Combretum species around Africa as alternative medicine: Ethnopharmacological and ethnobotanical importance

INTRODUCTION

Communicable ailments are significant sources of morbidity and death universally, notably in developing countries, accounting for about 50% of diseases in countries with low healthcare facilities and as much as 20% of mortality rates in industrialized countries (Khalil et al., 2020; Motsumi et al., 2020; Mtunzi et al., 2017a; Ntshanka et al., 2020). Despite the high level of innovation and antibiotic application in microbiology, the intermittent occurrences of epidemics caused by drug-resistant microbes and the emergence of unknown disease-causing microorganisms pose a significant threat to healthcare (Abubakar, 2010; Nguedia and Shey, 2014; Silber et al., 2016).

The development of resistant strains to some antibiotics has complicated the management of infectious diseases, given that drugs are only effective against one-third of existing ailments (Fankam et al., 2015; Sahu et al., 2014). Microbial drug resistance became persistent because of drug abuse and misuse of antibiotics. Most drugs are ineffective against diseases for which they had previously been misused. This results in resistant pathogens becoming virulent, increasing the risk of complications and death (Fankam et al., 2015; Nguedia and Shey, 2014; Sampedro et al., 2009). Most drugs are discovered from biological natural resources, and natural yields from microbes have been the major cradle of antibiotic delivery. With the cumulative approval of herbal medicine as a substitute form of healthcare, the selection of herbal plants for bioactive constituents has become a very imperative aspect of the health system because they serve as a favorable cradle of innovative antibiotic exemplars (Khan et al., 2022; Sabo and Knezevic, 2019; Serralheiro et al., 2020). Antibiotics derived from fungi or living organisms are produced industrially using a fermentative process (Alfadil et al., 2014; Silber et al., 2016; Wright et al., 2014).

The predominance of other diseases like hematological and autoimmune disorders, human immunodeficiency virus (HIV) infection, cancer, and important immune system dysfunction may cause symbiotic microbes to change to pathogens under definite circumstances, typically called opportunistic contamination. Opportunistic pathogens consist of fungi, viruses, protozoa, and bacteria, taking advantage of immunocompromised patients and displaying new health challenges worldwide. Opportunistic diseases involve diminishing host defenses, occurring because of genetic deficiencies, introduction to antibiotics, and immunosuppressive substances or due to communicable diseases possessing immunosuppressive properties (Nagata et al., 2011; Ntshanka et al., 2020; Ryan and Ray, 2004; Yang et al., 2013).

Some chemotherapeutic mediators presently used are noxious with accompanying antagonistic side effects. Hence, there is a general necessity for novel chemotherapeutic mediators against several disease pathoaetiologies that are exceedingly resourceful, have low toxicity, and exhibit minor ecofriendly impacts. Herbal medications have various traditional claims, such as managing infectious sources. Several extracts of plant species were established against hundreds of microbial strains via various in vitro models and some had good action pharmacological consequences (Bhat, 2014; Fankam et al., 2015; Khumalo et al., 2018; Luís et al., 2016; Motsumi et al., 2020; Nguedia and Shey, 2014). However, a limited number of these herbal plant extracts have been screened in animal or human studies to regulate safety and efficiency. Natural products and their byproducts characterize about 50% of all drugs in clinical use (Cragg and Newman, 2013; Fankam et al., 2015; Khumalo et al., 2018; Lahlou, 2013).

Natural products from natural cradles like plants, animals, and microorganisms, dated before human antiquity, perhaps thousands of years (Ji et al., 2016; Khan, 2018). These products can be categorized into four diverse groups according to their biosynthetic derivation, polyketides, alkaloids, terpenoids, and phenylpropanoids (Bisht et al., 2021; Guo, 2017), and continue to offer novel chemical structures with high levels of biological activity (Guo, 2017; Khan, 2018; Moloney, 2016). The mechanisms underlying many biological properties have been ascribed to numerous types of propolis, including antitumor, anti-inflammatory, wound healing, antioxidant, antimicrobial, and immunomodulatory activities (Shaikh et al., 2016). Plants do produce potentially toxic substances aside production of beneficial phytochemicals; therefore, toxicity assays incorporation in the bioactivity evaluation of medicinal plants is very important in understanding their therapeutic effects (Alam et al., 2018; Araújo et al., 2013; Cundell, 2014; Luís et al., 2016; Ntshanka et al., 2020; Shah et al., 2010; Verma, 2016). The Chinese traditional medicine community is the world’s largest medicinal plant user is, with more than 5,000 plants and plant products registered in their pharmacopeia (Ji et al., 2016).

Traditional medicine in South Africa supports using abundant plant species for the treatment or management as prophylaxis against several kinds of ailment (infectious and noninfectious) (Masoko et al., 2010, 2012; Mtunzi et al., 2017a, 2017b; Street and Prinsloo, 2013). In South Africa, medicinal species are being traded for usage in local medicines since most are from ethnopharmacological guides (De Wet et al., 2013; Mabona and Van Vuuren, 2013; Street and Prinsloo, 2013). The sustainable use and control of medicinal plants are of a significant contest to all shareholders. Parts of many medicinal plants, like the stem, bark, and roots, are being harvested and merchandized in an unmanageable routine that may lead to the augmented death of the tree that is the source of medication. Assessment and authentication of leaf extract bioactivity as a promising substitute for stem, roots, and bark use to afford a viable opportunity for safeguarding medicinal plants (De Wet et al., 2013; Street and Prinsloo, 2013). Herbal medicine is the most significant medicine for most people on planet earth, specifically those who do not have access to modern and expensive drugs. Interestingly, it has formed the foundation of every medicine, the mother of all remedies in modern days. The exploitation of medicinal plants as herbal medicine alongside their curative perspective is well documented (Alam et al., 2018; Bhat, 2014; Cundell, 2014; Motsumi et al., 2020; Mtunzi et al., 2017a, 2017b; Sabo and Knezevic, 2019; Street and Prinsloo, 2013). The World Health Organization estimates that populace about 80% residing in developing nations exclusively practice traditional medicine (Eloff, 1998; Motsumi et al., 2020; Mtunzi et al., 2017a).

Medicinal plant therapies have also been featured conspicuously in the ailments treatment of production and domestic animals, and ethnoveterinary therapeutic practices remain an imperative aspect of animal healthcare in unindustrialized countries (Ji et al., 2016; Khan, 2018). Combretum species is featured conspicuously among the utilized medicinal plants in South African traditional medicine as agents for handling communicable diseases like diarrhea (Combretum imberbe Wawra, Combretum vendee A.E.van Wyk), malaria (Combretum ghasalense), stomach disorders (Combretum molle R. Br. ex G. Don.), and coughs [C. molle R. Br. ex G. Don., C. imberbe Wawra, Combretum erythrophyllum (Burch.) Sond.] (Eloff et al., 2008; Mtunzi et al., 2017b; Ntshanka et al., 2020). Combretum erythrophyllum is a member of the Combretaceae family, generally used for venereal disease management (Van Wyk and Gericke, 2000). Root parts are used as a laxative, while dried and pulverized gum is applied to blisters (Venter and Venter, 1996).

The roots and bark decoctions of C. erythrophyllum are utilized to treat cough and unproductiveness and as an aphrodisiac (Ahmed et al., 2014; Mtunzi et al., 2017b). The leaves are used to treat cough and stomach pains, while the seeds, which have been reported to be poisonous, are used to remove intestinal worms in dogs (Van Wyk et al., 2009). Combretum erythrophyllum is commonly scattered in the Southern Africa region, most commonly found in South Africa along the coast in the Eastern Province, namely Zimbabwe, KwaZulu-Natal, Northern South Africa (Mpumalanga, Gauteng, Limpopo, and the eastern parts of Northwest regions), Swaziland, and Mozambique, and marginally into the eastern parts of Botswana (Silén et al., 2023).

Martini et al. (2004a) isolated seven different flavonoids from leave extract C. erythrophyllum (Burch.) collected from a tree within the Pretoria National botanic gardens, South Africa, known to be antibacterial phenolic compounds which include four flavonols: rhamnocitrin (1), rhamnazin (2), 5,7,4′-trihydroxyflavonol (kaempferol) (3), and 7,4′-dihydroxy-5,3′-dimethoxyflavonol (quercetin-5,3′-dimethylether) (4); three flavones: 5,7,4′-trihydroxyfavone (5), 5,4′-dihydroxy-7-methoxyflavone (6), and 5-hydroxy-7,4′-dimethoxyflavone (7) (Fig. 1). All compounds possessed good activity against Enterococcus faecalis and Vibrio cholera, with the minimal inhibitory concentration (MIC) value <100 µg/ml. Rhamnocitrin and quercetin-5,3′-dimethyl ether inhibited Shigella sonnei and Micrococcus luteus with a MIC value of 25 µg/ml (Martini et al., 2004a, 2004b; Mawoza and Ndove, 2015).

In literature, medicinal plants have presented interesting ethnopharmacological potentials as chemotherapeutic agents. The Combretum species has great prospects for the management of various infectious diseases (Eloff et al., 2008) and will have a vital relevance with economic benefit to the perfumery industry (Alam et al., 2018; Barrales-Cureno et al., 2021; Crovadore et al., 2012; Mohaddese, 2016; Sabo and Knezevic, 2019). Nevertheless, the tangible potential of Combretum has not been exploited to the fullest. Hence, this review has made an effort to present a comprehensive overview of the summary of earlier research data regarding ethnopharmacological properties, antimicrobial, antifungal, antioxidant, cytotoxicity activities, and other noteworthy effects of Combretum species as alternative medicine.

METHODS AND LITERATURE QUEST

An epistemological paradigm grounded in a qualitative research approach was utilized for this study. The study seeks to explain, clarify, define, elucidate, and expand more on the understanding of the ethnopharmacological potentials of medicinal plants concerning Combretum species as chemotherapeutic agents for drug discovery.

Available reports and references on the medicinal plant species were accessed from published scientific peer-reviewed journals, books, short communications, reports from national, regional, and international organizations and institutions, theses, conference papers, and other materials. International online databases, including ISI Web of Science, SCOPUS, EBSCO, MEDLINE (National Library of Medicine), chemical abstracts service, Science Direct, SCIMAGO, ProQuest, EMBASE, and Google Scholar, were utilized for literature search using precise search terms. Selected keywords were used but not limited to Combretum species, ethnopharmacological promises, properties of the Combretum genus, phytochemicals, pharmacological, antibiotics, medicinal plants, biological assays, chemical constituents, chemotherapeutic agents, traditional medicine, and traditional uses of medicinal plants of about 600 studies and research articles consulted, articles from 1970 to 2022.

Snowball sampling technique was used in this study, followed by content and semantic analysis of data collected from the literature for systematic documentation of the biological, pharmacological, and traditional uses of medicinal plants: Combretum species around Southern Africa region as alternative medicine.

Figure 1. Chemical structures of flavonoids found in Combretum erythrophyllum (Martini et al., 2004a). [Click here to view]

RESULTS AND DISCUSSION

Therapeutic potentials of Combretum species

Combretum species as an antioxidant agent

An important development that produces free radicals in living systems, substances, and even in food is referred to as oxidation (Barku et al., 2013). Oxidation is also the chemical reaction involving electron transfer from the electron-rich to the electron-deficient entity (Poljsak et al., 2021). The electron-scarce molecule is labeled an oxidizer or oxidizing agent. Enzymes such as hydroperoxidase and catalase translate hydroperoxides and hydrogen peroxide (H₂O₂) to nonradical forms and perform natural antioxidants’ role in the human body (Ofoedu et al., 2021). The prescribed oxidation state refers to the postulated charge an atom has if all bonds to other atoms of different elements are completely ionic. It is generally epitomized by integers that can either be zero, positive, or negative (Norman and Pringle, 2022). Free radicals are reactive species containing unpaired electron that attacks macromolecules, including protein, lipid, and DNA. Free radicals are the products of natural human metabolism. Varieties of endogenous free radicals destroying antioxidants exist in the body, while others are obtained from dietary sources like vegetables, fruits, and teas. At present, accessible synthetic antioxidants like gallic esters, butylated hydroxyl toluene, butylated hydroxyl anisole, and tertiary butylated hydroquinone are assumed to bring about or hasty negative health consequences (Mongalo et al., 2012).

Antioxidants preclude oxidative impairment of cells, biomolecules, and reactive oxidative species oxidative species (ROS)-induced illnesses by reacting with free radicals, destroying free radicals, and chelating free catalytic metals (Pizzino et al., 2017). Antioxidant consumption possesses numerous health benefits, including oxidative damage associated with free radical damage and its role in diseases (Ejidike et al., 2019). Antioxidant nutrients, either endogenous or exogenous, natural or synthetic, can search for free radicals in the system and neutralize them before they further damage the body cells (Mandal et al., 2022; Medrano-Macías et al., 2022; Poljsak et al., 2021). Antioxidants are important constituents in the human body that safeguards it from impairment caused by oxidative stress induced by free radicals (Ejidike and Ajibade, 2015; Poljsak et al., 2021). There is emerging interest in the exploration of the antioxidant activities of secondary metabolites from medicinal species to compounds with greater potency and lower toxicities than the presently accessible synthetic ones (Medrano-Macías et al., 2022; Motsumi et al., 2020; Mtunzi et al., 2017a; Ntshanka et al., 2020; Poljsak et al., 2021).

Recent epidemiological evaluations have revealed that many antioxidant compounds possess antibacterial, anticarcinogenic, anti-inflammatory, antiviral, antitumor, antiatherosclerotic, or antimutagenic activities to a bigger or smaller extent (Owen et al., 2000; Verma, 2016). The antioxidant perspective of natural plant products is attributable to several compounds such as phenols and flavonoids, which have a distinct mechanism of action. Consequently, one antioxidant compound was sequestered from C. erythrophyllum and is 5-hydroxy-7,4′-dimethoxyflavone but exhibited the weakest activity (Martini et al. 2004a, 2004b). Oxidative stress is the inequality between the generation and eradication of ROS or reactive nitrogen species (RNS) in support of ROS (Ejidike and Ajibade, 2015; Poljsak et al., 2021; Zhang et al., 2009). Oxidative stress is proficient in triggering cells to lose their function and structure and ultimately cause cell dysfunction. ROS/RNS can be produced within the airway epithelial cells in answer to proinflammatory cytokines like tumor necrosis factor-alpha (TNF-α) (Ejidike and Ajibade, 2015; Lü et al., 2010; Mandal et al., 2022; Medrano-Macías et al., 2022; Poljsak et al., 2021).

ROS and RNS perform various functions, including regulation of gene expression (Mandal et al., 2022) and stimulation of apoptosis (Huang and Zhou, 2021). The manufacture of ROS/RNS might have very detrimental effects and is neutralized by the antioxidant fortifications under standard circumstances in healthy people (Mandal et al., 2022; Medrano-Macías et al., 2022). Oxidative stress arises when there is a variation of balance in support of ROS/RNS and may happen in several situations, like in infection or malnutrition with deficient micronutrients to achieve the requirement for antioxidant defenses (Ejidike and Ajibade, 2015; Mandal et al., 2022; Medrano-Macías et al., 2022). It has been recognized that oxidative stress is among the chief contributory elements of various chronic and deteriorating ailments initiators comprising cancer, ischemic heart disease, atherosclerosis, diabetes mellitus, ageing, immunosuppressant, and neurodegenerative illnesses (Ejidike and Ajibade, 2015; Malekmohammad et al., 2019; Poljsak et al., 2021).

Combretum species as an antimicrobial and antiviral agent

Antimicrobial-resistant strains are the major causes of copious clinical problems (Fennel et al., 2004; Gangoué-Piéboji et al., 2009) and have increased the world’s mortality rate (Ejidike and Ajibade, 2015; Motsumi et al., 2020; Mtunzi et al., 2017a, 2017b; Ntshanka et al., 2020). The resistance built by pathogenic against antibiotics has brought about great interest and the quest for novel antimicrobial drugs/agents from nature (Bouzidi et al., 2016; Dorman and Deans, 2000; Ejidike and Ajibade, 2015; Liouane et al., 2010). The unethical usage of antibiotics has brought about their resistance to bacterial strains (Martini and Eloff, 1998). Plants are an imperative basis for the growth of new chemotherapeutic agents, given that they are made up of potentially useful constituents (Barku et al., 2013). Since time immemorial, traditional plants have been used to prepare drugs, thus acting as a good source of medicine. Moreover, Combretum species have been shown to exhibit potential activities as antibacterial and antiviral agents (Adamu et al., 2005; Filho et al., 2015; Fyhrquist et al., 2006; Katerere et al., 2003; Maregesi et al., 2007; Martini et al., 2004a, 2004b; Martini and Eloff, 1998; Masika and Afolayan, 2002; Masoko et al., 2007, 2010; Mawoza and Ndove, 2015; McGaw et al., 2000; Ntshanka et al., 2020; Olukoya et al., 1993).

Different components of the Combretum plants have been utilized in the native system of medicine for the management of several human ailments ranging from ulcers, wounds, cholera, and snakebite to abdominal disorders (Begum et al., 2002; Maregesi et al., 2007; Masoko et al., 2010; Mawoza and Ndove, 2015). The leaves, stems, roots, and flower parts of Combretum species have been used traditionally for the treatment of neuralgia, throat contagions, wounds, eruptions, and a varied range of skin diseases like rashes, ringworm, and ulcers (Eloff et al., 2008; Masoko et al., 2007, 2010); treatment of related bacterial infections and diseases including pneumonia, chest infections, syphilis, diarrhea, coughs, and colds (Ahmed, 2012; Ahmed et al., 2014; Dawe et al., 2013; Fyhrquist et al., 2006; Gathirwa et al., 2011; Komape et al., 2014; McGaw et al., 2001; Ntshanka et al., 2020); treatment of digestive infections, bleeding, and throat contagions (Dimitrova et al., 2015; Hsouna and Hamdi, 2012); and also menopausal and menstrual complications, breast congestion, cellulite, and fluid retention (Pietrovski et al., 2006; Saraswathi et al., 2011). The leaf extracts have also been reported to treat childhood diseases like measles, chickenpox, and mumps (Brendler and Van Wyk, 2008). The following species have prominently featured as agents for treating contagious diseases: C. imberbe, C. vendee against diarrhea; C. ghasalense Engl. & Diels against malaria; C. molle against stomach disorders; C. molle, C. imberbe, and C. erythrophyllum against coughs (Eloff et al., 2008).

Table 1. Antimicrobial activities and uses of constitutes sequestered from the Combretum species in traditional medicine. [Click here to view]

The medicinal benefits of Combretum species lie in some vital chemical constituents responsible for certain physiological exploit on the human body (Edeoga et al., 2005; Filho et al., 2015; Masoko et al., 2007; Masoko and Eloff, 2007; Nagata et al., 2011; Uzor and Osadebe, 2016) and are significant in pharmacological research and drug development (Ademola and Eloff, 2010; Moraes et al., 2016; Roy et al., 2014a, 2014b). Combretum species possess extractable organic substances in quantities sufficient to exhibit antimicrobial activities (Adamu et al., 2005; Katerere et al., 2003; Masika and Afolayan, 2002; Olukoya et al., 1993). Chemicals constituents from Combretum species hold complex arrangements that are not obtainable in synthetic compound collections; hundreds of chemical constituents have been consequential for use as antibacterial agents and other drugs (Aderogba et al., 2012; Facundo et al., 1993; Katerere et al., 2012; Kgatle, 2007; Longhi-Balbinot et al., 2009, 2011; Sabo and Knezevic, 2019; Welch, 2010). The species of Combretum has featured conspicuously as an agent for handling infectious diseases as exemplified in Table 1.

Evidence for medical efficacy of Combretum species

Phytochemical investigations to determine the medical efficacy of Combretum, the most widespread genus of Combretaceae, has paved the way several constituents comprising flavonoids, triterpenoids, phenanthrenes and their derivatives, diarylpropanes, and stilbenoids and their derivatives. Isolates or extracts from this class of species have shown several bioactivities, including antibacterial, antiradical, antifungal, antidiabetic, antihyperglycemic, cytotoxicity, and inhibitory activities, against different human tumor cell lines, anti-inflammatory, antimalarial, anti-snake venom, and anti-HIV/AIDS properties. Also, they have been used for the management of diverse infirmities and diseases (Aderogba et al., 2012; Ares et al., 2006; Belkaid and Hand, 2014; Chika and Bello, 2010; Dawe et al., 2013; De Morais Lima et al., 2012; Kemvoufo et al., 2008; Khumalo et al., 2018; Masoko et al., 2007; Motsumi et al., 2020; Nagata et al., 2011; Uzor and Osadebe, 2016). Antidiabetic activity through adenosine monophosphate-activated protein kinase activation by quercetin from flower extracts of C. lanceolatum has been reported (Dechandt et al., 2013). Anti-candidiasis agents from African Tanzanian plant: C. zeyheri (Runyoro et al., 2013), while lignin derivative from C. alfredii (Bai et al., 2016). Combretum species have also shown great potential as a source of various secondary metabolites. Metabolites and their related endophytic fungus Nigrospora oryzae as proof of a metabolic conglomerate from C. dolichopetalum have been reported by Uzor et al. (2015).

Studies on the antioxidant, antibacterial, cytotoxicity, and antifungal potentials of solvent-to-solvent fractionations of C. erythrophyllum (Burch.) leave elixirs revealed that Combretum species are nontoxic for usage in traditional medicine for the management of infectious and stress-related diseases (Mtunzi et al., 2017b). Methanolic extract of the C. adenogonium Steud. ex A. Rich stem barks inhibited C. chauvoei (Jakari strain) neuraminidase activity as reported by Useh et al. (2004) at 100–1,000 μg/ml with an estimated LC₅₀ value of 150 μg/ml. Extracts from the stem bark, root, and leaf have the potential as antibacterial, antifungal, and antiproliferative agents (Fyhrquist et al., 2006; Maregesi et al., 2007). Ethanolic stem bark, root, and leaf elixirs have displayed antibacterial by microdilution methods, an anti-HIV-1 protease with LC₅₀ value of 24.7 and 26.5 μg/ml for root and stem bark extracts, respectively, and cytotoxic activities using brine shrimp’s lethality assay (Mushi et al., 2012).

Acetone elixir of Combretum mole stem bark had inhibited the evolution of Mycobacterium Tuberculosis typus humanus (ATCC 27294) (Asres et al., 2001), inhibits HIV-1 reverse transcriptase (Bessong et al., 2005). Aqueous-methanol stem bark elixir of C. mole has exhibited anthelmintic activity in infected lambs with H. contortus via faecal egg count reduction test (Simon et al., 2012; Suleiman et al., 2013). Interestingly, powdered and decoctions of C. mole root part have been used as a wound dresser for treatments of leprosy, fever, snake bite, stomach pains, all-purpose body swelling, hookworm, and abortion, While the activities of this C. mole associated with bioactive compounds such as hydrolysable tannin and punicalagin demonstrated antimycobacterial properties (Asres et al., 2001). Compounds such as maslinic acid, ursolic acid; combretastatin B5-O-2′-beta glucopyranoside, corosolic acid, arjunolic acid, combretastatin B1-O-2′-beta glucopyranoside (Ahmed, 2012) isolated from C. vendee A.E. van Wyk have exhibited antimicrobial and antifungal activities (Ahmed et al., 2009; Suleiman et al., 2010); antiradical activity with the EC₅₀ lesser or analogous to the control (Ahmed, 2012).

CONCLUSION

The reports detailed in this review advocate using medicinal plants as alternative medicine. Combretaceae species has displayed a broad spectrum of ethnopharmacological potentials for treating infectious diseases, exhibits significant antimicrobial and antifungal potentials against varieties of bacterial and fungal species, respectively, and also exhibit good antioxidant, anti-inflammatory, antimalarial, antituberculosis, antidiarrhoea, cytotoxicity, anthelmintic, antischistosomal, COX-1 inhibition, and HIV-1 integrase inhibition. Phytochemical constituents of the species are great prospective agents for averting and treating many related oxidative stress diseases. Even though the oils from some of these species have not been harnessed as a fragrance in the perfumery, food, and beverage industry; the oils and active compounds may also possess great potential for protecting food and cosmetics from microbial spoilage. Hence, medicinal plants can be seen as an alternative to medicine if properly used as prescribed or as a precursor for synthesizing chemotherapeutic agents for disease control. Concerning the above investigation, it is evident that Combretaceae species contain bioactive compounds such as triterpenoids, glycosylated triterpenes, and phytochemical constituents of biological importance. Given these outstanding values, few pharmacological and phytochemical analyses have been conducted. Hence, it will greatly benefit the health sector and medicinal chemistry if further research is encouraged and carried out toward identifying bioactive compounds and corroborating their medicinal and pharmacological properties. Areas of research in the economy, domestication, and proliferation, as well as quality control and procedures for sustainable utilization of these plant species as future potential antibiotic and chemotherapeutic agents, should be prioritized. This should be a priority for researchers and stakeholders as these plants can increase the well-being of the populace who finds solace in them.

ACKNOWLEDGMENTS

The authors gratefully acknowledge the Directorate of Research, Vaal University of Technology, South Africa, The University of Winnipeg, Winnipeg, Canada, and Anchor University, Lagos, Nigeria, for the support provided.

AUTHOR CONTRIBUTIONS

Involved authors contributed substantially from the conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting and revising the article. Authors are eligible to be an author as per the International Committee of Medical Journal Editors requirements/guidelines.

FINANCIAL SUPPORT

This project was supported by the National Research Foundation (Grant No. 120790) and the Directorate of Research, Vaal University of Technology, South Africa, South Africa.

CONFLICTS OF INTEREST

The authors proclaim that they have no conflicts of interest.

ETHICAL APPROVALS

This study does not involve experiments on animals or human subjects.

DATA AVAILABILITY

All data generated and analyzed are included in this research article.

PUBLISHER’S NOTE

This journal remains neutral with regard to jurisdictional claims in published institutional affiliation.

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