Background

Despite the advances in the field of pharmaceutical microbiology, the challenge of drug resistance, emerging and remerging microbial infections still occurs (Izah et al., 2018). According to Ezeigbo et al. (2016), Ejikeugwu et al. (2014), drug resistant to different microbial strain is a major factor leading to search of new antimicrobial agents. Plants have proven to be a suitable alternative for the synthetic and semi-synthetic based drug for the cure of several disease conditions. Buba et al. (2016) reported that plants are major source of novel drug compounds, and as such it has contributed immensely to human health and well-being. Several plants have demonstrated their usefulness in the field of phytomedicine, pharmacognosy, herbal science, pharmaceutical chemistry among others. Their usefulness could have stemmed from the presences of bioactive and chemical compounds in the essential oil found in different parts of plants.

Authors have variously reported that medicinal plants are plants whose one or more parts (including leaves, fruits, barks, stems, roots, flowers, latex/juice) have medicinal properties (Kigigha et al., 2015, 2016; Epidi et al., 2016a, b; Kalunta, 2017; Kigigha and Kalunta, 2017). As such, plants are used for the treatment of several disease conditions. Medicinal plants are used in child delivery processes (including ante-natal, post-natal, cure of miscarriage, etc.) by traditional birth attendants especially in rural areas in developing countries. Medicinal plants are also plants whose active ingredients and/or part are involved in the production of drugs.

Several plants species are found all over the world and are distributed into several families. Some plants are found in a particular region under specific environmental conditions. Plants are grown in soil, surface water (macrophytes) and another plant (epiphytes). As such, the use of plant for the treatment of disease conditions depends on its availability in particular region, education status of the users, and knowledge about its efficacy.

According to Ikpeazu et al. (2017), plants are used globally in the treatment of different diseases using varying approach. According to the world health organization, about 80% of the world’s population depends on traditional medicine for cure of several diseases (Akinmoladun, 2007; Fatima et al., 2011; Gahlaut and Chhiller, 2013; Minochecherhomji and Vyas, 2014; Momoh et al., 2014; Kigigha et al., 2015, 2016; Buba et al., 2016; Epidi et al., 2016a, b). Most of the dependants of traditional medicine are in rural areas in many developing countries. The patronize of traditional medicine attendants is associated to low income size, unavailability of medical facilities to the inhabitants of rural dwellers in many developing countries. Furthermore, Amole and Ilori (2010) also attributed the use of herbal remedies to inaccessibility of modern drugs probably due to economic factor.

Medicinal plants have been widely been use as stimulants, analgesic, anti-pyretic, anti-inflammatory, anti-convulsant, anti-microbial, anti-malaria, anti-leukemia, anti-hypertensive, anti-platelet, anti-oxidant, anti-tumor, anti-asthmatics, anti-inflammatory, anti-diarrhoea, anti-spasmodic, anti-depressants, anti-rheumatism, immunomodulatory, anti-epilepsy, anti-convulsant, anti-thyroids, hepato-protective, anti-apoptotic, anti-metastatic, anti-mutagenic/anti-tumor, anti-spermatogenic, anti-colon toxin, pesticidal efficacy against insect, treatment of skin diseases, catarrh, headache, ear ache, memory booster, cough and eye effects. Medicinal plants have also been applied in the management of diabetes (Kalunta, 2017; Kigigha and Kalunta, 2017). The efficacy of some medicinal plants has been confirmed against specific ailment. While traditional medicine practitioners also claim that some of the plants have specific activities which have not been scientifically proven.

Some of the medicinal plants can be used to treat more than one disease condition. In addition, some are also major food resources to humans. Some medicinal plants that are taken have some traditional backing. For instance, several species of Kola nut is used to receive visitors in several part of Nigeria. Furthermore, some Kola used in Nigeria has been validated to have medicinal plants against some ailment. Some of this Kola nut include Garcinia kola (bitter kola) (Okigbo and Mmeka, 2008; Ghamba et al., 2011; Ezeigbo et al., 2016), Buchholzia coriacea (Wonderful Kola) (Ezekiel and Onyeoziri, 2009; Mbata et al., 2009; Nwachukwu et al., 2014; Eze et al., 2015; Umeokoli et al., 2016), Cola nitida and C. acuminata. For instance, Buba et al. (2016), Faphonda et al. (2017) have reported that Garcinia kola have anti-oxidant, anti-microbial, anti-inflammatory, anti-hypocholesterolemic, anti-viral, anti-diarrhoea, anti-proliferative, anti-androgenic and anti-coronary activities. Like, nutmeg, clove, cinnamon, lime, garlic, moringa and pepper fruit, wonderful kola have been used as alternative medications to promote good health in Nigeria through treatment of different ailments. This practice is still on till date (Ejikeugwu et al., 2014).

Wonderful Kola which belonging to the Capparidaceae family is an evergreen shrub found in some African countries including Cameroon, Central African Republic, Gabon, Congo, Angola, Nigeria, Ghana, Liberia, etc. (Ezekiel and Onyeoziri, 2009; Ibrahim and Fagbohun, 2014; Ijarotimi et al., 2015; Umeokoli et al., 2016). The medicinal efficacy of the seed earned the plant its common name “wonderful kola” (Ezekiel and Onyeoziri, 2009; Ibrahim and Fagbohun, 2014; Nwachukwu et al., 2014; Ijarotimi et al., 2015; Lapshak et al., 2016). Wonderful kola can grow up to 20 meter in height and are characterized by large, glossy, leathery leaves and conspicuous creamy white flower (Mbata et al., 2009; Anowi et al., 2012). Wonderful kola bears edible fruit which taste peperish (Mbata et al., 2009; Nwaichi and Olua, 2015) with sharp pungent taste (Ezekiel and Onyeoziri, 2009). The fruit is usually about 5 inches in length and 2-3 inches in width which contain 1 inch seed (Mbata et al., 2009). The seed is consumed by humans, and studies have demonstrated that it medicinal properties to several disease conditions (Ezekiel and Onyeoziri, 2009; Mbata et al., 2009; Nwachukwu et al., 2014; Eze et al., 2015; Umeokoli et al., 2016).

Therefore, this study assessed the medicinal potential of wonderful kola. The proximate and mineral composition, phytochemical and chemical constituent and all possible medicinal properties were discussed. The study concludes by suggesting future direction of research into wonderful kola.

1 Proximate and Mineral Composition of Wonderful Kola

Proximate analysis is one of the parameters used in assessing the nutritional value of edible plant. Beside plant, proximate composition has been analyzed in biomass of microorganisms such as Saccharomyces cerevisiae (Izah et al., 2017a). In this study, the proximate composition of wonderful kola varies; this could be due to differences in processing. For instance, Ijarotimi et al. (2015) reported that there is difference in raw, blanched and fermented seed of wonderful kola. In addition, the moisture content (Ezekiel and Onyeoziri, 2009; Okoli et al., 2010), age and environmental condition could also affect the proximate compositions. Based on Table 1, carbohydrate content ranged from 66-77%. This indicates that wonderful kola is a carbohydrate plant. Furthermore, the protein content ranged from 10-15%. The seed also have calorific value of 375.75 kcal (Ibrahim and Fagbohun, 2012) and 384.33 kcal (Amaechi, 2009). The energy value further elucidate that the seed is an energy plant.

Wonderful kola seed contain essential trace metals, cations, and phosphorus (Table 2). The presents of amino acids, fatty acids, mineral such as cations (calcium, magnesium, sodium and potassium), phosphorus, trace metals (copper, zinc, manganese, cobalt and nickel) and absence of non-essential trace metals such as lead and chromium is an indication that it could promote good health through diet. The role of trace metals in human nutrition as well as pathological effects high concentration in human body have been various reported by Izah et al. (2016, 2017a, b), Izah and Angaye (2016). The health benefits of cations such as sodium, magnesium, potassium and calcium have been documented by Izah et al. (2015), Izah et al. (2017d), Aigberua et al. (2018), Ibrahim and Fagbohun (2012).

Wonderful kola also contains amino acids and essential oil. Ijarotimi et al. (2015) reported that fermented, raw, and blanched seed of wonderful kola contain amino acids such as alanine, arginine, aspartic, cysteine, glutamic, glycine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, threoinine, tryptophan, tyrosine, serine, valine with total amount of 68.96-73.31 mg/100 g. The authors further reported that the seed also contain varying fatty acids including palmitic, palmitoleic, stearic, oleic, linoleic, linolenic, arachidic and behenic acid. Furthermore, the authors conclude by indicating that blanched seed flour has superior effect with regard to most of the parameters.

2 Phytochemical Constituent of Wonderful Kola

Bioactive constituents have been reported in seed of wonderful kola. Authors have reported the presence of alkaloids, saponins, tannins, flavonoids, oxalates, phytates cardiac glycosides, steroids, resins, carbohydrate, anthraquinone, glycosides in seed of wonderful kola (Mbata et al., 2009; Ibrahim and Fagbohun, 2012; Nwachkwu et al., 2014; Obiudu et al., 2015; Okere and Ladeji, 2016; Umeokoli et al., 2016). Authors have variously reported that different extracts of wonderful kola have different effects depending on the specific bioactive ingredients. For instance, Umeokoli et al. (2016) reported seed extracts of wonderful kola contain weak alkaloid using methanol and strong alkaloids using n-hexane, chloroform and aqueous extract. The authors have also reported that chloroform extract do not contain steroids. In a quantitative determination of dried seed of wonderful kola, Ibrahim and Fagbohun (2012) reported that methanol extract of wonderful kola have superior effect compared to ethanol extract with regard to alkaloids, glycosides, saponins, steroids, tannins, flavonoids and sugar content while ethanol extract is superior with regard to phenols and terpenes.

Mbata et al. (2009) reported that both hot water and methanol extracts of wonderful kola seeds/leaves contain anthraquinone, whereas Umeokoli et al. (2016), Osadebe et al. (2011) reported that absence of anthraquinone. Furthermore, Osadebe et al. (2011) reported that alkaloid is not found in leaves of wonderful kola. Ejikeugwu et al. (2014), Anowi et al. (2012) reported the presence of phlobatannins, carbohydrates, proteins, tannins, saponins, alkaloids and flavonoids in leave of wonderful kola.

Age is one of the essential considerations often made in determining bioactive constituents in plants. The presence of phytochemicals/bioactive ingredients or compounds in plants is an indication that they have biological activity (Kigigha et al., 2015, 2016; Epidi et al., 2016a, b). Ibrahim and Fagbohun (2012) considered alkaloids as the most efficient therapeutic constituents of plant. Alkaloids have some medicinal potential including central nervous system, stimulant, pain reliever, pyretic action, anesthetics in ophathalmology (Heikens et al., 1995). Agu and Thomas (2012), Epidi et al. (2016a, b), Kigigha et al. (2015) reported that alkaloids have mechanisms to wade off pests including microorganisms. Probably due to the pain relieving potentials of alkaloids, it can be used as analgesics. Doherty et al. (2010), Okwu (2005), Ibrahim and Fagbohun (2012), Opoku and Akoto (2015), Osuntokun and Oluwafoise (2015) reported that derivatives of alkaloids can be used as analgesic, antispasmodic and anti-bacteria.

The presents of phenol compounds in plants are an indication of its pesticidal properties. Typically, phenolic compounds are used for disinfection, and it also remain a standard which other bacteria are compared (Ibrahim and Fagbohun, 2012). Phenol compounds can easily oxidize to form phenolate ion, an electron acceptor (Ibrahim and Fagbohun, 2012). Flavonoids which is an example hydroxylated phenolic compounds help plants to resist disease causing microbes (Opoku and Akoto, 2015; Epidi et al., 2016a, b). Probably due to this, it has anti-oxidant, anti-microbial and anti-tumor properties (Osuntokun and Oluwafoise, 2015; Epidi et al., 2016a, b), anti-allergies, anti-inflammation, platelet aggregation, free radicals, anti-ulcer and hepatoxins potentials (Okwu, 2004; Ibrahim and Fagbohun, 2012).

The hot taste of wonderful kola seed is probably due to the presence of tannin (Ibrahim and Fagbohun, 2012). Tannin is highly toxic to microbes. Tannins also play essential role in wound healing including varicose ulcers, hemorrhoids, frostbite and burns (Okwu and Okwu, 2004; Doherty et al., 2010; Ibrahim and Fagbohun, 2012; Kigigha et al., 2015; Osuntokun and Oluwafoise, 2015; Epidi et al., 2016a, b). Saponin helps to inhibit sodium ion efflux by blockage of the entrance of the sodium ion out of the cells (Ibrahim and Fagbohun, 2012). The presence of saponin suggests that the plant could be used as cough suppressant (Osuntokun and Oluwafoise, 2015). Many other bioactive constituents of plants also have medicinal potentials.

3 Chemical Constituents of Essential Oil from Wonderful Kola

The essential oil of wonderful kola contains chemical constituents (Table 3) (Omorogie et al., 2015; Umeokoli et al., 2016; Ikpeazu et al., 2017). Most wonderful kola seed oil contains both long chain saturated and unsaturated fatty acids, alcohols and their esters and high concentration of Estra-1, 3, 5 [10]-trien-17ß-ol (Umeokoli et al., 2016). Steroid is the major constituents which differs from estradiol (a sex hormone), with the absence of an OH functional group at carbon atom number 3 (Umeokoli et al., 2016). Oleic acid is unsaturated fatty acid and is considered as a healthy source of fat in human diets (Umeokoli et al., 2016). Many fatty acids constituents of wonderful kola contain anti-microbial properties (Umeokoli et al., 2016).

2-Methyl-pyrrolidine-2-carboxylic acid which a major constituent of wonderful kola essential oil is a Methyl-Guanidine-Inhibitor (Duke, 1996; Ikpeazu et al., 2017), and it can hinders the action of the hydrolase enzyme which hydrolyzes methyguanidinase to urea (Nakajima, 1980; Ikpeazu et al., 2017). Hexadecanoic acid is an arachidonic acid inhibition, while Beta-vinyl acrylic acid is beta-glucuronidase inhibitor (Ikpeazu et al., 2017). n-Hexadecanoic acid has haemolytic, 5-alpha reductase inhibitor, anti-oxidants, anti-hypocholesterolemic, anti-inflammatory, anti-androgenic, flavour, nematicide, pesticidal, anti-oxidant, anti-microbial activities and larvicidal effect (Bodoprost and Rosemeyer, 2007; Falodun et al., 2009; Hema et al., 2011; Omorogie et al., 2015; Fapohunda et al., 2017). Like, hexadecanoic, 15-methyl-, methyl ester, (Z)-Docos-13-enoic acid has antioxidant properties (Omorogie et al., 2015).

9-Octadecynoic and linoelaidic acid is urine acidifier (Duke, 1996) that play essential role in the body pH, food digestion especially in achlorhydria patients (Ikpeazu et al., 2017). 9, 12-Octadecadienoic acid tends to inhibit uric acid production (Ikpeazu et al., 2017). According to Ikpeazu et al. (2017), Pasalic et al. (2012), uric acid inhibitor inhibits the acidification of urine thereby minimizing the risk of formation of uric acid stones and deposition of uric acid crystals in the joints. 9, 12-Octadecadienoic acid and 9, 12 Octadecadienoyl chloride (Z,Z) have anti-inflammatory, anti-hypocholesterolemic, anti-tumor, anti-arthritic, anti-coronary, anti-ache, anti-histaminic, anti-eczemic, anti-androgenic, hepato protective, nematicide, 5-alpha reductase inhibitor and insectifuge properties (Yu et al., 2005; Maruthupandian et al., 2011; Omorogie et al., 2015; Fapohunda et al., 2017). Phenol, 3, 5-bis (1, 1-dimethylethyl), Cyclopropaneoctanoic, 2-hexyl-, methyl-, methyl ester has antimicrobial activities (Omorogie et al., 2015).

Methyl 14-methylpentadecanoate (catechol-O-methyl transferase) is an inhibitor that can be used to treat Parkinson disease (Duke, 1996; Ikpeazu et al., 2017). Furthermore, Ikpeazu et al. (2017) reported that Catechol-O-methyltransferase is involved in the degradation of neurotransmitters but the inhibitors oppose the degradation of neurotransmitters. Typically, dopamine, noradrenaline, anandamide and adrenaline are neurotransmitters (Ikpeazu et al., 2017). Based on Table 3, different extraction solvent lead to variation in the chemical constituents of wonderful kola seed essential oil. The difference may be attributed to the polarity of the solvents.

4 Medicinal Properties of Wonderful Kola

Traditional medicine practitioners have variously claimed that fruits/seeds and leaves of wonderful kola have medicinal properties to various disease conditions. Furthermore, scientific claims have been made with regard to the decoction containing different parts of wonderful kola plant as active ingredients. Therefore, this section discusses the medicinal properties of wonderful plant with regard to traditional claims and scientific validations.

4.1 Scientific validation of wonderful kola

In the scientific validation of the medicinal potency of wonderful kola, several species of microbes including bacteria (gram positive and negative) and fungi have been studied. Also in the non- microbial caused disease condition, organisms such as rat and mice have been widely used as experimental organisms. For helminthes studies, Trypanosoma brucei.brucei and T. congolense have been used. This section of the paper elucidates the scientific claims using these organisms as test subjects.

4.1.1 Anti-microbial

Studies have variously shown that wonderful kola seed contain antimicrobial (antibacterial and antifungal) activities (Ezekiel and Onyeoziri, 2009; Mbata et al., 2009; Osadebe et al., 2011; Ejikeugwu et al., 2014; Ibrahim and Fagbohun, 2014; Umeokoli et al., 2016). Furthermore, the antimicrobial properties have been widely attributed to bioactive components (Doherty et al., 2010; Kigigha et al., 2015, 2016; Epidi, 2016; Epidi et al., 2016a, b; Kalunta, 2017; Kigigha and Kalunta, 2017) such as alkaloids and tannins. Studies have indicated that seed of wonderful kola is sensitive to both gram positive and gram negative organisms (Table 4). This is an indication that the plant can be further studied and be used as broad spectrum antibiotics.

In sensitivity studies of plant materials, the solvent used for extraction have effect on the final result. For instance, Fagbohun (2014) reported methanolic extracts of seed of wonderful plant have superior effect compared to ethanol extract against a wide range of microorganisms. Ezekiel and Onyeoziri (2009) reported that fresh express extract of wonderful kola has better effect compared to methanol and hexane extracts. Nwachukwu et al. (2014) reported that fresh express extract of wonderful kola seed have superior efficacy compared to oven dried uncooked and cooked seed. Osadebe et al. (2011) reported that methanol has better effect compared to aqueous leaf extract of wonderful kola. Mbata et al. (2009) also reported that methanol extract has better effect against some gram positive and negative bacteria compared to hot water extracts. Umeokoli et al. (2016) also reported that methanolic extracts of seed of wonderful plant had better performance against most microbes compared to n-hexane and aqueous extracts. The authors further showed that not all aqueous and n-hexane extracts of seed of wonderful kola have effect on some microbes. The variation could be due to differences in polarity (Ezekiel and Onyeoziri, 2009), specificity and affinity level of the solvents. Furthermore, the zone of inhibition produces could be due to the concentration of the plant extract used for the study. Also, the physiology, metabolism, nutrition and biochemistry of the microbial isolates could influence the sensitivity of an extract against and organisms (Kigigha et al., 2016; Epidi et al., 2016a, b; Izah et al., 2018). The age and part of the plants used, environmental influence etc. could also contribute to variation in the sensitivity (Kigigha et al., 2016; Epidi et al., 2016a, b).

Ejikeugwu et al. (2012) reported that n-hexane, methanol and chloroform extracts of wonderful kola leave possess modest antibacterial activities against E. coli, Staphylococcus aureus, Shigella species, Klebsiella pneumoniae and Bacillus subtilis. The authors further reported that chloroform extract exhibited no activity against ESBL positive E. coli isolates, with n-hexane and methanol extracts showing moderate inhibitory effects. Osadebe et al. (2011) findings showed that methanolic leave extracts of wonderful kola have minimum inhibitory concentration and minimum bactericidal concentration in the range of 0.5-9.0 mg/ml and 2.0-9.0 mg/ml, respectively for E.coli, K. pneumonia, B. subtilis, B. cereus, S.aureus, S.typhi, P.aeruginosa.

Based on comparison methanol extract appears to have superior anti-microbial properties compared to ethanol, n-hexane, chloroform and aqueous (hot and cold) extract of different parts of wonderful kola plant. The superior effect may be associated to polarity and affinity level of methanol.

The anti-microbial potential could also be due to the presence of flavonoids, n-Hexadecanoic acid, 9,12-Octadecadienoic acid and 9,12 Octadecadienoyl chloride (Z,Z), Phenol, 3,5-bis (1,1-dimethylethyl), Cyclopropaneoctanoic, 2-hexyl-, methyl ester.

4.1.2 Anti-diabetes

Diabetes mellitus is a metabolic disorder that has mainly two forms viz: Type 1 and Type 2 (Nwaehujor et al., 2012; Ndiok et al., 2016; Eledo et al., 2017). Type 1 diabetes mellitus is characterized by autoimmune-mediated destruction of pancreatic β-cells of the islets and the patients rely on exogenous insulin for survival, while Type 2 diabetes mellitus is characterized by dysfunctioning of normal insulin levels to stimulate glucose uptake and patients are not dependent on exogenous insulin (Nwaehujor et al., 2012; Eledo et al., 2017). The disorders is characterized by hyperglycaemia and associated abnormalities in the metabolism of carbohydrate, fat and protein (Okoye et al., 2012). The incidence of Type 2 accounts for more than 90% of the diabetic cases worldwide. Nwaehujor et al. (2012) is with the opinion that approximately 80% of rural dwellers in Africa communities use herbs control diabetes mellitus. Furthermore, botanicals have demonstrated positive effects towards the control of diabetes. Adisa et al. (2011) demonstrated that ethanol and butanol seed extracts of wonderful kola is potent to hypoglycemic agent. The authors further reported that hypoglycemic and antioxidant properties of wonderful kola ameliorated the secondary effects of diabetes such as nephropathy, hepatotoxicity, and deranged lipid metabolism in diabetic animals. Nwaehujor et al. (2012) reported that methanol fruit extract of wonderful kola have significant anti-diabetic, hypolipidemic properties and also known to reduce lipid peroxidation in diabetic rats. Okoye et al. (2012) reported that methanol seed extracts of wonderful kola has hypoglycaemic activity, and in laboratory study, it exhibited synergistic actions with metformin, a standard oral hypoglycaemic agent. Egwu et al. (2017a) reported that ethanol seed extract of wonderful kola at high dose and vildagliptin reduces plasma glucose levels in alloxan-induced diabetic rats. Egwu et al. (2017b) reported that ethanol seed-extract at high doses improves lipid profile of rat under diabetic condition and concludes by indicating that the plant could be used for effective medication for addressing dyslipidemia in diabetes. Obiudu et al. (2015) reported that crude and methanolic seed extracts of wonderful kola has the tendency to reduce blood glucose level and this could be the reason while its used in the management of diabetes. Lapshak et al. (2016) reported that aqueous seed extract of wonderful kola has hypolidemic and hypoglycemic properties, and therefore, a possible botanical for the management of diabetes. Ijarotimi et al. (2015) reported that blanched, raw and fermented seed of wonderful kola has anti-diabetic potential. The authors further reported blanched seed has higher effect compared to when its used raw and fermented. Ezeigbo (2011) reported that methanolic seed extract of wonderful kola have anti-diabetic properties.

4.1.3 Anti-depressant

Several decades ago psychiatric conditions are managed with herbs, and it was discovered that some patients showed significant relief from severe psychotic depression (Onasanwo et al., 2016). Approximately 70% of the depressed patients respond to treatment using available therapies but with some level of disappointment (Onasanwo et al., 2016). The pathophysiology of depression is associated with the deficiency of one or more monoamines among psychiatric patients (Onasanwo et al., 2016). Hence, plants have demonstrated positive efficacy for the management of neurological problems such as depression, epilepsy, convulsion (Romeiras et al., 2012). Onasanwo et al. (2013) reported that methanolic seed extract of wonderful kola has antidepressant activity. Furthermore, Onasanwo et al. (2016) reported that methanol seed extract of wonderful kola have antidepressant potentials may be mediated by cholinergic, adrenergic systems.

4.1.4 Anti-plasmodial activity

Mosquitoes transmit several diseases including malaria (Bassey and Izah, 2017a). Authors have variously reported that malaria is endemic in over 109 countries, infecting 190-330 million people and causing about 1 million deaths per annum (Ndiok et al., 2016; Owoeye et al., 2016; Bassey and Izah, 2017a). Africa is the major endemic area of malaria in the world (Bassey and Izah, 2017b). Nigeria, Democratic Republic of Congo, Ethiopia and Uganda are the most endemic region of malaria in Africa. Malaria is caused by Plasmodium falciparum, and other species of Plasmodium including P. ovale, P. vivax and P. malariae. Instance of drug resistance have been reported. As such, research is ongoing for the discovery of more effective drugs. Plants have also join the host of materials/substances that new drug can be synthesis from for effective control of malaria. Malaria leads to dysfunctioning of the liver function, which could lead to complications if not properly managed (Enechi et al., 2016; Ndiok et al., 2016). Bassey and Izah (2017a) have reported several botanicals that are used to control mosquito at its various stage of development in Nigeria. Furthermore, Okoli et al. (2010) reported that aqueous seed extract of wonderful kola have anti-malarial activity using mice as experimental animal. Enechi et al. (2016) reported that methanol seed extract of wonderful kola significantly reduce parasitaemia level in infected experimental mice and restored altered haematological indices in malaria parasite infected mice as well.

4.1.5 Analgesic, anti-anxiety and anti-inflammatory activity

Analgesics are drugs or agents temporarily used minimize and/or block the sensation of pain (Patel et al., 2016). Typically, pain is an unpleasant sensation leading to abnormality in or part of the body. Pain can either physical or psychic/mental depending on its source. Like inflammation, analgesics are used to treat pain caused by physical stimuli, while mental pain is treated with antipsychotic agents (including anti-depressant, anti-anxiety and anti- manic drugs) (Patel et al., 2016). Plants have demonstrated positive potential for the used as analgesics (Patel et al., 2016). Some of the plants such as wonderful kola have demonstrated potential for pain reliving. Olaleye et al. (2012) reported that ethanol seed extracts of wonderful kola have analgesics and anti-inflammatory activity based on their study in which male rats was used as experimental animal. Ezeja et al. (2011) reported that methanolic seed extract of wonderful kola has analgesic activity. Umeokoli et al. (2016) reported that hexane seed extract of wonderful kola has anti-inflammatory potential. Ezike et al. (2015) reported that leave extract of wonderful kola plant have anti-inflammatory activity. Enechi et al. (2009) reported that ethanol seed extracts of wonderful kola have anti-inflammatory and analgesic activities. Okere and Ladeji (2016) reported that aqueous and methanol seed extract of wonderful kola have positive potency on carrageenan-induced inflammation in rats. Onasanwo et al. (2013) reported that methanolic seed extract of wonderful kola has anxiolytic (anti-anxiety) and analgesic potentials. The authors further reported that it has stabilizing effect on the motor activity probably due to secondary metabolites. The anti-inflammation may be associated to the presence of n-Hexadecanoic acid, 9,12-Octadecadienoic acid and 9,12 Octadecadienoyl chloride (Z,Z).

4.1.6 Anti-oxidants

Anti-oxidants are essential in maintaining optimum cellular functions in humans (Akinyede et al., 2015). According to Akinyede et al. (2015), humans have evolved highly complex antioxidant systems that work together to protect the body from aging and pathogenesis of age related disorders such as cancer, hypertension, atherogenesis, alzheimer and parkinson disease. Anti-oxidants also play essential role in detoxifying some toxicant in the human body. Adisa et al. (2011) also reported that seed extract of wonderful kola have antioxidant activity. Nwaehujor et al. (2012) reported that reported that methanol fruit extract of wonderful kola possesses antioxidant activities. Adisa et al. (2011) demonstrated that ethanol and butanol seed extracts of wonderful kola is has antioxidant activity. The anti-oxidant potency of wonderful kola may be associated to the presence of n-Hexadecanoic acid, hexadecanoic, 15-methyl-, methyl ester, (Z)-Docos-13-enoic acid, 9,12-Octadecadienoic acid and 9,12 Octadecadienoyl chloride (Z,Z).

4.1.7 Hyperlipidemia, anti-hypercholesterolemic and anti-atherogenic activity

Nwaichi et al. (2017) described hyperlipidemia as an anomalistic increase of lipids in the blood, abundance of triglycerides and cholesterol. This is due to uneven rise in lipoproteins that play essential role in the transportation of lipids in the blood, branded as hyperlipoproteinemia (Nwaichi et al., 2017; Saunders, 2017). Rerkasen et al. (2008), Nwaichi et al. (2017) reported that hypercholesterolemia is the most prevalent variety of dyslipidemia that could predispose an individual to cardiovascular diseases such as atherosclerosis, and pancreatitis. Botanicals such as wonderful kola have demonstrated clinic efficacy for the management of hyperlipidemia using male wistar rats as test organisms (Nwaichi et al., 2017).

Hypercholesterolemia is a condition characterized with high level of cholesterol in the blood (Olaiya and Omolekan, 2013) and it’s the major cause of atherosclerosis (Omolekan and Olaiya, 2013). According to Omolekan and Olaiya (2013), atherosclerosis is a major cause of chronic non –infectious diseases such as stroke and some other cardiovascular. Hypercholesterolemia has the tendency to predispose an individual to hypertension and cardiovascular diseases (Edijala et al., 2005; Olaiya and Omolekan, 2013). The disease is basically cause by both genetic and environmental factors. Botanicals have showed to have positive effect towards its management. Olaiya and Omolekan, (2013) demonstrated that ethanolic seed extract of wonderful kola contain anti-hypercholesterolemic agent using rat as experimental organisms. Omolekan and Olaiya (2013) reported that ethanolic seed extract of wonderful kola has anti-atherogenic activity which the authors attributed to the presence of flavonoids, saponins and plant sterols. Furthermore, anti-hypocholesterolemic potentials of wonderful kola may be associated to the presence of n-Hexadecanoic acid, 9,12-Octadecadienoic acid and 9,12 Octadecadienoyl chloride (Z,Z).

4.1.8 Anti-trypanosomal

Trypanosoma genus is a flagellated protozoan that causes trypanosomiasis (Abubakar et al., 2017; Assefa, 2017) sleeping sickness. Trypanosomiasis has been reported in human and animals especially in Africa and South America. In Africa, animal trypanosomiasis has adverse impact on livestock’s and is presently characterized by toxicity and resistance development to trypanocidal drugs (Assefa, 2017). This has necessitated to the search of alternative drugs. Botanicals have emerged as a credible substitute. Several plants species have demonstrated positive efficacy towards some species of Trypanosoma including T. brucei, T. congolense, T. evansi etc. (Abubakar et al., 2017; Assefa, 2017). Nweze et al. (2011a) have reported that crude seed extract of wonderful kola have anti-trypanosomal activities against T. brucei. Brucei in an in-vitro study. Nweze et al. (2011b) have reported that methanolic seed extract of wonderful kola have no anti-trypanosomal activities against T. congolense in a field study. This suggests that the efficacy of the extracts depends on dose and choice of solvent, species of Trypanosoma as well as its source. Nweze et al. (2009) reported that ethanolic seed extract of wonderful kola have Trypanocidal activity against T. brucei. brucei. Abubakar et al. (2017) reported that ethanol seed extract of wonderful kola is effective against T. brucei. brucei.

4.1.9 Anti-modulatory activities

The immune system can be manipulated by the use of immunomodulators. This is usually done to achieve immunostimulation or immune suppression (Eze et al., 2015). Modulation of immune response is a vital method through which some disease conditions can be control (Eze et al., 2015). Eze et al. (2015) studied immunomodulatory activity of methanolic seed extract of wonderful kola on Trypanosoma brucei. brucei infected mice and reported that the extract possess immunostimulatory activity.

4.1.10 Anti-spasmodic and anti-diarrhoea properties

Diarrhoea is one of the major disease conditions that cause morbidity and mortality (Fletcher et al., 2013; Gautam et al., 2015; Varela et al., 2015). Diarrhoea is caused by diverse group of organisms including viruses, fungi, parasites and bacteria (Nguyen et al., 2006; Sang et al., 2012; Gautam et al., 2015). Some of the bacteria associated diarrhoea includes Salmonella, Shigella, Campylobacter, Yersinia enterocolitica, Vibrio cholera, diarrheagenic E. coli pathotypes (Varela et al., 2015). Diarrhoea is transmitted from person-to-person and consumption of foods and water contaminated with human fecal materials with a pathogenic strain (Ali et al., 2014; Gautam et al., 2015). Botanicals have proven to be effective toward managing diarrhoea. While anti-spasmodic are medicines used to relax muscle cramps. Anowi et al. (2012) reported that methanol leave extract of wonderful kola has anti-diarrhoea and anti-spasmodic activity. The authors further reported that the metabolites in the leaves could act in synergism to produce the anti-diarrhoea effects.

4.1.11 Anti-ulcer

Stomach or gastric ulcers, are painful sores in the lining of the stomach lining and if not properly managed could lead to complications. Botanicals have demonstrated positive effect toward effective management of ulcer. Salami et al. (2017) reported that seed of wonderful kola enhanced gastric healing on ischemic reperfused gastric ulcer. Enechi and Nwodo (2014) reported ethanol seed extract of wonderful kola has anti-ulcer properties. The authors further stated that the anti-ulcer activities of the seed extract could be due to the ability of the extract to suppress histamine-induced gastric acid secretion as well as to antagonize histamine-induced contractile response.

4.1.12 Anti-helmintic

Helminths are invertebrates characterized by elongated, flat or round bodies and are generally called worm. The parasite has several types including flukes (trematodes), tapeworms (cestodes), roundworms (nematodes) etc. Botanicals have been used to managing helminthes. Nweze and Asuzu (2006) reported that seed of wonderful kola have anti-helmintic properties. Ajaiyeoba et al. (2001) demonstrated that the leaves of wonderful kola are effective against Fasciola hepatica, Phertima posthuma and Taenia solium. Nweze et al. (2006) reported that ethanolic seed extracts of wonderful kola have larvicidal action against Haemonchus contortus and Heligmosomoides polygyrus. Fred-Jaiyesimi et al. (2011) reported chloroform and methanol seed extracts of wonderful kola have anti-helmintic potentials against Eudrilus eugeniae (earthworm) and Bunostomum phlebotomum (cattle hookworm).

4.1.13 Anti-fertility

Fertility is the natural tendency to produce offspring. Fertility rate is the number of offspring born per mating pair within a given population. In recent times, fertility issues are becoming a major challenge in some part of the world. Some botanicals have demonstrated the potentials to be used as anti-fertility agents. Obembe et al. (2012) demonstrated that seed extracts of wonderful kola have anti-fertility effects in male rats and indicated that epididymis is the most probably site of action.

4.2 Traditional claims

Traditionally, several claims have been made on the medicinal efficacy of wonderful kola. Erhenhi and Obadoni (2015) reported that the seeds are crushed into paste and applied on the stomach of pregnant woman under labour. Other traditional claims include its potential for stimulant, tonic, aphrodisiac (Anowi et al., 2012), memory booster (Ibrahim and Fagbohun, 2012; Nwachukwu et al., 2014), expelling worms (anti-helmintics), treatment of ulcer (Anowi et al., 2012; Erhenhi and Obadoni, 2015), malaria and fever (Titanji et al., 2008), cough, hypertension (by drinking the fluid squeezed out of the leaves with pea leaves and small quantity of salt), relieving headache, sinusitis, and nasal congestion especially in Ivory Coast, small pox for skin itching in Gabon (by inhaling the pulp made from the bark) (Anowi et al., 2012; Erhenhi and Obadoni, 2015; Nwaichi et al., 2017). Anowi et al. (2012) also reported that the extracts from the bark of wonderful kola plant is used as a lotion against scabies. The pulp made from bark is robbed in the chest as treatment against chest pains and boils (Anowi et al., 2012; Erhenhi and Obadoni, 2015). Wonderful kola is also used for the treatment of syphilis, sinusitis, earache, smallpox, headache, gonorrhea and convulsion in children (Ajaiyeoba et al., 2003; Nwaichi et al., 2017). Decoction made from the seed of wonderful kola together with lime or local gin is used for the treatment of diabetes mellitus, hypertension, rheumatism, cold, cough and catarrh by traditional medicine practitioners (Adisa et al., 2011).

5 Conclusion and the Future Direction

The wonderful kola has been scientifically found to have analgesic, anti-depressant, anti-plasmodial, anti-anxiety, anti-diabetes, anti-inflammatory, anti-oxidants, anti-hypercholesterolemic, anti-atherogenic, anti-trypanosomal, anti-modulation, anti-spasmodic, anti-diarrhoea, anti-ulcer, anti-helmintics, anti-fertility activities. The scientific studies validates the claim of traditional medicine practitioners on the potency of wonderful kola. Therefore, further studies need to be carried out to elucidate on the mode/mechanisms of action, the dose that is required, purification of the chemical constituents, most suitable solvent to be used for extraction, age of the plants for the leave extract, and environmental conditions suitable for cultivation of wonderful kola with regard to its nutritional values. Also, studies need to be focused on effect on stimulant, tonic, aphrodisiac, fever, cough, hypertension headache, sinusitis, and catarrh, small pox, scabies, chest pains, boils, syphilis, earache, headache, gonorrhea, rheumatism, cold and catarrh potentials of the wonderful plants so as to validate its efficacies as widely claimed by traditional medicine practitioners.

Author’s contributions

Author SCI conceived the idea, managed literature search, wrote the initial draft and managed correspondence. Authors EJU and BOE proof read the manuscript and corrected tense. All authors read and approved the final manuscript.

References

Abubakar A., Jigam A.A., Kabir A.Y., and Adefolaju O.V., 2017, Phytochemical Constituents and In Vitro Antitrypanosomal Activity of Ethanol Seed Extract of Buchholzia Coriacea, J. Pure Appl. Sci., 4: 43-48

Adisa R.A., Choudhary M.I., and Olorunsogo O.O., 2011, Hypoglycemic activity of Buccholzia coriacea (Capparaceae) seeds in streptozotocin-induced diabetic rats and mice, Exp Toxicol Pathol, 63:619-25

https://doi.org/10.1016/j.etp.2010.05.002

PMid:20965120

Agu G.C. and Thomas B.T., 2012, Antibacterial Activities of Ethanol and Aqueous Extracts of Five Nigerian Medicinal Plants on Some Wound Pathogens, Nature and Science, 10(2):78-84

Aigberua A.O., Alagoa K.J., and Izah S.C., 2018, Macro Nutrient Composition in Selected Seasonings used in Nigeria, MOJ Food Processing and Technology, 6(4): 00155

Ajaiyeoba E.O., Onocha P.A., and Olarenwaju O.T., 2001, In vitro Anthelmintic Properties of Buchholzia coriaceae and Gynandropsis gynandra Extracts, Pharmaceutical Biology, 39(3): 217-220

https://doi.org/10.1076/phbi.39.3.217.5936

Ajaiyeoba E.O., Onocha P.A., Nwozo S.O., and Sama W., 2003, Antimicrobial and cytotoxicity evaluation of Buchholzia coriacea stem bark, Fitoterapia, 74(7-8):706-9

https://doi.org/10.1016/S0367-326X(03)00142-4

Akinyede K.A., Oyewusi H.A., Ologunde C.A., and Adeniyi O.A., 2015, The Amelioration of Carbon Tetracholride – Induced Toxicities by Methanolic Extract of Buchholzia coriacea Leave in Male Albino Rat, International Journal of Science and Research, 5(5): 56-61

Ali M.M.M., Ahmed S.F., Klena J.D., Mohamed Z.K., and Moussa T.A.A., 2014, Ghenghesh KS, Enteroaggregative Escherichia coli in diarrheic children in Egypt: molecular characterization and antimicrobial susceptibility, J Infect Dev Ctries, 8(5):589-596

https://doi.org/10.3855/jidc.4077

PMid:24820462

Amaechi N.C., 2009, Nutritive and Anti-Nutritive Evaluation of Wonderful Kola (Buccholzia coricea) Seeds, Pakistan Journal of Nutrition, 8: 1120-1122

https://doi.org/10.3923/pjn.2009.1120.1122

Amole O.O. and Ilori O.O., 2010, Antimicrobial Activity of the Aqueous and Ethanolic Extracts of the Stem Bark of Alstonia boonei, International Journal of Phytopharmacology, 1(2): 119-123

Anowi F.C., Ike C., Ezeokafor E., and Ebere C., 2012, The Phytochemical, Antispamodic and Antidiarrhoea properties of the methanol extract of the leaves of Buchholzia coriacea family Capparaceae, Int J Curr Pharm Res, 4(3): 52-58

Assefa S., 2017, Potential anti-trypanosomal plants against African animal trypanosmiasis, Journal of Pharmacognosy and Phytochemistry, 6(5): 77-85

Bassey S.E. and Izah S.C., 2017a, Nigerian plants with insecticidal potentials against various stages of mosquito development, ASIO Journal of Medical and Health Sciences Research, 2(1): 07-18

Bassey S.E. and Izah S.C., 2017b, Some determinant factors of Malaria Prevalence in Nigeria, Journal of Mosquito Research, 7(7): 48-58

https://doi.org/10.5376/jmr.2017.07.0007

Bodoprost J. and Rosemeyer H., 2007, Analysis of phenacylester derivatives of fatty acids from human skin surface sebum by reversed-phase HPLC: chromatographic mobility as a function of physico-chemical properties, International Journal of Molecular Sciences, 8(11):1111-24

https://doi.org/10.3390/i8111111

Buba C.I., Okhale S.E., and Muazzam I., 2016, Garcinia kola: the phytochemistry, pharmacology and therapeutic applications, International Journal of Pharmacognosy, 3(2): 67-81

Doherty V.F., Olaniran O.O., and Kanife U.C., 2010, Antimicrobial activities of Aframomum Melegueta (Alligator pepper), International Journal of Biology, 2(2): 126-131

https://doi.org/10.5539/ijb.v2n2p126

Duke's Phytochemical and Ethnobotanical Databases, 1996, U.S. Department of Agriculture, Agricultural Research Service, [Online]

https://phytochem.nal.usda.gov/phytochem/search

Edijala J.K., Asagba S.O., Eriyamuremu G.E., and Atomatofa U., 2005, Comparative effects of garden eggfruit, oat and apple on seum lipid prefile in rats fed on high cholesterol diet, Pakistan Journal of Nutrition, 4: 245-249

https://doi.org/10.3923/pjn.2005.245.249

Egwu C.O., Offor C.E. and Alum E.U., 2017a, Anti-diabetic effects of Buchholzia coriacea ethanol seed extract and vildagliptin on alloxan-induced diabetic albino rats, International Journal of Biology, Pharmacy and Allied Sciences, 6(6): 1304-1314

Egwu C.O., Offor C.E. and Aja P.M., 2017b, Anti-Dyslipidemic Effects of Buchholzia Coriacea Ethanol Seed-Extract on Alloxan-Induced Diabetic Albino Rats, Journal of Experimental Sciences, 2(1):130-138

Ejikeugwu C., Umeokoli B., Iroha I., Ugwu M., and Esimone C., 2014, Phytochemical and antibacterial screening of crude extracts from leaves and wonderful kola, American Journal of Life Sciences, 2(6): 9-12

Ejikeugwu C., Ikegbunam M., Ugwu C., Araka O., Iroha I., Adikwu M., and Esimone C., 2012, Evaluation of antibacterial activity of the leave extracts of Buchholzia coriacea, Asian J. Pharm. Biol. Res., 2(4): 2014-2018

Eledo B.O., Nwoga M.I., Okamgba O.C., and Izah S.C., 2017, Assessment of Some Haemostatic Parameters Among Diabetes Mellitus Patients in Bayelsa State: A Case Study at the Federal Medical Centre, Yenagoa, European Journal of Clinical and Biomedical Sciences, 3(5): 91-96

Enechi O.C., F.C. Ibeafu, H. Ledee, and O.F.C. Nwodo, 2009, Anti-inflammatory, analgesic and antipyretic activities of the ethanol extract of seeds of Buchholzia coriacea in experimental animals, Bio-research, 7(1)

Enechi O.C., Okpe C.C., Ibe G.N., Omeje K.O., and Ugwu Okechukwu P.C., 2016, Effect of Buchholzia coriacea Methanol Extract on Haematological Indices and Liver Function Parameters in Plasmodium berghei-Infected Mice, Global Veterinaria, 16(1): 57-66

Enechi O.C. and Nwodo O.F.C., 2014, Anti-ulcer and gastric anti-secretory activities of seed extract of Buchholzia coriacea in Wistar albino rats, African journal of biotechnology, 13: 2755-2761

https://doi.org/10.5897/AJB2014.13858

Epidi J.O., Izah S.C., and Ohimain E.I., 2016a, Antibacterial and synergistic efficacy of extracts of Alstonia boonei tissues, British Journal of Applied Science, 1(1): 21-26

Epidi J.O., Izah S.C., Ohimain E.I., and Epidi T.T., 2016b, Antibacterial and synergistic potency of tissues of Vitex grandifolia, Biotechnological Research, 2(2): 69-76

Erhenhi A.H. and Obadoni B.O., 2015, Known medicinal and aphrodisiac plants of Urhonigbe forest reserve, Edo State, Nigeria, Journal of Medicinal Plant Studies, 3(4): 101-106

Eze J.I., Ekelozie C.F., and Nweze N.E., 2015, Immunomodulatory Activity of the Methanolic Extract of Buchholzia coriacea Seeds on Trypanosoma brucei Brucei Infected Mice, Global Veterinaria, 14(4): 582-588

Ezeigbo I.I., 2011, The Antidiabetic Potentials of the Methanolic Seed Extract of Buchhlozia coriacea, Annals of Medical and Health Sciences Research, 1(2): 159-163

PMid:23209970 PMCid:PMC3507116

Ezeigbo O.R., Ejike E.N., Nwachukwu I., and Ejike B.U., 2016, Comparatie antibacterial activity of methanolic, ethanolic and aqueous extract of Garcinia kola (bitter kola) and Cola nitida (Kola nut), Internatonal Journal of Plant Research, 6(3): 53-56

Ezeja M.I., Ezeigbo I.I., and Madubuike K.G., 2011, Analgesic activity of the methanolic seed extract of Buchholzia coriacea, Research Journal of Pharmaceutical, Biological and chemical Sciences, 2:187-193

Ezekiel O.O. and Onyeoziri N.F., 2009, Preliminary studies on the antimicrobial properties of Buchholzia coriacea (wonderful kola), Afr J Biotechnol, 8: 472-4

Ezike A.C., Onyeto C.A., Nwabunike I.A., Mbaoji F.N., Attah B.E., Amanambu S.O., and Okoli C.O., 2015, Anti-Inflammatory Activity Of Buchholzia coriacea Engl. (Capparaceae) Leaf Extract: Evaluation Of Components Of The Inflammatory Response Involved, J Complement Integr Med, 2:153-158

https://doi.org/10.1515/jcim-2014-0046

Falodun A., Siraj R., and Choudhary M.I., 2009, GC-MS analysis of insecticidal leaf essential oil of Pyrenacantha staudtii Hutch and Dalz (Icacinaceae), Tropical Journal of Pharmaceutical Research, 8(2)

https://doi.org/10.4314/tjpr.v8i2.44522

Fapohunda S., Awoyinka A., Oluchi A., Banji A., David J., Aderiike A., Abimbola A., and Adebayo O., 2017, Evaluation of the nutraceutical potentials of Garcinia kola seed, J. Pharm. Phytochem, 6(5): 1894-1901

Fatima N., Ahmad T., Khan S.J., Deeba F., and Zaidi N., 2011, Assessment of antibacterial activity of in vitro and in vivo grown garlic (Allium sativum L.), Pakistan Journal of Botany, 43(6): 3029-3033

Fletcher S.M., McLaws M-L., and Ellis J.T., 2013, Prevalence of gastrointestinal pathogens in developed and developing countries: systematic review and meta-analysis, Journal of Public Health Research, 2(9): 42-53

https://doi.org/10.4081/jphr.2013.e9

Fred-Jaiyesimi A.A., Adepoju A., and Egbebunmi O., 2011, Anthelmintic activities of chloroform and methanol extracts of Buchholzia coriacea Engler seed, Parasitol Res., 109(2): 441-4

https://doi.org/10.1007/s00436-011-2274-y

PMid:21344210

Gahlaut A. and Chhillar A.K., 2013, Evaluation of Antibacterial Potential of Plant Extracts using Resazurin based Microtiter Dilution Assay, International journal of pharmaceutical sciences, 5(2): 372-376

Gautam K., Pokhrel B.M., Shrestha C.D., and Bhatta D.R., 2015, Prevalence of Diarrheagenic E.coli (DEC) Determined by Polymerase Chain Reaction (PCR) in Different Tertiary Care Hospitals in Nepal, JSM Microbiology, 3(2): 1021

Ghamba P.E., Agbo E.B., Umar A.F., and Bukbuk D.N., 2011, The effects of diethyl ether and aqqueous Garcinia kola seeds extracts on some bacteria isolates, Academia Arean, 3(2): 87-94

Heikens H.E., Fherse E., Endert M., Ackerman S., and G. Van Mont Frans, 1995, Liquorice-induced hypertension, a new understanding of an old disease, J. Medicine, 5: 230-234

Hema R., Kumaravel S., Alagusundaram K., 2011, GC/MS determination of bioactive components of Murraya  koenigii, Journal American Science, 7(1): 80-83

Ibrahim T.A. and Fagbohun E.D., 2012, Phytochemical and Nutritive Qualities of Dried Seeds of Buchholzia Coriacea, Greener Journal of Physical Sciences, 2(5): 185-191

Ibrahim T.A. and Fagbohun E.D., 2014, Antibacterial and antifungi activities of ethanolic and methanolic extract of dried seeds of buchhlozia coriacea, Research and Reviews: Journal of Microbiology and Biotechnology, 3(2): 5-9

Ijarotimi O.S., Nathaniel F.T., and Faramade O.O., 2015, Determination of chemical composition, nutritional quality and anti-diabetic potentials of raw, blanched and fermented wonderful kola (Buchholzia coriacea) seed flour, J. Hum Nutr. Food Sci., 3(2): 1060

Ikpeazu O.V., Otuokere I.E., and Igwe K.K., 2017, Preliminary Studies on the Secondary Metabolites of Buchholzia coriacea (Wonderful Kola) Seed Ethanol Extract by GC-MS Analysis, International Journal of Research in Engineering and Applied, 7(3): 17-26

Izah S.C., Zige D.V., Alagoa K..J., Uhunmwangho E.J., and Iyamu A.O., 2018, Antibacterial Efficacy of Aqueous Extract of Myristica fragrans (Common Nutmeg), EC Pharmacology and Toxicology, 6(4): 291-295

Izah S.C., Bassey S.E., and Ohimain E.I., 2017a, Amino acid and proximate composition of Saccharomyces cerevisiae biomass cultivated in Cassava mill effluents, Molecular Microbiology Research, 7(3): 20-29

https://doi.org/10.5376/mmr.2017.07.0003

Izah S.C., Inyang I.R., Angaye T.C.N. and Okowa I.P., 2017b, A review of heavy metal concentration and potential health implications in beverages consumed in Nigeria, Toxics, 5(1): 1-15

https://doi.org/10.3390/toxics5010001

PMid:29051433 PMCid:PMC5606672

Izah S.C., Bassey S.E., and Ohimain E.I., 2017c, Assessment of Some Selected Heavy Metals in Saccharomyces cerevisiae Biomass Produced from Cassava Mill Effluents, EC Microbiology, 12(5): 213-223

Izah S.C., Bassey S.E., and Ohimain E.I., 2017d, Cyanide and Macro-Nutrients Content of Saccharomyces cerevisiae Biomass Cultured in Cassava Mill Effluents, International Journal of Microbiology and Biotechnology, 2(4): 176-180

Izah S.C., Chakrabarty N., and Srivastav A.L., 2016, A Review on Heavy Metal Concentration in Potable Water Sources in Nigeria: Human Health Effects and Mitigating Measures, Exposure and Health, 8: 285-304

https://doi.org/10.1007/s12403-016-0195-9

Izah S.C., Orutugu L.A., and Kigigha L.T., 2015, A review of the quality assessment of zobo drink consumed in Nigeria, ASIO Journal of Microbiology, Food Science and Biotechnology Innovations, 1(1): 34-44

Izah S.C. and Angaye T.C.N., 2016, Heavy metal concentration in fishes from surface water in Nigeria: Potential sources of pollutants and mitigation measures, Sky Journal of Biochemistry Research, 5(4): 31-47

Kalunta C.G., 2017, Antimicrobial effect of different seed extracts of Piper nigrum against Escherichia coli, Staphylococcus aureus and Candida albican. Biotechnol Res, 3(3): 71-76

Kigigha L.T., Biye S.E., and Izah S.C., 2016, Phytochemical and antibacterial activities of Musanga cecropioides tissues againstEscherichia coli, Pseudomonas aeruginosa Staphylococcus aureus, Proteus and Bacillus species, International Journal of Applied Research and Technology, 5(1): 100-107

Kigigha L.T., Izah S.C., and Ehizibue M., 2015, Activities of Aframomum melegueta Seed Against Escherichia coli, S. aureus and Bacillus species, Point Journal of Botany and Microbiology Research, 1(2): 23-29

Kigigha L.T. and Kalunta C.G., 2017, Antimicrobial efficacy of leaf extracts of Piper nigrum against Escherichia coli, Staphylococcus aureus and Candida albicans, Journal of Basic Pharmacology and Toxicology, 1(2): 32-36

Lapshak L.J., Domkat L.C., and Nansah L.S., The effect of aquous extract of Buchholzia coriacea seed and some biochemical parameters in normal and alloxan-indduced diabtetic rats, International Journal of Biochemistry Research, 11(1): 1-10

Malomo R.O., Bankole O.E., and Sorinola A.O., 2017, Phytochemical and Chemical Properties of Raw, Cooked and Dried Seeds of Buchholzia coriacea, Journal of Scientific Research & Reports, 16(4): 1-8

https://doi.org/10.9734/JSRR/2017/36098

Maruthupandian A., and Mohan V.R., 2011, GC/MS analysis of  some bioactive constituents of Pterocarpus marsupium Roxb, International Journal of ChemTech Research, 3(3): 1652-1657

Mbata T.I., Duru C.M., and Onwumelu H.A., 2009, Antibacterial activity of crude seed extracts of Buchholzia coriacea E. on some patogenic bacteria, Journal of Developmental Biology and Tissue Engneering, 1(1): 1-5

Minocheherhomji F.P. and Vyas B.M., 2014, Presence of alkaloids in medicinal plants and their importance in antimicrobial activities of some pathogenic microbial strains, Journal of Environmental Research and Development, 9(1): 144-150

Momoh J., Longe A.O., and Campbell C.A., 2014, In vivo anti-plasmodial and in vitro antioxidant activity of ethanolic leaf extract of Alstonia boonie (Ewe ahun) and its effect on some biochemical parameters in Swiss albino mice infected with Plasmodium berghei NK 65, European Scientific Journal, 10(8): 68-82

Nakajima M., Shirokane Y., and Mizusawa K., 1980, A new amidino hydrolase, methylguanidineamidino hydrolase from Alcaligenes sp. N-42", FEBS Lett., 110(1): 43-46

https://doi.org/10.1016/0014-5793(80)80018-4

Ndiok E.O., Ohimain E.I., and Izah S.C., 2016, Incidence of Malaria in Type 2 Diabetic patients and the effect on the liver: a case study of Bayelsa state, Journal of Mosquito Research, 6(15): 1-8

Nguyen T.V., Van P.L., Huy C.L., Gia K.N., and Weintraub A., 2006, Etiology and epidemiology of diarrhea in children in Hanoi, Vietnam, International Journal of Infectious Diseases, 10: 298-308

https://doi.org/10.1016/j.ijid.2005.05.009

PMid:16458564

Nwachukwu M.I., Duru M.K.C., Amadi B.A., and Nwachukwu I.O., 2014, Comparative evaluation of phytoconstituents, antibacterial activities and proximate contents of fresh, oven dried uncooked and cooked samples of Buchholzia coriacea seed and their effects on hepatocellular integrity, International Journal of Pharmaceutical Invention, 3(6): 41-49

Nwaehujor C.O., Ode O.J., Nwinyi F.C., and Udeh N.E., 2012, Effects of Methanol Extract of Buchholzia coriacea Fruit in Streptozotocin-induced Diabetic Rats, Journal of Pharmacology and Toxicology, 7: 181-191

https://doi.org/10.3923/jpt.2012.181.191

Nwaichi E.O. and Olua V., 2015, Antioxidants and Phytochemical Profile of Various Extracts from Buccholzia coriacea, Indian Journal Of Applied Research, 5(6): 415-420

Nwaichi E.O., Osuoha J.O., and Monanu M.O., 2017, Nutraceutical Potential of Tetracarpidium conophorum and Buccholzia coriacea in Diet-induced Hyperlipidemia, Journal of Chemical Health Risks, 7(3): 157-170

Nweze N.E., Anene B.M., and Asuzu I.U., 2011a, In vitro anti-trypanosomal activities of crude extracts, β-sitosterol and α-sulphur from Buchholzia coriacea seed, Afr J Biotechnol, 10: 15626-32

https://doi.org/10.5897/AJB11.865

Nweze N.E., Anene B.M., and Asuzu I.U., 2011b, Investigation of the antitrypanosomal activity of Buchholzia coriacea seed extract against a field strain of Trypanosoma congolense, Afr J Tradit Complement Altern Med, 8(S): 175-180

Nweze N.E. and Asuzu I.U., 2006, The anthelmintic effects of Buchholzia coriacea seed, Niger Vet J, 27: 60-5

Nweze N.E., Fakae L.B., and Asuzu I.U., 2009, Trypanocidal activity of the ethanolic extract of Buchholzia coriacea seed, Niger. Vet. J., 1-6

Obembe O.O., Onasanwo S.A., and Raji Y., 2012, Preliminary study on the effects of Buchholzia coriacea seed extract on male reproductive parameters in rats, Niger. J. Physiol. Sci., 27: 165-169

PMid:23652231

Obiudu I.K., A.C. Okolie, K.N. Agbafor, M.E. Unaegbu, G.A. Engwa, and C.V. Obiudu, 2015, Anti-Diabetic Property and Phytochemical Composition of Aqueous and Methanol Extracts of Buchholzia coriacea Seeds in Alloxan-Induced Diabetic Rats, Journal of Medical Sciences, 15: 241-245

https://doi.org/10.3923/jms.2015.241.245

Okere O.S. and Ladeji O., Comparative Effect of Aqueous and Methanol Extract of Buchholzia coriacea Seeds on Carrageenan-Induced Inflammation in Rats, Scientific Review, 2(2): 22-30

Okigbo R.N. and Mmeka E.C., 2008, Antimicrobial effects of three tropical plant extracts on Staphylococcus aureus, Esherichia coli and Candida albicans, African Journal of Traditional, Complementary and Alternative Medicines, 5(3): 226-229

https://doi.org/10.4314/ajtcam.v5i3.31277

Okoli B.J., Okere O.S., and Adeyemo S.O., 2010, The Antiplasmodial Activity Of Buchholzia Coriacea, Journal of Medical and Applied Biosciences, 2: 21-29

Okoye T.C., Akah P.A., Ilogu C.L., Ezike A.C., and Onyeto C.A., 2012, Anti-diabetic Effects of Methanol Extract of the Seeds of Buchholzia coriacea and its Synergistic Effects with Metformin, Asian Journal of Biomedical and Pharmaceutical Sciences, 2(12): 32-36

Okwu D.E., 2005, Phytochemicals, Vitamins and Mineral contents of two Nigeria Medicinal Plants, International Journal of Molecular Medicine and Advance Sciences, 1(4): 375-381

Okwu D.E. and Okwu M.E., 2004, Chemical composition of Spondias mombia Linn plant parts, Journal of Sustain Agricultural Environment, 6: 140-147

Okwu, D.E., 2004, Phytochemicals and vitamin content of Indigenous spices of South Eastern Nigeria, Journal of Sustain Agricultural Environment, 6: 30-34

Olaiya C.O. and Omolekan T.O., 2013, Antihypercholesterolemic activity of ethanolic extract of Buchholzia coriacea in rats, African Health Sciences, 13(4): 1084-1090

PMid:24940336 PMCid:PMC4056488

Olaleye S.B., Ige A.O., Michael O.S., and Owoyele B.V., 2012, Analgesic and Anti-Inflammatory effects of Ethanol Extracts of Buchholzia coriacea Seeds in Male Rats, Afr. J. Biomed. Res, 15: 171-176

Omolekan T.O. and C.O.O. Olaiya, 2013, Anti-Atherogenic Activity of Ethanol Extract of Buccholzia coriacea Seeds on Hypercholesterolemic Rats, International Journal of Biochemistry Research & Review, 3(3): 190-199

https://doi.org/10.9734/IJBCRR/2013/2858

PMid:23455407

Omoregie G.O., Macdonald I., and Ovuakporie-Uvo O., 2015, GC-MS analysis of the aqueous extracts of BuchholziaCoriacea Engl (Capparidaceae), Seeds, International Journal of Life Science and Pharma Research, 5(3): 26-32

Onasanwo S.A., Faborode S.O., and Ilenre K.O., 2016, Antidepressant-like Potentials of Buchholzia Coriacea Seed Extract: Involvement of Monoaminergic and Cholinergic Systems, and Neuronal Density in the Hippocampus of Adult Mice, Niger. J. Physiol. Sci., 31: 093-099

Onasanwo S.A., Obembe O.O., Faborode S.O., Elufioye T.O., and Adisa R.A., 2013, Neuro-pharmacological potentials of Buchholzia coriacea (Engl.) seeds in laboratory rodents, African journal of medicine and medical sciences, 42(2): 131-42

PMid:24377198

Opoku F. and Akoto O., 2015, Antimicrobial and Phytochemical Properties of Alstonia Boonei Extracts, Organic Chemistry Current Research, 4(1)

Osadebe P.O., Awemu G.A., Ezealisiji K.M., and Agbo M.O., 2011, Phytochemical and antimicrobial studies of the leaf extracts of Bucholzia coriaceae, International Journal of Current Research and Review, 03(12): 17-22

Osuntokun O.T. and Oluwafoise B.O., 2015, Phytochemical screening of ten Nigerian medicinal plants, International Journal of Multidisplinary Research and Development, 2(4): 390-396

Owoeye J.A., Akawa O.B., Akinneye J.O., Oladipupo S.O., and Akomolede O.E., 2016, Toxicity of Three Tropical Plants to Mosquito Larvae, Pupae and Adults, Journal of Mosquito Research, 6(16): 1-7

Pasalic D., Marinkovic N., and Feher-Turkovic L., 2012, Uric acid as one of the important factors in multifactorial disorders – facts and controversies, Biochemia Medica, 22(1): 63-7

https://doi.org/10.11613/BM.2012.007

Patel P.K., Sahu J., and Chandel S.S., 2016, A Detailed Review on Nociceptive Models for the Screening of Analgesic Activity in Experimental Animals, International Journal of Neurologic Physical Therapy, 2(6): 44-50

Rerkasen K., Gallagher P.J., Grimble R.F., Calder P.C., and Shearman C.P., 2008, Management of hypercholesterolemia and its correlation with carotidplaque morphology in patients undergoing carotid endoterectomy, Vascular Health Risk Management, 4(6): 1259-1264

https://doi.org/10.2147/VHRM.S3729

Romeiras M.M., Duarte M.C., Indjai B., and Catarino L., Medicinal plants used to treat neurological disorders in West Africa: A case study with Guinea-Bissau flora, Amer. J. Plant Sci., 3: 1028-1036

https://doi.org/10.4236/ajps.2012.327122

Salami A.T., Odukanmi O.A., Faniyan O.F., Omayone T.P., and Olaleye S.B., 2017, Seeds of Buchholzia coriacea in Diet Mitigate Ischemic Reperfusion–Induced Gastric Ulceration in Experimental Rats, Journal of Dietary Supplements,

https://doi.org/10.1080/19390211.2017.1404544

PMid:29278952

Sang W.K., Oundo V., and Schnabel D., 2012, Prevalence and antibiotic resistance of bacterial pathogens isolated from childhood diarrhoea in four provinces of Kenya, J Infect Dev Ctries, 6(7): 572-578

https://doi.org/10.3855/jidc.2196

PMid:22842944

Saunders M., 2007, Relationship between hyperlipidemia and hyperlipoproteinemia, Brit J Pharm Sci., 12(2): 405-16

Titanji V.P.K., Zofou D., and Ngemenya M.N., 2008, The Antimalarial Potential Of Medicinal Plants Used For The Treatment Of Malaria In Cameroonian Folk Medicine, African Journal of Traditional, Complimentary and Alternative Medicines, 5(3): 302-321

Umeokoli B.O., Abba C., Ezeh P., and Ajaghaku D., 2016, Antimicrobial, anti-inflammatory, and chemical evaluation of Buchholzia coriacea seed (Wonderful kola), American Journal of Life Sciences, 4(5): 106-112

https://doi.org/10.11648/j.ajls.20160405.12

Varela G., Batthyány L., Bianco M.N., Pérez W., Pardo L., Algorta G., Robino L., Suárez R., Navarro A., Pírez M.C., and Schelotto F., 2015, Enteropathogens Associated with Acute Diarrhea in Children from Households with High Socioeconomic Level in Uruguay, International Journal of Microbiology

https://doi.org/10.1155/2015/592953

PMid:25861274 PMCid:PMC4377524

Yu F.R., Lian X.Z., Guo H.Y., McGuire P.M., Li R.D., Wang R., Yu F.H., 2005, Isolation and characterization of methyl esters and derivatives from Euphorbia kansui (Euphorbiaceae) and  their inhibitory effects on the human SGC-7901 cells, J. Pharm. Pharm. Sci., 8: 528-535

PMid:16401398