Abstract: Azanza garckeana is an important food plant and herbal medicine in tropical Africa. This study was aimed at reviewing the nutritional value, the phytochemical compounds, ethnomedicinal uses and validated pharmacological properties of A. garckeana. The extensive literature survey revealed that ripe fruit carpels of A. garckeana are edible and widely used as food additives throughout the distributional range of the species. Azanza garckeana is also traditionally used to treat or manage at least 22 human diseases and ailments. The species is used as herbal medicine for diseases and ailments such as chest pains, cough, infertility, liver problems, menstruation problems and sexually transmitted infections. Multiple classes of compounds including alkaloids, amino acids, ascorbic acid, carotenoids, cyanogenic glucosides, flavonoids, lipids, phenols, saponins and tannins have been isolated from A. garckeana. Pharmacological studies on A. garckeana indicate that the species has a wide range of pharmacological activities such as antibacterial, antifungal, antihyperglycemic, antimalarial, antioxidant and iron absorption. Azanza garckeana is worth to be subjected to detailed scientific investigations for elucidating its chemical, nutritional and toxicological properties. Such detailed research should also include experimental animal studies, randomized clinical trials and target-organ toxicity studies involving A. garckeana and its derivatives.
INTRODUCTION
In tropical Africa, Azanza garckeana (F. Hoffm.) Exell and Hillc. is among the popular multipurpose fruit trees, characterized by edible fruits with different plant parts used as herbal medicines and plant products sold to local markets generating substantial incomes for the household1. The World Agroforestry Centre identified A. garckeana as one of the fruit trees that should be integrated in the domestication process in farming systems to support nutritional, health and income security of local communities in tropical Africa2. For centuries, local communities in developing countries and marginalized areas have relied on wild edible fruits as food, medicines and nutritional supplements. In recent decades, there has been a resurgence of interest in wild edible fruits as they are known to broaden the food, nutritional security and livelihood needs of the poor and those people living in marginalized areas3,4. Accumulated evidence generated over the years categorize large proportion of wild edible fruits as both food and medicines as the plants are characterized by several micronutrients and allelochemicals that are important for human nutrition and health5,6. These nutritional and medicinal properties of wild edible fruits enable some people to use wild edible fruits as medicines and also broaden the diversity of the human diet, nutritional options, vitamins and minerals. Medicinal properties of wild edible fruits include their antioxidant effects which play a crucial role in the prevention of chronic ailments such as heart disease, cancer, diabetes, hypertension, stroke and alzheimer’s disease by combating oxidative stress5. Research by Glew et al.1 and Lamien-Meda et al.6 revealed that wild edible fruits are characterized by remarkable nutrient values as well as being an excellent source of minerals, fibre, vitamins C, A and E, polyphenols, ascorbic acid and fatty acids that add flavour and colour to the diet. Some researchers like Leonti7 argued that the consumption of fruits, spices and vegetables are perceived as healthy and endowed with prophylactic effects against modern lifestyle diseases.
This study reviewes on A. garckeana throughout its distributional range in tropical Africa. Therefore, this study was aimed at reviewing the nutritional value, the phytochemical compounds, ethnomedicinal uses and validated pharmacological properties of A. garckeana. This review focusing on A. garckeana is important as the species is deemed essential and opens the possibility for utilizing both its nutritional and nutraceutical properties. Azanza garckeana has great potential as high-value nutraceutical and an important source of several bioactive compounds which can be used as dietary supplements of functional foods.
Plant profile: Azanza garckeana is a member of the Malvaceae family. The generic name "Azanza" is derived from the word "Azania", a word meaning black and surviving in Zanzibar8. The specific name "garckeana" is in honour of Professor August Garcke (1819-1904), a German botanist and plant collector who specialized in pharmacognosy8,9. Synonyms of A. garckeana include Bupariti garckeana (F. Hoffm.) Rothm., Shantzia garckeana (F.Hoffm.) Lewton and Thespesia garckeana F. Hoffm.8 Azanza garckeana has been recorded in Botswana, Burundi, Democratic Republic of Congo (DRC), Kenya, Malawi, Mozambique, Namibia, Nigeria, South Africa, South Sudan, Sudan, Tanzania, Zambia and Zimbabwe. The species occurs in a wide range of warmer parts of Southern, Eastern and Western Africa in open woodlands, wooded grasslands, thickets, riverine vegetation and rocky places. It grows naturally over a range of altitudes from 0-2000 m above sea level, from semi-arid areas receiving lowest annual rainfall of 250 mm and highest rainfall of 1270 mm10.
Azanza garckeana is a shrub or small tree, growing up to 10 m tall, with stem diameter at breast height of upto 25 cm9,10. The leaves are alternate, simple, round, 3-5 lobe upto 20×20 cm in size, subcircular in outline and palmately with 3-5 lobes9. The leaf lobes are rounded to broadly tapering at the apex, the base is cordate, margins are entire, 5-7 veined from the base, sparsely hairy above, woolly and leathery below with a petiole upto 13 cm long9. The flowers are 6 cm in diameter, yellow or purplish in colour with dark purple or dark red centre9. The peduncle is 2-7 cm long, the calyx is fused, with 9-10 teeth, each tooth up to 12 mm long and petals are 6×4 cm in size9. The staminal tube is 10-12 mm long with 2-5 cm long filaments9. The fruit is a round woody capsule about 35 mm in diameter, red when mature, covered with short dense hairs, clearly divided into 4 or 5 segments9. The seeds are 10×7 mm in size, hemispheric, with a brownish woolly floss9.
Dietary and medicinal uses of Azanza garckeana: The ripe fruit carpels of A. garckeana are edible and widely consumed throughout the distributional range of the species (Table 1). Azanza garckeana is also used a food additive (Table 1) with the jelly or syrup from the species added into soups or made into porridge and occasionally dried to be reconstituted later11. Considerable quantities of A. garckeana fruits are sold in local markets in Botswana, Kenya, Zambia and Zimbabwe2,12,13. The species is semi domesticated in Botswana, Nigeria, Zambia and Zimbabwe where local people grow the species in home gardens and crop fields2,13-16.
| Table 1: | Food value and ethnomedicinal uses of Azanza garckeana in tropical Africa |
Azanza garckeana has been identified as one of the few plant species that should be integrated in the domestication process in farming systems in sub-Saharan Africa to support nutritional, medicinal and income security of local communities2,17,18. According to Van Wyk18, the fruits of A. garckeana have potential in the development of new food and beverage products.
The bark, fruits, leaves, roots and stems of A. garckeana are reported to possess diverse medicinal properties and used to treat or manage various diseases and ailments throughout its distributional range (Table 1). Total of 22 traditional medicinal uses of A. garckeana are documented in literature (Table 1) from 9 countries in tropical Africa, representing 64.3% of the countries where the species is indigenous. The country with the highest ethnomedicinal uses is Nigeria (nine) based on 4 literature records, followed by Zimbabwe with 7 uses and 2 literature records, Democratic Republic of Congo (DRC) with 4 uses based on 2 literature records and Malawi with three uses based on a single literature record (Table 1). Root infusion of A. garckeana is taken orally as remedy for chest pains, cough and menstruation in Nigeria, Zimbabwe and Kenya19-21. The root and stem bark decoction of A. garckeana is taken orally as remedy for gonorrhoea, sexually transmitted diseases and syphilis in Malawi, Nigeria and Zambia22-25. The leaf, stem, root decoction or ripe fruits of A. garckeana are taken orally as remedy for infertility and liver problems in Botswana, Kenya, Malawi, Nigeria16,20,22,24,26,27. In Nigeria, fruit poultices are applied on abscesses16,21 and ripe fruits are taken orally as aphrodisiac27. In Sudan, ripe fruits are taken orally for anemia28, while in Tanzania, the root decoction is taken by pregnant women to induce labour29. In Zimbabwe, the root decoction of A. garckeana is taken orally as antiemetic, as remedy for madness or mental illness, retained placenta and root infusion is dropped into ear as remedy for earache19,30,31. In the DRC, the leaf or root decoction of A. garckeana is taken orally as remedy for diabetes, edema, epilepsy and membrane rupture32,33. In Malawi, the root decoction of A. garckeana is taken orally for fever while in Zambia, people suffering from malaria are advised to eat raw fruit of the species or cook the fruit and eat it as relish23,34. The root decoction of A. garckeana is mixed with roots of Sterospermum kunthianum Cham. and taken orally as remedy for asthma in Malawi22.
Phytochemical composition of Azanza garckeana: Multiple classes of compounds including alkaloids, amino acids, ascorbic acid, carotenoids, cyanogenic glucosides, flavonoids, lipids, phenols, saponins and tannins (Table 2, 3) have been isolated from A. garckeana fruits, leaves, roots, seeds and stem bark25,39,40.
| Table 2: | Chemical composition of fruits, leaves, roots, seeds and stem bark of Azanza garckeana |
| *Range represents standard deviation | |
Some of the documented phytochemicals are recommended by nutritionists because of their health benefits as they are considered to be responsible for positive health outcomes. Zhang et al.41 argued that phytochemicals such as alkaloids, flavones, saponins, steroids, tannins and triterpenoids isolated from fruits, vegetables and grains exert a protective effect against the development chronic diseases such as cardiovascular diseases (CVD), diabetes and cancers. According to Zhang et al.41 the protective role of phytochemicals may be associated with their antioxidant activity, since over production of oxidants (reactive oxygen species and reactive nitrogen species) in the human body is involved in the pathogenesis of many chronic diseases. Nkafamiya et al.25 isolated amino acids from fruits and leaves of A. garckeana with aspartic acid, glutamic acid, leucine and lysine being the most abundant amino acids constituting 9.67-12.97 g/100 g (Table 3).
Detection, isolation and purification of chemical compounds from fruit pulp, heartwood, roots and stem bark of A. garckeana has been done through mass spectrometry (MS) and nuclear magnetic resonance (NMR) for structural elucidation of the compounds (Table 4). Letcher and Shirley42 isolated the following compounds from heartwood of A. garckeana, O-naphthoquinones 6, mansonones E 7, mansonones F 8, mansonones G 9, mansonones H 10, azanzone A 11 and azanzone B 12 (Table 4). Mutindi43 isolated the following phenolic compound disesquiterpene aldehydes from the crude root extract of A. garckeana, gossypol 1, 6, 6-Dimethoxygossypol 2, 6-Methoxygossypol 3, stigmasterol 4, E-docosyl 3-(3,4-dihydroxyphenyl) acrylate 5 and betulinic acid 13. Masila et al.44 isolated gossypol 1, 6, 6-Dimethoxygossypol 2, 6-Methoxygossypol 3 from the root extract of A. garckeana and the stem bark yielded stigmasterol 4, E-Docosyl- 3-(3,4-dihydroxyphenyl) acrylate 5 and betulinic acid 13.
Pharmacological activities: A number of pharmacological activities of A. garckeana have been reported in literature justifying some of its ethnomedicinal uses. These include antibacterial27,43,44, antifungal27,43,44, antihyperglycemic32, antimalarial45, antioxidant21 and iron absorption28 activities.
Antibacterial: Mutindi43 evaluated antibacterial activities of crude root extract of A. garckeana and pure compounds isolated from the roots of the species which included gossypol 1, 6, 6-Dimethoxygossypol 2, 6-Methoxygossypol 3, stigmasterol4, E-docosyl 3-(3,4-Dihydroxyphenyl) acrylate 5 and betulinic acid 13 against Eschericia coli, Enterococcus faecalis, Enterococcus faecium and Staphylococcus aureus using ciprofloxacin as control. Compounds gossypol 1, 6, 6-Dimethoxygossypol 2 and 6-Methoxygossypol 3 exhibited antibacterial activities against Enterococcus faecalis and Enterococcus faecium with half maximal inhibitory concentration (IC50), minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values ranging from 0.89-20 μg mL–1 43. Gossypol 1 exhibited antibacterial activity against Staphylococcus aureus with IC50 value of 6.98 μg mL–1 43. Similarly, Masila et al.44 evaluated antibacterial activities of compounds gossypol 1, 6, 6-Dimethoxygossypol 2 and 6-Methoxygossypol 3 isolated from A. garckeana against Enterococcus faecium and Staphylococcus aureus using ciprofloxin, methicillin and vancomycin as controls. Compound gossypol 1 showed strong activity against Enterococcus faecium with IC50/MIC/MBC values of 1.71/4.82/19.31 μM44.
| Table 3: | Amino acids isolated from fruits and leaves of Azanza garckeana |
| Nkafamiyaet al.25 | |
| Table 4: | Chemical compounds isolated and characterized from Azanza garckeana |
Compounds 6, 6-Ttramethoxygossy pol 2 and 6-Methoxygossypol 3 were less active with IC50/MIC/MBC values of 2.73/4.70/9.40 μM and 6.14/18.32/18.32 μM against Enterococcus faecium. Compound gossypol 1 demonstrated modest activities against Staphylococcus aureus with IC50 value of 9.15 μM44. In another study, Dikko et al.27 evaluated antibacterial activities of fruit pulp ethyl acetate, n-hexane and methanol extracts of A. garckeana against Enterococci, Escherichia coli, Helicobacter pylori, Proteus mirabilis, Pseudomonas aeruginosa and Staphylococcus aureus using agar diffusion method. Ethyl acetate fraction of A. garckeana was the most active with MIC value of 0.625 mg mL–1 against Escherichia coli, while MIC and MBC values of fractions against the rest of bacteria species ranged between 1.25-2.5 mg mL–1 27. These findings somehow confirm the species’ antibacterial potential and its usefulness in the treatment and management of abscesses16,21 and syphilis24 in Nigeria, gonorrhoea in Malawi22 and Nigeria25 and sexually transmitted diseases in Zambia23.
Antifungal: Mutindi43 evaluated antifungal activities of crude root extract of A. garckeana and pure compounds isolated from the roots of the species which included gossypol 1, 6, 6-Dimethoxygossypol 2, 6-Methoxygossypol 3, stigmasterol 4, E-docosyl 3-(3,4-Dihydroxyphenyl) acrylate 5 and betulinic acid 13 against Candida albicans, Candida glabrata, Candida krusei and Aspergillus fumigatus using ampotericin B as control. Azanza garckeana crude root extract showed strong antifungal activity of 100 % inhibition against Candida glabrata at a concentration of 50 μg mL–1. Compound 6-Methoxygossypol 3 exhibited strong antifungal activity against Candida glabrata with IC50 value of <0.8 μg mL–1 while gossypol 1 exhibited activity against Candida glabrata with IC50 value of 3.2 μg mL–1 43. Similarly, Masila et al.44 evaluated antifungal activities of compounds gossypol 1, 6, 6-Dimethoxygossypol 2 and 6-Methoxygossypol 3 isolated from A. garckeana against Candida glabrata using amphotericin B as control. Compound gossypol 1 demonstrated modest activities against Candida glabrata with IC50 values of 0.73 μM44. In another study, Dikko et al.27 evaluated antifungal activities of fruit pulp ethyl acetate, n-hexane and methanol extracts of A. garckeana against Candida albicans, Candida krusei and Candida tropicalis using agar diffusion method. Best antifungal activities were demonstrated by ethyl acetate, n-hexane and methanol fractions of A. garckeana with MIC value of 1.25 mg mL–1 against Candida krusei27. Ethyl acetate extract demonstrated the best minimum fungicidal concentration (MFC) of 2.5 mg mL–1 against Candida albicans and Candida tropicalis27.
Antihyperglycemic: Amuri et al.32 evaluated the hypoglycemic and antihyperglycemic activities of aqueous leaf extracts of A. garckeana by administering 500 mg kg–1 to guinea pigs (Cavia porcellus), both in glucose baseline conditions and in oral glucose tolerance test with follow-up over 210 min. In oral glucose tolerance test, A. garckeana was active with inhibition of glycemia increase of 36.9% compared with the hyperglycemic inhibition rate of glibenclamide (50%)32. This data support the traditional use of A. garckeana leaf decoction as herbal medicine for diabetes in DRC32.
Antimalarial: Connelly et al.45 evaluated antimalarial activities of aqueous and organic fractions of A. garckeana against Plasmodium falciparum. Azanza garckeana showed weak antimalarial activity with median inhibitory concentration which was >3 μg mL–1 43. Antimalarial evaluations carried out by Connelly et al.45 demonstrated weak activities but such findings may imply that A. garckeana has bioactive constituents with potential in controlling mosquito vectors.
Antioxidant: Mshelia et al.21 evaluated antioxidant potential of petroleum ether, ethyl acetate, acetone, methanol and water stem bark extracts of A. garckeana using the DPPH (2,2-Diphenyl-1-picrylhydrazyl) radical scavenging activity. The methanol stem bark extracts exhibited antioxidant activity with IC50 value of less than 100 μg mL–1 while acetone extracts exhibited activity with IC50 value of 160 μg mL–1 against the standard ascorbic acid activity with IC50 value of 220 μg mL–121. These antioxidants activities of stem bark are probably due to the presence of flavonoids and phenolics46. There is now a global trend towards the use of natural phenolics as antioxidants and functional ingredients due to their perceived safety and prevalence in wild edible fruits47.
Iron absorption: Ahmed et al.28 evaluated iron absorption capability of aqueous extract of A. garckeana fruits in vivo by using everted gut sacs of wistar albino rats. Ahmed et al.28 administered 2 g kg–1 b.wt. of A. garckeana aqueous extract to iron deficient rats for 3 weeks in a nutritional anemia experimental model. Administration of A. garckeana extracts caused slight alterations on hematological parameters of the nutritionally iron deficient rats except on red blood cells counts of these animals28. Thus, A. garckeana extract was found to have stimulating iron absorption properties when used on in vitro iron absorption model. This effect may justify its use for treatment of iron deficiency anemia in Sudan28 as this plant contributes to enhancement of iron deficiency rather than providing the body with rich iron source. Thus this effect of A. garckeana extract may be attributed to its saponins contents causing an increase in production of red blood cells and hence increasing their numbers28.
Cytotoxicity: Mshelia et al.21 evaluated cytotoxicity activities of petroleum ether, ethyl acetate, acetone, methanol and water stem bark extracts of A. garckeana using the brine shrimp lethality test. The concentration killing 50% (LC50) of the shrimps was 3.98 μg mL–1 for acetone extract, methanol extract exhibited LC50 of 47.66 μg mL–1, ethyl acetate extracts (LC50 of 100 μg mL–1), water extracts (LC50 of 138.04 μg mL–1) and petroleum ether extract exhibited LC50 value of greater than 1000 μg mL–1. Recently, Omosa et al.48 evaluated the cytotoxicity of dichloromethane and methanol (1:1) extract of A. garckeana stem bark using the resazurin reduction assay against CCRF-CEM leukemia cell line. The dichloromethane and methanol extract of A. garckeana stem bark displayed cytotoxicity towards leukemia CCRF-CEM cells with IC50 value of 85.0 μg mL–1 48. Compound gossypol 1 isolated from Thespesia populnea exhibited cytotoxic and elastase inhibitory activities49,50. These results obtained from cytotoxic evaluations indicate the possibility that some plant parts of A. garckeana may be toxic or contain some cytotoxic compounds. Previous research by Randel et al.51 revealed that gossypol 1 is toxic to non-ruminant animals and this has limited the use of cotton seed meal as a dietary source of protein for mono-gastric animals.
CONCLUSION AND RECOMMENDATION
It was concluded that such detailed research will be important as an indication of the potential nutraceutical and economical utility of A. garckeana as an important source of bioactive phytochemicals, edible fruits and food additive. Some of the pharmacological properties of A. garckeana documented so far, may be attributed to various compounds including alkaloids, flavonoids and phenolics. The contemporary research done so far involving A. garckeana is promising as some of the nutritional, phytochemical and pharmacological evidence may be used to explain and support the documented ethnomedicinal uses, nutritional and nutraceutical values.
Further research on the phytochemistry, pharmacological properties, pharmacokinetics and clinical studies of A. garckeana will enhance the ethnopharmacology, nutritional and nutraceutical value of the species and also create awareness on the species’ importance in improving human health in tropical Africa. There should be experimental animal studies, randomized clinical trials and target-organ toxicity studies involving A. garckeana and its derivatives. It will be important to investigate the isolation of the bioactive compounds, mechanisms of action and safety of such bioactive compounds. Such information may be useful for further studies on A. garckeana fruit for its applications in pharmaceutical industries. Further research on the antinutritive, enzymatic and molecular effects on human health will be needed to motivate further interest in the use of A. garckeana fruits.
SIGNIFICANCE STATEMENT
Azanza garckeana demonstrated several ethnomedicinal uses, nutritional and nutraceutical values throughout its distributional range in tropical Africa. The overall results suggest that A. garckeana parts contain nutrients, minerals phytochemical compounds that are useful for human health. Azanza garckeana fruits are a good source of flavonoids and tannins, indicating considerable potential of A. garckeana fruit as a resource for dietary health supplement.
ACKNOWLEDGMENTS
The author would like to express his gratitude to the National Research Foundation (NRF grant number T398) and Govan Mbeki Research and Development Centre (GMRDC, grant number C169), University of Fort Hare for financial support to conduct this research.