, Khandelwal P, et al. Cetyl triacontanoate and other constituents from Acacia jacquemontii and Kigelia pinnata. Journal Indian Chem Soc. 2010;87:1403-1407.
25. Houghton PJ, Akunyili. DN Iridoids from Kigelia pinnata bark, Fitoterapia. 1993;65:473-474.
26. Akah, P. Antidiarrheal activity of Kigelia africana in experimental animals. J Herbs Spices Med Plants. 1996;4(2).
27. Gouda Y, Abdel-baky A, Darwish F, Mohammed K, Kasai R, Yamasaki K. Iridoids for Kigelia pinnata DC. Fruits. Phytochemistry. 2003;63:887-892.
28. Kupeli E, Harput U, Varel M, Yesilada E, Saracoglu I. Bioassay guided isolation of iridoid glucosides with antinociceptive and anti-inflammatory activites from Veronica anagallis-aquatica L. J Ethnopharmacol. 2005;102:170-176.
29. Picerno P, Autore G, Marzocco S, Meloni M, Sanogo R, Aquino R. Anti-inflammatory activity of verminoside from Kigelia africana and evaluation of cutaneous irritation in cell cultures and reconstituted human epidermis. J Nat Prod. 2005;68:1610-1614.
30. Bharti N, Singh S, Naqvi F, Azam A. Isolation and in vitro antiamoebic activity of iridoids isolated from Kigelia pinnata. ARKIVOC. 2006;69-76.
31. Gouda Y, Abdel-baky A, Darwish F, Mohamed K, Kasai R, Yamasaki K. Iridoids from Kigelia pinnata DC. Fruits. Phytochemistry. 2003;63: 887-892.
32. Gouda Y, Abdel-Baky A, Mohamed K, Darwish F, Kasai R, Yamasaki K. Phenylpropanoid and phenylethanoid derivatives from Kigelia pinnata DC. Fruits. Nat Prod Res. 2006;20(10):935-939.
33. Malerich J, Trauner D. Biomimetic synthesis of Pinnatal and Sterekunthal A. J Am Chem Soc. 2003;125(32), 9554-9555.
34. Grace O, Light M, Lindsey K, et al. Antibacterial activity and isolation of active compounds from fruit of the traditional African medicinal tree Kigelia africana. S Afr J Bot. 2002;68:220-222.
35. Jackson SJ, Houghton PJ, Retsas S, Photiou A. In vitro cytotoxicity of norviburtinal and isopinnatal from Kigelia pinnata against cancer cell lines. Planta Med. 2000;66:758-761.
36. Fouche G, Cragg G, Pillay P, Kolesnikova N, Maharaj V, Senabe J. In vitro anticancer screening of South African Plants. J Ethnopharmacol. 2008;119:455-461.
37. Higgins C, T Bell, et al. Growth inhibitory activity of extracted material and isolated compounds from the fruits of Kigelia pinnata. Planta Med. 2010;76:1840-1846.
38. Azuine M, Ibrahim K, Enwerem N, Wambebe C, Kolodziej H. Protective role of Kigelia africana fruits against benzo[a]pyrene-induced forestomach tumourgenesis in mice and against albumen-induced inflamation in rats. Pharm Pharmacol Lett. 1997:2(3):67-70
39. Graham J, Quinn ML, Fabricant D, Farnsworth NR. Plants used against cancer – an extension of the work of Jonathan Hartwell. J Ethnopharmacol. 2000;73:347-377.
40. Carey W, Rao V, Kumar R, Mohan K. Anti-nociceptive and anti-inflammatory activity of methanolic extract of Kigelia pinnata DC fruits. Pharmacogn Mag. 2008;4(15):149-154.
41. Carey W, Rao N, et al. Anti-inflammatory and analgesic activities of methanolic extract of Kigelia pinnata DC flower. J Ethnopharmacol. 2010;130:179-182.
42. Azu, O., F. Duru, et al. Preliminary study on the antioxidant effect of Kigelia africana fruit extract (Bignoniacieae) in male Sprague-Dawley rats. Afr J Biotechnol. 2010;9(9):1374-1381.
43. Sharma U, Singh A, et al. Wound healing activity of Kigelia pinnata bark extract. Asian J Pharm Clin Res. 2010;3(4):73-75
44. Alam G, Singh M. Wound healing potential of some medicinal plants. Int J Pharm Sci Rev Res. 2011;9(1):136-145.
45. Khan MR, Ndaalio G, Nkunya MHH, Wevers H, Sawney AN. Studies on medicinal plants. Part 1. Preliminary screening of medicinal plants for antibacterial activity. Planta Med. 1980; Suppl.:91-97.
46. Akunyili DN, Houghton PJ, Raman A. Antimicrobial activities of the stem bark of Kigelia africana. J Ethnopharmacol. 1991;35:173-178.
47. Sikder M, Hossian AKM, et al. In vitro antimicrobial screening of four reputed Bangladeshi medicinal plants. Phcog J. 2011;3(24):72-76.
48. Oluyege J, Olaleye A, et al. Antibacterial effect on some Nigerian medicinal plants on drug-resistant Salmonella species isolated from environmental sources. CJMB. 2010;4:25-30.
49. Akarele O. Summary of WHO Guidelines for the Assessment of Herbal Medicines. HerbalGram. 1994;28:13.
50. Gessler M, Msuya D, Nkunya M, Mwasumbi L, Schar A, Heinrich M, Tanner M. Traditional healers in Tanzania:the treatment of malaria with plant remedies. J Ethnopharmacol. 1994;48:131-144.
51. Zofou D, Tene M, et al. Antimalarial drug interactions of compounds isolated from Kigelia africana (Bignoniaceae) and their synergism with artemether, against the multidrug-resistant W2mef Plasmodium falciparum strain. Parasitol Res. 2012 Feb;110(2):5398-544.
52. Zofou D, Kengne A, et al. In vitro antiplasmodial activity and cytotoxicity of crude extracts and compounds from the stem bark of Kigelia africana (Lam) Benth (Bignoniaceae). Parasitol Res. 2011;108:1383-1390.
53. Olaleye M, Rocha B. Acetaminophen-induced liver damage in mice: Effects of some medicinal plants on the oxidative defense system. Exp Toxicol Pathol. 2008;59:319-327
54. Olalye M, Rocha J. Commonly used tropical medicinal plants exhibit distinct in vitro antioxidant activities against hepatotoxins in rat liver. Exp Toxicol pathol. 2007;58(6):433-438.
55. Sunderland T, Harrison S, Ndoye O. Commercialisation of non-timber forest products in Africa: history, context and prospects. In: Sunderland T, Ndoye O. (eds). Forest Products, Livelihoods and Conversation: Case Studies on Non-Timber Forest Product Systems. Vol 2 – Africa. Bogor, Indonesia: CIFOR. 2004;1-24
56. Retsas S, Photiou A, Jackson SJ. Pharmaceuticals from plants. The Lancet. 1994;344:8917.
57. Houghton PJ, Jackson S, Photiou A, Retsas S. Activity of extract of the fruit of Kigelia pinnata against cultured melanoma cells. [Abstract/Poster] Presented at UK Association of Pharmaceutical Scientists. Kings College London; November 18, 1994.
58. Katumba B, Boffa J, Abigaba G, Okorio J. Domestication of medicinal tree species in the Victoria lakeshore region. UJAS. 2004,9:84-88
59. Blumenthal M. African natural plant products: A foreword to the science and challenges. In: Juliani HR, Simon JE, Ho C-T. African natural plant products: New discoveries and challenges in chemistry and quality. Washington, DC: American Chemical Society, 2009.
60. Owolabi O, Omogbai E, Obasuyi O. Antifungal and antibacterial activities of the ethanolic and aqueous extract of Kigelia africana (Bignoniaceae) stem bark. Afr J Biotechnol. 2007;6(14):1677-1680.