Smith B. Babiaka†
ab,
Fidele Ntie-Kang†‡
*ab,
Lydia L. Lifongo
ab,
Bakoh Ndingkokhar
ab,
James A. Mbah
*b and
Joseph N. Yong
*b
aDepartment of Chemistry, Chemical and Bioactivity Information Centre, Faculty of Science, University of Buea, P.O. Box 63, Buea, Cameroon. E-mail: ntiekfidele@gmail.com; fidele.ntie-kang@ubuea.cm; Tel: +237 677915473
bDepartment of Chemistry, Faculty of Science, University of Buea, P.O. Box 63, Buea, Cameroon. E-mail: ajeck.james@ubuea.cm; joseph.yong@ubuea.cm; Tel: +237 677 30 67 42 Tel: +237 677 53 73 80
First published on 14th April 2015
As a whole, the African continent is highly endowed with a huge floral biodiversity. Natural products which have been isolated from plants growing in this region have shown interesting chemical structures with diverse biological activities, which could serve as a starting point for drug discovery. In this study, a literature survey led to the collection of 864 secondary metabolites from 101 plant species from 57 plant families. A correlation between the known biological activities of isolated compounds and the ethnobotanical uses of the plants has been attempted. This review is a survey of the bioactivities of alkaloids and terpenoids which have been isolated from Southern African flora versus the ethnobotanical uses of the plants used in Southern African traditional medicine.
The region of Southern Africa has a rich biological and ethnic diversity.8 More than three centuries of botanical research and exploration in South Africa and neighbouring countries have revealed promising floristic diversity, with approximately 25000 plant species and more than 50% endemism in the region.9,10 The cultural value of biodiversity and its importance in effective biodiversity conservation planning and ecotourism have also been recognised recently.11 As a result of the existing account of the importance and uses of flora of Southern Africa, there is growing need for ethnobotanical research.
It has been the objective of the Chemical Bioactivity Information Centre to document knowledge from African flora, relevant for drug discovery programs on the continent. Previous review papers have been focused on the bioactivity versus ethnobotanical survey of medicinal plants from Central, Western and Northern Africa has been done and published by this research group,3,7,12,13 including the development of natural product databases (CamMedNP, ConMedNP, AfroDb, p-ANAPL)14–17 and the pharmacokinetic profiling of natural products from African flora,17–19 with the view of drug discovery. Recent review articles have focused on anti-malarial and anti-tubercular principles from African flora,19–21 while also focusing on different countries/regions in Africa.3,20–22 This has received significant attention from the readership involved in drug discovery from medicinal plants and thus has prompted the need to explore other regions of the continent, including Southern Africa. To the best of our knowledge there has not been a recent review focusing on the phytochemical and bioactivity of natural products from the Southern Africa region (covering the countries; Angola, Botswana, Madagascar, Malawi, Mozambique, Namibia, South Africa, Swaziland and Zimbabwe), in spite of the rich floral biodiversity and phytochemistry of this region.8 In this review series, the chemistry and biological activity of Southern Africa flora would be discussed. In the present paper, our main focus would be on alkaloids and terpenoids to highlight the medicinal value and potentials of the isolated phytochemicals by discussing the bioactivity of the isolated principles versus ethnobotanical uses of the plant species.
Compound subclass | Isolated metabolites | Plant species (country) | Family | Ethnobotanical use | Measured activity | Author, reference |
---|---|---|---|---|---|---|
Crinane alkaloids | Buphanidrine (1) and distichamine (2) | Boophone disticha (South Africa) | Amaryllidaceae | As an arrow poison as well as a narcotic; use decoctions, extracts and infusions of bulbs for numerous ailments including treatment of burns, wounds, pain, inflammation, anxiety, gynaecological conditions and psychosis23 | Antibacterial activity | Cheesman et al.24 |
Indole | Voacangine (3) and dregamine (4) | Tabernaemontana elegans (South Africa) | Apocynaceae | Applied as a wash to wounds, and drunk for pulmonary diseases and chest pains, treatment of heart diseases and cancer25,26 | Antimicrobial activity | Pallant et al.32 |
Hypophorine (5) | Erythrina lysistemon (Botswana) | Leguminosae | The extracts from this plant have been used in traditional medicine and have also shown antiviral, anticancer and cytotoxic activities34,35 | Antimicrobial activity | Juma et al.33 | |
Aporphine | Neolitsine (6) and dicentrine (7) | Spirospermum penduliflorum (Madagascar) | Menispermaceae | Decoction of all parts is traditionally used as anticholinergic and vasorelaxant and the decoction of leaves is also used for the treatment of malaria and as a chloroquine adjuvant, the decoction of roots was taken as cholagogue, tonic and for hepatic disorders39 | Antihypertensive activity | Rafamantanana et al.40 |
Furoquinoline | Flindersiamine (8) and maculosidine (9) | Vepris uguenensis (Kenya) | Rutaceae | Treatment of malaria41 | Anti-malarial activity | Cheplogoi et al.44 |
Evoxine (10) and 7-(γ,γ-dimethylallyloxy)-γ-fagarine (11) | Teclea gerrardii (South Africa). | Bark decoctions are taken for chest complaints45 | Antiplasmodial activity | Waffo et al.46 |
Compound subclass | Isolated metabolites | Plant species (country) | Family | Ethnobotanical use | Measured activity | Author, reference |
---|---|---|---|---|---|---|
Acridone alkaloids | Tegerrardin A (12), tegerrardin B (13), arborinine (14), evoxanthine (15), 1,3-dimethoxy-N-methylacridone (16) and tecleanone (17) | Teclea gerrardii (South Africa) | Rutaceae | Bark decoctions are taken for chest complaints45 | Antiplasmodial activity | Waffo et al.46 |
Mesembrine | Mesembrine (18), mesembrenone (19), mesembrenol (20) and mesembranol (21) | Sceletium tortuosum (South Africa) | Mesembryanthemaceae | Used for centuries as a mood-altering drug, used also in the management of psychiatric and psychological conditions including depression, anxiety, drug dependence, bulimia and obsessive-compulsive disorder47–49 | Psychoactive activity | Shikanga et al.50 |
Isoquinoline | Norprotosinomenine (22) | Erythrina lysistemon (Botswana) | Leguminosae | The extracts from this plant have been used in traditional medicine and have also shown antiviral, anticancer and cytotoxic activities51,52 | Antimicrobial activity | Juma et al.33 |
Boophone disticha (Amaryllidaceae) is a common bulbous plant used traditionally by the local populations of Southern Africa, mostly as a narcotic substance and for the treatment of a host of ailments, including inflammation, wounds, gynaecological conditions and psychosis.23 Cheesman et al. have isolated the crinane alkaloids; buphanidrine (1) and distichamine (2) from the bulbs of this plant, collected in the Mpophomeni area of KwaZulu-Natal (South Africa).24 The isolated compounds were novel, broad spectrum moderately active, antibacterial agents with the best MIC value detected at 0.063 mg mL−1 for Staphylococcus aureus, Escherichia coli and Klebsiella pneumonia.24 MIC values for Bacillus subtilis were two-fold less than those observed for the other three bacteria, suggesting that the extract and pure compounds were selective in their interaction with the bacterial pathogens. The close structural similarity of these two compounds (1 and 2) may have bearing on their similar activity profiles. Moreover, the bioactivities of these chemical structures of compounds 1 and 2 may be the basis of the reputed traditional use of the plant for wounds and infections.24
There are several reports on the ethnomedical use of Tabernaemontana elegans (toad tree) pertaining to antibacterial activity, as well as on the screening of the plant extracts.25–31 Some of these reports pertain to the antibacterial activity: a root decoction is applied as a wash to wounds, and drunk for pulmonary diseases and chest pains by the VhaVenda25 and Zulu26 people of South Africa. Other ethnomedical uses of this plant include the treatment of heart diseases with the seeds, stem-bark and roots and the root-bark and properties.27 Extracts of this plant has previously demonstrated antibacterial activity against S. aureus and antimycobacterial activity against M. smegmatis,28 as well as anti-fungal activity against Candida albicans.30 Extracts from T. elegans, along with those from seven other species of the genus Tabernaemontana have shown antibacterial activity against Gram-positive bacteria.31 Pallant et al. have isolated the indole alkaloids; voacangine (3) and dregamine (4) as the active antibacterial components of the plant.32 The study confirms both the antibacterial activity of T. elegans and supports its potential for being investigated further for the development of a novel antibacterial compound. Hypophorine (5) is an indole alkaloid isolated from Erythrina lysistemon, a leguminous plant harvested in Botswana.33 The extracts from this plant have been used in traditional medicine and have also shown antiviral, anticancer and cytotoxic activities.34,35 Although erythrinaline alkaloids36,37 and prenylated flavonoids are known to be prevalent in the plant species,33,38 compound 5 is known to contribute to its antimicrobial activities.33
Spirospermum penduliflorum (Menispermaceae) is endemic in Madagascar.39 Moreover, the decoctions of all parts of this plant are traditionally used as anticholinergic and vasorelaxant, among other uses.39 Rafamantanana et al. have isolated two aporphine alkaloids; neolitsine (6) and dicentrine (7) from the leaves of this plant.40 Both dicentrine and neolitsine are known to possess antihypertensive activities, dicentrine having an EC50 value of 0.15 ± 0.04 μg mL−1 on rat aorta relaxation.40
A review on plants traditionally used for the treatment of malaria in Madagascar, showed Vepris ampody as a key component in anti-malarial preparations in Madagascan traditional medicine.41 In Kenya, a decoction of the roots of Vepris glomerata is used traditionally in the treatment of malaria, while the vapour is used to treat eye problems. A decoction of the bark is used in the treatment of cardiac pain while epilepsy, stroke and psychosis is treated using an aqueous root extract of the plant mixed with tea.42,43 The furoquinoline alkaloids; flindersiamine (8) and maculosidine (9) have been isolated from the sister species Vepris uguenensis, harvested in Kenya.44 Compounds 8 and 9 were tested against 3D7 (chloroquine susceptible, CQS) and FCM29 (chloroquine resistant, CQR) strains of Plasmodium falciparum. It was found that while compound 8 was completely inactive against both strains of the parasite, compound 9 displayed mild activity, with IC50 values of 13.0 ± 1.5 μg mL−1 and 13.8 ± 1.0 μg mL−1 against the CQS and CQR strains, respectively.44
The Flaky cherry-orange tree, Teclea gerrardii (Rutaceae), which occurs in riverine thicket and dry forest along the eastern seaboard of Southern Africa (South Africa, Swaziland and Southern Mozambique) has been included in this study. Bark decoctions of the plant are employed traditionally by the Zulus for chest complaints.45 Waffo et al. identified the furoquinoline alkaloids; evoxine (10) and 7-(γ,γ-dimethylallyloxy)-γ-fagarine (11), among other compounds including the acridone alkaloids; tegerrardin A (12), tegerrardin B (13), arborinine (14), evoxanthine (15), 1,3-dimethoxy-N-methylacridone (16) and tecleanone (17) from the stem bark of this plant and tested their antiplasmodial activity against the CQS D10 strain of P. falciparum.46 Compound 10 exhibited an IC50 of 24.5 μM, while arborinine showed the best activitity (IC50 = 12.3 μM).46
Sceletium tortuosum or Mesembryanthemum tortuosum (Mesembryanthemaceae) is endemic to the Cape Region of South Africa. This plant is one of South Africa's most popular plants, mainly for its use of this plant as a mood-altering drug can be traced back probably to centuries.47 Due to the popularity of this plant, whole plantations have been established and diverse consumer products are commercially available from the plant. The alkaloids of S. tortuosum (mainly mesembrine alkaloids) exhibit important pharmacological properties and are used for the treatment of psychiatric and psychological conditions, including depression, anxiety, drug dependence, bulimia and obsessive-compulsive disorder.47–49 Four alkaloids from this sub-class; mesembrine (18), mesembrenone (19), mesembrenol (20) and mesembranol (21) have been recognized for their remarkable psychoactive properties.47,50 These compounds are currently being used in pharmaceutical formulations for the management of psychiatric and psychological conditions like depression, anxiety, drug dependence, bulimia and obsessive-compulsive disorder.49 Moreover, mesembrine alkaloids have a particular ability to treat conditions of the central nervous system (CNS).50 This has been attributed to their capacity to act as serotonin re-uptake inhibitors, thereby contributing to regulating the balance of neurochemicals in the brain.51,52 Among the uses of Erythrina lysistemon (Leguminosae), the extracts from this plant have been used in traditional medicine and have shown antiviral, anticancer and cytotoxic activities. The antimicrobial activity of the isoquinoline alkaloid precursor norprotosinomenine (22), isolated from the plant harvested in Botswana, partly justifying its use in ATM.33
Compound subclass | Isolated metabolites | Plant species (country) | Family | Ethnobotanical use | Measured activity | Author, reference |
---|---|---|---|---|---|---|
Monoterpenes | (E)-2(3)-Tagetenone epoxide (23), myrcenone (24), piperitenone or 3-methyl-6-(1-methylethylidene)-cyclohex-2-en-1-one (25) | Lippia javanica (Mozambique) | Verbenaceae | Its infusion is commonly used in Africa as a tea against various ailments like influenza, measles, rashes, malaria, stomach problems, fever, colds, cough, headaches, in Botswana it is used as a caffeine-free tea and in Zimbabwe and Malawi as a nerve tonic54–57 | Antitubercular and anti-HIV activity | Mujovo et al.53 |
Piperitenone or 3-methyl-6-(1-methylethylidene)-cyclohex-2-en-1-one (25), major component of the essential oil | Lippia javanica (South Africa) | Used in South Africa against various chest ailments, influenza, measles, rashes, stomach problems and headaches, depending on the traditional healer, and is therefore known as fever tea or musudzungwane in Tshivenda, its essential oil has also been found to have good insect repellent activity. In Botswana it is used as a caffeine free tea. In Zimbabwe and Malawi it is used mainly as a nerve tonic54–57 | Antimicrobial and antimalarial activity | Manenzhe et al.58 | ||
Meroterpenoid | 7a,8,9,9a,9b,10b-Heptahydro-4H-10,10-dimethyl-1,7-dioxa-5-hydroxy-2-hydroxymethylcyclobutyl[1,2,3:3,3a,4]indeno[5,6-a]naphtalen-4-one or ptaerobliquol (26) | Ptaeroxylon obliquum (Mozambique) | Rutaceae | Used in southern Africa for the treatment of various diseases, from headaches to tick control60,61 | Antiprotozoan activity | Agostinho et al.62 |
Sesquiterpenes | Farnesylamine (27) | Vernonia auriculifera (South Africa) | Asteraceae | Used as a poultice, to relieve headache, to treat conjunctivitis, to treat fever associated with viral and bacterial infections, treat toothache and snake poison65–68 | Antibacterial activity | Kiplimo et al.70 |
Tutin (28) and hyenanchin (29) | Hyaenanche globosa (South Africa) | Euphorbiaceae | Fruits were formerly used to poison carcasses in order to destroy hyenas and other vermin71 | Antibacterial activity, cytotoxicity and antioxidant activity | Momtaz et al.71 | |
Dihydro-β-agarofuran sesquiterpene polyesters | 1β-Furanoyloxy-9α-benzoyloxy-dihydro-β-agarofuran (30), 1α-furanoyloxy-9β-benzoyloxy-2-oxo-dihydro-β-agarofuran (31), 1β,9α-difuranoyloxy-8β-acetoxy-2-oxo-3-ene-dihydro-β-agarofuran (32), 1β-furanoyloxy-9α-benzoyloxy-8β-acetoxy-2-oxo-3-ene-dihydro-β-agarofuran (33) and 1β,9α-difuranoyloxy-2,8-dioxo-3-ene-dihydro-β-agarofuran (34) | Osyris lanceolata (Botswana) | Santalaceae | To treat a wide variety of kidney infection, diarrhoea, cholera, coughs, malaria, gynaecological disorders, infertility, venereal diseases, cancer, and insanity75,76 | Antimicrobial activity | Yeboah et al.77 |
Sesquiterpene lactones | 3-Oxoeudesma-1,4(15),11(13)-triene-12,6a-lide (35) | Dicoma anomala (South Africa) | Asteraceae | Treatment of coughs and colds, fevers, ulcers, dermatosis, venereal diseases, labour pains, dysentery, intestinal parasites, stomach pains, toothache and internal worms82 | Antimalarial activity | Becker et al.87 |
Compound subclass | Isolated metabolites | Plant species (country) | Family | Ethnobotanical use | Measured activity | Author, reference |
---|---|---|---|---|---|---|
Abietane diterpenes | Parviflorone D (36) and parviflorone F (37) | Plectranthus ecklonii (South Africa) | Lamiaceae | For treatment of gastro-intestinal disorders, as anti-microbial agents for the treatment of wounds, the alleviation of respiratory conditions and for malaria90–97 | Antiplasmodial activity | van Zyl et al.98,99 |
11-Hydroxy-19-(methyl-buten-2-oyloxy)-abieta-5,7,9 (11),13-tetraene-12-one (38) | Plectranthus lucidus (South Africa) | |||||
11-Hydroxy-19-(4-hydroxy-benzoyloxy)-abieta-5,7,9(11),13-tetraene-12-one (39) and 11-hydroxy-19-(3,4-dihydroxy-benzoyloxy)-abieta-5,7,9(11),13-tetraene-12-one (40) | Plectranthus tongaensis (South Africa) | |||||
Labdane-type diterpenes | 9,13-Epoxy-6-hydroxy-16,15-labdanolide (41) and 9,13:15,16-diepoxy-6,16-labdanediol (42) | Leonotis leonurus (South Africa) | Treating colds, bronchitis, tuberculosis, coughs, asthma, feverish headaches, dysentery and chest infections101–104 | Antimycobacterial activity | Naidoo et al.106 | |
Methyl-8α,15-epoxylabdan-16β-oate (43), 8α,15-epoxylabdan-16β-ol (44), 8α,15-epoxy-16-norlabdan-13β-ol (45), 8α,15-epoxy-16-norlabdan-13-one (46), 8α,15-epoxylabdan-16β-oic acid (47) and 16-acetoxy-8α,15-epoxylabdane (48) | Eragrostis viscose (Angola) | Poaceae | Used in folk medicine as a poison against snakes107,108 | Mutagenic activity, cytotoxic activity and genotoxicity | Sebastião et al.109 | |
Limonoid diterpenoid | Methyl uguenesonate (49) | Vepris uguenensis (Kenya) | Rutaceae | Treatment of malaria118 | Antimalarial activity | Cheplogoi et al.119 |
Kaurene diterpene | ent-14S*-Hydroxykaur-16-en-19-oic (50), ent-14S*,17-dihydroxykaur-15-en-19-oic (51), ent-kaur-16-en-19-oic acid (52), ent-kaur-16-en-19-al (53), ent-12β-hydroxykaur-16-en-19-oic acid (54), ent-12β-acetoxykaur-16-en-19-oic acid (55) | Croton pseudopulchellus (South Africa) | Euphorbiaceae | A decoction from the roots is used to treat asthma, the powdered root taken as a snuff for headaches and leaves are applied by Tanzanians to their chest for chest ailments57,120–124 | Antiviral, cytotoxicity and antiplasmodial activity | Langat et al.125 |
Compound subclass | Isolated metabolites | Plant species (country) | Family | Ethnobotanical use | Measured activity | Author, reference |
---|---|---|---|---|---|---|
Pentacyclic triterpenoids | Lupenyl acetate (56), oleanolic acid (57), β-amyrin acetate (58), α-amyrin (59) and β-amyrin (60), friedelanone (61) and friedelin acetate (62). | Vernonia auriculifera (Kenya) | Asteraceae | Used as a poultice, to relieve headache, to treat conjunctivitis, to treat fever associated with viral and bacterial infections, treat toothache and snake poison64–69 | Antibacterial activity | Kiplimo et al.70 |
α-Myrin (59) and betulinic acid (63) | Artemisia afra (South Africa) | To treat coughs, colds, diabetes, malaria, sore throat, asthma, headache, dental care, gout and intestinal worms131–133 | Antimicrobial activity | More et al.137 | ||
Lup-20(30)-ene-3α,29-diol (64), lup-20(29)-ene-30-hydroxy-3-one (65) and Ψ-taraxastanonol (66) | Elaeodendron transvaalense (South Africa) | Celastraceae | To treat coughs, diarrhoea, stomach ailments, herpes and sexually associated diseases, treatment of arthritis, cancer and precbribed presently for HIV/AIDS139 | Cytotoxicity activity | Tshikalange et al.138 | |
1α,23β-Dihydroxy-12-oleanen-29-oic-acid-23β-O-α-4-acetylrhamnopyranoside (67) and 1,22-dihydroxy-12-oleanen-30-oic acid (68) | Combretum padoides (South Africa) | Combretaceae | Use in traditional medicine for relieving symptoms that appear to be caused by infective agents e.g. bloody diarrhoea, wounds and conjunctivitis142 | Antibacterial activity | Angeh et al.144 | |
67 and 68 | Combretum padoides (South Africa) | Eloff et al.145 | ||||
Lupeol (69) | Terminalia sericea (South Africa) | Use traditional in South Africa to treat diabetic146 | Antidiabetic activity | Nkobole et al.146 | ||
1,3-Dihydroxy-12-oleanen-29-oic (70), 1-hydroxy-12-olean-30-oic acid (71), 3,30-dihydroxyl-12-oleanen-22-one (72), 1,3,24-trihydroxyl-12-olean-29-oic acid (73) and 1,23-dihydroxy-12-oleanen-29-oicacid-3-O-2,4-di-acetyl-1-rhamnopyranoside (74) | Combretum imberbe (Zimbabwe) | Treating abdominal disorders, backache, bacterial infections etc.147 | Antimicrobial activity | Eloff et al.145 |
Compound subclass | Isolated metabolites | Plant species (country) | Family | Ethnobotanical use | Measured activity | Author, reference |
---|---|---|---|---|---|---|
Pentacyclic triterpenoids | 1α,3,β-Hydroxyimberbic acid-23-O-α-L-4-acetylrhamnopyranoside (75), 1α,3,β-hydroximberbic acid-23-O-α-L-3,4-diacetylrhamnopyranoside (76), 1α,3,β-hydroxyimberbic acid-23-α-[L-3,4-diacetyl-rhamnopyranosyl]-29-O-α-rhamnopyranoside (77), and 1,3,-hydroxyimberbic acid (78) | Combretum imberbe (Zimbabwe) | Combretaceae | Used in African traditional medicine for diverse uses23,27,148–150 | Antimicrobial activity | Katererea et al.151 |
75 and 1α,3,β-hydroxyimberbic acid-23-O-α-[L-4-acetyl-rhamnopyranosyl]-29-O-α-rhamnopyranoside (79) | Terminalia stuhlmannii (Zimbabwe) | Used in African traditional medicine for diverse uses154–158 | Antimicrobial activity | Katererea et al.151 | ||
Terminaliaside A (80), arjunglucoside I (81) and sericoside (82) | Terminalia tropophylla (Madagascar) | Used in African traditional medicine for diverse uses154–158 | Antiproliferative activity | Cao et al.153 | ||
3β-(5-Hydroxyferuloyl)-Lup-20(30)-ene (83), lupene (84), 69 and betulin (86) | Euclea divinorum (Zimbabwe) | Ebenaceae | Bark of the roots is used in the treatment of diarrhoea, convulsions, cancer, skin diseases and gonorrhoea.26,85 | Cytotoxicity | Mebe et al.163 | |
69, 86 and α-amyrin-3-O-β-(5-hydroxy) ferulic acid (87) | Euclea undulate (South Africa) | Treatment of diabetes165,166 | Hypoglycaemic activity | Deutschländer et al.167 | ||
3β-(3′′,4′′-Dihydroxy)-(E)-cinnamoyloxylup-20(29)-ene (88) | Eragrostis viscose (Angola) | Poaceae | Used in folk medicine as a poison against snakes107,108 | Mutagenic activity, cytotoxic activity, genotoxicity activity | Sebastião et al.109 | |
1β,3β,11α,26-Tetrahydroxy-7,24E-euphadiene (89), 3β,26-dihydroxy-8,24E-euphadien-11-one (90) and (24S)-1β,3β,24,25-tetrahydroxy-7,9(11)-euphadiene (91) | Cassipourea lanceolata (Madagascar) | Rhizophoraceae | Not specified | Antiproliferative activity | Hou et al.169 | |
Friedelin (92) | Garcinia goudotiana (Madagascar) | Clusiaceae | Used for antiparasitic, antitussive and antimicrobial properties171 | Antimicrobial and cytotoxic activity | Sania et al.171 | |
3-O-[β-D-Glucopyranosyl-(1→2)]-[α-L-arabinopyranosyl-(1→3)]-[α-L-arabinofuranosyl-(1→4)]-β-D-glucuronopyra-nosyl-21-O-(2-acetoxy-2-methylbutanoyl)-R1-barrigenol (93), 3-O-[β-D-glucopyranosyl-(1→2)]-[α-L-arabinopyranosyl-(1→3)]-[α-L-arabinofuranosyl-(1→4)]-β-D-glucuronopyranosyl-21-O-(2-acetoxy-2-methylbutanoyl)-28-O-acetyl-R1-barrigenol (94), 3-O-[β-D-glucopyranosyl-(1→2)]-[α-L-arabinopyranosyl-(1→3)]-[α-L-arabinofuranosyl-(1→4)]-β-D-glucuronopyra-nosyl-21-O-β,β-dimethylacryloyl-22-O-angeloyl-R1-barrigenol (95) and senaciapittoside B (96) | Pittosporum verticillatum (Madagascar) | Pittosporaceae | Some species are used in traditional medicine as anti-inflammatory, antimicrobial and antispasmodic agents173 | Cytotoxicity | Mahenina et al.175 |
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Fig. 2 Chemical structures of monoterpenes, meroterpenoid and sesquiterpenes from Southern African flora (23–35 and 102–104). |
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Fig. 3 Chemical structures of abietane diterpenes, labdane-type diterpenes, limnoid diterpenes and kaurene diterpenes from Southern African flora (36–48). |
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Fig. 4 Chemical structures of abietane diterpenes, labdane-type diterpenes, limnoid diterpenes and kaurene diterpenes from Southern African flora (49–55). |
Ptaeroxylon obliquum (Rutaceae), also known as sneezewood, grows only in Southern Africa. This plant is traditionally used in Southern Africa for the treatment of various ailments, including headaches and tick control.60,61 Agostinho et al. isolated ptaerobliquol (26), a new monoterpene-chromone (or meroterpenoid) from the roots of this plant for the first time.62 The compound demonstrated a moderate activity when tested on Toxoplasma gondii replication using CPRG-based colorimetric assay,63 inhibiting parasite replication at 5 and 10 μM, with an IC50 of 5.13 μM. Lower concentrations of the compound (0.1 and 1 μM) tested were totally inactive, while cellular toxicity appears at concentration of 25 μM, giving ptaerobliquol a low therapeutic index.
Two sesquiterpenes (28 and 29) have also been isolated from Hyaenanche globosa (Euphorbeaceae), a narrow endemic poisonous plant restricted to a single flat-topped mountain near Van Rhynsdrop in southern Namaqualand. In vitro studies of the ethanolic extract of the fruits of the plant displayed a significant anti-tyrosinase, antibacterial, and cytotoxic effects. Momtaz et al. isolated the tutin (28) and hyenanchin or mellitoxin (29) from the ethanolic extract of the fruits of the plant which did not exhibit any significant cytotoxic effects on the on ‘Hela cells’.71 This could be explained by the fact that the compounds responsible for the activity were not isolated and that activity in the crude extract is due to synergy. It has been reported by several studies that compound 28 is the major neurotoxin in the New Zealand shrubs of the genus Coriaria and compound 29 is a major active component in toxic honey.72–74
The shrub Osyris lanceolata (Santalaceae), also called ‘African sandalwood’, is used in traditional medicine in Botswana, South Africa, East Africa, Ethiopia and parts of Asia to treat a wide variety of diseases including; kidney infection, diarrhoea, cholera, coughs, malaria, gynaecological disorders, infertility, venereal diseases, cancer, and insanity. The ethnomedicinal applications of Osyris species in traditional medicine has been published in different parts of the world, including the NAPRALERT database75 and the Prelude Medicinal Plants Database.76 Yeboah et al. isolated five new dihydro-β-agarofuran polyesters from the root bark and stem bark of the plant, harvested in Botswana.77 The compounds include 1β-furanoyloxy-9α-benzoyloxy-dihydro-β-agarofuran (30), 1α-furanoyloxy-9β-benzoyloxy-2-oxo-dihydro-β-agarofuran (31), 1β,9α-difuranoyloxy-8β-acetoxy-2-oxo-3-ene-dihydro-β-agarofuran (32), 1β-furanoyloxy-9α-benzoyloxy-8β-acetoxy-2-oxo-3-ene-dihydro-β-agarofuran (33) and 1β,9α-difuranoyloxy-2,8-dioxo-3-ene-dihydro-β-agarofuran (34). The compounds have received considerable attention recently and they are considered as ‘privileged structures’ because they typically display multiple pharmacological activities due to their unique framework that can provide ligands to interact with multiple receptors. They have been reported to have insecticidal, anti-HIV, anti-cancer, multidrug resistance (MDR) reversal and acetylcholinesterase (AChE) inhibition activities in literature.78–81
Another set of abietane diterpenes isolated by Zyla et al. from Plectranthus tongaensis (Lamiaceae) and tested similarly as above include 11-hydroxy-19-(4-hydroxy-benzoyloxy)-abieta-5,7,9(11),13-tetraene-12-one (39) and 11-hydroxy-19-(3,4-dihydroxy-benzoyloxy)-abieta-5,7,9(11),13-tetraene-12-one (40).98 Compound 40 was more active than quinine with an IC50 value of 4.7 μM compared to compound 39 with an IC50 value of 14.7 μM when screened against chloroquine-resistant strain of Plasmodium falciparum. These results justify the use of Plectranthus sp. in the treatment of malaria among other uses.
The nutritive value of Eragrostis species (Poaceae) has been reported in literature.107,108 Eragrostis viscosa (Poaceae) is used in folk medicine as a poison against snakes in Angola but the plant is not eaten by cattle. Phytochemical investigation of the toluene and dichloromethane extracts of the aerial parts of this plant by Sebastião et al. afforded three new 8α,15-epoxylabdanes namely; methyl 8α,15-epoxylabdan-16β-oate (43), 8α,15-epoxylabdan-16β-ol (44), 8α,15-epoxy-16-norlabdan-13β-ol (45) together with other known compounds.109 Some of the known compounds in this class include 8α,15-epoxy-16-norlabdan-13-one (46), 8α,15-epoxylabdan-16β-oic acid (47) and 16-acetoxy-8α,15-epoxylabdane (48). The genotoxicity of the compounds isolated from this plant was studied using a cytokinesis-block micronucleus assay and the Ames test was also used to assess mutagenicity. Compounds 44, 46 and 48 gave negative results on both assays and compound 44 was the most cytotoxic of the tested compounds using MTT assay.
Other triterpenes correlating biological activity and ethnobotanical uses of species from the Artemisia genus. As a typical example, the ethnobotanical uses of A. afra (Asteraceae) have been investigated by van Wyk et al.131–133 The African wormwood, A. afra, is a common species in South Africa with a wide distribution from the Cederberg Mountains in the Cape, northwards to tropical East Africa and stretching as far north as Ethiopia.131,132 In southern Africa, this plant is used to treat coughs, colds, diabetes, malaria, sore throat, asthma, headache, dental care, gout and intestinal worms.133 In vitro studies of this plant have revealed that the plant is a potential antidepressant, cardiovascular, spasmolytic effects, antioxidant, and antimycobacteria.134–136 The crude ethanolic extract of this plant exhibited strong antimicrobial activity by inhibiting the growth of all tested microbial species at concentration range of 1.6 mg mL−1 to 25 mg mL−1 thus prompted the further investigation. More et al. isolated compound 59 and betulinic acid (63) from this plant and other known compounds.137 The compounds were evaluated for antimicrobial activity against Gram positive (Actinomyces naeslundii, Actinomyces israelii, and Streptococcus mutans), Gram negative bacteria (Prevotella intermedia, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans previously known as Actinobacillus actinomycetemcomitans), and Candida albicans. The isolated compounds showed activity range at 1.0 mg mL−1 to 0.25 mg mL−1. Compound 63 was one of the best compounds that showed good antimicrobial activity and the antioxidant activity was done on the compound using the DPPH scavenging method. The result revealed that compound 63 exhibited a decreased scavenging activity with an IC50 of 2.42 μg mL−1. Compound 63 showed a smooth trend of non-toxic effects with IC50 value 30.96 of μg mL−1. Thus the results obtained in this study confirm the use of this plant in the treatment of microbial infections.
Tshikalange et al. isolated the three known triterpenoids lup-20(30)-ene-3α,29-diol (64), lup-20(29)-ene-30-hydroxy-3-one (65) and Ψ–taraxastanonol (66) together with other known compounds from stem bark of Elaeodendron transvaalense (Celastraceae), collected from Venda (Northern Limpopo), South Africa.138 Extracts from this plant have been used in traditional medicine by the Vhavenda people of South Africa (Limpopo province) to treat coughs, diarrhoea, stomach ailments, herpes and sexually associated diseases. The stem bark is mostly used to prepare infusions and decoctions.139 This plant is also used in the treatment of arthritis, cancer, coughs, diarrhoea and stomach ailaments and is being prescribed presently to people who are suffering from HIV/AIDS by traditional healers.140 The cytotoxicity of the isolated compounds was determined using XTT colorimetric assay against Vero and MCF-7 breast cancer cell lines.141 Compounds 64 and 66 showed weaker activities with the IC50 ranging from 66.6 to over 100.00 μg mL−1 in both cell lines, while compound 65 exhibited a good cytotoxicity activity IC50 value of 25.1 μg mL−1 for Vero cells and 19.4 μg mL−1 for breast cancer cell line. The cytotoxicities of the isolated compounds (64–66) may partly justify the use of E. transvaalense in the treatment of several ailments in ATM, including cancer related problems.139
Some Combretum species have been used in traditional medicine for relieving symptoms that appear to be caused by infective agents like bloody diarrhoea, wounds and conjunctivitis.142 This confirms the preliminary data gathered by Eloff,143 which demonstrated that crude extracts of Combretum padoides (Combretaceae) were active against the four most important nosocomial bacterial pathogens. Angeh et al. isolated a new oleanene-type triterpenoid glycoside known as 1α,23β-dihydroxy-12-oleanen-29-oic-acid-23β-O-α-4-acetylrhamnopyranoside (67), 1,22-dihydroxy-12-oleanen-30-oic acid (68) and a known steroids from the dichloromethane extract of this plant using antibacterial activity guided fractionation against Staphylococcus aureus.144 Compounds 67 and 68 exhibited a reasonable antibacterial activity with MIC of 0.031 and 0.063 mg mL−1 against S. aureus and Escherichia coli. This result confirms the antibacterial activity of this plant that the isolated triterpenes are non-cytotoxic.144 Eloff et al. also isolated compounds 67 and 68 from this same plant using bioassay-guided fractionation.145 The compounds demonstrated a reasonable antibacterial activity as described Angeh et al.,144 which could partly justify its use in the treatment of wounds and other infectious diseases.
Terminalia sericea (Combretaceae) stem bark extract showed the best results against α-glucosidase and α-amylase enzymes in an in vitro screening exercise of a number of South African medicinal plants, in an attempt to discover new antidiabetic agents. A bioassay-guided fractionation of an acetone extract of the stem bark of this plant by Nkobole et al. led to the isolation of lupeol (69) and other known compounds.146 The result demonstrated that compound 69 was one of the secondary metabolite that showed the best inhibitory activity on α-glucosidase with an IC50 value of 66.48 μM. Additionally, bio-evaluation of compound 69 inhibitory activity on α-amylase demonstrated that the compound had an IC50 value of 140.72 μM against the enzyme, thus validating the use of the plant in traditional medicine to treat diabetic in South Africa.
Combretaceae species are widely traded in the traditional medicine market in Southern Africa and are used medicinally in several continents in the world.147 Traditional healers in Eastern and Southern Africa have used Combretum species, for many applications including treating abdominal disorders, backache, bacterial infections, bilharzia, cancer, chest coughs, cleansing the urinary system, colds, conjunctivitis, constipation, diarrhoea, dysentery, dysmenorrhoea, earache, fever, gastric ulcers, general weakness, gonorrhoea, headaches, heart diseases, hookworm, hypertension, jaundice, leprosy, nosebleeds, oedema, pneumonia, skin diseases, sore throats, stomach and gastric problems, swelling caused by mumps, syphilis, toothache, venereal diseases.23,27,148–150 Extract from Combretum imberbe (Combretaceae) leaves, obtained using intermediate polarity extractants, had reasonable to very good activity with MICs as low as 40 μg mL−1, thus validating the traditional use of the plant in the treatment of infectious diseases. Five antibacterial triterpenoids; 1,3-dihydroxy-12-oleanen-29-oic (70), 1-hydroxy-12-olean-30-oic acid (71), 3,30-dihydroxyl-12-oleanen-22-one (72), 1,3,24-trihydroxyl-12-olean-29-oic acid (73) and 1,23-dihydroxy-12-oleanen-29-oicacid-3-O-2,4-di-acetyl-1-rhamnopyranoside (74) were isolated from the leaves of this plant. The compounds had levels of antibacterial activity MIC values against S. aureus and E. coli ranging from 16 to 62 μg mL−1. ref. 145 and 147 The antibacterial activity of the isolated compounds was much lower than expected from the activity of the crude extracts this can be due to synergy. Katererea et al. also isolated the two novel derivatives of 1α,3β,23-trihydroxyolean-12-en-29-oic acid; 1α,3,β-hydroxyimberbic acid-23-O-α-L-4-acetylrhamnopyranoside (75), 1α,3,β-hydroximberbic acid-23-O-α-L-3,4-diacetylrhamnopyranoside (76) and the known compounds 1α,3,β-hydroxyimberbic acid-23-α-[L-3,4-diacetyl-rhamnopyranosyl]-29-O-α-rhamnopyranoside (77), and 1,3-hydroxyimberbic acid (78) form the leaves of the this plant.151 The antimicrobial activity of the isolated compounds was done using a microtitre dilution assay (MDA),152 showing. Compound 77 to have inhibitory activity against P. vulgaris (12.5 μg mL−1) and S. aureus (6.25 μg mL−1). Compound 75 inhibited S. aureus at 12.5 μg mL−1, while compound 76 inhibited S. aureus at 6.25 μg mL−1 and M. fortuitum at 12.5 μg mL−1. Compound 78, the free aglycone, showed activity against Mycobacterium fortuitum at a concentration of 1.56 μg mL−1 and S. aureus at 3.13 μg mL−1, which was a surprising case because the Mycobacterium was generally resistant to the other test samples. The activity of these compounds validates the use of this plank in folk medicine. Escherichia coli was resistant to these compounds, thus the constituents of these species of Combretaceae may not be active against Gram negative bacteria.
Katererea et al. isolated compound 75 and 1α,3,β-hydroxyimberbic acid-23-O-α-[L-4-acetyl-rhamnopyranosyl]-29-O-α-rhamnopyranoside (79) from the stem bark of this plant.151 Thus, this study established that there is a chemotaxonomic link between the genus Combretum and Terminalia due to the occurrence of the trihydroxy-olean-12-en-29-oate aglycone; compound 75 and 79 in the species which had not been previously reported. The isolated compounds were screened using a microtitre dilution assay (MDA).152 Compound 79 was active against Candida albicans (12.5 μg mL−1) and S. aureus to a lesser extent (25 μg mL−1).
In the search for bioactive compounds from the Madagascar forests as part of an International Cooperative Biodiversity Group (ICBG) program, extracts of the roots of Terminalia tropophylla (Combretaceae) were screened and exhibited an activity against the A2780 ovarian cancer cell line, with an IC50 value of 11 μg mL−1.153 Some metabolites isolated from Terminalia species have shown a wide range of biological activities, including antimalarial,154 antifungal,154–156 antibacterial,155–157 and cytotoxic activities.156,158 Cao et al. isolated the new oleanane-type triterpenoid saponin terminaliaside A (80), the known triterpenoids saponins; arjunglucoside I (81), sericoside (82) and a lignan derivative form the roots of this plant.153 The compounds were tested in the A2780 assay. Compound 80 was the most active with an IC50 value of 1.2 μM, while compound 81 was weakly active with an IC50 value of 16.5 μM and compounds 82 inactive with IC50 values >30 μM. The antiproliferative activity of compound 80 is enhanced by substituents at the 3-, 16-, 21-, and 28-positions.159 The activity of the isolated compounds provides the importance of oleanane-type saponins as potential anticancer agents for further investigation.
Euclea divinorum (Ebenaceae) root bark is used in traditional medicine for the treatment of diarrhoea, convulsions, cancer, skin diseases and gonorrhoea.26,85 Previous chemical studies of this plant and other Euclea species revealed the presence of naphthoquinones, triterpenes and flavonoids.160–162 Mebe et al. isolated the new triterpenoid; 3β-(5-hydroxyferuloyl)-Lup-20(30)-ene (83) with some of the known compounsds lupene (84), 7-methyljuglone (85), lupeol (69) and betulin (86) from the chloroform extract of this plant.163 The isolated compounds were tested for their cytotoxic activity (ED50 < 20 μg mL−1) against a panel of cell lines using cell culture systems as described.164 The results indicate that, the new compound 83 and compound 85 displayed cytotoxic activity, while the other compounds were classed as being inactive. Compound 85 was cytotoxic against all cell lines and its most intense responses were observed with KB (human nasopharyngeal carcinoma), P-388 (murine lymphocytic leukemia), LNCaP (human prostate cancer), ZR-75-1 (human breast cancer) and U373 (human glioblastoma) cells at 4.8, 0.1, 0.8, 2.2 and 2.7 μg mL−1, respectively. But, compound 83 was selective, and only showed activity against two cell lines: P-388 and ZR-75-1 at 2.1 and 4.2 μg mL−1, respectively. Thus the cytotoxic activities of the isolates correlate with the ethnobotanical use of this plant.
Euclea undulata (Ebenaceae) is used by traditional healers in the Venda area, Limpopo Province in the treatment of diabetes. Previous chemical investigation revealed that naphthoquinones have been isolated from the root, stem and fruit of this plant by van der Vyver and Gerritsma.165,166 Deutschländer et al. isolated a new triterpene, α-amyrin-3-O-β-(5-hydroxy) ferulic acid (87), in addition to some of the known compounds; lupeol (69) and betulin (86) from the crude acetone extract of the root bark of this plant.167 The isolated compounds were evaluated for, their hypoglycaemic activities by executing in vitro assays on C2C12 myocytes, as well as their ability to inhibit the carbohydrate hydrolising enzyme α-glucosidase.168 The in vitro results on C2C12 myocytes showed that compound 87 has the ability to inhibit α-glucosidase at a concentration of 200.00 μg mL−1 with an IC50 value of 4.79 μg mL−1 that correlates with that of the positive control acarbose with an IC50 value 4.75 μg mL−1. This study validates the ethnomedicinal use of this plant used by traditional healers for the treatment of diabetes (Fig. 9).
The nutritive value of Eragrostis species (Poaceae) has been reported in literature.107,108 Sebastião et al. isolated the known triterpenoids 3β-(3′′,4′′-dihydroxy)-(E)-cinnamoyloxylup-20(29)-ene (88) in addition to other compounds from the toluene and dichloromethane extracts of aerial parts of Eragrostis viscose.109 The genotoxicity of the compounds isolated from this plant was studied using a cytokinesis-block micronucleus assay and the Ames test was also used to assess mutagenicity. The results revealed that compound 88 was cytotoxic including other compounds from this plant.
Extract from Cassipourea lanceolata (Rhizophoraceae) showed weak antiproliferative activity when tested against the A2780 human ovarian cancer cell line and had an IC50 value of 17 μg mL−1. Hou et al. isolated the three new euphane triterpenoids; 1β,3β,11α,26-tetrahydroxy-7,24E-euphadiene (89), 3β,26-dihydroxy-8,24E-euphadien-11-one (90) and (24S)-1β,3β,24,25-tetrahydroxy-7,9(11)-euphadiene (91) from the ethanol extract of the leaves and fruit of this plant collected from Madagascar.169 The isolated compounds were tested using the A2780 ovarian cancer cell line assay as described.159 The compounds 89–91 showed weak antiproliferative activities with IC50 values of 25, 25, and 32 μM, respectively. Compound 89 was found to have IC50 values >5 μM when tested against the BT-549 and MCF-7 breast cancer, DU 145 prostate cancer, NCI-H460 and H522-T1 NSCLC, HCC-2998 and HT-29 colon cancer, OVCAR-5 ovarian cancer, SF-539 CNS cancer, SR and U937 lymphoma, and UACC-257 and MDA-MB-435 melanoma cell lines. The weak antiproliferative activity of the extract can be due to masking or other compounds not isolated in this study.
Garcinia goudotiana (Clusiaceae) is used traditionally for its antiparasitic, antitussive and antimicrobial properties. The crude acetonic extract in addition to its dichloromethane and ethyl acetate partitions showed a selective moderate to high antimicrobial activity (100 μg mL−1 < MIC < 500 μg mg mL−1 or MIC ≤ 100 μg mL−1) against Gram-positive bacteria, in particular against three strains of Enteroccocus, six strains of Staphyloccocus and M. smegmatis, in addition to the yeast Candida albicans.170 Bioassay-guided fractionation of the crude acetonic extract of the leaves of this plant led to the isolation of two new prenylated benzoylphloroglucinol derivatives, in addition to a known xanthone and the known triterpenoid friedelin (92).171 Human colon carcinoma HT29 and human fetal lung fibroblast MRC5 cells was also used to evaluate the cytotoxic activities of the extracts and isolated compounds. The prenylated compounds showed a high antimicrobial activity against some Gram-positive bacteria with a moderate cytotoxicity while the activity of compound 92 was not reported.
The Pittosporum is the only genus of the Pittosporaceae family found in Malagasy flora.172 Some of the species are used in traditional medicine as anti-inflammatory, antimicrobial and antispasmodic agents.173 In the search for biologically active triterpenoids saponins from Pittosporaceae,174 phytochemical investigation of the ethanol extract from the root barks of Pittosporum verticillatum (Pittosporaceae) led to the isolation of three new triterpene saponins, 3-O-[β-D-glucopyranosyl-(1→2)]-[α-L-arabinopyranosyl-(1→3)]-[α-L-arabinofuranosyl-(1→4)]-β-D-glucuronopyranosyl-21-O-(2-acetoxy-2-methylbutanoyl)-R1-barrigenol (93), 3-O-[β-D-glucopyranosyl-(1→2)]-[α-L-arabinopyranosyl-(1→3)]-[α-L-arabinofuranosyl-(1→4)]-β-D-glucuronopyranosyl-21-O-(2-acetoxy-2-methylbutanoyl)-28-O-acetyl-R1-barrigenol (94), 3-O-[β-D-glucopyranosyl-(1→2)]-[α-L-arabinopyranosyl-(1→3)]-[α-L-arabinofuranosyl-(1→4)]-β-D-glucuronopyra-nosyl-21-O-β,β-dimethylacryloyl-22-O-angeloyl-R1-barrigenol (95) and senaciapittoside B (96) (Fig. 10).175 Saponins have been reported to possess cytotoxic activity.176,177 Thus, the isolated compounds 93–96 were tested for cytotoxicity against one human cancer cell line, SW480 (colorectal adenocarcinoma), and one embryonic heart-derived cell line H9c2 (rat cardiomyoblast), using the XTT method as described.178 Doxorubicin (IC50 1.00 μM on SW480 and 0.50 μM on H9c2) and methotrexate (IC50 N 20.00 μM on SW480 and 5.00 μM on H9c2) were used as positive controls. The result showed that, compound 95 exhibited a moderate cytotoxicity on SW480 cell line, which was however higher than the positive control methotrexate, whereas a weak activity was observed on the H9c2 cell line. Compounds 93, 94 and 96 were found to be inactive on both cell types. All the isolated compounds 93–96 were inactive in comparison with the positive control doxorubicin. The results displayed a marginal cytotoxicity of triterpenoids saponins of this plant as previously reported for the structural analog of compound 95 isolated from Pittosporum viridifolium.179
Polycarpaea corymbosa (Caryophyllaceae) is a cosmopolite species, that has been recently studied and the results revealed hepatoprotective activity after administration of the whole plant extract to mammals.180,181 This plant has wide applications in traditional medicine in some part of the world. It is used to treat cough in traditional Chinese medicine,182 the leaves are used in Indian to treat inflammatory swellings and jaundice.183 Previous chemical investigation of this plant revealed the presence of triterpenes, steriods184 and flavonoids.183 In the search for biologically active triterpenoid saponins from the Caryophyllaceae family.185,186 Mahenina et al. isolated four new triterpenoids saponins (97–100) and a known triterpenoid saponins (101) from the methanolic extracts of leaves and roots of this plant.187 The compounds were 3β-O-(β-D-xylopyranosyl-(1→2)-β-D-glucopyranosyl-(1→4)-[β-D-glucopyranosyl-(1→2)]-α-L-arabinopyranosyl)-13β,28-epoxyolean-11-en-16α-ol (97), 3β-O-(β-D-xylopyranosyl-(1→2)-β-D-glucopyranosyl-(1→4)-[β-D-glucopyranosyl-(1→2)]-α-L-arabinopyranosyl)-oleana-11,13(18)-diene-16α,28-diol (98), 3β-O-(β-D-xylopyranosyl-(1→2)-β-D-glucopyranosyl-(1→4)-[β-D-glucopyranosyl-(1→2)]-α-L-arabinopyranosyl)-camelliagenin A (99),16α,22α-diacetoxy-3β-O-(β-D-xylopyranosyl-(1→2)-β-D-glucopyranosyl-(1→4)-[β-D-gluco-pyranosyl-(1→2)]-α-L-arabinopyranosyl)-olean-12-en-28-ol (100) and apoanagallosaponin IV (101). Triterpenoid saponins have been known to possess cytotoxic activity.176,177 Thus, the isolated compounds 97, 99–101 were evaluated for their cytotoxic activities against two human cancer cell lines (colorectal SW480, and prostate DU145), and one mouse tumour cell line (mammary EMT6) using a XTT assay.178 The results showed that compound 97 was the most active compound exhibiting cytotoxicity against these cell lines with IC50 values ranging from 4.61 to 22.61 μM. This activity level was greater than that of the anticancer drug, etoposide, which was used as positive control. Compounds 99–101 were inactive (IC50 > 10 μM). Compound 98 was tested only against the SW480 cell line and an embryonic rat heart-derived cell line (cardiomyoblast H9c2) by a XTT assay, and was inactive (IC50 > 10 μM).
Croton pseudopulchellus (Euphorbiaceae) commonly known as the Small Lavender Croton is used in the coastal area of Kenya and other parts of Africa to treat various ailments.57,120–124 Langat et al. isolated two new ent-kauren-19-oic acid derivatives; compounds 50–51 together with the known compounds; 52–55, 60, eudesm-4(15)-ene-1β,6α-diol (102), (−)-7-epivaleran-4-one (103), germacra-4(15),5E,10(14)-trien-9β-ol (104) and acetyl aleuritolic acid (105) from the hexane and methylene chloride extracts of the stem bark of this plant.125 Quantitative assessment of anti-plasmodial activity in vitro was determined via the parasite lactate dehydrogenase assay using a modified method described by Makler et al.126 The activity of some of the compounds was not reported in this study (Fig. 11).
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Fig. 11 Chemical structures of a sesquiterpene and triterpenoids from Southern African flora (105–117). |
Sutherlandia humilis (Fabaceae) commonly known as cancer bush is used traditionally for a myriad of indications, ranging from poor appetite to the prevention and treatment of cancer.188–190 Analysis of the methanolic leaf extract of this plant using thin layer chromatography (TLC) revealed the presence of the triterpenoids sutherlandiosides A (106) and Sutherlandiosides B (107).191 Denise et al. also isolated the new cycloartane-type triterpene glycoside 24,25-O-β-D-diglucopyranosyl-6α-hydroxycycloart-3-one (SU3) (108) as the major compound in this plant.192
Phyllanthus polyanthus (Phyllanthaceae) also known as Forest Potato-bush is a rare species of plant in South Africa.193 A similar species of this plant P. delpyanus decocotions of the roots are used by the Digo of Kenya in the treatment of sexually transmitted diseases.194 Ndlebe et al. isolated two new triterpenoids phyllanthol (109), phyllanthone (110) in addition to the known compounds (20S)-3β-acetoxy-24-methylenedammaran-20-ol (111), and (20S)-3α-acetoxy-24-methylenedammaran-20-ol (112), lupenone (113), δ-amyrin acetate (114) from the stem bark and leaves of this plant.195 Compounds 109–110 has not been isolated previously from a natural source but have been synthesised.196–200
An ethonobotanical survey of medicinal plants revealed the wide application of Mimusops obtusifolia (Sapotaceae) in the management of malaria in Zulu traditional medicine.201 Crude extracts from the stem bark of this plant showed an in vitro anti-plasmodial activity against a CQS of Plasmodium falciparum (D10) with an IC50 value of 32.5 μg mL−1. Mthokozisi et al. isolated the known triterpenoids taraxerol (115) and sawamilletin (116) from the stem bark of this plant.202 Quantitative assessment of anti-plasmodial activity in vitro was determined.126 The results showed that the compounds had IC50 > 100 μg mL−1.
Mthokozisi et al. isolated the triterpenoid ursolic acid (117) from the leaves of Mimusops caffra (Sapotaceae) collected from Durban, KwaZulu-Natal Province, South Africa.202,203 This plant is used in traditional medicine because of its healing properties against sores and wounds.204 Several triterpenoids isolated from plants have been reported in literature to demonstrate both in vitro and in vivo anti-plasmodial activity.205–207 Compound 117 has been previously reported to possess anti-plasmodial activity.208 and in this study the compound showed an appreciable anti-plasmodial activity with an IC50 value of 6.8 μg mL−1 at the tested concentration using CQS of P. falciparum. The lower activity of the compound as compared to the crude extract could be due to synergistic effect with other compounds, decomposition during fractionation.
Morus nigra (Moraceae) also known as black mulberry extracts have been reported to have antibacterial and fungicidal activity.209 This plant is used economically for sericulture, as a feed for the domesticated silkworm, the bark of this plant is being used to expel tape worm. Mazimba et al. isolated the known compounds 62 and 63 in addition to other compounds from the stem bark of this plant.70,137,210
Footnotes |
† These authors contributed equally. |
‡ Present address: Department of Pharmaceutical Chemistry, Martin-Luther-University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06120 Halle (Saale), Germany. |
This journal is © The Royal Society of Chemistry 2015 |