The uniqueness and therapeutic value of natural products from West African medicinal plants, part III: least abundant compound classes

Abstract

In this review, a continuation of our in-depth coverage of natural products derived from West African medicinal plants with diverse biological activities has been given. In the previous parts of this review series, the most abundant bioactive compound classes: terpenoids, flavonoids and alkaloids from West Africa were thoroughly investigated. We now focus on the least abundant compound classes (quinones, steroids, phenolics, glycosides, and other classes), having remarkable biological activities. A correlation between the biological activities of the derived compounds and the uses of the plants in African traditional medicine has been established.

---

Conrad V. Simoben

Conrad Simoben was born in 1990 in Cameroon. He obtained his undergraduate degree in Chemistry after successful studies from 2008 to 2011 at the University of Buea, Cameroon. He is currently pursuing the Master's of Science degree in Chemistry with a focus on the application of cheminformatics concepts on the development of natural product databases for West African medicinal plants, and the development of a knowledge base and rules for the prediction of environmentally harmful chemicals. He is currently a trainee at the Chemical and Bioactivity Information Centre, University of Buea, Cameroon.

Fidele Ntie-Kang

Fidele Ntie Kang studied Chemistry at the University of Douala in Cameroon between 1999 and 2004, completing his bachelor's and master's degrees. His PhD work at the Centre for Atomic Molecular Physics and Quantum Optics (CEPAMOQ) was based on the computer-aided design of anti-tubercular agents. He has an experience in molecular modeling and has been involved in the design and management of 3D structural databases of natural products from African flora for virtual screening. He currently works as a scientific manager/senior instructor at the Chemical and Bioactivity Information Centre (CBIC), hosted at the Chemistry Department of the University of Buea, Cameroon.

Lydia L. Lifongo

Lydia Lifongo is a lecturer/head of laboratory and coordinator of programs in the Department of Chemistry, University of Buea, Cameroon. She concurrently manages the Chemical and Bioactivity Information Centre, hosted at the department. Lydia obtained her bachelor's degree in Chemistry from the University of Buea, Cameroon in 1996, and later obtained her master's in Chemistry in 1998 at the same institution before moving to East Anglia (United Kingdom) where she obtained her PhD in Environmental Science. Currently, her focus is on the research activities of the centre, which include developing a knowledge base for bioactivity data and environmental toxicity.

Smith B. Babiaka

Smith Babiaka studied Chemistry at the University of Buea, Cameroon, where he subsequently obtained his bachelor's and master's degree in 2005 and 2011, respectively. Since 2012, he has been pursuing his PhD in chemistry at the same university and is working on natural products/organic synthesis. His previous work has been focused on the extraction, purification and characterisation of natural products from African medicinal plants. His current assignment at the Chemical and Bioactivity Information Centre consists of developing natural product databases for African medicinal plants and a knowledge base for environmentally harmful chemicals.

Wolfgang Sippl

Wolfgang Sippl studied Pharmacy at the University of Berlin. He later obtained a PhD in Pharmaceutical Chemistry at the University of Düsseldorf in the group of Hans-Deiter Höltje and was a post-doctoral fellow at the Université Louis-Pasteur in Strasbourg (France), where he worked with Camille G. Wermuth. He then took a senior researcher position in Düsseldorf before moving to the University of Halle-Wittenberg as a full professor of Medicinal Chemistry in 2003. Since 2010, he has been the director of the Institute of Pharmacy in Halle. His main interests are focused on computational chemistry and structure-based drug design.

Luc Meva'a Mbaze

Luc Meva'a Mbaze is currently associate professor/head of the Chemistry Department, University of Douala, Cameroon. He studied at the University of Pau (France) where he obtained his undergraduate degree in Chemistry, followed by a master's degree in Physical Chemistry before moving to the University of Poitier (France) to study for his PhD in Organic Chemistry with a focus on organic synthesis. On returning to his home country, i.e. Cameroon, his postdoctoral research has been focused on natural products chemistry, searching for lead compounds for the treatment of tropical diseases and the development of databases for African medicinal plants.

---

1 Introduction

Plants have been used by humans for various purposes since the existence of human civilization,^1–4 including healthcare, food, clothing, shelter, agriculture, agrochemicals, pharmaceuticals, and narcotics. The study of traditional uses of plants is generally referred to as ethnobotany.^5,6 According to the World Health Organization's (WHO) traditional medicine strategy for 2014–2023, traditional medicine (TM) has a long history and is defined as the sum total of practices, knowledge and belief systems which use minerals, plants and animal based remedies, spiritual therapies and exercises to prevent, treat and maintain well being.^7,8 This knowledge became enriched over numerous generations due to experimentation, as well as through observations of animal behaviour.^5,9 The knowledge of African traditional medicine (ATM) is facing the danger of being forgotten in favour of Western medicine (WM), as there is little communication between the aged traditional healers and the younger generation and/or the scientific community on a number of species reported. Moreover, the method of transmission of indigenous knowledge is similar (inherently passed down through oral communication).^10,11 In developing or poor countries of the world (mostly in Africa, Asia and Latin America) access to WM is limited. Consequently, most families have resorted to traditional medicine, based on various plant extracts. This has rendered TM as the most affordable and easily accessible source of treatment in the primary healthcare system for poor communities. This local therapy remains the most reliable means of medical treatment for such communities.¹⁰

It is estimated that about 80% of the populations in some Asian, Latin American and African countries depend on TM for their primary healthcare,^12–15 and some of these plants have been documented in journal articles, as well as in master's and doctoral theses of university libraries.^12,16 In traditional African societies, phytotherapy is highly valued and widely utilised. Thus, the majority of the populations use plant materials as their sources of primary healthcare.¹⁷ The importance of the useful aspects of traditional medicine and practices being incorporated to healthcare delivery at the primary healthcare level has been the subject of many studies.^18,19 In the last two and a half decades, drug discovery utilizing ethnopharmacological and traditional uses of herbal remedies in particular have received a lot of attention in Africa.²⁰ It is well known that traditional healers make use of a large variety of herbs in the treatment of several ailments. A wide proportion of herbal remedies dispensed by traditional healers are widely accepted by their clients to be effective; thus, the practice of TM in Africa is mostly driven by habits, low purchasing power and belief systems.^21,22 Phytochemical investigation of the plant species, based on the ethnobotanical knowledge may provide the chemical lead for the discovery of a new generation drug molecules or as hits/leads for synthetic modifications, which could lead to more potent or less toxic analogues with improved drug metabolism and pharmacokinetic (DMPK) profiles.^9,23–25

African flora has a huge potential and remains an interesting reservoir for new drugs that can target a variety of diseases.¹² This is because the region is ethnobotanically highly diverse, and these plants are used in the treatment of several diseases, which is a common practice in Africa.^25,26 Recent review papers on the potential of natural products (NPs) isolated from African medicinal plants have been focused on specific plant families, genera or species;^27–32 particular diseases;^33–35 and particular countries or regions.^34,36–38 It is believed that the derived NPs hold enormous potential for drug discovery.¹² Due to the diverse use of these plants in TM practices, research groups in Africa have started extraction, bioassay-guided fractionation, isolation and characterisation of bioactive metabolites from the plants commonly used in ATM,^39–44 with a view of identifying the active ingredients, which might have implications in drug discovery programs.^45–48

West Africa is a natural environment, which consists of subtropical and tropical regions with semi-arid and humid climates, and it occupies an area of over 6 140 000 km², including sixteen countries.⁴⁹ The floral diversity in West Africa and their wide use against many diseases, extending from endemic tropical diseases, such as malaria,^50–56 trypanosomiasis^9,55–59 and leishmaniasis,^60–62 to complex illnesses like asthma,⁶³ psychosis,^64,65 hepatitis,^66,67 diabetes^68,69 and cancer^70,71 is well documented. Unique NPs isolated from West African flora have been reviewed and published in the first part of this series of reviews.⁴⁵ The objective of the present review is to highlight the least abundant molecular compound classes from West African flora, along with a correlation between the biological activities of the derived compounds and the uses of the plants in ATM.

2 Ethnobotany versus bioactivity survey

The biological activities of the selected compounds along with the ethnobotanical uses of the plants, from which they were derived have been summarised in Tables 1–5. Whenever there is a correlation between bioactivity and ethnobotany, these correlations have been highlighted in bold in the tables. The discussion that follows is arranged according to the various compound classes identified, with a focus on quinones, steroids, phenolics, glycosides and other compound classes from West African flora.

Table 1 Bioactivity of derived quinones versus ethnobotanical uses of plant species

Compound	Plant species (country)	Family	Ethnobotanical use	Measured activity	Ref.
1	Abrus precatorius (Nigeria)	Leguminosae	Treatment of malaria	Antimicrobial activity	Muhammad et al.^74 Limmatvapirat et al.^75
2	Diospyros mespiliformis (Nigeria)	Ebenaceae	Leaf decoction for whooping cough and root extract as worm expellants	Cytotoxicity	Adeniyi et al.^76
3	Cassia siamea (Nigeria)	Leguminosae	Treatment of malaria	Antiplasmodial activity	Ajaiyeoba et al.,^77 Morita et al.,^78 Oshimi et al.^79
4 and 5	Aframomum danielli (Nigeria)	Zingiberaceae	Used as traditional food spice and also as anti-inflammatory agent	Lipoxygenase inhibition	Odukoya et al.^81

---

2.1 Quinones

Quinones are widely distributed among plant genera in Africa, including the Vismia species (Guttiferae), Tectona species (Lamiaceae) and Psorospermum species (Guttiferae). The summary of the most important findings on bioactive quinones from West African flora are given in Table 1.

Abrus precatorius (Fabaceace) is a perennial shrub and the seed of the plant, commonly known as rosary beads, is widely used traditionally for several medicinal purposes in Africa, the US and Asia for a wide range of pharmacological applications.^72,73 Muhammad and Amusa investigated and reported the use of the stem bark of Abrus precatorius in the treatment of malaria.⁷⁴ Limmatvapirat et al. isolated abruquinone B (1) from the stem bark of this plant, which showed in vitro anti-plasmodial activity with IC₅₀ = 1.5 μg mL⁻¹ against the K1 strain of P. falciparum.⁷⁵

Diosquinone (2), isolated from the roots of Diospyros mespiliformis (Ebenaceae), has shown very good anticancer activity against all the cell lines tested with ED₅₀ values ranging between 0.18 μg mL⁻¹ against human glioblastoma (U373) and 4.5 μg mL⁻¹ against hormone-dependent human prostate cancer (LNCaP).⁷⁶ However, the relationship with the ethnobotanical use of this plant has not been established because the leaf decoction has been used for the treatment of whooping cough and root extracts have been used as worm expellants. The use of the leaves and stem bark of Cassia siamea have been reported in the treatment of malaria.⁷⁷ Investigation of the leaves of this plant by Morita et al.⁷⁸ and Oshimi et al.⁷⁹ led to the isolation of emodin or 1,6,8-trihydroxyl-3-methyl-anthraquinone (3).

Aframomum danielli (Zingiberaceae), also known as alligator pepper, is most common in tropical and subtropical regions where it is used traditionally as a food spice, as well as an anti-inflammatory agent and for crop protection.⁸⁰ The long chain polypropenyl benzoquinone derivatives: phytyl plastoquinone (4) and heptaplastoquinone (5) have been isolated from the active petrol and alcohol extracts.⁸¹ Both compounds inhibited 5-lipoxygenase at 6.25 and 18.5 μM, respectively, as compared to Fisetin (the standard drug), which inhibited the enzyme at 0.92 μM.

2.2 Steroids

Among the bioactive steroids derived from West African flora, summarised in Table 2 are those from Alchornea cordifolia (Euphorbiaceae). This plant is used locally as a traditional remedy for arthritis, muscle pain and other inflammatory disorders.⁸² The crushed leaves are usually rubbed on painful joints or made into a paste and applied to painful stingray wounds, as they are believed to possess remarkable anti-inflammatory and pain-relieving properties. Ethyl iso-allocholate (6) isolated from the leaves of A. cordifolia possesses anti-inflammatory effect, which have been well documented.^83–86

Table 2 Bioactivity of derived steroids versus ethnobotanical uses of plant species

Compound	Plant species (country)	Family	Ethnobotanical use	Measured activity	Ref.
6	Alchornea cordifolia (Nigeria)	Euphorbiaceae	Remedy for arthritis, muscle pain and other inflammatory disorders	Anti-inflammatory activity	Okoye et al.^85
7 and 8	Loranthus micranthus (Nigeria)	Loranthaceae	As an immunostimulant and antioxidant, particularly in several debilitating diseases, including cancer, flu and other viral infections but not limited to these diseases	Proliferative activity	Ogechukwu et al.^86

---

Loranthus micranthus (Loranthaceae) is widely used in folkloric medicine as an immunostimulant and antioxidant. Recent research reports for this practice have provided preliminary scientific evidence.^87,88 The stigmastane steroids stigmast-7,20-(21)-diene-3β-hydroxy-6-one (7) and 3β-hydroxystigmast-23-ene (8) at the highest concentration of 100 mg mL⁻¹ showed statistically significant (p < 0.05) stimulatory activity on the C57B1/6 splenocytes.⁸⁶

2.3 Phenolics

Bioactive phenolics have been isolated from a broad range of West African flora species and families (Table 3). Among these phenolic compounds, ellagic acid (9),⁸⁹ identified from the stem of Alchornea cordifolia (Euphorbiaceae), is responsible for its antimalarial activity.^34,55

Table 3 Bioactivity of derived phenolic compounds versus ethnobotanical uses of plant species

Compound	Plant species (country)	Family	Ethnobotanical use	Measured activity	Ref.
9	Alchornea cordifolia (Nigeria)	Euphorbiaceae	Source of treatments to cure malaria symptoms traditional healers	Antiplasmodial activity and cytotoxicity	Banzouzi et al.^89
10–19	Loranthus micranthus (Nigeria)	Loranthaceae	Treatment of diarrhea, epilepsy, hypertension and rheumatism	Antioxidant activity	Agbo et al.^93
20	Chrozophora senegalensis (Mali)	Euphorbiaceae	Treatment of diarrhea, rheumatism, teniasis, stomach ache, rachitis, and venereal diseases. The leaf and root decoctions are taken orally for hair loss	Antioxidant activity	Vassallo et al.^94
21	Spathodea campanulata (Nigeria)	Bignoniaceae	Treatment of diseases (ulcers, dysentery, oedemas, skin eruptions, scabies, wound healing and urethral discharge) and veterinary application have been attributed to the plant in different cultures	Antioxidant activity	Elusiyan et al.^97
22	Securinega virosa (Mali)	Euphorbiaceae	It is used in traditional medicine for many diseases, including diarrhea, rheumatism, malaria, liver disease, inflammation and pain. Extracts of the plant are used for the expulsion of worms and in the treatment of bilharziasis, and for other urinary and genital tract disorders	Antioxidant activity	Sanogo et al.^100
23–25	Ixora coccinea (Nigeria)	Rubiaceae	Treatment of a variety of infections, hypertension, menstrual irregularities, sprains, chronic ulcers and skin diseases	Antioxidant activities	Idowu et al.^101

---

Loranthus micranthus (Loranthaceae) grows on many host trees,^90,91 and the leaves are traditionally used in folk medicine for the treatment of numerous ailments such as diarrhea, epilepsy, hypertension and rheumatism.⁹² Compounds 10 to 19 have been isolated from the leaves of this plant from Nigeria and their antioxidant activities were evaluated using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, with IC₅₀ values varying from 23.8 to 50.1 μM, compounds 10 to 19 being more active than the reference drug chlorogenic acid (with IC₅₀ = 67.9 μM).⁹³ Vassallo et al. also investigated antioxidant flavonoid glycosides from Chrozophora senegalensis, also known as Croton senegalensis (Euphorbiaceae), which is harvested in Mali.⁹⁴ It is a small tree widely distributed in Mali and is used as folk medicine for the treatment of diarrhoea, rheumatism, teniasis, stomach ache, rachitis, and venereal diseases. The leaf and root decoctions are also taken orally to control hair loss.^95,96 In order to justify the ethnobotanical use of C. senegalensis, the leaf extracts were assayed for in vitro antioxidant activity. Bioassay-guided fractionation revealed the methanol extract as active. The separation of this extract led to the isolation of three new flavonoids, along with known flavonoids, a phenolic derivative, i.e. 4-hydroxyphenyl-O-α-L-rhamnopyranosyl-(1→6)-β-D-glucopyranoside (20), and three megastigmane glycosides. All isolated compounds were tested for their antioxidant activity on DPPH stable radical, superoxide anion, metal-chelating activity and DNA cleavage induced by the photolysis of H₂O₂.

The antioxidant activity of caffeic acid (21), derived from the fruits and leaves of Spathodea campanulata (Bignoniaceae), popularly known as the African tulip tree, has been used to endorse the use of the plant in southwestern Nigeria for ulcer treatment by the oral intake of the decoction of its stem bark.⁹⁷ Securinega virosa (or Flueggea virosa) is a small tree widely distributed in Mali^98,99 and is used in traditional medicine for the treatment of many diseases, including diarrhoea, rheumatism, malaria, liver disease, inflammation and pain. Antioxidant bioassay-guided fractionation of S. virosa methanol extract by Sanogo et al. led to the isolation of 11-O-caffeoylbergenin (22) and other compounds.¹⁰⁰ Among these compounds, 11-O-caffeoylbergenin (22), kaempferol 3-O-(4-galloyl)-β-D-glucopyranoside and glucogallin exhibited the highest antioxidant capacity being also able to modulate hydroxyl radical formation more efficiently than other compounds acting as direct hydroxyl radical scavengers and chelating iron.

Idowu et al.¹⁰¹ identified procyanidin A2 (23), ixoratannin A-2 (24), cinnamtannin B-1 (25) and other constituents from Ixora coccinea (Rubiaceae) leaves. The antioxidant properties of the identified compounds were also investigated. This revealed that ixoratannin A-2 (24) and cinnamtannin B-1 (25) were the most active compounds in DPPH, through the inhibition of lipid peroxidation and nitric oxide radical scavenging assays. This could explain why the plant is effective in the treatment of chronic ulcers.^101,102

2.4 Glycosides

Ximenia americana (Olacaceae) is widely distributed in Africa from Senegal to West Cameroon, in tropical America and Asia as a shrubby tree, which can grow up to 5 m high.¹⁰³ The use of roots and leaves has been reported for the treatment of various ailments, such as throat infections, malaria, dysmenorrhea, wound healing, leprotic ulcers and skin diseases.^104–106 Sambunigrin (26) was found to be the main compound in the EtOAc extract of this plant, and it showed strong inhibitory effects of 15-lipoxygenase and xanthine oxidase.¹⁰⁷

From Chrozophora senegalensis (previously described), three megastigmane glycosides, namely, roseoside (27), icariside B5 (28) and ampelopsisionoside (29), were isolated and tested for their antioxidant activity on DPPH stable radical, superoxide anion, metal-chelating activity and DNA cleavage induced by the photolysis of H₂O₂.⁹⁴ The antioxidant activities of compounds 30 to 32 isolated from the flowers, fruits, leaves and stem bark of Spathodea campanulata (Bignoniaceae) were also investigated by Elusiyan et al.⁹⁷ They showed that the antioxidant products isolated from the various parts of the plant are verminoside (from the leaves, stem bark and flowers; EC₅₀ = 2.04 μg mL⁻¹), specioside (30) (from the flowers with EC₅₀ = 17.44 μg mL⁻¹), Kaempferol diglucoside (from the leaves with EC₅₀ = 8.87 μg mL⁻¹), and caffeic acid (21) (from the leaves and fruits). In addition, non-antioxidant components also were isolated in the study, including ajugol (from the stem bark and fruits) and phytol (from the leaves).⁹⁷

Russelia equisetiformis (Fabaceae) is a medicinal plant used by traditional healers to treat malaria, cancer and inflammatory diseases, as well as an analgesic and to stabilize membranes.^108,109 Awe et al.¹¹⁰ studied and examined the ethylacetate (most active) fraction for its antinociceptive effect, and isolated russetinol (33) and russelianoside A (34) from it. Compounds 33 and 34 both displayed tremendous activity on acetic acid induced writhing with less activity on a tail-flick response by mice. This result confirms the traditional uses of R. equisetiformis in the treatment of inflammation and pain.

2.5 Other compound classes

Table 5 is a summary of other bioactive compounds isolated from West African flora. Allium sativum (Alliaceae), commonly known as garlic, is a plant that is traditionally used in Nigeria for the treatment of malaria,^34,111 among other diverse uses.^68,112 From this plant, ajoene (35) and allicin (36) have been isolated. Ajeone was active against Plasmodium berghei in mice,¹¹³ thus validating the ethnobotanical use of the plant, whereas allicin was reported as a P. falciparum cysteine protease inhibitor.¹¹⁴

Table 4 Bioactivity of derived glycosides versus ethnobotanical uses of plant species

Compound	Plant species (country)	Family	Ethnobotanical use	Measured activity	Ref.
26	Ximenia Americana (Mali)	Olacaceae	Treatment throat infection, malaria, dysmenorrhea, leprosy, ulcers, skin diseases, wound healing	Antioxidant activity	Le et al.^107
27–29	Chrozophora senegalensis (Mali)	Euphorbiaceae	Treatment of diarrhea, rheumatism, teniasis, stomach ache, rachitis, and venereal diseases. The leaf and root decoctions are also taken orally for hair loss	Antioxidant activity	Vassallo et al.^94
30–32	Spathodea campanulata (Nigeria)	Bignoniaceae	Treatment of diseases (ulcers, dysentery, oedemas, skin eruptions, scabies, wound healing and urethral discharge) and veterinary application have been attributed to the plant in different cultures	Antioxidant activity	Elusiyan et al.^97
33 and 34	Russelia equisetiformis (Nigeria)	Fabaceae	Medicinal plant used by traditional healers to treat malaria, cancer, and inflammatory diseases, as an analgesic and to stabilize membranes	Antinociceptive activity	Johnson et al.,^108 Kolawole and Kolawole,^109 Awe et al.^110

---

Table 5 Bioactivity of other derived compounds versus ethnobotanical uses of plant species

Compound	Plant species (country)	Family	Ethnobotanical use	Measured activity	Ref.
35 and 36	Allium sativum (Nigeria)	Alliaceae	Treatment of malaria	Antiplasmodial activity	Adebayo et al.,^34 Perez et al.,^113 Coppi et al.^114
37	Cassia siamea (Nigeria)	Leguminosae	Treatment of malaria. In Asia, stem bark is used as a mild, pleasant, safe purgative for treating diabetes. A paste is used as a dressing for ringworm and chilblains. The roots are used as an antipyretic, and the leaves are used for the treatment of constipation, hypertension, and insomnia	Antiplasmodial activity, vasodialator effect	Ajaiyeoba et al.,^77 Morita et al.,^115 Oshimi et al.^116
38	Guiera senegalensis (Nigeria, Mali)	Combretaceae	Treatment of malaria, fevers, hepatitis, diabetes, pain, chemoprevention, anti-Helicobacter pylori, whereas the external application of dried leaves on wounds and infusion of leaves for the treatment of measles	Antiplasmodial activity	Iwalewa et al.,^117 Ancolio et al.,^118 Combier et al.^119
39–43	Quassia amara (Nigeria)	Simaroubaceae	Treatment of malaria	Antiplasmodial activity	Bertani et al.,^121 Kitagawa et al.,^122 Ajaiyeoba et al.^120
44	Bryophyllum pinnatum (Nigeria) Ximenia Americana (Mali)	Crassulaceae	Treatment of ulcers, allergic inflammation and epilepsy	Antibacterial activity	S. Pal and A. K. N. Chaudhuri,^124 Ogungbamila et al.^125
45 and 46	Ximenia Americana (Mali)	Olacaceae	Treatment of throat infection, malaria, dysmenorrhea, leprosy, ulcers, skin diseases, wound healing	Antioxidant activity	Le et al.^107
47–49	Alchornea cordifolia (Nigeria)	Euphorbiaceae	Remedy for arthritis, muscle pain and other inflammatory disorders	Anti-inflammatory activity	Okoye et al.^129
50–61	Alchornea floribunda (Nigeria)	Euphorbiaceae	Leaves are traditionally used as a remedy for arthritis, muscle pain and other inflammatory disorders	Anti-inflammatory activity	Okoye and Osadebe,^127 Okoye et al.^129
62	Jatropha gossypifolia (Nigeria)	Euphorbiaceae	Treatment of various disease conditions such as cough, tuberculosis, bacterial infections and cancerous growths. Traditionally, the leaves of the plant are applied to boils, carbuncles, eczema, skin irritation, and veneral diseases, used as febrifuge, whereas its bark is used as emmenagogue. The roots are used to treat leprosy, and stem latex possesses coagulant activity	Antifungal activity	Abiodun et al.^88
63 and 64	Cajanus cajan (Nigeria)	Fabaceae	Cancer treatment	Cytotoxicity	Ashidi et al.^131
65	Mitracarpus scaber (Benin)	Rubiaceae	To treat a variety of skin diseases such as eczema or ringworm	Antimicrobial activity against Dermatophilus congolensis	Gbaguidi et al.,^135 Lagnika et al.^136
66 and 67	Struchium sparganophora (Nigeria)	Asteraceae	Treatment of diseases (ulcers, dysentery, oedemas, skin eruptions, scabies, wound healing and urethral discharge) and veterinary application have been attributed to the plant in different cultures. It is also used in the treatment of malaria and measles, cutaneous, subcutaneous parasitic infection, rheumatic pains, diarrhea, dysentery as well as venereal diseases as an abortifacient, and in the treatment of inflammatory and tumor-related ailments. Also used in the preparation of soup in the southwestern regions of Nigeria	Antioxidant activity, antimicrobial and antitumour activities	Kasim et al.,^138 Liobikas et al.,^139 Gnoatto et al.^140
68	Fagara macrophylla (Guinea)	Rutaceae	For the cure of toothache, rheumatism and urogenital affections as well as to prepare poisonous arrows. This plant is also known to be rarely attacked by insects	Antifeedant activity	Tringali et al.^144
69	Keetia leucantha (Benin)	Rubiaceae	To treat parasitic diseases	Anti-trypanosomal activity	Bero et al.^146
70	Dennettia tripetala (Nigeria)	Annonaceae	The leaves of the plant are used by local herbalists in combination with other medicinal plants to treat various kinds of ailments, including fever, infantile convulsions, typhoid, cough, worm infestation, vomiting and stomach upset	Anticonvulsant, hypnosis and anxiolytic activities.	Oyemitan et al.^149
71	Sorghum bicolor (Burkina Faso)	Poaceae	Globally used for cereal production. In Africa, it is used for malaria, fever, blood tonic and sickle-cell	Not specified	Khalil et al.^152
72	Cassia alata (Nigeria)	Leguminosae	Treatment of skin diseases such as ringworm, eczema, pruritis, itching, scabies, ulcers and other related diseases	Antibacterial activity	Okwu and Nnamdi^153

---

Investigation of the leaves of Cassia siamea (Leguminosae) led to the isolation of emodin (37).⁷⁷ This plant is traditionally used in the treatment of malaria. In Asia, stem bark is used as a mild, pleasant, safe purgative for treating diabetes, and the paste is used as a dressing for ringworm and chilblains. The roots show antipyretic activity, and the leaves are used for the treatment of constipation, hypertension, and insomnia.^115,116 Guiera senegalensis (Combretaceae) is commonly used in treatment of malaria, fevers, hepatitis, diabetes, pain, for chemoprevention and as anti-Helicobacter pylori, whereas the dried leaves are externally applied on wounds and the infusion of leaves is used for the treatment of measles.^117–119 The leaf extract of this plant, harvested in Mali, led to the isolation of guieranone A (38), which acts as one of the active principles.^118,119

Among the compounds isolated from Quassia amara (Simaroubaceae) are simalikalactone D (39), samaderine X (40), samaderine Z (41), samaderine B (42) and samaderine E (43), all exhibiting anti-plasmodial activities.^120–122 This could explain the use of the leaves and stem of this plant for anti-malarial preparations. Q. amara (also called bitterwood tree) displayed the highest anti-malarial reputation for curative and preventive purposes in the Simaroubaceae family.^113,120

Bryophyllum pinnatum (Crassulaceae) has diverse uses in ATM, particularly in the treatment of ulcers, allergic inflammation and epilepsy.^123,124 Gallic acid (44) has been identified as the main active principle responsible for the antibacterial activity of this plant, which explains why it is used in many West African traditional medicine recipes for the treatment of ulcers.¹²⁵ From Ximenia americana (previously described and in part I of this review series),⁴⁷ gallic acid has also been isolated along with gallotannins, β-glucogalline (45) and 1,6-digalloyl-β-glucopyranose(46).¹⁰⁷

Alchornea floribunda and Alchornea cordifolia (Euphorbiaceae) are used locally as traditional remedies for malaria, arthritis, muscle pain and other inflammatory disorders.⁸² The crushed leaves are usually rubbed on painful joints or made into paste and applied to painful stingray wounds because of its local, as well as its systemic anti-inflammatory properties. Various extracts and fractions of A. floribunda and A. cordifolia have been validated by the results of some pharmacological studies.^83,126–128 Okoye et al.¹²⁹ reported the isolation and identification of compounds 47–61 from the n-hexane fractions of the A. floribunda and A. cordifolia leaves with topical anti-inflammatory properties. This could be used to validate the work of Mavar-Manga et al.¹³⁰ in which it was shown that the topical anti-inflammatory effect of A. cordifolia is due to the highly lipophilic constituents of the n-hexane fraction of the leaf extract. This also validates the claimed ethnomedicinal use of the crushed leaves of A. cordifolia and A. floribunda in the topical management of arthritis and other inflammatory diseases.

The compound 9-acetoxynerolidol (62) has been isolated as the main active ingredient from the seed extract of Jatropha gossypifolia (Euphorbiaceae).⁸⁸ This plant is used to treat various disease conditions such as cough, tuberculosis, bacterial infections, boils, carbuncles, eczema, skin irritation and cancerous growths.^131,132 Cajanus cajan is used in cancer treatment. The two constituent stilbenes, i.e. longistylins A (63) and C (64), isolated from the active dichloromethane (CH₂Cl₂) fraction of the leaves of this plant had IC₅₀ values of 0.7–14.7 μM against a range of cancer cell lines.¹³¹

Mitracarpus scaber (Rubiaceae) is used in Benin and the neighboring countries of West Africa traditionally as a medicine to treat a variety of skin diseases such as eczema or ringworm.^133,134 Gbaguidi et al. verified the presence of 2-azaanthraquinone (65) in extracts and samples of M. scaber grown in Benin while evaluating its antimicrobial activity against D. congolensis and reported it to have an MIC value of 7.5 μg mL⁻¹.¹³⁵ Lagnika et al. isolated three compounds (methoxy-4-acetophenone, 3,4,5-trimethoxybenzoic acid and azaanthraquinone) from the alcoholic extract of M. scaber and evaluated their antibacterial and free-radical scavenging activities using the p-iodonitrotetrazolium and DPPH methods.^136,137 Azaanthraquinone was the most interesting with MIC values of 7.5 μg mL⁻¹, 19 μg mL⁻¹, 38 μg mL⁻¹, 150 μg mL⁻¹ and >10 000 μg mL⁻¹ on Dermatophilus congolensis, Staphylococcus aureus, Enteroccocus feacalis, Escherichia coli and Pseudomonas aeruginosa, respectively. All three compounds showed mild scavenging activity in the DPPH test, with IC₅₀ values between 12 μg mL⁻¹ and 45.74 μg mL⁻¹.

Kasim et al. investigated the leaves of Struchium sparganophora (Asteraceae), a plant traditionally used to treat malaria and measles.^138–140 The isolated compounds; i.e. luteolin, vernodalin (66) and 3-methyl,2,6-hexacosedienol (67) demonstrated antimicrobial activities against the bacteria: Staphylococcus aureus, Klebsiella aerogenes, Escherichia coli and Proteus vulgaris, as well as against the fungal strains Candida albicans and Aspergillus niger.

Fagara macrophylla (Rutaceae) is used traditionally as a remedy for several diseases, in particular for the cure of tooth ache, rheumatism and urogenital infections, as well as to prepare poisonous arrows.^141,142 This plant is also known to be rarely attacked by insects.¹⁴³ The EtOH extract obtained from the bark of this plant led to the isolation and identification of sesamin (68) and magnoflorine (68′), which is a rare aporphine alkaloid that is unique to West Africa, along with other secondary metabolites.¹⁴⁴

Keetia leucantha is a West African tree used in traditional medicine to treat several ailments, including parasitic diseases.¹⁴⁵ Twenty-seven compounds were identified as constituents of the essential oil and their antitrypanosomal activity on Trypanosoma brucei brucei bloodstream forms (Tbb BSF) and procyclic forms (Tbb PF) were performed to identify their activity on the glycolytic process of trypanosomes. The oil showed an IC₅₀ of 20.9 μg mL⁻¹ on Tbb BSF, and no activity was observed on Tbb PF. Three triterpenic acids and β-ionone (69) showed inhibitory activities on GAPDH with oleanolic acid being the most active with an inhibition of 72.63% at 20 μg mL⁻¹.¹⁴⁶

Dennettia tripetala (Annonaceae) is a medium-sized tree and is widely distributed in the tropical rainforests of some West African countries. The leaves are used as spices for certain local dishes, whereas the ethanolic extract has been used traditionally in Nigeria to combat the growth of Ostrinia nubilaris that significantly affects corn and cotton, as well as other vegetable crops.^147,148 Oyemitan et al. investigated the hypnotic, anticonvulsant and anxiolytic effects of 1-nitro-2-phenylethane (70) obtained from the oil of this plant and established its mechanism of action.¹⁴⁹

Sorghum spp (Poaceae), cultivated worldwide, are rich in polyphenols belonging to the flavonoids and phenolic acid families and is ranked fifth in global cereal production.¹⁵⁰ Sorghum bicolor is medicinally used in the treatment of malaria, fever, blood tonic and sickle-cell diseases in Nigeria and other West African countries.^1,151 The extraction from the leaf sheath of the plant by Khalil et al. using a mixture of 1,3-butanediol and ethanol led to the isolation of 8-hydroxy-2-(4′-hydroxyphenyl)-5-(4′′-hydroxyphenyl)-pyrano[4,3,2-de]1-benzopyrylium (71).¹⁵² The antibacterial activity of 4-butylamine-10-methyl-6-hydroxycannabinoid dronabinol (72) isolated from Cassia alata (Leguminosae) could explain the use of this plant in the treatment of ulcers, as well as other skin diseases.¹⁵³

3 Conclusions

In this review series, emphasis has been given to NPs derived from medicinal plants that are from West Africa, whose experimentally measured bioactivities have been used to validate the ethnobotanical uses of the plant species from which they were derived. The entire study showed about 700 NPs from 97 plant species grouped into 41 families, exhibiting diverse biological activities. How these plants and/or derived NPs could be employed in drug discovery programs now depends on a number of factors. It becomes important to properly address the most critical issues involved as most of the research is currently being carried out mainly by academic groups. Research projects funded via collaborative programs should be tailored such that the African researchers play more than just the role of plant sample collectors. Synergistic efforts, such as those being promoted by the African Network for Drugs and Diagnostic Innovations (ANDI),^154,155 may be promising way forward, since the most ‘equipped’ laboratories in Africa barely host sufficient instrumentation for performing extractions and purifications. Another approach would be to set up national and regional repositories for biological screenings of readily affordable samples, similar to that of the pan-African natural products library (p-ANAPL).¹⁵⁶

Acknowledgements

Financial support is acknowledged from Lhasa Ltd., Leeds, UK, through the Chemical and Bioactivity Information Centre (CBIC), University of Buea, Cameroon.

Notes and references

1. J. D. Olowokudejo, A. B. Kadiri and V. A. Travih, Ethnobotanical Leaflets, 2008, 12, 851.
2. J. D. McChesney, S. K. Venkataraman and J. T. Henri, Phytochemistry, 2007, 68, 2015.
3. F. M. D. Ogbe, O. L. Eruogun and U. Marilyn, Sci. Res. Essays, 2009, 4(3), 120.
4. E. M. Abdallah, J. Appl. Pharm. Sci., 2011, 01(06), 16.
5. S. Y. Kamble, S. R. Patil, P. S. Sawant, S. Sawant, S. G. Pawar and E. A. Singh, Indian J. Tradit. Knowl., 2010, 9(3), 591.
6. J. W. Harsh burger, Bot. Gaz., 1896, 21, 146.
7. WHO, Traditional medicine, http://apps.who.int/iris/bitstream/10665/92455/1/9789241506090_eng.pdf?ua=1, accessed on 04th April 2014.
8. WHO, Tradional medicine strategy 2014 to 2023, http://www.who.int/medicines/areas/traditional/definitions/en/, accessed on 04th April 2014.
9. S. E. Atawodi, D. A. Ameh, S. Ibrahim, J. N. Andrew, H. C. Nzelibe, E. O. Onyike, K. M. Anigo, E. A. Abu, D. B. James, G. C. Njoku and A. B. Sallau, J. Ethnopharmacol., 2002, 79, 279.
10. H. Yineger and D. Yewhalaw, J. Ethnobiol. Ethnomed., 2007, 3, 24.
11. M. A. Sonibarea and Z. O. Gbile, Afr. J. Tradit., Complementary Altern. Med., 2008, 5(4), 340.
12. K. Hostettmann, A. Marston, K. Ndjoko and J. L. Wolfender, Curr. Org. Chem., 2000, 4, 973.
13. Y.-J. Xu, R. Capistrano, L. Dhooghe, K. Foubert, F. Lemière, S. Maregesi, A. Baldé, S. Apers and L. Pieters, Planta Med., 2011, 77, 1139.
14. I. A. Bello, G. I. Ndukwe, O. T. Audu and J. D. Habila, Org. Med. Chem. Lett., 2011, 1, 14.
15. K. Patel, N. Kumar and N. K. Sharma, J. Adv. Sci. Res., 2011, 2, 42.
16. S. A. Ali, E. A. Taiwo, A. O. Rafat, A. S. Sikirat, A. B. Ramat and I. Mohammed, Nat. Sci. Res., 2012, 2(7), 2224.
17. N. R. Farnsworth, A. D. Kinghorn, D. D. Soejarto and D. P. Waller, Siberian Ginseng (Eleutherococcus senticosus) current status as an Adaptogen, in Economic and Medicinal Plant Research, ed. H. Wagner, H. Hikino and N. R. Farnsworth, Academic Press, Orlando, FL, 1985, vol. 1, pp. 155–215.
18. Z. O. Gbile, F. A. Adeyemi and T. K. Odewo, Nigerian flora and its pharmaceutical potential no. 3, Mitteilungen aus dem Institut für Allgemeine Botanik, Hamburg 23b, pp. 1033–1038; Proceedings of the 12th Plenary Meeting of Aetifat, ed. H. Baijnah, M. Cheek, F. N. Hepper, J. Lejoly, G. L. Lucas, F. P. Malaise, C. R. Peters and D. C. J. Wessels, HamburgMittectiengen aus dem Institute fur Allgemeine Botanik, Hamburg 23b, 1990, pp. 1033–1046.
19. World Health Organization (WHO), General Guidelines for Methodologies on Research and Evaluation of Traditional Medicine, World Health Organization, Geneva, 2000.
20. E. O. Ajaiyeobaa, O. Oladepob, O. I. Fawole, O. M. Bolaji, D. O. Akinboye, O. A. T. Ogundahunsi, C. O. Falade, G. O. Gbotosho, O. A. Itiola, T. C. Happi, O. O. Ebong, I. M. Ononiwu, O. S. Osowole, O. O. Oduola, J. S. Ashidi and A. M. J. Oduola, J. Ethnopharmacol., 2003, 85, 179.
21. G. C. Kirby, Plants as sources of antimalarial components, Tropical Doctor, 1997, 27(suppl. 1), 7–11.
22. D. A. Warrell, Herbal remedies for malaria, Tropical Doctor, 1997, 27(suppl. 1), 5–6.
23. S. Tagboto and S. Townson, Adv. Parasitol., 2001, 50, 199.
24. O. Akerele, Herbalgram, 1993, 28, 13.
25. S. M. N. Efange, Natural products: a continuing source of inspiration for the medicinal chemist, in Advances in Phytomedicine, vol. 1, Ethnomedicine and Drug Discovery, ed. M. M. Iwu & J. C. Wootton, Elsevier Science, Amsterdam, The Netherlands, 2002, pp. 61–69.
26. K. Chibale, M. Davies-Coleman and C. Masimirembwa, Drug discovery in Africa: impacts of genomics, natural products, traditional medicines, insights into medicinal chemistry, and technology platforms in pursuit of new drugs, Springer, 2012.
27. R. M. G. Perez, S. Mitchell and R. V. Solis, J. Ethnopharmacol., 2008, 117, 1.
28. J. C. Coetzee and A. E. V. Wyk, Afr. J. Biotechnol., 2009, 8(22), 6007.
29. J. P. Yadav, V. Arya, S. Yadav, M. Panghal, S. Kumar and S. Dhankhar, Fitoterapia, 2010, 81, 223.
30. J. H. A. Paul, C. E. Seaforth and T. Tikasingh, Fitoterapia, 2011, 82, 302.
31. S. A. Audu, A. E. Taiwo, A. R. Ojuolape, A. S. Sani, A. R. Bukola and I. Mohammed, J. Nat. Sci. Res., 2012, 2(7), 1.
32. T. J. Ngeh and V. Rob, J. Ethnopharmacol., 2013, 146(3), 681.
33. Y. Achille, G. Joachim, A. Dissou, M. Mansourou, A. Bigot, S. Anagonou, F. Portaels, J. Quetin-Leclercq and M. Anandi, Planta Med., 2011, 77, 641.
34. J. O. Adebayo and A. U. Krettli, J. Ethnopharmacol., 2011, 133, 289.
35. N. R. Cláudio and L. M. X. Lucia, Molecules, 2011, 16, 2146.
36. B.-E. Van Wyk, J. Ethnopharmacol., 2008, 119, 342.
37. B.-E. Van Wyk, J. Ethnopharmacol., 2008, 119, 331.
38. O. O. Oyesiku, African Journal of Agricultural Research, 2012, 7(31), 4352.
39. H. Zhang, Characterization of bioactive phytochemicals from the stem bark of African mahogany Khaya senegalensis (Meliaceae), PhD Thesis, Clemson University, 2008.
40. A. Falodun, T. C. Onwudiwe and Nnena, Bayero J. Pure Appl. Sci., 2011, 4(2), 1.
41. F. A. Aladedunye, D. A. Okorie and M. O. Ighodaro, Nat. Prod. Res., 2008, 22(12), 1067.
42. A. T. Choumessi, M. Danel, S. Chassaing, I. Truchet, V. B. Penlap, A. C. Pieme, T. Asonganyi, B. Ducommun and A. Valette, Cell Div., 2012, 7, 8.
43. M. A. Aderogba, L. J. McGaw, M. Bezabih and B. M. Abegaz, Nat. Prod. Res., 2011, 25(13), 1224.
44. J. A. Mbah, N. N. Moses, A. L. Ashime, S. B. Babiaka, N. N. Lina, N. D. Kennedy, N. Lemuh and S. M. N. Efange, Ann. Clin. Microbiol. Antimicrob., 2012, 11, 10.
45. F. Ntie-Kang, L. L. Lifongo, C. V. Simoben, S. B. Babiaka, W. Sippl and L. Meva'a Mbaze, RSC Adv., 2014, 4, 28728,  10.1039/c3ra03038a.
46. F. Ntie-Kang, D. Zofou, S. B. Babiaka, R. Meudom, M. Scharfe, L. L. Lifongo, J. A. Mbah, L. Meva'a Mbaze, W. Sippl and S. M. N. Efange, PLoS One, 2013, 8(10), e78085.
47. G. A. Cordell, M. L. Quinn-Beattie and N. R. Farnsworth, Phytother. Res., 2001, 15, 183.
48. A. Gaulton, L. J. Bellis, A. P. Bento, J. Chambers, M. Davies, A. Hersey, Y. Light, S. McGlinchey, D. Michalovich, B. Al-lazikani and J. P. Overington, Nucleic Acids Res., 2012, 40, D1100.
49. P. S. Njomnang and F. Benoit-Vical, J. Ethnopharmacol., 2007, 114, 130.
50. P. Amoa Onguéné, F. Ntie-Kang, L. L. Lifongo, J. C. Ndom, W. Sippl and L. Mbaze Meva'a, Malar. J., 2013, 12, 449.
51. L. L. Lifongo, C. V. Simoben, F. Ntie-Kang, S. B. Babiaka and P. N. Judson, Nat. Prod. Bioprospect., 2014, 4, 1.
52. F. Ntie-Kang, P. Amoa Onguéné, L. L. Lifongo, J. C. Ndom, W. Sippl and L. Mbaze Meva’a, Malar. J., 2014, 13, 81.
53. J. S. Kayembe, K. M. Taba, K. T. Ntumba, M. T. C. Shiongo and T. K. Kazadi, J. Med. Plants Res., 2010, 4(11), 991.
54. I. Addae-Mensah, F. Fakorede, A. Holtel and S. Nwaka, Malar. J., 2011, 10(suppl. 1), S9.
55. K. Kamanzi Atindehou, C. Schmid, R. Brun, M. W. Koné and D. Traore, J. Ethnopharmacol., 2004, 90, 221.
56. J. X. Kelly, M. J. Smilkstein, R. Brun, S. Wittlin, R. A. Cooper, K. D. Lane, A. Janowsky, R. A. Johnson, R. A. Dodean, R. Winter, D. J. Hinrichs and M. K. Riscoe, Nature, 2009, 459, 270.
57. S. Hoet, F. Opperdoes, R. Brun and J. Quertin-Leclerg, Nat. Prod. Rep., 2004, 21, 353.
58. N. J. Nwodo and O. F. C. Nwodo, Asian Pac. J. Trop. Med., 2012, 1, 857.
59. S. Hoet, F. Opperdoes, R. Brun, V. Adjakidjé and J. Quetin-Leclercq, J. Ethnopharmacol., 2004, 91, 37.
60. J. Bero, V. Hannaert, G. Chataigné, M.-F. Hérent and J. Quetin-Leclercq, J. Ethnopharmacol., 2011, 137, 998.
61. O. Kayser, A. F. Kiderlen, H. Laatsch and S. L. Croft, Acta Trop., 2000, 77, 307.
62. L. G. Rocha, J. R. G. S. Almeida, R. O. Macedo and J. M. Barbosa-filho, Phytomedicine, 2005, 12, 514.
63. M. A. Sonibare and Z. O. Gbile, Afr. J. Tradit., Complementary Altern. Med., 2008, 5(4), 340.
64. A. Adamu, E. M. Abdurahman, H. Ibrahim, M. S. Abubakar, M. G. Magaji and A. H. Yaro, Niger. J. Pharm. Sci., 2007, 6(2), 1.
65. L. Cheesman, J. J. Nair and J. V. Staden, J. Ethnopharmacol., 2012, 140, 405.
66. O. Silva, A. Duarte, M. Pimentel, S. Viegas, H. Barroso and J. Machado, J. Ethnopharmacol., 1997, 57, 203.
67. D. Potdar, R. R. Hirwani and S. Dhulap, Fitoterapia, 2012, 83, 817.
68. A. Mohammed, M. A. Ibrahim and M. S. Islam, Planta Med., 2014, 80, 354.
69. (a) A. A. Adewale, J. Ethnopharmacol., 2012, 144, 705; (b) K. A. Abo, A. A. Fred-Jaiyesimi and A. E. A. Jaiyesimi, J. Ethnopharmacol., 2008, 115, 67.
70. P. B. K. Kouamé, C. Jacques, G. Bedi, V. Silvestre, D. Loquet, S. Barillé-Nion, R. J. Robins and I. Tea, Phytother. Res., 2013, 27(6), 835,  DOI:10.1002/ptr.4787.
71. M. S. Abubakar, A. M. Musa, A. Ahmed and I. M. Hussaini, J. Ethnopharmacol., 2007, 111, 625.
72. Z. H. Xiao, F. Z. Wang, A. J. Sun, C. R. Li and C. G. Huang, Molecules, 2012, 17, 295.
73. D. J. Taur and R. Y. Patil, Asian Pac. J. Trop. Biomed., 2011, 1(1), 40.
74. S. Muhammad and N. A. Amusa, Res. J. Agric. Biol. Sci., 2005, 1, 254.
75. C. Limmatvapirat, S. Sirisopanaporn and P. Kittakoop, Planta Med., 2004, 70, 276.
76. B. A. Adeniyi, M. F. Robert, H. Chai and H. H. S. Fong, Phytother. Res., 2003, 17, 282.
77. E. O. Ajaiyeoba, J. S. Ashidi, L. C. Okpako, P. J. Houghton and C. W. Wright, Phytother. Res., 2008, 22, 254.
78. H. Morita, S. Oshimi, Y. Hirasawa, K. Koyama, T. Honda, W. Ekasari, G. Indrayanto and N. C. Zaini, Org. Lett., 2007, 9, 3691.
79. S. Oshimi, Y. Tomizawa, Y. Hirasawa, T. Honda, W. Ekasari, A. Widyawaruyanti, M. Rudyanto, G. Indrayanto, N. C. Zaini and H. Morita, Bioorg. Med. Chem. Lett., 2008, 18, 3761.
80. D. W. Thomas, J. Thomas, W. N. Bromley and F. T. Mbenkum, Korup ethnobotany survey, final report, The World Wide Fund for Nature, Penda House, Weyside Park, Godalming, Surrey, UK, 1989.
81. O. A. Odukoya, P. J. Houghton and A. Raman, Phytomedicine, 1999, 6(4), 251.
82. J. A. Duke, J. B. Mary and D. Judi, Handbook of medicinal herbs, CRC Press, Boca Raton, 2002.
83. H. Mavar-Manga, M. Haddad, L. Pieters, C. Baccelli, A. Penge and J. Quetin-Leclercq, J. Ethnopharmacol., 2008, 115, 25.
84. C. O. Okoli and P. A. Akah, Pharmacology Biochemistry and Behaviour, 2004, 79, 473.
85. F. B. C. Okoye, P. O. Osadebe, C. S. Nworu, N. N. Okoye, E. O. Omeje and C. O. Esimone, Nat. Prod. Res., 2011, 25, 1941.
86. O. E. Ogechukwu, O. P. Ogoamaka, N. C. Sylvester, A. Hassan, A. Debbab, E. C. Okechukwu, A. Kawamura and P. Peter, Phytochem. Lett., 2011, 4, 357.
87. P. O. Osadebe and E. O. Omeje, J. Ethnopharmacol., 2009, 126, 287.
88. A. Falodun, T. C. Onwudiwe and Nnena, Bayero J. Pure Appl. Sci., 2011, 4(2), 1.
89. J. T. Banzouzi, R. Prado, H. Menan, A. Valentin, C. Roumestan, M. Mallie, Y. Pelissier and Y. Blache, J. Ethnopharmacol., 2002, 81, 399.
90. F. H. Ali, T. N. Intesar, W. A. Khylood and A. H. Saad, Int. J. Compr. Pharm., 2005, 17, 345.
91. P. O. Osadebe, C. C. Abba and M. O. Agbo, Asian Pac. J. Trop. Med., 2012, 5, 412.
92. P. Griggs, Biochemist, 1991, 13, 3.
93. M. O. Agbo, D. Lai, F. B. C. Okoye, P. O. Osadebe and P. Proksch, Fitoterapia, 2013, 86, 78.
94. A. Vassallo, G. Cioffi, F. De Simone, A. Braca, R. Sanogo, A. Vanella, A. Russo and N. De Tommasi, Nat. Prod. Commun., 2006, 1, 1089.
95. J. Kerharo and J. G. Adam, Pharmacopée Sénégalaise traditionelle: plantes médicinales et toxicologiques, ed. V. et Frères, Paris, 1974, p. 1011.
96. H. D. Neuwinger, African traditional medicine, A dictionary of plant use and application, Medpharm Scientific Publisher, 2000.
97. C. A. Elusiyan, N. C. Ani, C. O. Adewunmi and T. A. Olugbade, Afr. J. Tradit., Complementary Altern. Med., 2011, 8(1), 27.
98. E. J. Adjanohoun, L. Aké Assi, J. J. Floret, S. Guindo, M. Koumaré, A. M. R. Ahyi and J. Raynal, Contribution aux études ethnobotaniques et floristiques au Mali, ed. ACCT, Médecine traditionnelle et pharmacopée, Paris, 1985, p. 250.
99. J. Kerharo and A. J. Adam, Pharmacopée sénégalaise traditionnelle: Plantes médicinales et toxicologiques, Paris Vigot et Frères edn, 1974, p. 1011.
100. R. Sanogo, A. Vassallo, N. Malafronte, S. Imparato, A. Russo and F. Dal Piaz, Nat. Prod. Commun., 2009, 4, 1645.
101. T. O. Idowu, A. O. Ogundaini, A. O. Salau, E. M. Obuotor, M. Bezabih and B. M. Abegaz, Phytochemistry, 2010, 71, 2092.
102. S. Wiyakrutta, N. Sriubolmas, W. Panphut, N. Thongon, K. Danwiset-Kanjana, N. Ruangrungsi and M. Vithaya, World J. Microbiol. Biotechnol., 2004, 20, 265.
103. H. M. Burkill, The Useful Plants of West Tropical Africa, Families M-R, Royal Botanic Gardens, Kew, 2nd edn, 1997.
104. D. Diallo, C. Sogn, F. B. Samaké, B. S. Paulsen, T. E. Michaelsen and A. Keita, Pharm. Biol., 2002, 40, 117.
105. T. E. Grønhaug, S. Glæserud, M. Skogsrud, N. Ballo, S. Bah, D. Diallo and B. S. Paulsen, J. Ethnobiol. Ethnomed., 2008, 4, 26.
106. D. S. Ogunleye and S. F. Ibitoye, Trop. J. Pharm. Res., 2003, 2, 239.
107. N. H. T. Le, K. E. Malterud, D. Diallo, B. S. Paulsen, C. S. Nergård and H. Wangensteen, J. Ethnopharmacol., 2012, 139, 858.
108. C. E. Johnson, L. Lin, J. M. Harnly, F. O. Oladeinde, A. M. Kinyua, R. Michelin and Y. Bronner, J. Nat. Prod., 2011, 4, 57.
109. O. T. Kolawole and S. O. Kolawole, Biol. Med., 2010, 2(3), 38.
110. E. O. Awea, A. Adeloye, T. Idowu, O. A. Olajide and J. Makinde, Phytomedicine, 2008, 15, 301.
111. I. P. Dike, O. O. Obembe and F. E. Adebiyi, J. Ethnopharmacol., 2012, 144, 618.
112. A. Gbolade, J. Ethnopharmacol., 2012, 144, 1.
113. H. A. Perez, M. De La Rosa and R. Apitz, Antimicrob. Agents Chemother., 1994, 38, 337.
114. A. Coppi, M. Cabinian, D. Mirelman and P. Sinnis, Antimicrob. Agents Chemother., 2006, 50, 1731.
115. H. Morita, S. Oshimi, Y. Hirasawa, K. Koyama, T. Honda, W. Ekasari, G. Indrayanto and N. C. Zaini, Org. Lett., 2007, 9, 3691.
116. S. Oshimi, Y. Tomizawa, Y. Hirasawa, T. Honda, W. Ekasari, A. Widyawaruyanti, M. Rudyanto, G. Indrayanto, N. C. Zaini and H. Morita, Bioorg. Med. Chem. Lett., 2008, 18, 3761.
117. E. O. Iwalewa, L. Lege-Oguntoye, P. P. Rai, T. T. Iyaniwura and N. L. Etkin, West Afr. J. Pharmaceut. Drug Res., 1990, 9, 19.
118. C. Ancolio, N. Azas, V. Mahiou, E. Ollivier, C. Di Giorgio, A. Keita, P. Timon-David and G. Balansard, Phytother. Res., 2002, 16, 646.
119. H. Combier, M. Becchi and A. Cavé, Plant. Med. Phytother., 1977, 11, 251.
120. E. O. Ajaiyeoba, U. I. Abalogu, H. C. Krebs and A. M. J. Oduola, J. Ethnopharmacol., 1999, 67, 321.
121. S. Bertani, E. Houël, D. Stien, L. Chevolot, V. Jullian, G. Garavito, G. Bourdy and E. Deharo, J. Ethnopharmacol, 2006, 108, 155.
122. I. Kitagawa, T. Mahmud, K. I. Yokota, S. Nakagawa, T. Mayumi, M. Kobayashi and H. Shibuya, Chem. Pharm. Bull., 1996, 41, 2009.
123. H. M. Burkill, The useful plants of West Tropical Afiica – A revision of Dalziel's, Royal Botanical Gardens, Kew, London, 2nd edn, 1985, vol. 1.
124. S. Pal and A. K. N. Chaudhuri, Fitoterapia, 1992, 63(5), 451–459.
125. F. O. Ogungbamila, G. O. Onawunmi and O. Adeosun, Nat. Prod. Lett., 1997, 10, 201.
126. F. B. C. Okoye and P. O. Osadebe, Asian Pac. J. Trop. Med., 2009, 2(3), 7.
127. F. B. C. Okoye and P. O. Osadebe, Nat. Prod. Res., 2010, 24(3), 266.
128. F. B. C. Okoye, P. O. Osadebe, P. Proksch, R. A. Edrada-Ebel, C. S. Nworu and C. O. Esimone, Planta Med., 2010, 76(2), 172.
129. F. B. C. Okoye, P. O. Osadebe, C. S. Nworu, N. N. Okoye, E. O. Omeje and C. O. Esimone, Nat. Prod. Res., 2011, 25(20), 1941.
130. H. Mavar-Manga, D. Brkic, D. E. P. Marie and J. Quetin-Leclercq, J. Ethnopharmacol., 2004, 92, 209.
131. J. S. Ashidi, P. J. Houghton, P. J. Hylands and T. Efferth, J. Ethnopharmacol., 2010, 128, 501.
132. M. Kuroda, A. Yokosuka, R. Kobayashi, M. Jitsuno, H. Kando, K. Nosaka, H. Ishii, T. Yamori and Y. Mimaki, Chem. Pharm. Bull., 2007, 55, 1240.
133. E. J. Adjanonhoun, Rev. Méd. Pharm. Afri., 2001, 15, 103.
134. T. O. Ependu, P. A. Akah, A. A. Adesomoju and J. I. Okogun, Int. J. Pharmacogn., 1994, 32, 191.
135. F. Gbaguidi, G. Muccioli, G. Accrombessi, M. Moudachirou and J. Quetin-leclercq, Journal of Planar Chromatography, 2005, 18, 377.
136. L. Lagnika, F. Gbaguidi, E. Anago, Z. Adeoti, M. Moudachirou, A. Sanni and J. Quetin-leclercq, Int. J. Biol. Chem. Sci., 2010, 4(3), 820.
137. F. Gbaguidi, G. Accrombessi, M. Moudachirou and J. Quetin-leclercq, J. Pharm. Biomed. Anal., 2005, 39, 990.
138. L. S. Kasim, V. A. Ferro, O. A. Odukoya, A. Drummond, G. E. Ukpo, V. Seidel, A. I. Gray and R. J. Waigh, Microbiol. Antimicrob., 2011, 3(1), 13.
139. J. Liobikas, D. Majiene, S. Trumbeckaite, L. Kursvietiene, R. Masteikova, D. M. Kopustinskiene, A. Savickas and J. Bernatoniene, J. Nat. Prod., 2011, 74(7), 1640.
140. S. C. Gnoatto, A. Dassonville-Klimpt, S. Da Nascimento, P. Galéra, K. Boumediene, G. Gosmann, P. Sonnet and S. Moslemi, Eur. J. Med. Chem., 2008, 43(9), 1865.
141. F. R. Irvine, Woody plants of Ghana, O.U.P, 1961, pp. 498–500.
142. J. M. Watt and M. G. Breyer-Brandwijk, The medicinal and poisonous plants of Southern and Eastern Africa, Livingstone LTD, London: E. and S, 1962, p. 920.
143. I. Kubo, T. Matsumoto, J. A. Klocke and T. Kamikawa, Experientia, 1984, 40, 340.
144. C. Tringali, C. Spatafora, V. Calı and M. S. Simmonds, Fitoterapia, 2001, 72, 538.
145. J. Bero, V. Hannaert, G. Chataigne, M. F. Herent and J. Quetin-Leclercq, J. Ethnopharmacol., 2011, 137, 998.
146. J. Bero, C. Beaufay, V. Hannaert, M. Hérent, P. A. Michels and J. Quetin-Leclercq, Phytomedicine, 2013, 20, 270.
147. F. K. Ewete, J. T. Arnason, J. Larson and B. Philogene Jr, Entomol. Exp. Appl., 1996, 80, 531.
148. E. O. P. Agbakwuru, I. U. Osisiogu and G. Rucker, Niger. J. Pharmaceut. Res., 1979, 10, 203.
149. I. A. Oyemitan, C. A. Elusiyan, M. A. Akanmu and T. A. Olugbade, Phytomedicine, 2013, 20, 1315.
150. J. M. Awika, L. W. Rooney and R. D. Waniska, Food Chem., 2004, 90, 293.
151. C. Wambebe, H. Khamofu, J. A. Momoh, M. Ekpeyong, B. S. Audu, S. O. Njoku, N. R. Nasipuri, O. O. Kunle, J. I. Okogun, N. M. Enwerem, S. K. Gamaniel, O. O. Obodozie, B. Samuel, G. Fojule and P. O. Ogunyale, Phytomedicine, 2001, 8, 252.
152. A. Khalil, R. Baltenweck-Guyot, R. Ocampo-Torres and P. Albrecht, Phytochem. Lett., 2010, 3, 93.
153. D. E. Okwu and F. U. Nnamdi, Der. Chem. Sin., 2011, 2(2), 247.
154. T. Mboya-Okeyo, R. G. Ridley and S. Nwaka, Lancet, 2009, 373, 1507.
155. S. Nwaka, T. B. Ilunga, J. S. Da Silva, E. R. Verde, D. Hackley, R. D. Vré, T. Mboya-Okeyo and R. G. Ridley, PLoS Med., 2010, 7, e1000293.
156. F. Ntie-Kang, P. Amoa Onguéné, G. W. Fotso, K. Andrae-Marobela, M. Bezabih, J. C. Ndom, B. T. Ngadjui, A. O. Ogundaini, B. M. Abegaz and L. M. Mbaze, PLoS One, 2014, 9(3), e90655.

---