Introduction

The African continent is known to be rich in biodiversity with a high number of plants used for their medicinal properties (Ngbolua, 2020). Unfortunately, its populations are frequently exposed to a variety of diseases, resulting in a high rate of mortality, which is exacerbated by acute poverty (Hope, 2009; Ikejiaku, 2009; Mongeke et al., 2018; Ngbolua et al., 2019). In order to treat and/or prevent disease, a large percentage (70-80%) of African population uses medicinal plant-based folk medicine (Ngbolua et al., 2018; Ngbolua et al., 2019; Ngbolua, 2018). Among medicinal plants with therapeutic virtues, there are species belonging to the Cola genus (Adewale & Adekunle, 2018; Erukainure et al., 2019). The genus Cola belongs to the family Sterculiaceae (Dah-Nouvlessounon et al., 2015; Salahdeen, Omoaghe, Isehunwa, Murtala, & Alada, 2015).

This genus is well-known for its medicinal benefits as well as for its many uses throughout Africa (Ouattara et al., 2018; Sery et al., 2019). It contains several species, but only two are cultivated for their scientific and economic values. These are Cola acuminata and Cola nitida (Akinoso, Aremu, & Balogun, 2014; Gbedie et al., 2019; Lowor, Aculey, & Assuah, 2010; Ouattara et al., 2018). The first is reported to be native to Central African countries, while the second is recognized as being from West Africa (Atawodi et al., 2007; Dah-Nouvlessounon et al., 2015; Lowe et al., 2014). C. nitida (Figure 1) has long been used for its stimulating properties (Amadi & Nwachukwu, 2020), and it is used to enhance cultural, religious, and funeral ceremonies in a variety of ways (Atawodi et al., 2007; Atawodi, Mende, Pfundstein, & Preussmann, 1995; Sonibare, Soladoye, & Sonibare, 2009; Umoh, Emmanuel, & Nna, 2014).This plant has various medicinal properties and is involved in the treatment of many diseases such as coughs, asthma and malaria (Zailani et al., 2020).

Several phytochemical compounds have been isolated from C. nitida, such as catechin, caffeine, epicatechin, procyanidin B1, procyanidin B2, theobromine, polyphenols, alkaloids, tannins, saponins, and so on (Akinoso et al., 2014; Dah-Nouvlessounon et al., 2015). Because of its very high caffeine content, C. nitida is a significant source in the production of beverages such as Coca-Cola and Pepsi-Cola. In addition, it is also used for the production of drugs, soft drinks, and wines (Dah-Nouvlessounon et al., 2015). Because of its different secondary metabolites, C. nitida has a variety of biological properties, including anti-malarial activity (Zailani et al., 2020). The purpose of this mini-review was to summarize current understanding of the phytochemistry, pharmacology, and toxicity of Cola nitida, an African medicinal plant.

Methodology

Various electronic databases like Science Direct, PubMed, Web of Science, Scopus, Google Scholar, and SciELO were used in January 2021 to conduct a non-exhaustive literature review of pertinent publications available online. These terms were employed in conjunction with the plant's scientific name: phytochemistry, pharmaceuticals, and toxicology. The ChemBioDraw Ultra 12.0 software tool was used to sketch the chemical structures of chemicals isolated from this plant.

Results and Discussion

Botany description

In the literature, Cola nitida (Family: Malvaceae) is described as a tree that can reach a height of 25 meters. The large branches and stems are cracked and mixed with whitish or greyish lichen spots. The leaves have long petioles and vary in shape from obviate to oblanceolate, measuring about 15 cm in length. The ovary is yellow, light yellow, or lemon yellow. The fruit consists of 1 to 10 elongated green follicles, each containing 4 to 10 seeds. The seed, red, pink, or white in color, is also protected by a vitreous white arillus and includes 2 cotyledons, very rarely fragments. The inflorescences are panicle-like cymes with terminal flowers that grow in a determinate manner. C. nitida is functionally monoecious, with male and hermaphrodite flowers blooming in the same order. Male and female flowers are either produced on distinct inflorescences or coexist on the same inflorescence (Adebola, 2011; Bohou & Ijb, 2009; Burdock, Carabin, & Crincoli, 2009).

Figure 1

Pod and seeds of Cola nitida nut

https://www.nrfhh.com/f/fulltexts/145511/image1_min.jpg

Origin and geographic distribution

Cola nitida is a plant species native to Africa, particularly in West Africa (Atawodi et al., 1995; Mbete, Makosso, Lelou, Douh, & Ngokaka, 2011; Sunday et al., 2007). According to the literature, the first survey of this plant was carried out in 1594 in the Ivory Coast (Atawodi et al., 1995). Because of its increasing economic importance, C. nitida is nowadays cultivated in several countries around the African continent, in Asia, and various parts of Central and South America (during the Slave Trade of the 17th century) (Dah-Nouvlessounon et al., 2015; Gbedie et al., 2019; Niemenak, Onomo, Fotso, Lieberei, & Ndoumou, 2008).

Ethno-botany

The literature survey revealed that the use of C. nitida, especially its nuts or seeds, is very widespread in many countries in Africa. It takes a key place in various ceremonies (weddings, funerals, customary) in the West African country from which it originates (Atawodi et al., 1995).

For example, in Nigeria, C. nitida is known by several names, such as "kola nut" or "gworo", "guru nuts", "bissy nuts" or "sudan coffee". It has various uses, and is an essential item in cultural, religious, wedding, or funeral ceremonies (Abidoye & Chijioke, 1990; Atawodi et al., 2007). It is chewed for its stimulating virtues (Adewale et al., 2018). It is also known to have aphrodisiac properties (Abulude, 2004; Atawodi et al., 1995).

In addition, C. nitida is also an excellent remedy in the treatment of coughs and asthma (Akinoso et al., 2014). Consumption of cola nuts is more commonly reported in men than in women for the purpose of eliminating fatigue (Umoh et al., 2014). (Jayeola, 2001) has demonstrated that fresh C. nitida nuts can be used to produce a soft drink. (Dah-Nouvlessounon et al., 2015) reported that the nuts of Cola nitida are regularly chewed and have varied socio-cultural importance in Benin.

Phytochemistry

Phytochemical profiling of C. nitida showed several secondary metabolites. The nuts from C. nitida revealed the presence of various chemical compounds, including catechin, caffeine, epicatechin, procyanidin B1, procyanidin B2, polyphenols, alkaloids, tannins, saponins, bromelain, cardenolides, proanthocyanidins, triterpenes, glycosides, flavonoids, anthraquinones, steroids (Adedayo et al., 2019; Daels-Rakotoarison et al., 2003; Dah-Nouvlessounon et al., 2015; Ganiyu, Kate, Ayodele, & Adedayo, 2014; Momo, Ngwa, Dongmo, & Oben, 2009; Niemenak et al., 2008; Sonibare et al., 2009). Bark from C. nitida contains tanins, saponosides, anthocyanins, flavonoids, glycosides, alkaloids, and polyphenols (Dah-Nouvlessounon et al., 2015; Dawole, Dewumi, Alabi, & Adegoke, 2013; Eddy, 2010) (Figure 2 andTable 4). Table 1 gives the proximate composition of C. nitida.

Table 1

Proximate composition of Cola nitida

Parameter

Mean value

1

2

3

4

Moisture

2.30±0.33

9.81±0.01

12.46 ± 0.80

6.00±0.10

Dry matter

97.70±0.26

-

87.53 ± 0.80

-

Crude protein

10.50±0.14

15.24±0.58

10.06 ± 0.75

3.50± 0.10

Ash

3.10±0.60

2.21±0.01

3.00 ± 0.50

3.10±0.10

Crude fat

13.30±0.35

2.20±0.01

0.20 ± 0.00

-

Crude fiber

17.60±0.40

4.18±0.09

4.31 ± 1.02

-

Carbohydrate

53.20±0.22

66.45±0.53

5.18 ± 0.56

69.20±1.20

(Lowor et al., 2010) reported the moisture concentrations of different types of Cola nitida grains, from red to white to pink. The contents are 44.16 ± 0.5% for reds, 42.49 ± 1.3 for whites and 42.76 ± 1.0 for roses. Table 2 gives the mineral composition of C. nitida.

Table 2

Mineral composition (mg/Kg) of Cola nitida

Mineral/Vit

Mean value

1

2

Ca

4.72±0.16

4.33 ± 1.41

Mg

16.13±0.01

11.48 ± 0.05

Na

198.00±0.007

-

K

92.00±0.21

-

Fe

2.20±0.05

4.37 ± 0.53

Mn

0.04±0.01

-

Zn

0.80±0.04

0.69 ± 0.19

Cu

0.29±0.10

0.59 ± 0.08

Co

0.20±0.05

-

P

50.23±0.10

-

Vit C (mg/100ml)

-

6.26 ± 0.46

Table 3

Free amino-acids composition of kola nut (dry weight)

Amino acids

Total (%)

Free (%)

Aspartic acid

0.53 ± 0.28

0.53 ± 0.28

Arginine

1.06 ± 0.06

0.69 ± 0.06

Threonine

0.39 ± 0.01

-

Alanine

0.50 ± 0.01

0.20 ± 0.01

Proline

0.83 ± 0.04

0.53 ± 0.04

Valine

0.35 ± 0.01

-

Methionine

0.22 ± 0.00

-

Cysteine

0.27 ± 0.00

-

Lysine

0.30 ± 0.02

0.16 ± 0.02

Table 3 gives some phytochemicals isolated from the Cola nitida.

Table 4

Some compounds isolated from Cola nitida.

NO

Compound

References

1

Phenolic compounds (Catechin, Epicatechin, Apigenin, Narigenin)

(Ganiyu et al., 2014)

2

Flavonoids (Catechin, Quercetin, Kaempferol, Naringin, Epicatechin, Myricetin, Rutin)

(Azeez, Lateef, & Adebisi, 2017)

3

hexadecanoic acid, ethyl ester , 9, 12-Octadecadienoic acid, ethyl ester, 9-Octadecadienoic acid, ethyl ester, ethyl oleate, cyclohexanone, 2-methyl-5-(1-methylethenyl) Octadec-9-enoic acid decanoic acid, 10- (2-hexylcyclopropyl).

(Salahdeen et al., 2015)

4

2-Heptanol, trans-2-Decen-1-ol, Spilanthol, L-Methionine, N-(2-thienylcarbonyl)-, methyl ester, Cinchonine

(Erukainure et al., 2019)

5

Theobromine, Caffeine, Catechin

(Burdock et al., 2009)

6

Procyanidin B1, procyanidin B2

(Dah-Nouvlessounon et al., 2015)

Figure 2 gives the chemical structure of selected medically interesting secondary metabolites isolated from Cola nitida.

Figure 2

Chemical structure of compounds isolated from Cola nitida

https://www.nrfhh.com/f/fulltexts/145511/image2_min.jpg

Pharmaco-biology and toxicology

Antimicrobial activities

(Lateef et al., 2015; Lateef et al., 2015; Lateef, Ojo, Folarin, Gueguim-Kana, & Beukeskolanut, 2016) synthesized silver nanoparticles from Cola nitida and evaluated their antimicrobial and antioxidant properties, as well as their potential for usage as an antimicrobial addition in paint. The results indicated that silver nanoparticles significantly inhibited the growth of multi-resistant strains at concentrations between 50 and 150 μg/mL and that at 5 μg/mL, silver nanoparticles completely inhibited the growth of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Aspergillus niger, A. flavus, and A. fumigatus. Previously, the same scientists showed antibacterial activity of biogenically generated silver nanoparticles (AgNPs) derived from C. nitida seed and seed shell extracts against a number of multidrug-resistant clinical isolates.

The results indicated that AgNPs have high activity; at doses ranging from 50–150 μg/mL, the AgNPs suppressed the growth of multidrug-resistant Klebsiella granulomatis, P. aeruginosa, and E. coli by a factor of 10–32 mm. In comparison, seed shell extract-mediated AgNPs demonstrated superior activity with a minimum inhibitory concentration (MIC) of 50 g/mL against all tested isolates, whereas seed extract-mediated AgNPs demonstrated MICs of 50, 80, and 120 μg/mL against E. coli, P. aeruginosa (wound), and P. aeruginosa (burn), respectively (Lateef et al., 2015). Continuing the same research, (Lateef et al., 2016) discovered similar results one year later when they synthesized silver-gold alloy nanoparticles (Ag-AuNPs) from extracts of C. nitida leaves, seeds, seed envelopes, and pods and evaluated their antifungal, antiplasmodial, anticoagulant, and thrombolytic activities.

According to their findings, Ag-AuNPs suppressed the growth of A. flavus, A. fumigatus, and A. niger by 69.51-100 percent. Within 24 hours of exposure to Ag-AuNPs, Anopheles mosquito larvae died at a rate of 80-100%. After 24 hours, malachite green and methylene blue showed catalytic degradation of > 90 and > 60 percent, respectively. In the blood, the particles demonstrated significant anticoagulant and thrombolytic activity. (Ganiyu et al., 2014) examined the inhibitory effect of phenolic-rich extracts from C. nitida seeds on key enzymes associated with type-2 diabetes and Fe2+-induced pancreatic oxidative stress. C. nitida extract reduced the activities of amylase (EC50 = 0.34 mg/mL) and glucosidase (EC50 = 0.32 mg/mL).

Antioxidant activities

Several recent studies have demonstrated that the lipid peroxidation generated by iron in the rat pancreas can be inhibited by Cola nitida extract in a dose-dependent manner (Ganiyu et al., 2014), and that the extract also has high DPPH radical scavenging activity (EC50 = 2. 2 mg/mL) (Adedayo et al., 2019).

At concentrations ranging from 20 to 100 μg/mL, Cola nitida-based-Silver nanoparticles demonstrated significant antioxidant activity, with an IC50 of 43.98 mg/mL against the DPPH radical and a decrease in ferric ions of 13.62 to 49.96 percent at the concentrations of 20 to 100 μg/mL (Lateef et al., 2015). Aside from that, C. nitida extract had a scavenging impact on DPPH and oxygen radicals, as well as chelating activity against Fe2+ in rat brain homogenate (Ganiyu et al., 2018).

Anticholinesterase, antimonoamine oxidase and antioxidant effects

A rat brain homogenate was used in an in vitro investigation to examine the anti-disease Alzheimer's potential of alkaloid extracts from two species of Cola (C. nitida and C. acuminata). Researchers found that alkaloid extracts had an impact on disease pathophysiology pathways in vitro. Based on gas chromatography analysis, the alkaloids augustamine and undulatine were found to be the most prevalent. The inhibitory effects of the extracts on cholinesterase activity were not significantly different (p>0.05). However, the C. acuminata extract had substantially greater monoamine oxidase inhibitory activity than C. nitida (p< 0.05) (Ganiyu et al., 2018).

Antimalarial activity

(Zailani et al., 2020) reported that the ethanolic extract from C. nitida leaves showed the highest antiplamodial activity by reducing 97.05% of the parasiteamia. Indeed, to evaluate the antimalarial activity of Cola nitida leaf, 12.5, 25, and 50 mg/kg body weight were administered to mice per os. After treatment, parasitaemia was evaluated. The final results suggested that all used doses showed good antimalarial effects against Plasmodium berghei in a dose-dependent way.

Anti-fertility activity

(Adisa, Otamere, Osifo, Idonije, & Nwoke, 2010) investigated the effects of C. nitida aqueous extract on reproductive hormones in rats. Thirty adult male rats were randomly assigned to three groups: group A served as the control group and got just water; groups B and C received only kola nut extract (8 mg/kg body weight); and group C served as the recovery group. After four weeks of therapy, testosterone levels in the plasma were significantly elevated (p < 0.05), whereas luteinizing hormone levels were dramatically decreased (p < 0.05) in comparison to control animals.

Table 5 gives comparative bioactivity of Cola nitida and used model systems.

Table 5

Model system used and comparative bioactivity of Cola nitida

Parts used

Extracts

Bio- activities

Model system

Concentration

Period

Authors

Seeds

Aqueous extract

Pharmacokinetic interactions of C. nitida and metoclopramide

Male rabbits

0.5 mg/kg of metoclopramide alone and 0.5 mg/kg of metoclopramide with 0.7 mg/kg C. nitida

1 week

(Amadi et al., 2020)

Seed and seed shell

Aqueous extract

Antibacterial Activities

Strains of K. granulomatis, P. aeruginosa and E. coli

50 μg/mL for seed shell extract and 50, 80 and 120 μg/mL for seed extract

(Lateef et al., 2015)

Seeds

Methanol Extract

Anti-inflammatory and analgesic activities

Rats and mice

200 mg/kg

24 hours

(Adedayo et al., 2019)

Pod of seed

Aqueous extract

Antibacterial and antioxidant activities

K. granulomatis, P. aeruginosa, E. coli, S.aureus, A. niger, A. flavus and A. fumigatus

49.96 at 100 μg/mL

(Lateef et al., 2015)

Seeds

Aqueous extract

Anti-diabetic activity

Diabetic rats

150 mg/kg bw at 300 mg/kg bw

6 weeks

(Erukainure et al., 2019)

Seeds

Acetone Extract

Aminotransferase activity

Female Wistar rats

50 mg/kg at 100 mg/kg

(Imam-Fulani, Olajide, & Owoyele, 2019)

Leaves, fruits, seeds, seed shells and pod

Aqueous extract

Antimicrobial, antioxidant and anticoagulant activities

S. aureus, P. aeruginosaE. coli, K. Pneumonia, A. niger, F. solani and blood

20 at 80 μg/mL

24 hours

(Akinola et al., 2020)

Stem bark

Ethanol-water (80:20, v/v) and ethanol-water (20:80, v/v) mixture

Anti-gonadotropic activities

Rat pituitary cells

20 μg/mL

4 hours

(Benie & Thieulant, 2004)

Leaves and bark

Aqueous and ethanol extracts

Anti-plasmodial activity

Albino mice

4 days

(Zailani et al., 2020)

Bark

Ethanol and ethyl acetate extracts

Antimicrobial

Meat isolated Staphylococcus strains

20 mg/mL

(Dah-Nouvlessounon et al., 2015)

Seed

Aqueous extract

Anti-fertility activity

Male albino Wistar rats

2 mg/kg-10 mg/kg

6 weeks

(Umoh et al., 2014)

Seed

Aqueous Extract

Anti-fertility activity

Male rats

8 mg/kg

4 weeks

(Adisa et al., 2010)

Seed

Ethanolic Extract

Cytotoxic effect

Wistar albino rats

100-2000 mg/kg for acute toxicity studies and 6 mg/kg to 11.9 mg/kg) for Chronic toxicity studies

48 hrs and 90 days

(Salahdeen et al., 2015)

The recovery group demonstrated values that were not statistically different from those of the control animals but were slightly closer to those of the control animals. (Umoh et al., 2014) verified a similar observation by examining the effects of C. nitida aqueous seed extract on serum reproductive hormones and sperm count in male albino Wistar rats.

The results indicated a considerable decrease in luteinizing hormone and testosterone levels in the serum. All animal groups showed a drop in sperm count. However, no significant difference in testicular or epididymis weight was seen between the experimental groups.

Anti-diabetic activity

An anti-diabetic property of the hot water extract of C. nitida seeds against type 2 diabetic rats was carried out. The doses of 150 mg/kg bw (low dose) and 300 mg/kg bw (high dose) were administered to the rats for six weeks. The final results indicated the reduction of levels of blood glucose, triglycerides, LDL-c, and fructosamine. Additionally, serum insulin and HDL-c decreased (Erukainure et al., 2019).

Antisicking activity

An ethno-medicinal survey carried out by Amujoyegbe and coworkers revealed that the medicinal plant species Cola nitida is traditionally used in Southern Nigeria as medicine for the management of sickle cell disorder (Amujoyegbe, Idu, Agbedahunsi, & Erhabor, 2016).

Cytotoxic effect of C nitida seeds

(Salahdeen et al., 2015) extracted caffeine from kola nuts and used rats as a model system to assess the extract's acute and chronic toxicity in vivo. The results demonstrated that prolonged caffeine administration reduced animal body weight significantly (p < 0.05). Total plasma protein, creatinine, bilirubin, VLDL, LDL, and total serum cholesterol levels all increased considerably (p < 0.05). On the other hand, the caffeine-treated groups had significantly reduced urea levels (p < 0.05). (Erukainure et al., 2019) by using FTIR spectroscopy, they analyzed the hepatic metabolites after consumption of the infusion of caffeine-rich C. nitida seeds, and the results of their experiments revealed the restoration of functional groups depleted by oxidation during infusion.

The liquid chromatography-mass spectroscopy analysis of the hepatic metabolites also revealed the restoration of most of the depleted metabolites with the concomitant generation of 4-o-methylgallic acid, (-)-epicatechin sulfate, L-arginine, L-tyrosine, citric acid, and decanoic acid in the infusion-treated tissues. The prediction of the oral toxicity of caffeine showed that it belonged to class 3, with a lethal dose 50 (LD50) of 127 mg/kg. These results indicate that the seeds of this plant should be consumed in moderation to prevent toxicity.

Conclusion and future directions

The aim of this mini-review was to document knowledge of the phytochemistry, pharmacology, and toxicity of Cola nitida, a medicinal plant species traditionally used in Africa for multiple purposes. Results revealed that C. nitida contains various phyto-compounds (like catechin, caffeine, epicatechin, procyanidin B1, procyanidin B2, polyphenols, alkaloids, tanins, saponins, bromelain, cardenolides, proanthocyanidins, triterpenes, glycosides, flavonoids, anthraquinones, steroids, etc.) that are responsible for the displayed bioactivity. Thus, C. nitida could serve as a raw material for manufacturing efficient medication against various diseases, including Sickle cell disease. 

Conflicts of interest

The authors declare no conflict of interest.

Author contributions

BMM, KNN - Research concept and design, BMM, CLI, JJOA - Collection and/or assembly of data, BMM, CMA -Data analysis and interpretation, BMM, KNN - Writing the article, KNN, JMSN, PTM - Critical revision of the article, MS - Final approval of the article.