A Systematic Review of Medicinal Plants of Kenya used in the Management of Bacterial Infections

Kenya's vision 2030 partly aims at ensuring adequate health care for all, and the integration of traditional healthcare practices into the national healthcare system would present a more rapid alternative towards the realization of universal health coverage in Kenya. Currently, research on Kenyan medicinal plants with potential antibacterial activity remains vastly fragmented across numerous literature studies and databases; thus, it is imperative to collate and appraise these data for the ease of future research and possible clinical application. Objective. This review aims at exploring and compiling research evidence on medicinal plants used in the management of bacterial infections in Kenya, with a focus on their efficacy and safety. Methodology. A comprehensive web-based systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was executed to highlight the Kenyan medicinal plants used for the management of bacterial infections in Kenya. This review includes studies published until January 2021 from the PubMed, Science Direct, AJOL, and Google Scholar databases. Results. A total of 105 Kenyan medicinal plants belonging to 43 families have their in vitro activity against various human pathogenic bacteria evaluated. Plants from the Lamiaceae, Rutaceae, and Fabaceae families were the most commonly studied. Aloe secundiflora, Toddalia asiatica, Senna didymobotrya, Warbugia ugandensis, Tithonia diversifolia, Fuerstia africana, Olea africana, and Harrisonia abyssinica were the plants frequently evaluated within Kenya. The plants with the strongest antimicrobial activities were Toddalia asiatica, Hagenia abyssinica, Ocimum gratissimum, Harrisonia abyssinica, Senna didymobotrya, Olea Africana, Camellia sinensis, and Tarmarindus indica. Conclusion. Based on a published work, it is evident that traditional medicine is seemingly an acceptable and efficient system among Kenyan communities in the management of bacterial infections. Kenya's rich biodiversity with diverse secondary metabolites presents a promising source of new therapeutic alternatives with possibly different mechanisms of action against bacteria.


Introduction
Despite the remarkable investment in health care witnessed over the past decade, microbial infections remain a major threat to human and animal health and are a cause of morbidity and mortality especially in low-and middle-income countries (LMICs). e rising cases of antibiotic resistance present a major health problem globally, and there is an immediate need for strategies to manage it as it relentlessly compromises the effectiveness of antimicrobial therapy and increases the threat of therapeutic failure [1][2][3]. Due to an inefficient antimicrobial resistance (AMR) surveillance system, the exact liability of AMR in Kenya is indefinite although cases such as reduced susceptibility of communityacquired pneumococci, Vibrio cholera outbreaks, and methicillin-resistant Staphylococcus aureus (MRSA) from hospitalized patients have been reported [4].
Herbalism is the most preferred form of traditional medicine and is highly lucrative in the international market with annual sales ranging from US dollar 5 billion in Western Europe to US dollar 14 billion in China [5]. In Africa, herbal products are available in most markets in the urban centers and rural areas [6]. Irrespective of the accessibility to modern medicines, various communities in Kenya (either deliberately or due to economic limitations) utilize medicinal plants for the management of microbial infections and other diseases; thus, various legislations are actively being formulated to regulate this practice [7]. Presently, there are over 400 plant species used for the management of common diseases in East Africa documented in several ethnobotanical [8][9][10].
As a developing nation with numerous healthcare challenges such as the high costs of medications, Kenya needs to grow its scientific base and create logical and effective solutions to manage them. Laboratory investigations and various clinical trials have often suggested the positive effects of phytomedicines both in vivo and in vitro; however, there has been little systematic appraisal of their benefits [11]. Due to their unrivaled chemical diversity, plants offer the infinite potential for innovative and effective antimicrobial agents, but there is the scantiness of information in regard to their efficacy and their safety levels [12]. Critical consideration to the prospect of producing pharmaceutical products using local raw materials is a worthy endeavor to ensure the affordability of drugs. In a bid to provide herbal practitioners and consumers with insight, this study primarily aimed at evaluating the bioactivity of Kenyan medicinal plants useful in the management of bacterial infections.

Materials and Methods
A comprehensive web-based systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines on identification, screening, eligibility, and inclusion was executed to highlight the medicinal plants used for the management of bacterial infections in Kenya. is review covers published literature from 1994 up to January 2021 obtained from the PubMed, Science Direct, African Journals Online (AJOL), and Google Scholar databases. Grey literature [13] from the local university repositories and conference proceedings were also included in this review [14]. e literature search was performed using search terms identified from previous similar reviews. e Boolean search operators (AND and OR) were used to effectively combine the search terms [15]. e following search terms were used: Kenya AND antimicrobial plants OR Kenyan AND antimicrobial plants. Kenyan [16].
Screening of search outputs was performed in two stages. First, the title and abstract of identified journal articles/ theses were overviewed based on PICO (Participants Intervention Comparison and Outcomes) and the studies classified as "yes" or "no" based on the information provided by the title and abstract. ereafter, suitable articles/theses were downloaded and critically assessed for inclusion in the review [16]. e studies eligible for inclusion were limited to the English language. e assessment of eligibility of studies was performed by at least two people, independently, using the Critical Appraisal Skills Programme (CASP) appraisal checklist as a guide [16]. is study excluded research data from papers with poor methodology and retracted studies. e quality of the papers was assessed based on study design, description of the subject, method and assay, variables assessment, control groups, and data collection. To minimize bias, data extraction from selected study reports was independently performed by two reviewers and any disagreements resolved through discussion with the third reviewer [17].

Results
e study included research data from the pharmacological assays/ethno-medicinal studies reporting on Kenyan medicinal plants used for the treatment of bacterial infections. e initial database search identified a total of 105, 157 articles. After removing the duplicates (n � 15000), 89857 studies were excluded based on the title and abstract. ree hundred (300) full-text articles were assessed for eligibility, from which 211 were excluded based on scope, methodological approach, and very little/no bioactivity reported. A total of seventy-nine (79) studies regarding the in vitro antibacterial activity of Kenyan medicinal plants were ultimately included in the review. No in vivo studies within Kenya on Kenyan medicinal plants with antibacterial activity were found.
Data collected included herbal plant name, plant family, part of plant used for extraction, extraction/preparation method, concentrations of extracts, bacteria species, data on reported activity, toxicity, exposure time, geographical information, the year of publication, and the first author (Table  1). A total of 105 medicinal plants from 43 families were studied for in vitro activity against various human pathogenic bacteria. Plants from Lamiaceae, Rutaceae, and Fabaceae families were the most common (Table 1).

Discussion
Plants generally accumulate diverse bioactive compounds in varying concentrations in the different parts of a plant, and this eventually affects the efficacy of medicinal plants. e leaves (37%), bark/stem bark (47%), and roots (24%) were the most utilized plant parts against bacterial infections. e variances in their antimicrobial activities could be due to the synergistic or antagonistic actions of various secondary metabolites present [60].  [67]. e aqueous crude green tea extracts at a concentration of 400 mg/ml exhibited ZOI of 20 ± 0.0 mm which was similar to that of streptomycin against S. aureus. e extract also displayed a ZOI of 18 ± 0.0 mm against E. coli compared to ZOI of 10 ± 0.0 mm of streptomycin against E. coli 20 ± 0.0 mm, ZOI of 18 ± 0.0 mm, and MIC 200 mg/ml against E. coli compared to streptomycin 10 ± 0.0 mm [69]. e Bambara nut (Vigna subterranea) had an MIC value of 7.72 ± 0.35 μg/ml for E. coli, 12.5 ± 0.32 μg/ml for S. aureus and 7.95 ± 0.10 μg/ml for P. aeruginosa at 100 μg/ml, and showed zone of inhibition of 27 ± 0.74 mm, 25.3 ± 0.40 mm, and 25.1 ± 0.24 mm E. coli, S. aureus, and P. aeruginosa, respectively [109].

Complementary Medicine.
As has been shown in previous ethnomedical surveys by Omwenga et al., traditional medicine is widely practiced in Kenya and is culturally acceptable. It is estimated that about 75% population in Kenya seeks health care among traditional healers [8][9][10]150]. In certain instances, people utilize both traditional and modern medicine simultaneously. Njoroge and Kibunga noted that herbal products were used as complementary therapy in the management of diarrhea by residents in ika, Kenya [151]. e lack of enquiry about Traditional Complementary and Alternative Medicine (TCAM) use and the conventional healthcare providers' negative attitude towards TCAM were cited as some of the reasons why patients fail to reveal their TCAM use [152].  Evidence-Based Complementary and Alternative Medicine e regulatory framework for the practice of traditional medicine in Kenya is still underway [153], but several crude drugs or formulated herbal products with reported antibacterial activity are already available in the Kenyan market, for example, the Lifebuoy germ protection antibacterial herbal hand and body soap and the Dettol herbal bar soap. Skin care products (soaps and lotions) formulated from plant extracts ( evetia peruviana, Tithonia diversifolia, Azadirachta indica, Aloe secundiflora) had antimicrobial properties. Soap made from Tithonia diversifolia plant extract was the most effective against E. coli, while Azadirachta indica soap was the most effective against C. albicans. T. diversifolia soap exhibited the highest activity against E. coli [154]. e ethanolic extract of E. divinorum root bark had a MIC of 25, 50, and 25 μg/ml for Streptococcus pyogenes, Staphylococcus aureus, and Escherichia coli, respectively (Table 1). A herbal toothpaste formulated with the ethanol extract of E. divinorum root bark had a higher antimicrobial activity against the tested microorganisms compared to Colgate herbal toothpaste formulated with fluoride [77]. Also, the formulation containing the aqueous extracts of T. asiatica (50 mg/ml) stem bark exhibited pronounced antimicrobial activity as indicated by zone of inhibition diameters of 24 mm (MRSA) and 22 mm (M. gypseum) compared to 22 mm and 14 mm, respectively, by the commercial hand wash (50 mg/ml). In the model hand washes efficacy experiment, the formulated herbal detergent attained a 78.8% reduction of pathogenic load as compared to 67.9% reduction with the commercial hand wash [37].
Unfortunately, despite the surge in the consumption herbal products and the limited number of standardized herbal products in the Kenyan market, the pharmacovigilance for herbal medicines is nonexistent in Kenya [155]. e increased demand for herbal products has resulted in the market being flooded with adulterated products and false herbal claims on the products' labels for marketing purposes. For instance, 50% of the investigated products by Ngari et al. [75] lacked antimicrobial activity against test bacteria (Staphylococcus aureus, Pseudomonas aeruginosa, Proteus vulgaris, Bacillus subtilis, Candida albicans, Escherichia coli, Streptococcus mutans, Enterococcus faecalis, and Lactobacillus acidophilus). e evaluation of herbal suspensions (used in the management of oral health in Nairobi County, Kenya) by Ngari et al. [75] reported a lack of detectable phytochemicals in the suspensions and noted that this occurrence could be due to very low concentrations of phytochemicals that could not be detected by standard laboratory methods or mineral adulterants might have been used. Studies have demonstrated that antimicrobial properties of natural products can be enhanced by the addition of metal ions [14,156].

Polyherbalism.
e use of herbs as combinations is common practice with many herbal practitioners and aimed at giving better results as compared to single herbs and also treating more than one ailment [157]. Ngari et al. [75] evaluated herbal pastes and suspensions used in the management of oral health in Nairobi County, Kenya, and various products showed significant antimicrobial activity that is comparable to positive control. For example, product HS4 composed of W. ugandensis, M. piperita, and S. aromaticum had ZOI of 33.1 ± 0.85 mm, 20.3 ± 1.71 mm, and 19.3 ± 1.65 mm against E. coli, S. aureus, and P. aeruginosa, respectively, compared to that of co-trimoxazole of 27.5 ± 0.7 mm, 8.5 ± 0.5 mm, and 10 ± 0.0 mm, respectively. Product HS5 composed of Aloe vera gel, W. ugandensis, and W. sominifera had a ZOI of 25.3 ± 0.25 mm, 20.25 ± 1.26 mm, and 21.5 ± 1.71 mm against E. coli, S. aureus, and P. aeruginosa, respectively, compared toco-trimoxazole 27.5 ± 0.7 mm, 8.5 ± 0.5 mm, and 10 ± 0.0 mm, respectively. is biological activity is attributed to the presence of various secondary metabolites in plants [14].
Mbuthia et al. evaluated the synergistic properties of water-soluble green and black tea extracts with penicillin G. e antimicrobial results showed a marked increase in the inhibition zone diameters on the combination of green tea extracts with penicillin G. e catechins, theaflavins, and thearubigins are the antimicrobial agents present in tea [67].4 Synergistic inhibition by green tea extracts and penicillin G is due to the presence of dual binding sites on the bacterial surface for antibiotic and tea extract [158].

Bioactivity/Assay
Methods. Disc diffusion method was the preferred method to assay for antibacterial activity. A clearing zone of 9 mm or greater for Gram-positive and Gram-negative bacteria was used as the criterion for designating significant antibacterial activity [159]. e in vitro MIC results were classified as described in the study by Pessini et al., 2003: the antimicrobial activity of the extracts that displayed MIC lower than 100 μg/ml was considered very high; 100-500 μg/ml, high; 500-1000 μg/ ml, moderate; 1000-4000 μg/ml, low; and anything above this, inactive. e plants with the strongest antimicrobial activities were Toddalia asiatica, Hagenia abyssinica, Ocimum gratissimum, Harrisonia abyssinica, Conyza sumatrensis, Senna didymobotrya, Aloe secundiflora, Olea Africana, Vernonia glabra, Camellia sinensis, Tetradenia riparia, and Tarmarindus indica as they exhibited high mean inhibition zone values or low minimum inhibitory concentration (MIC) values.
Several plants exhibited a high activity superior or comparable to the standard antibiotic drugs (Table 1); the methanol-dichloromethane extract (100 mg/ml) of Harrisonia abyssinica had a ZOI of 20 ± 1.6 mm compared to gentamycin (ZOI of 18 ± 1.2 mm) against S. aureus and a ZOI of 30. ± 1.7 mm against E. coli compared to gentamycin ZOI of 15.1.3 mm against E. coli [41]. e methanolic extract of Croton macrostachyus exhibited ZOI (23.66 mm) compared to (21.33 mm) amoxicillin against S. aureus and ZOI (18.0 mm) compared to (17.58 mm) amoxicillin against P. aeruginosa. e methanolic extract had an MIC of 37.50 mg/ml compared to 18.75 mg/ml cefpodoxime against S. aureus and 18.75 mg/ml compared to 9.372 mg/ml cefpodoxime against P. aeruginosa [79].
Plants such as Toddalia asiatica, Hagenia abyssinica, Senna didymobotrya, Aloe secundiflora, and Camellia sinensis displayed good activities; thus, they may be considered for the assessment of in vivo activity and possibly formulated into different consumable forms. Korir et al. recommended that for plants with very low or no activity, bioactivity on all parts of the plants, for example, root, stem bark, and leaves combined ought to be done against a wide variety of pathogenic bacteria in order to conclusively report that a certain plant is inactive [29].

Toxicity.
Despite herbal remedies being affordable, their lack of efficacy and safety evaluation is a great impediment to their acceptance into mainstream medicine. e safety assessment of herbal remedies remains a challenge as most of the studies of herbal medicines are directed at the toxicological properties of single plant formulations, yet most herbal preparations, especially those used in traditional medicine, contain multiple herbs [160].
From this review, 45% of the plants were relatively safe, 44% of the plants have not been assessed for their safety, and 11% of the plants were reported to have high toxicity ( Table 1). e plants with very high toxicity can be further explored for the antitumor activity or as insecticides.

Plant Conservation Status.
Other than W. ugandensis and Prunus africana, most of the plants identified in this review are largely available and are not under any serious threat to become extinct. Since most of them are obtained from wild habitats, sustainable use of the reported medicinal plants against bacterial infections is advised as a conservation measure. e cultivation of wild medicinal plants is an important approach to safeguard the herbal industry. Biotechnological techniques such as plant cell or tissue culture, biochemical conversions, and clonal propagation of indigenous medicinal plants are another potential strategy in improving herbal medicine [161].

Conclusion
is review demonstrates the potential of medicinal plants to treat bacterial infections alongside justifying the use of these plant traditional medicine. It may serve as a starting point of research geared towards the clinical application of these plants. ere is a need for standardization to improve the acceptance of herbalism by mainstream health practitioners.

Recommendation
Further research into the in vivo activity of plants displayed remarkable in vitro activity. Plants exhibiting strong antibacterial activity can be evaluated for their interactions with conventional antibiotics, and those displaying synergistic activity may provide useful leads in antibiotic therapy.

Data Availability
No data were used in the study.

Conflicts of Interest
e authors declare that they have no conflicts of interest.