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Evidence-based Complementary and Alternative Medicine : eCAM logoLink to Evidence-based Complementary and Alternative Medicine : eCAM
. 2021 Jul 29;2021:7341124. doi: 10.1155/2021/7341124

A Review of Plant-Based Therapies for the Treatment of Urinary Tract Infections in Traditional Southern African Medicine

Ian Cock 1,2, Nothando Mavuso 3, Sandy Van Vuuren 3,
PMCID: PMC8346297  PMID: 34367307

Abstract

Urinary tract infections (UTIs) are amongst the most common bacterial infections globally, with ∼11% of the world's population contracting at least one infection annually. Several South African plants are used in traditional healing systems to treat UTIs, yet the therapeutic potential of these plants against bacteria that cause UTI remains poorly explored. This study documents southern African plant species used traditionally to treat UTIs. An extensive literature review was undertaken to document the southern African plant species that are used in traditional South African medicine to treat UTIs, thereby highlighting gaps in the current research that require further study. One hundred and fifty-three southern African plant species that are used to treat UTIs were identified. Eighty-five southern African plants were identified as having noteworthy inhibitory activity against the major UTI-causing bacteria. Few of those studies screened against all of the bacterial causes of UTIs, and none of those studies examined the mechanism of action of the plant preparations. Furthermore, many of those studies did not test the toxicity of the plant extracts, so an evaluation of the safety for therapeutic usage was lacking. Substantial further research is to determine their potential for therapeutic use.

1. Introduction

Urinary tract infections (UTIs) are amongst the most common human infections globally. Indeed, it has been estimated that nearly 800 million people (equating to approximately 11% of the global population) develop at least one UTI in any given year [1, 2]. They are substantially more common in women than in men, with the prevalence in women estimated to be approximately five times higher than in males [3]. Indeed, it is expected that more than half of female population of the world will contract at least one UTI in their lifetime, with a substantial proportion experiencing recurrent infections [1]. With the exception of a spike in UTI occurrence in women aged 14–24 years old, the prevalence of UTIs generally increases with age, with the highest incidence in women over 65 years of age [4]. The difference in rates of UTIs between men and women is related to anatomical differences between the genders. As the urethra is located closer to the anus and is shorter in women than in men, women are substantially more susceptible to infections by uropathogens [5]. Additionally, individual health status affects the incidence of UTIs. For example, immunocompromised individuals and sufferers of chronic uncontrolled diabetes mellitus have substantially increased incidences of UTIs as their weakened immune systems are unable to effectively combat infections [3].

Lifestyle and environmental factors also contribute to the prevalence of UTIs. Older adults often accumulate multiple medical conditions, and their treatment and management regimens may increase the risks of contracting UTIs. In particular, catheterisation substantially increases the incidence of UTIs, especially by Gram-negative bacterial pathogens [1]. Indeed, healthcare-associated UTIs have been estimated to account for approximately 10% of UTI cases, with 75% of these being reported in female patients [6, 7]. Additionally, prolonged antibiotic usage to treat other medical conditions weakens the immune response, thereby increasing the susceptibility to UTIs. In younger women, increased sexual activity between the ages of 18 to 39 years of age increases both the incidence of UTIs and the frequency of recurrence [4]. Any region of the urinary tract may become infected, including the kidneys, bladder, urethra, and ureter [8]. When the UTIs occur in the lower regions of the urinary tract, the infection is known as a bladder infection (cystitis). Infections in the upper urinary tract (pyelonephritis) are commonly referred to as kidney infections.

1.1. Types of Urinary Tract Infections

Urinary tract infections are classified as either complicated or uncomplicated. Complicated infections occur in people with underlying conditions or abnormalities in any part of the genitourinary tract, making the infection more serious and more challenging to treat than uncomplicated infections. In contrast, uncomplicated UTIs are classified as infections occurring in the absence of comorbidities or other anatomical urinary tract and renal abnormalities [9]. The incidence of complicated UTIs is substantially lower than that of uncomplicated UTIs, which occur in otherwise healthy people with normal genitourinary tract anatomy [10]. However, uncomplicated infections are generally easier to manage, and treatment with a short course of antibiotics is usually effective. Urinary tract infections in children and males are generally categorised as uncomplicated infections due to their low probability of comorbidities [8]. Notably, complicated UTI-causative pathogens are linked to increased rates of antimicrobial resistance. Therefore, the development of effective therapies to treat these conditions is vital, not only to decrease the effects of these infections, but also to slow the development of further antibiotic-resistant bacterial strains.

1.2. Causes of Urinary Tract Infections

Interestingly, there can be notable differences between the infectious agents responsible for uncomplicated and complicated UTIs. The vast majority of these pathogens are normal components of the gastrointestinal or vaginal microflora, thereby increasing the chances that they cause UTIs. For both classes of UTI, uropathogenic Escherichia coli are the leading infective agent, accounting for approximately 75 and 65% for uncomplicated and complicated UTIs, respectively [1]. Klebsiella pneumoniae accounts for a further 6% and 8% of uncomplicated and complicated UTIs. The bacterium Staphylococcus saprophyticus causes about 6% of uncomplicated UTIs yet does not significantly contribute to complicated UTIs. In contrast, Enterococcus spp. contribute substantially to complicated UTI cases (∼11%), yet contribute less to uncomplicated UTIs (∼6%). Other bacteria also contribute significantly, albeit with substantially lower rate, to the incidence of UTIs. In particular, Proteus spp. (particularly Proteus mirabilis) and Pseudomonas aeruginosa each cause approximately 2% of both uncomplicated and complicated cases of UTIs. Other pathogens may occasionally also cause UTIs. For example, Staphylococcus aureus induces a low number of cases of UTIs, although these are generally considered a special case as they are usually secondary to blood S. aureus infections. UTIs can also be caused by fungal and viral pathogens, albeit with a substantially lower prevalence than reported for bacterial UTIs. In this review, we focus on the major bacterial causes of UTIs. Therefore, whilst numerous studies have screened traditional medicines for the ability to inhibit S. aureus, those studies generally focussed on other diseases (e.g., skin disorders), and we have not listed those studies herein due to the minor role of this bacterium in inducing UTIs. Likewise, Candida albicans infections are a common cause of urethra infections and are thus commonly classed as urethritis rather than a UTI. Therefore, we do not include studies examining the effects of southern African plants to inhibit C. albicans growth in this review. Numerous other studies have examined the effects of southern African plants against C. albicans, and the reader is directed to those studies [1113]. Notably, those studies generally screened against C. albicans for reasons not associated with UTIs.

The pathogens that cause UTIs usually enter the urinary tract via the urethra. Bacteria are transferred to the urethra from the bowel. When they colonise the bladder, they attach to the bladder wall and form a biofilm, which helps the pathogens to evade the host's immune response [14]. Improper urogenital area hygiene, sexual intercourse, and exposure to unfavourable hygiene products (e.g., scented and chemical filled feminine products and contraceptives) may aid in the introduction of pathogens to the urinary tract and create suitable growth conditions for infections to develop [10]. Other risk factors for contracting an uncomplicated UTI include sexual intercourse with a new sexual partner, use of contraceptives, and a history of previous recurrent UTIs. Risk factors for complicated UTIs are underlying diseases, use of catheters, abnormal genitourinary anatomy and physiology, hospitalisation, and exposure to antibiotics [10].

1.3. Symptoms of Urinary Tract Infections

Urinary tract infections may present in several ways including increased and persistent urgency to urinate, painful burning sensations associated with urination, increased frequency of urination, lower volumes for each urinary event, and cloudy and foul smelling urine. Pain in the lower abdomen, back, and pelvic area is also a relatively common symptom of UTIs, especially in women [8]. Occasionally, UTIs may result in blood in the urine, which may present as red-, pink-, or cola-coloured urine. Infection in the kidney may present with symptoms including nausea and vomiting, fever, and upper back pain (most commonly on a single side) [10]. Many of these signs and symptoms are generic, and UTIs are frequently overlooked or misdiagnosed as other conditions, particularly in older people.

1.4. Current Treatments

In most cases, UTIs are relatively easy to treat with a course of broad-spectrum antibiotics, although fluoroquinolones (including ciprofloxacin) are generally avoided as the side effects are often regarded as outweighing the benefits. The most common treatments include trimethoprim/sulfamethoxazole, fosfomycin, nitrofurantoin, cephalexin, and ceftriaxone. However, due to overuse and misuse of commonly used clinical antibiotics, the emergence of antibiotic-resistant pathogens is increasingly common, resulting in the failure of the main antibiotic chemotherapy options [15]. Antibiotic resistance has been a driving force of new drug development initiatives, and implementation of alternative treatment identification and new antibiotic therapies are urgently required.

The development of antibiotic-resistant bacteria is increasingly resulting in antibiotic therapy failures, and chronic UTIs are becoming more frequent [1]. Additionally, the relatively high rate of UTI recurrence poses a challenge to the effective treatment of these infections [16]. Indeed, that study estimated that approximately 24% of people contracting a UTI will develop a recurrent infection within six months of the original infection. Of further concern, approximately 5% of people who develop a UTI will experience more than three recurrences per year [17].

Foxman and Buxton [18] suggest that empirical treatments of UTIs should be reconsidered due to the following reasons:

  1. The frequency of antibiotic-resistant E. coli strains, many of which have resistance to multiple antibiotics including fluoroquinolones [15], is increasing. The increasing incidence of extended spectrum β-lactamase (ESBL) UTI pathogens that are resistant to the commonly used β-lactam class of antibiotics is particularly concerning [19, 20].

  2. Even relatively short courses of currently used antibiotic therapies may significantly affect the gut microflora, resulting in other health issues developing [21]. These therapies may also disrupt the urogenital microbiome, resulting in other unforeseen issues. Thus, the benefits of empirical antibiotic therapy may not outweigh the risks [22, 23]. New and innovative strategies to prevent UTI recurrences and alternative therapies for their treatment are considered a high priority [18].

1.5. The Use of Medicinal Plants in Urinary Tract Infection Treatment

The launch and development of the WHO Traditional Medicine Strategy 2014–2023 aimed to support the development and implementation of proactive policies and action plans to improve the role traditional medicine plays in population health [24]. The strategy focuses on developing new health systems (including the use of complementary and traditional medicinal products) as a high priority. A re-examination of traditional medicines is an attractive option for the development of new therapies to treat pathogenic infections as plant-derived medicines have often been used for hundreds (in some cases, thousands) of years. Furthermore, the traditional use by some cultures has been relatively well documented. Asian, Middle Eastern, and African traditional systems are perhaps the most extensively documented, although many of the therapies are yet to be extensively studied and verified, and substantially more work is needed in this field.

It is estimated that approximately 700,000 tons of plant materials are used each year in South Africa to produce herbal remedies worth 1.2 to 2.5 billion South African Rands annually [2528]. Not only are these products widely used in South Africa by practitioners of traditional medicine, but they are also becoming increasingly popular as complementary and alternative medicines in combination with allopathic pharmaceuticals. Indeed, some plant products (e.g., Harpagophytum procumbens (Burch.) DC. Ex Meisn., commonly known as devil‘s claw extracts) are commonly sold at pharmacies globally, and it is no longer necessary to visit a traditional Muthi market to obtain products developed from them. However, a substantial portion of traditional plant use in South Africa does use plant materials obtained and prepared following traditional methods. Depending on the plant species used, a variety of different parts including roots, flowers, leaves, bulbs, and stems may be used medicinally, and the individual parts may have substantially different properties and uses [29]. Traditional beliefs have a deep influence within the majority of the ethnic cultures in South Africa and are particularly prevalent in rural communities [30]. Even in urban communities, a large portion of the South African population is reliant on traditional medicine as their primary mode of healthcare [31]. Indeed, that study postulated that the demand for traditional medicines in South Africa will increase in future years due to stress associated with urban lifestyles.

Despite their widespread use, there is a relative lack of information on the proper use and preservation of plant medicines. Medicinal plants are considered (often erroneously) to have fewer adverse effects [32] and are often more accessible and affordable than Western/allopathic medications [33]. A substantial number of South Africans (especially rural populations) are dependent on self-medication with plant-based medicines, and the involvement of the community in managing the use and preservation of plant species may result in successful strategies for sustainable use [34]. South African ethnobotanical literature has been relatively well recorded, although the medicinal properties of many species used traditionally are yet to be rigorously verified. There has been a substantial increase in studies screening and validating the use of South African traditional medicines in recent years, highlighting the potential of several species [35]. Of the therapeutic properties examined, the antibacterial activity of South African plants has received the most attention, although many species remain relatively neglected. Numerous plants have been reported to have antimicrobial activity, with a substantial recent increase in interest in this field. However, very few of those studies have specifically focussed on UTIs. Instead, screening against bacterial pathogens that cause gastrointestinal diseases [36, 37], skin disease [38, 39], or autoimmune diseases [40, 41] have received far greater attention. Notably, many of the same bacterial species screened in the other studies are also amongst the pathogenic causes of UTIs. Whilst the focus of those studies is not UTIs, they are included in this study as they were screened against the same bacterial species.

2. Materials and Methods

This study aimed to record and document the southern African medicinal plants that are used traditionally to treat UTIs. A variety of ethnobotanical books [4246], as well as multiple peer reviewed journal articles, were consulted to compile this list. The online resources Google Scholar, PubMed, Scopus, and ScienceDirect were used to identify and access original scientific research studies. The following terms were used as filters and were searched for both alone and as combination: “Southern Africa,” “South African,” “Lesotho,” “Swaziland,” “Namibia,” “Botswana,” “Zimbabwe,” “Zambia,” “Mozambique,” “traditional medicinal plant,” “ethnobotany,” “urinary tract infection,” “UTI,” “bladder,” and “uropathogens.” The initial search aimed to document all of the plant species used in southern Africa to treat UTIs. Our study was nonbiased and did not favour the traditional knowledge of one ethnic group over others. Despite this, substantially more information was available about Zulu traditional medicine due to the prevalence of reports on that topic in the available literature. Whilst most of these species are native South African plants, introduced species were not excluded, where they had been incorporated into the traditional medicine systems of at least one South African ethnic group. Following the initial literature review, a further review was undertaken to identify the species that have been screened for their ability to inhibit one or more of the bacterial pathogens that cause UTIs.

2.1. Eligibility Criteria

Ethnobotanical books and peer reviewed journal articles were searched using the specific key words noted above. Published studies were identified and their abstracts were read to establish their relevance to this study. The full content of publications that were deemed relevant were then examined thoroughly to ensure that the eligibility criteria were met.

2.2. Inclusion Criteria

The following inclusion criteria for eligibility of the study were considered:

  1. Publications written in English and prior to April 2021 were used in this review.

  2. Our study was nonbiased and without any taxonomic preference.

  3. For the ethnobotanical survey (Table 1), only plant species that are recorded to treat UTIs are included. Any plants recorded to treat individual nonspecific symptoms were excluded unless it could be determined that they were specifically used to treat UTIs.

  4. For the biological activity studies presented in Table 2, only studies that screened against the major bacterial causes of UTIs were included, irrespective of whether the focus of the study was UTIs or the bacteria tested were selected because of their association with a different disease.

  5. Only studies screening against the common causes of UTIs were evaluated in this review, irrespective of their focus. For example, studies that screened southern African plants against E. coli were included in this study, even if their focus was on gastrointestinal diseases rather than UTIs.

  6. Ethnobotanical studies on the flora of southern African region included South Africa and those countries immediately surrounding it.

Table 1.

Southern African plants traditionally used to treat urinary tract infections.

Plant species Family Common name Part of plant used Uses References
Acacia sieberiana var. woodii (Burtt Davy) Keay & Brenan Leguminosae Paperbark thorn (Eng); papierbasdoring (Afr) Bark and roots Urinary tract ailments [46]
Acokanthera oppositifolia (Lam.) Codd Apocynaceae Inhlungunyembe (Zulu) Not specified Urinary tract infection [43]
Afroaster hispida (Thunb.) J.C.Manning & Goldblatt Asteraceae Udlutshana (Zulu) Not specified Urinary ailments [47]
Agathosma betulina (P.J.Bergius) Pillans Rutaceae Buchu (Eng); boegoe (Afr); bocho (Sotho) Leaves Bladder and kidney ailments [45, 48, 49]
Agathosma capensis (L.) Dummer Rutaceae Spicy buchu (Eng); anysboegoe, steenbokboegoe (Afr) Leaves Urinary ailments [50]
Agathosma serratifolia (Curtis) Spreeth Rutaceae Langblaarboegoe, kloofboegoe (Afr); long buchu (Eng) Leaves Bladder and kidney ailments [45]
Albizia adianthifolia (Schum.) W.Wight Leguminosae Isiyengelele, usolo, umgadankawu (Zulu) Not specified Urinary tract infection [47]
Aloe ferox Mill. Xanthorrhoeaceae Bitteraalwyn (Afr); bitter aloe (Eng) Leaves, roots, and stems Kidney and bladder ailments [51]
Aloe zebrina Baker Xanthorrhoeaceae Sebra-aalwyn (Afr); zebra aloe (Eng) Leaves Urinary and bladder ailments [46]
Antiphiona pinnatisecta (S.Moore) Merxm. Compositae Unknown Roots Bladder ailments [46]
Antizoma angustifolia (Burch.) Miers ex Harv. Menispermaceae Maagbitterwortel (Afr) Roots Kidney and bladder ailments [52]
Aptosimum procumbens (Lehm.) Burch. ex Steud Scrophulariaceae Brandbos (Afr) Leaves Bladder ailments [4244]
Arctopus echinatus L. Apiaceae Platdoring (Afr) Roots Bladder ailments [4244, 53]
Artemisia afra Jacq. ex Willd. Compositae Alsem (Afr); African wormwood (Eng); mhlonyana (Zulu) Leaves, roots, and stems Bladder and kidney ailments [49, 51]
Asparagus africanus Lam. Asparagaceae Bush asparagus, African asparagus (Eng); katdoring (Afr); isigobo (Zulu) Not specified Bladder and kidney ailments [46]
Asparagus asparagoides (L.) Druce Asparagaceae Makholela (Sotho) Roots Urinary tract infection [48]
Aster bakerianus Burtt Davy ex C.A.Sm. Compositae Idlutshane, uhloshana (Zulu) Leaves Urinary tract infection [43]
Baccharoides adoensis var. kotschyana (Sch.Bip. ex Walp.) Compositae Innyathelo (Zulu) Stems and leaves Urinary tract infection [43]
Ballota africana (L.) Benth. Lamiaceae Kattekruid (Afr) Leaves Bladder and kidney ailments [50]
Berkheya Setifera DC. Compositae Ikhakhasi, umalumvuba (Zulu); leleme-la-khomo (Sotho) Root Urinary and kidney ailments [47, 54]
Bolusanthus speciosus (Bolus) Harms Leguminosae Umholo (Zulu); tree wisteria (Eng); vanwykshout (Afr) Barks, leaves, and stems Kidney ailments [55]
Boophone disticha (L.f.) Herb. Amaryllidaceae Gifbol (Afr) Bulb Bladder ailments [4244]
Bowiea volubilis Harv. Asparagaceae Climbing onion (Eng); knolklimop (Afr); iguleni (Zulu) Bulb Bladder ailments [43, 48]
Brachylaena discolor DC. Compositae Bosvaalbos (Afr); ipahla (Zulu) Leaves Urinary ailments [43]
Bulbine abyssinica A.Rich Xanthorrhoeaceae Wildekopieva (Afr) Leaves Bladder ailments [56, 57]
Bulbine latifolia (L.f.) Spreng. Xanthorrhoeaceae Red carrot (Eng); rooiwortel (Afr) Root Bladder and kidney ailments [48, 57]
Cardiospermum halicacabum L. Sapindaceae Balloon vine (Eng); blaasklimop (Afr) Stems and leaves Bladder ailments [43, 46, 58]
Carica papaya L. Caricaceae Papaya, pawpaw (Eng) Not specified Bladder ailments [42]
Cenchrus ciliaris L. Poaceae Buffalograss (Eng); bloubuffelgras (Afr); idungamuzi (Zulu) Roots Urinary tract infection [43, 59, 60]
Centaurea benedicta (L.) L. Compositae Karmedik (Afr) Not specified Urinary and kidney ailments [50]
Chironia baccifera L. Gentianaceae Bitterbos, sarsaparilla (Afr) Not specified Urinary ailments [50]
Chrysanthemoides monilifera (L.) Norl. Compositae Bietou, bessiebos (Afr) Whole plant Urinary and kidney ailments [50]
Cissampelos capensis L.f. Menispermaceae David's root (Eng); gifhondjie, dawidjieswortel (Afr) Roots and leaves Bladder ailments [4244, 46]
Cleome gynandra L. Cleomaceae African cabbage, spiderwisp (Eng); snotterbelletjie (Afr) Not specified Bladder ailments [42]
Cliffortia odorata L.f. Rosaceae Wildewingerd (Afr); wild vine (Eng) Leaves Bladder ailments [48]
Clivia miniata (Lindl.) Bosse Amaryllidaceae Benediction lily (Eng); boslelie (Afr); umayime (Zulu) Bulb Urinary ailments [43]
Coix lacryma-jobi L. Poaceae Job's tears, adlay (Eng) Not specified Bladder ailments [42]
Combretum kraussii Hochst. Combretaceae Umduba, umdubu omhlophe, umdubo wamanzi (Zulu) Not specified Urinary and bladder ailments [47]
Commelina africana L. Commelinaceae Idangabane (Zulu); khopo (Sotho) Root Bladder ailments [43]
Conostomium natalense (Hochst.) Bremek. Rubiaceae Wild pentas (Eng); umbophe, ungcolosi (Zulu) Not specified Urinary ailments [61]
Conyza scabrida DC. Compositae Oondbos, bakbos, paddabos (Afr) Leaves Bladder infection [51]
Crinum macowanii Baker Amaryllidaceae River fly (Eng); umduze (Zulu) Bulb Urinary ailments [43]
Crinum moorei Hook. f. Amaryllidaceae Umduze (Zulu) Bulb Urinary ailments [43]
Crossyne guttata (L.) D.Müll.-Doblies & U.Müll.-Doblies Amaryllidaceae Gifbol (Afr) Bulb Bladder ailments [4244]
Cryptolepis oblongifolia (Meisn.) Schltr. Apocynaceae Bokhoring, melkbos (Afr); mukangaza (Sotho) Not specified Bladder ailments [42]
Cussonia paniculata Eckl. & Zeyh. Araliaceae Motsetse (Sotho) Not specified Kidney and bladder ailment [54, 62]
Cyathula achyranthoides (Kunth) Moq. Amaranthaceae Unknown Not specified Bladder ailments [63]
Cynodon dactylon (L.) Pers. Poaceae Dog's tooth (Eng); krookgras (Afr) Rhizome Urinary ailments [46]
Datura stramonium L. Solanaceae Thornapple, jimsonweed, devil's snare (Eng) Leaves Bladder ailments [42]
Dicoma capensis Less. Compositae Karmedik, wilde karmedik (Afr) Leaves Bladder and kidney ailments [44, 45, 56, 57]
Diosma oppositifolia L. Rutaceae Buchu, Bitter buchu (Eng) Leaves Bladder and kidney ailments [48]
Diosma prama I.Williams Rutaceae Steenbokkboegoe (Afr) Not specified Urinary and kidney ailments [50]
Diospyros mespiliformis Hochst. ex A.DC Ebenaceae Ikhambi lesduli, umazambezi (Zulu) Not specified Urinary ailments [47]
Dipcadi gracillimum Baker Asparagaceae Oumasegroottoon (Afr) Not specified Bladder ailments [63]
Dipcadi viride (L.) Moench Asparagaceae Ugibizisila, uguleni, umakhweyana (Zulu) Not specified Urinary tract infection [47]
Dipcadi gracillimum Baker Asparagaceae Oumasegroottoon (Afr) Not specified Urinary ailments [64]
Dodonaea viscosa (L.) Jacq. Sapindaceae Basterolen, sandolien, ysterbos (Afr); sand olive (Eng) Leaves Bladder and kidney ailments [5, 50, 51]
Drimia elata Jacq. Asparagaceae Satin squill (Eng); brandui, jeukbol (Afr); umqumbu (Zulu) Not specified Urinary ailments [44]
Dysphania ambrosioides (L.) Mosyakin & Clemants Amaranthaceae Ikhambi leslumo, uzansikwesibaya (Zulu) Not specified Urinary ailments [47]
Elytropappus rhinocerotis (L.f.) Less. Asteraceae Renosterbos (Afr) Leaves Bladder and kidney disorders [49]
Elymus repens (L.) Gould Poaceae Couch grass (Eng) Not specified Bladder ailments [42]
Empleurum unicapsulare (L.f.) Skeels Rutaceae Bergboegoe, langblaarboegoe (Afr) Whole plant Urinary and kidney ailments [50]
Eriocephalus punctulatus DC. Compositae Kapokbos (Afr) Whole plant Urinary and kidney ailments [50]
Eriosema distinctum N.E.Br. Leguminosae Ubangalala omkhulu (Zulu) Roots Urinary ailments [43]
Erythrina caffra Thunb. Leguminosae Coral tree (Eng); kaffirboom (Afr); umsinsi (Zulu) Leaves Urinary ailments [43]
Erythrina lysistemon Hutch. Leguminosae Umsinsi (Zulu) Leaves Bladder ailments [47]
Euclea natalensis A.DC. Ebenaceae IsiZimane, umshekisane (Zulu) Bark Urinary tract infection [47, 65]
Euclea undulata Thunb. Ebenaceae Ghwarrie, ghwarrieboom, ghwarriebos (Afr) Whole plant Urinary and kidney ailments [43, 50]
Eucomis autumnalis (Mill.) Chitt Asparagaceae Mathethebane (Sotho) Tubular roots Urinary ailments [58]
Euphorbia milii Des Moul. Euphorbiaceae Crown of thorns (Eng) Not specified Bladder ailments [64, 66]
Euphorbia tithymaloides L. Euphorbiaceae Redbird flower (Eng) Not specified Bladder ailments [64, 66]
Exomis microphylla (Thunb.) Aellen Amaranthaceae Hondepisbos, hondebossie (Afr) Whole plant Urinary ailments [50]
Faidherbia albida (Delile) A.Chev. Leguminosae Anatree (Eng); anaboom (Afr) Bark Bladder ailments [46]
Foeniculum vulgare Mill. Apiaceae Vinkel, makuinkel, soetvinkel (Afr) Whole plant Urinary ailments [50]
Galenia africana L. Aizoaceae Kraalbos (Afr) Leaves Bladder ailments [4244]
Galium tomentosum Thunb. Rubiaceae Red storm (Eng); rooistorm, doodlief (Afr) Root Bladder ailments [48, 56]
Geranium incanum Burm.f. Geraniaceae Carpet geranium (Eng); horlosie, bergtee, vrouetee (Afr); tlako (Sotho) Not specified Bladder ailments [56, 64]
Grewia caffra Meisn. Malvaceae Upata, iphatha (Zulu) Roots, bark Bladder ailment [67]
Grewia occidentalis L. Malvaceae Cross berry (Eng); iklolo, imahlehle (Zulu) Roots Bladder ailments [43]
Grewia robusta Burch. Malvaceae Bokbos (Afr) Whole plant Urinary ailments [50]
Gunnera perpensa L. Gunneraceae Ugobho, izibu (Zulu) Not specified Bladder ailments [47]
Helichrysum crispum (L.) D. Don Compositae Kooigoed (Afr) Leaf Bladder and kidney ailments [49]
Helichrysum odoratissimum (L.) Sweet Compositae Phefo (Sotho); kooigoed, kooibos (Afr) Leaves, roots, and stems Bladder ailments [50, 56]
Helichrysum patulum (L.) D.Don Compositae Honey everlasting (Eng); kooigoed (Afr); impepho (Zulu) Not specified Bladder ailments [42]
Hibiscus pusillus Thunb. Malvaceae Blaasbossie (Afr) Whole plant Urinary ailments [50]
Hibiscus mastersianus Hiern Malvaceae Monarch rosemallow (Eng) Stems and Leaves Urinary ailments [46]
Hibiscus pedunculatus L.f. Malvaceae Pink mallow (Eng); indola ebomvu (Zulu) Leaves Urinary ailments [43]
Hoslundia opposita Vahl Lamiaceae Bird gooseberry (Eng); uyaweyawe (Zulu) Not specified Urinary ailments [46]
Hypoxis hemerocallidea Fisch., C.A.Mey. & Avé-Lall. Hypoxidaceae Inkanfe (Zulu); yellow star (Eng) Not specified Bladder ailments [47, 50]
Hypoxis rigidula Baker Hypoxidaceae Ilabatheka, inkomfe, umhungulo (Zulu); African potato (Eng) Not specified Bladder ailments [47, 50]
Indigofera cassioides DC. Leguminosae Unknown Not specified Bladder ailments [42]
Ipomoea pes-caprae (L.) R.Br. Convolvulaceae Beach morning glory, goat's foot (Eng); strandpatat (Afr) Not specified Bladder ailments [42]
Jasminum abyssinicum Hochst. ex DC. Oleaceae Mthundangazi Roots Bladder ailments [68]
Kedrostis capensis A. Meeuse Cucurbitaceae Sesepa sa linoha (Sotho) Tubular roots and leaves Urinary tract infection [69]
Ledebouria marginata (Baker) Jessop Asparagaceae Bokhoe (Sotho) Root bulb Urinary tract infection [70]
Leonotis leonurus (L.) R.Br. Lamiaceae Klip dagga, wild dagga (Afr) Stems with leaves and flowers Bladder and kidney disorders, [49]
Lessertia frutescens (L.) Goldblatt & J.C.Manning Leguminosae Kalkoenblom, keurtjie (Afr) Leaves Kidney and urinary ailments [50, 56]
Matricaria chamomilla L. Compositae Chamomile (Eng) Not specified Bladder ailments [42]
Melianthus pectinatus Harv. Melianthaceae Kriekiebos, lidjiebos (Afr) Root Urinary tract infection [56]
Mentha longifolia (L.) L. Lamiaceae Wild mint (Eng); ufuthana lomhlanga (Zulu) Leaves Bladder and kidney ailments [49, 52, 68]
Merwilla plumbea (Lindl.) Speta Asparagaceae Inguduza, untabosizi, untangana zibomvana (Zulu) Not specified Bladder ailments [47, 50]
Mesembryanthemum cordifolium L.f. Aizoaceae Ibohlololo (Zulu) Leaves Bladder ailment [44, 47, 53]
Mesembryanthemum crystallinum L. Aizoaceae Common ice plant, crystalline ice plant (Eng); soutslaai, volstruisslaai (Afr) Not specified Bladder ailments [42]
Mikania capensis DC. Compositae Umdlonzo, umhlozo (Zulu) Leaves Urinary ailments [42, 43]
Millettia oblata Dunn Leguminosae Unknown Roots Bladder ailments [42]
Notobubon galbanum (L.) Magee Apiaceae Blister bush (Eng); bergseldery (Afr) Not specified Kidney and bladder ailment [42, 52]
Nymphaea nouchali Burm.f. Nymphaeaceae Blue water lily (Eng); blouwaterlelie (Afr); izubu, iziba, ugobho (Zulu) Leaves Urinary tract infection [46, 47, 49]
Ocimum americanum L. Lamiaceae Hoary basil (Eng); wilde basielkruid (Afr) Not specified Urinary tract infection [46]
Ocotea bullata (Burch.) E. Meyer in Drege Lauraceae Stinkwood, laurel wood (Eng); umnukani, umhlungulu (Zulu) Bark Urinary ailments [43, 58]
Olea europaea L. Oleaceae Wild olive (Eng); olyfhout, olienhout (Afr); isadlulambezo (Zulu) Roots and bark Urinary tract infection [43, 46]
Oncoba spinosa Forssk. Salicaceae Snuff-box tree (Eng); snuifkalbassie (Afr) Not specified Bladder ailments [42]
Opuntia ficus-indica (L.) Mill. Cactaceae Foie e kubedu (Sepedi); mudoro (Venda) Roots Urinary ailments [63]
Pedalium murex L. Pedaliaceae Large caltrops (Eng) Leaves Bladder ailments [42]
Pegolettia baccharidifolia Less. Compositae Ghwarrieson, heuningdou (Afr) Leaves and twigs Bladder and kidney ailments [44, 45]
Pelargonium grossularioides (L.) L'Hér. Geraniaceae Rooirabas (Afr); gooseberry-leaved Pelargonium (Eng) Leaves and stems Urinary tract infection [51, 68]
Pelargonium hypoleucum Turcz. Geraniaceae Rooirabas (Afr) Roots Urinary tract infection [56]
Pelargonium ramosissimum Willd. Geraniaceae Dassieboegoe, dassiebos (Afr) Leaves and stems Bladder and kidney ailments [51, 68]
Pentanisia prunelloides (Klotzsch) Walp. Rubiaceae Sooibrandbossie (Afr); icimamlilo (Zulu) Roots Bladder and kidney ailments [43]
Petroselinum crispum (Mill.) Nyman ex A.W.Hill. Apiaceae Pietersielie (Afr); parsley (Eng) Leaves Bladder ailments [49, 66]
Phytolacca heptandra Retz. Phytolaccaceae Inkbessie (Afr); ingubivumile (Zulu) Not specified Urinary ailments [43]
Portulaca quadrifida L. Portulacaceae Pigweed, wild purslane (Eng); kanniedood (Afr) Not specified Bladder and kidney ailments [42, 46]
Prunus persica (L.) Batsch Rosaceae Peach (Eng) Leaves Bladder ailments [42]
Ranunculus multifidus Forssk. Ranunculaceae Botterblom, brandblare (Afr); uxhaphozi (Zulu) Leaves Urinary ailments [43]
Rhamnus prinoides L'Hér. Rhamnaceae Mofifi (Sotho) Root Kidney and bladder ailment [54]
Rhoicissus tridentata (L.f.) Wild & R.B.Drumm. Vitaceae Wild/bitter grape (Eng); bobbejaantou, wildedruif (Afr); isinwazi (Zulu) Stems Urinary ailments [43, 64]
Rhynchosia caribaea (Jacq.) DC. Leguminosae Snoutbean (Eng); rankboontjie (Afr); isihlahlasenqomfi (Zulu) Roots Urinary ailments [46]
Rhynchosia minima (L.) DC. Leguminosae Least snoutbean, burn-mouth-vine (Eng) Roots Bladder ailments [46]
Rhynchosia sublobata (Schum.) Meikle Leguminosae Twiner of barren ground (Eng) Roots Bladder ailments [46]
Ricinus communis L. Euphorbiaceae Olieboom, olieblaar (Afr) Leaves Urinary and kidney ailments [47, 50]
Rotheca hirsuta (Hochst.) R.Fern Lamiaceae Butterfly bush, wild violet (Eng); umathanjana, lusikisiki (Zulu) Not specified Urinary ailments [64]
Ruta graveolens L. Rutaceae Wynruit (Afr) Leaves Urinary tract infection and bladder ailments [49, 56]
Salix woodii Seemen Salicaceae Wild willow (Eng) Bark Urinary ailments [69]
Salix mucronata Thunb. Salicaceae Cape willow (Eng); vaalwilger (Afr) Bark Bladder ailments [46]
Salvadora persica L. Salvadoraceae Toothbrush tree, real mustard tree (Eng); kerriebos (Afr) Roots Urinary tract infection [46]
Salvia microphylla Kunth Lamiaceae Baby sage, Graham's sage, blackcurrant sage (Eng) Roots Urinary ailments [50]
Scadoxus puniceus (L.) Friis & Nordal Amaryllidaceae Idumbe likahloyile, uhloyile, umphompo (Zulu) Not specified Urinary ailments [47]
Solanum aculeastrum Dunal Solanaceae Gifappel (Afr); umthuma, untumane (Zulu) Fruit Urinary tract infection and kidney ailments [47, 48]
Sutherlandia frutescens (L.) R.Br. Fabaceae Keurtjies, kankerbossie (Afr) Leaves and stems Bladder and kidney ailments [49]
Tarchonanthus camphoratus L. Compositae Camphor bush (Eng); wilde kanferbos (Afr); igceba elimhlope (Zulu) Not specified Urinary ailments [64]
Teucrium trifidum Retz. Lamiaceae Katjiedriebaar (Afr) Leaves Bladder ailments [56, 57]
Thesium hystrix A.W.Hill Santalaceae Kleinswartstorm (Afr) Roots Bladder ailments [42]
Tragia meyeriana Müll.Arg. Euphorbiaceae Stinging nettle (Eng); ubangalala, imbabazane (Zulu) Not specified Bladder ailments [42, 43]
Tragia rupestris Sond. Euphorbiaceae Ubangalala, imbabazane (Zulu) Roots Bladder ailments [43]
Trichilia emetica Vahl Meliaceae Red rash (Eng); basteressenhout (Afr); ixolo, umkhuhlu (Zulu) Bark Kidney ailments [43]
Trifolium africanum Ser. Leguminosae Erasmus clover, wild clover (Eng); wildeklawer (Afr); moqoiqoi, moqophi (Sesotho) Not specified Bladder ailments [63]
Typha capensis (Rohrb.) N.E.Br. Typhaceae Papkuil (Afr) Not specified Bladder and kidney ailments [46]
Urtica urens L. Urticaceae Small nettle (Eng); dog nettle Eng) Bark Bladder pains [58]
Warburgia salutaris (G.Bertol.) Chiov. Canellaceae Isibaha (Zulu) Leaves Urethral ailments [67]
Withania somnifera (L.) Dunal Solanaceae Winter cherry (Eng); geneesblaar (Afr) Roots Bladder ailments [46]
Xanthium strumarium L. Compositae Kankerroos (Afr) Not specified Bladder ailments [42]
Xysmalobium undulatum (L.) W.T.Aiton Apocynaceae Wild cotton (Eng); melkbos (Afr) Not specified Bladder ailments [46]
Zantedeschia albomaculata (Hook.) Baill. Araceae Arum lilies, calla lilies, pig lily (Eng.); varkblom (Afr); mohalalitoe (Sotho) Not specified Urinary ailments [54, 6264]
Zea mays L. Poaceae Corn (Eng); umbila (Zulu) Not specified Bladder ailments [42]

Table 2.

Plant species with noteworthy activity that have been tested against urinary tract bacterial pathogens.

Plant species Plant part used Pathogens screened MIC values Toxicity evaluation References
Acacia karoo Hayne Leaves E. coli (M) 414 μg/mL; (W) 458 μg/mL Non-toxic in Artemia lethality assay [71]

Acacia nicolitica (L.) Delile Root and bark E. coli Root and bark: (E) 780 μg/mL; (W) 6250 μg/mL Not determined [72]

Acacia sieberiana DC. Root and bark E. coli Root and bark: (E) 92–780 μg/mL; (W) 1560 μg/mL Not determined [72]
Agathosma betulina (Berg.) Pillans Leaves E. coli (W) > 8000 μg/mL Not toxic in human epithelial kidney cells [73]
K. pneumoniae (M) 1876 μg/mL; (W) 2387 μg/mL Non-toxic in Artemia lethality assay [41]
P. mirabilis (M) 878 μg/mL [40]

Alchornea cordifolia (Schumach. And Thonn.) Müll. Arg. Leaves, stem E. coli Leaves: (M) 63 μg/mL; (E) 63 μg/mL Not determined [74]
Stem (M) 63 μg/mL; (E) 63 μg/mL
K. pneumoniae Leaves: (M) 125 μg/mL; (E) 125 μg/mL
Stem (M) 125 μg/mL; (E) 125 μg/mL
P. mirabilis Leaves: (M) 125 μg/mL; (E) 125 μg/mL
Stem (M) 125 μg/mL; (E) 250 μg/mL
S. saprophyticus Leaves: (M) 63 μg/mL; (E) 63 μg/mL
Stem (M) 63 μg/mL; (E) 63 μg/mL

Alchornea laxiflora (Benth.) Pax & Hoffm. Leaves, roots, stem E. coli Leaves: (M) 125 μg/mL; (E) 125 μg/mL LC50 = 100–140 μg/mL in HeLa cells [74]
Roots: (M) 500 μg/mL; (E) 500 μg/mL
Stem: (M) 500 μg/mL; (E) 250 μg/mL
K. pneumoniae Leaves: (M) 63 μg/mL; (E) 63 μg/mL
Roots: (M) 125 μg/mL; (E) 125 μg/mL
Stem: (M) 500 μg/mL; (E) 500 μg/mL
P. mirabilis Leaves: (M) 8000 μg/mL; (E) 2000 μg/mL
Roots: (M) 250 μg/mL; (E) 250 μg/mL
Stem: (M) 4000 μg/mL; (E) 4000 μg/mL
S. saprophyticus Leaves: (M) 63 μg/mL; (E) 63 μg/mL
Roots: (M) 63 μg/mL; (E) 63 μg/mL
Stem: (M) 63 μg/mL; (E) 63 μg/mL

Aloe ferox Mill. Leaves E. coli (W) > 8000 μg/mL Not toxic in human epithelial kidney cells [73]

Aloe marlothii A.Berger Leaves E. coli (M) 1250 μg/mL Not determined [75]
P. aeruginosa (M) 1250 μg/mL

Apodytes dimidiata E.Mey ex am. Not stated E. coli (A) 2500 μg/mL Not determined [76]
P. aeruginosa (A) 310 μg/mL

Artemisia afra Jacq. Ex Willd. Leaves E. coli (W) 3000 μg/mL Not toxic in human epithelial kidney cells [74]

Ballota africana (L.) Benth. Leaves K. pneumoniae (M) 438 μg/mL; (W) 379 μg/mL Non-toxic in Artemia lethality assay [41]
P. mirabilis (M) 4278 μg/mL [40]

Bolosanthus speciosis (Bolus) Harms Leaves E. coli (A) 80 μg/mL LC50 = 53 μg/mL in Vero cells [77]

Brachylaena discolor Not stated E. coli (A) 630 μg/mL Not determined [76]
P. aeruginosa (A) 310 μg/mL

Calpurnia aurea (aiton) Benth. Leaves E. coli (A) 40 μg/mL LC50 = 57 μg/mL in Vero cells [77]

Carpobrotus edulis (L.) N.E. Br. Leaves P. mirabilis (M) 205 μg/mL; (W) 561 μg/mL Non-toxic in Artemia lethality assay [40]
Proteus vulgaris (M) 670 μg/mL; (W) 1246 μg/mL

Cissius quadrangularis (Linn.) Stems E. coli (M) 1259 μg/mL Not determined [75]
P. aeruginosa (M) 2500 μg/mL

Clausena anisata (Willd.) Hook ex Benth. Not stated E. coli (A) 310 μg/mL Not determined [76]
P. aeruginosa (A) 310 μg/mL

Clerodendron glabrum E.Mey Not stated E. coli (A) 310 μg/mL Not determined [76]
P. aeruginosa (A) 630 μg/mL

Combretum kraussii Hochst. Leaves E. coli Root and bark: (E) 1560 μg/mL; (W) 3125 μg/mL Not determined [72]

Cremaspora triflora (Thonn.) K.Schum. Leaves E. coli (A) 50 μg/mL LC50 = 14 μg/mL in Vero cells [77]

Cryptocarya latifolia Sond. Bark E. coli (M) 4000 μg/mL; (W) > 8000 μg/mL; (D) > 8000 μg/mL; (EA) > 8000 μg/mL; (H) > 8000 μg/mL Not determined [78]
P. aeruginosa (M) 4000 μg/mL; (W) > 8000 μg/mL; (D) > 8000 μg/mL; (EA) 2000 μg/mL; (H) 4000 μg/mL

Curtisia dentata (Burm.f) C.A. Sm. Not stated E. coli (A) 600 μg/mL Not determined [79]
P. aeruginosa (A) 600 μg/mL

Cussonia spicata Thunb. Bark E. coli (M) 1250 μg/mL Not determined [75]
P. aeruginosa (M) 1250 μg/mL

Cussonia zuluensis Strey. Not stated E. coli (A) 880 μg/mL Not determined [79]
P. aeruginosa (A) 880 μg/mL

Cyathea dregei (Kunze.) R.M.Tyron Not stated E. coli (A) 310 μg/mL Not determined [76]
P. aeruginosa (A) 310 μg/mL

Dicerocaryum ericarpum (Decne.) Shoots E. coli (M) 1250 μg/mL Not determined [75]
P. aeruginosa (M) 1250 μg/mL

Ekebergia capensi Sparrm. Leaves E. coli (M) 1000 μg/mL; (W) > 8000 μg/mL; (D) 1000 μg/mL Non-toxic in Artemia lethality assay [80]

Ekebergia pterophylla (C.DC) Hofmeyr Leaves E. coli (M) 1000 μg/mL; (W) > 8000 μg/mL; (D) 4000 μg/mL Non-toxic in Artemia lethality assay [80]

Elaeodendron croceum (Thunb.) DC. Leaves E. coli (A) 110 μg/mL LC50 = 5 μg/mL in Vero cells [77]

Euclea crispa (Thunb.) Gürke Leaf E. coli (M) 1750 μg/mL; (D) 1750 μg/mL; (EA) 1280 μg/mL Not determined [81]
P. aeruginosa (M) 2000 μg/mL; (D) 2000 μg/mL; (EA) 1500 μg/mL

Euclea natalensis A. DC. Leaf E. coli (M) 1250 μg/mL; (D) 1750 μg/mL; (EA) 1380 μg/mL Not determined [81]
P. aeruginosa (M) 1000 μg/mL; (D) 2000 μg/mL; (EA) 2000 μg/mL

Eucomis autumnalis (Mill.) Chitt. Bulb E. coli (M) > 8000 μg/mL; (W) > 8000 μg/mL; (D) > 8000 μg/mL; (EA) > 8000 μg/mL; (H) > 8000 μg/mL Not determined [78]
P. aeruginosa (M) > 8000 μg/mL; (W) > 8000 μg/mL; (D) > 8000 μg/mL; (EA) > 8000 μg/mL; (H) 2000 μg/mL

Ficus sur Forssk. Root and bark E. coli Root and bark: (E) 1560 μg/mL; (W) 4600 μg/mL Not determined [72]

Gymnosporia senegalensis (Lam.) Loes. Roots E. coli (M) 156 μg/mL; (W) 312 μg/mL; (E) 156 μg/mL; (A) 312 μg/mL Not determined [82]

Hydnora africana Thunb. Bark E. coli (M) > 8000 μg/mL; (W) > 8000 μg/mL; (D) > 8000 μg/mL; (EA) > 8000 μg/mL; (H) > 8000 μg/mL Not determined [78]
P. aeruginosa (M) 2000 μg/mL; (W) > 8000 μg/mL; (D) > 8000 μg/mL; (EA) > 8000 μg/mL; (H) > 8000 μg/mL

Heteromorpha arborescens (Spreng.) Cham & Schltdl. Leaves E. coli (A) 180 μg/mL LC50 = 81 μg/mL in Vero cells [77]

Hetromorpha trifoliata Wendl. Eckl. & Zeyh. Not stated E.coli (A) 630 μg/mL Not determined [76]
P. aeruginosa (A) 630 μg/mL

Heteropyxis natalensis Harv. Leaves E. coli (M) 382 μg/mL Non-toxic in Artemia lethality assay [71]

Hypericim roeperianum G.W.Schimp. ex A. Rich. Leaves E. coli (A) 130 μg/mL LC50 = 66 μg/mL in Vero cells [77]

Hypoxis hemerocallidea Fisch.Mey. & avé-Lall. Leaves E. coli (M) 4000 μg/mL; (W) 4000 μg/mL; (D) > 8000 μg/mL; (EA) > 8000 μg/mL; (H) > 8000 μg/mL Not determined [78]
P. aeruginosa (M) > 8000 μg/mL; (W) > 8000 μg/mL; (D) > 8000 μg/mL; (EA) > 8000 μg/mL; (H) > 8000 μg/mL

Indigofera daleoides Harv. Whole plant E. coli (M) 78 μg/mL; (E) 146 μg/mL; (A) 78 μg/mL Not dertermined [82]

Indigofera frutescens Linn. f. Not stated E. coli (A) 160 μg/mL Not determined [76]
P. aeruginosa (A) 310 μg/mL

Jatropha zeheri Sond. Root E. coli (M) 630 μg/mL Not determined [75]
P. aeruginosa (M) 2500 μg/mL

Kigelia africana (Lam.) Benth. Leaves E. coli (M) 827 μg/mL; (W) 681 μg/mL Non-toxic in Artemia lethality assay [71]
K. pneumoniae (M) 965 μg/mL; (W) 663 μg/mL [41]
P. mirabilis (M) 2483 μg/mL; (W) 285 μg/mL [40]

Leucosidea sericea Eckl. & Zeyh. Not stated E. coli (A) 80 μg/mL Not determined [76]
P. aeruginosa (A) 20 μg/mL

Lippia javanica (Burm.f.) Spreng. Leaves E. coli (M) 439 μg/mL; (W) 192 μg/mL Non-toxic in Artemia lethality assay [71]
K. pneumoniae (M) 538 μg/mL; (W) 654 μg/mL [41]
P. mirabilis (M) 313 μg/mL; (W) 1873 μg/mL [40]
Proteus vulgaris (M) 926 μg/mL; (W) 1728 μg/mL [40]

Maesa lanceolata Forssk. Leaves E. coli (A) 40–310 μg/mL LC50 = 2.4 μg/mL in Vero cells [76, 77]
P. aeruginosa (A) 20–310 μg/mL

Melletia grandis (E.Mey.) Skeels Not stated E. coli (A) 310 μg/mL Not determined [76]
P. aeruginosa (A) 310 μg/mL

Melia azedarach L. Not stated E. coli (A) 310 μg/mL Not determined [76]
P. aeruginosa (A) 630 μg/mL

Morus mesozygia Stapf. Leaves E. coli (A) 70 μg/mL LC50 = 41 μg/mL in Vero cells [77]

Nymania capensis (Thunb.) Lindb. Leaves E. coli (M) > 8000 μg/mL; (W) > 8000 μg/mL; (D) > 8000 μg/mL Non-toxic in Artemia lethality assay [80]

Ozoroa insignis Delile Stem bark E. coli (M) 156 μg/mL; (W) 156 μg/mL; (E) 156 μg/mL; (A) 156 μg/mL Not determined [82]

Pelargonium sidoides DC. Leaves E. coli (W) > 8000 μg/mL Non-toxic in Artemia lethality assay [73]

Pittosporum viridiflorum Sims Leaves E. coli (A) 110 μg/mL LC50 = 55 μg/mL in Vero cells [74]

Pelargonium fasiculata (L.) Alton Leaves K. pneumoniae (M) 374 μg/mL; (W) 432 μg/mL Non-toxic in Artemia lethality assay [41]
P. mirabilis (M) 806 μg/mL; (W) 1843 μg/mL [40]

Ptaerocarpus angolensis DC. Bark E. coli (M) 630 μg/mL Not determined [75]
P. aeruginosa (M) 2500 μg/mL

Ptaeroxylon obliquim (Thunb.) Radlk. Leaves K. pneumoniae (M) 1977 μg/mL Non-toxic in Artemia lethality assay [41]
P. mirabilis (M) 239 μg/mL; (W) 487 μg/mL [40]
Proteus vulgaris (M) 511 μg/mL; (W) 727 μg/mL

Prunus africana (Hook. f.) Kalkman Roots E. coli (M) > 8000 μg/mL; (W) > 8000 μg/mL; (D) > 8000 μg/mL; (EA) > 8000 μg/mL; (H) > 8000 μg/mL Not determined [78]
P. aeruginosa (M) > 8000 μg/mL; (W) > 8000 μg/mL; (D) > 8000 μg/mL; (EA) > 8000 μg/mL; (H) > 8000 μg/mL

Punica granatum L. Roots E. coli (M) 78 μg/mL; (W) 78 μg/mL; (E) 78 μg/mL; (A) 78 μg/mL Not determined [82]

Rhicinus communis Linn. Leaves and stem E. coli (M) 400 μg/mL Not determined [75]
P. aeruginosa (M) 780 μg/mL

Rhoicissus rhomboidea (E. Mey ex Harv.) Planch. Leaves E. coli (M) 306 μg/mL; (W) 333 μg/mL Non-toxic in Artemia lethality assay [71]

Rhoicissus tridentata (L.f.) Wild & R.B.Drumm. Roots E. coli (M) > 8000 μg/mL; (W) > 8000 μg/mL; (D) > 8000 μg/mL; (EA) > 8000 μg/mL; (H) > 8000 μg/mL Not determined [78]
P. aeruginosa (M) 2000 μg/mL; (W) > 8000 μg/mL; (D) > 8000 μg/mL; (EA) > 8000 μg/mL; (H) > 8000 μg/mL

Riccinus communis L. Leaves E. coli (A) 13130 μg/mL Not determined [83]
P. aeruginosa (M) 14670 μg/mL; (E) 16670 μg/mL
K. pneumoniae (M) 12670 μg/mL; (A) 11670 μg/mL

Sacrostemma viminale R. Br. Stem E. coli (M) 1250 μg/mL Not determined [75]
P. aeruginosa (M) 1250 μg/mL

Schkuhria pinnata (Lam.) Shoots E. coli (M) 310 μg/mL Not determined [75]
P. aeruginosa (M) 1250 μg/mL

Schotia bractopetalia Sond. Leaves E. coli (M) 505 μg/mL; (W) 312 μg/mL; (E) 491 μg/mL; (A) 312 μg/mL Non-toxic in Artemia lethality assay [71]

Spirostachys africana Sond. Stem bark E. coli (M) 156 μg/mL; (W) 312 μg/mL; (E) 156 μg/mL; (A) 156 μg/mL Not determined [82]

Syzygium cordatum (Hochst.) Leaves and bark E. coli (M) 499 μg/mL; (W) 790 μg/mL Non-toxic in Artemia lethality assay [71]
K. pneumoniae (M) 312 and 387 μg/mL (bark and leaves respectively); (W) 387 and 335 μg/mL (bark and leaves respectively) [41]
P. mirabilis (M) 969 and 474 μg/mL (bark and leaves respectively); (W) 932 and 49 μg/mL (bark and leaves respectively) [40]
P. vulgaris (M) 751 and 641 μg/mL (bark and leaves respectively); (W) 1325 and 658 μg/mL (bark and leaves respectively) [40]

Strychnos madagascariensis Poir. Leaves E. coli (M) 580 μg/mL; (W) 593 μg/mL Non-toxic in Artemia lethality assay [71]

Strychnos mitis S.Moore Not stated E. coli (A) 40 μg/mL Not determined [76]
P. aeruginosa (A) 160 μg/mL

Sutherlandia frutescens (L.) R.Br. Leaves E. coli (W) > 8000 μg/mL Not toxic in human epithelial kidney cells [73]

Terminalia phanerophlebia Engl. & Diels, Not stated E. coli (A) 80 μg/mL Not determined [79]
P. aeruginosa (A) 80 μg/mL

Terminalia pruinoides M.A. Lawson Leaves E. coli (M) 278 μg/mL; (W) 624 μg/mL Non-toxic in Artemia lethality assay [71]
K. pneumoniae (M) 432 μg/mL; (W) 531 μg/mL [41]
P. mirabilis (M) 313 μg/mL; (W) 224 μg/mL [40]
P. vulgaris (M) 926 μg/mL; (W) 379 μg/mL

Terminalia sambesiacia Engl. & Diels. Not stated E. coli (A) 60 μg/mL Not determined [79]
P. aeruginosa (A) 60 μg/mL

Terminalia sericea Burch. ex DC. Leaves E. coli (M) 396 μg/mL; (W) 276 μg/mL Non-toxic in Artemia lethality assay [71]
K. pneumoniae (M) 254 μg/mL; (W) 318 μg/mL [41]
P. mirabilis (M) 417 μg/mL; (W) 103 μg/mL [40]
P. vulgaris (M) 508 μg/mL; (W) 520 μg/mL

Trichilia dregeana Sond. Leaves E. coli (M) 1000 μg/mL; (W) > 8000 μg/mL; (D) 8000 μg/mL Non-toxic in Artemia lethality assay [80]
E. faecalis (M) 1500 μg/mL; (W) > 8000 μg/mL; (D) 4000 μg/mL

Trichilia emetica Vahl. Leaves E. coli (M) 1000 μg/mL; (W) > 8000 μg/mL; (D) 8000 μg/mL Non-toxic in Artemia lethality assay [80, 84]

Tulbaghia violaceae Harv. Leaves E. coli Roots: (M) 387 μg/mL; Leaves: (M) 30 μg/mL LC50 = 772 μg/mL in Artemia lethality assay [71]
K. pneumoniae Roots; (M) 526 μg/mL; (W) 613 μg/mL [41]
P. mirabilis Leaves: (W) 125 μg/mL [40]

Turraea floribunda Hochst. Leaves E. coli (M) 4000 μg/mL; (W) > 8000 μg/mL; (D) 4000 μg/mL Non-toxic in Artemia lethality assay [80]

Turraea obtusifolia Hochst. Leaves E. coli (M) 2000 μg/mL; (W) > 8000 μg/mL; (D) 8000 μg/mL Non-toxic in Artemia lethality assay [80]

Vepris reflexa I. Verd. Not stated E. coli (A) 600 μg/mL Not determined [79]
P. aeruginosa (A) 1250 μg/mL

Warburgia salutaris (Bertol.f.) Chiov. Leaves and bark E. coli Leaves: (M) 239 μg/mL; (W) 304 μg/mL Non-toxic in Artemia lethality assay [71]
K. pneumoniae (M) 624 μg/mL (bark); (W) 677 μg/mL (bark) [41]
P. mirabilis (M) 623 and 465 μg/mL (bark and leaves respectively); (W) 417 μg/mL (bark) [40]
P. vulgaris (M) 450 and 688 μg/mL (bark and leaves respectively); (W) 1203 μg/mL (leaves) [40]

Ximenia caffra Sond. Stem bark E. coli (M) 156 μg/mL; (W) 312 μg/mL; (E) 312 μg/mL; (A) 312 μg/mL Not determined [82]

Zanthoxylem capensis (Thunb.) Harv. Not stated E. coli (A) 310 μg/mL Not determined [76]
P. aeruginosa (A) 310 μg/mL

Ziziphus murconata Willd. Bark E. coli (M) 2500 μg/mL Not determined [75]
P. aeruginosa (M) 1250 μg/mL

2.3. Exclusion Criteria

The following criteria were used to exclude some studies:

  1. Where name changes and families of plant species were encountered, particularly in older publications, websites such as The Plant List (http://www.theplantlist.org/) and South African National Biodiversity Institute (SANBI) (http://www.sanbi.org) were used to confirm species identification.

  2. Plant species that were recorded to treat generic symptoms of UTIs that are common to other illnesses, without specifically stating their use in treating UTIs, were excluded from this study.

  3. Studies that screened against bacteria that only cause UTIs secondary to other diseases were excluded. Therefore, studies screening South African plants for S. aureus, which only causes UTIs secondary to blood S. aureus infections, were not included in this study.

  4. Only screening studies that tested against bacterial pathogens were included in this study. Publications that screened South African plants for fungi, viruses, or protozoa were excluded.

  5. The use of introduced plant species were excluded from this study unless they are extensively used as part of southern African traditional medicine of at least one South African ethnic group.

2.4. Data Collection

A thorough literature search for publications on southern African medicinal plants used traditionally to treat UTIs was undertaken and is summarised in this study. Additionally, in vivo and in vitro biological screening of South African medicinal plants for bacterial pathogens that cause UTIs are summarised, regardless of the origin of the study. The following data was collected for each species:

  1. Species name, family name, and common name for each species recorded in the individual publications were collected

  2. Common names and the names used by different ethnic groups (where appropriate) were collected from individual publications and from the SANBI red list website

  3. The plant part used, method of preparation, and mode of administration were recorded where that information was provided

Microsoft Excel was used for statistical data analysis.

3. Results

3.1. Plants Used Traditionally to Treat Urinary Tract Infections

Numerous South African plant species have been recorded to treat pathogenic diseases. This knowledge has traditionally been passed down from generation to generation by word of mouth, and some of this knowledge has now been recorded in ethnobotanical publications, although it is likely that substantial information is not yet readily available. A total of 153 plants from fifty-two families were recorded in the literature for the treatment of UTIs (Table 1). Out of the fifty-two families, Compositae had the greatest representation, with nineteen species reported as treatments for UTIs (Figure 1). Leguminosae were also commonly used as UTI therapies, with fourteen plant species reported [42, 43]. Asparagaceae, Rutaceae, and Lamiaceae were also well represented, with eight, six, and six species used to treat UTIs, respectively. Five species each of Amaryllidaceae, Solanaceae, and Malvaceae, as well as four species of both Euphorbiaceae and Poaceae, and three species of Geraniaceae and Xanthorrhoeaceae were also used for this purpose. A further twenty-four plant families were represented by two or fewer individual species. Of these, Aptosimum procumbens (Lehm.) Burch. ex Steud, Arctopus echinatus L., Boophone disticha (L.f.) Herb., Bowiea volubilis Harv., Cardiospermum halicacabum L., Cissampelos capensis L.f., Galenia africana L., Helichrysum odoratissimum (L.) Sweet, and Zantedeschia albomaculata (Hook.) Baill have been cited by several sources that also experimentally validated their use for the treatment of UTIs [47, 62, 64]. Approximately 47% of the plant species identified in our study were cited by multiple sources as traditional UTI therapies, indicating that screening and validation of those species should be prioritised.

Figure 1.

Figure 1

The number of species per plant family used to treat urinary tract infections. “2 or less” indicates families where there were ≤ two plant species represented.

The main plant parts used to prepare therapies to treat UTIs are leaves (27%), followed by roots, bulbs, and rhizomes (22%) (Figure 2). For 48 plant species (31%), the specific plant part used was not specified in the cited literature. For Solanum capense L. and Pelargonium ramosissimum Willd., both leaves and stems were used to treat UTIs, so both parts are recorded in Table 1 for that purpose [43, 58]. Fruits were found to be the least used parts as they are only available for short periods seasonally and may not be always readily available.

Figure 2.

Figure 2

Frequency of use of different plant parts used to treat urinary tract infections in southern African traditional medicine.

3.2. Dosage and Toxicity

Long term use of medicinal plants to treat diseases has resulted in the assumption that medicinal plants are nontoxic and safe for therapeutic use [39]. Of the plants specified for traditional use for UTIs (Table 1), none had their therapeutic dosage ranges recorded. It is noteworthy that several of these species have been reported to contain cardiac glycoside toxins (for example, Bowiea volubilis and Acokanthera oppositifolia) [70, 85, 86] and cucurbitacin (widely distributed in the Cucurbitaceae, Rubiaceae, Euphorbiaceae, and Cruciferae families), which have several adverse effects and toxicities [87]. Thus, further studies into the pharmacological and safety profiles of the majority of the plants listed in Table 1 are required to determine their safety for the treatment of UTIs. Indeed, a common trend noted was that information on dosage and toxicity is lacking, not only for the treatment of UTIs, but in the records listing South African plant use against many other diseases.

3.3. Scientific Studies on the Effects of Southern African Plants against Urinary Tract Infections

In a review of South African plants that have been studied for their antimicrobial properties, it was concluded that, before 2017, there had been no specific uropathogenic studies focusing on the antimicrobial activities of southern African medicinal plants [35]; however, pathogens such as E. coli were included in other screening studies. For example, E. coli is also associated with gastrointestinal diseases, and some strains of this pathogen cause diarrhoea [88]. It is therefore not surprising that studies screening South African plants against E. coli more frequently focus on its involvement in those diseases [73, 77, 82]. Escherichia coli is also a widely studied bacterium and is often included in studies performing screening against generic bacterial panels. Whilst these studies do not focus on the involvement of E. coli in UTIs, they have still been reported in this study as they demonstrate inhibitory activity against this bacterium, regardless of infection site. Similarly, P. mirabilis and K. pneumoniae are also associated with other diseases, including the autoimmune diseases, rheumatoid arthritis, and ankylosing spondylitis, respectively [40, 41]. Furthermore, Pseudomonas aeruginosa not only causes UTIs, but also has been associated with several other diseases [89]. Studies that screened southern African plant extracts for these bacteria were also included, regardless of the disease state that was the focus of the study.

A total of 85 plants used in southern African traditional medicine to treat UTIs have been tested for inhibitory activity against at least one UTI-causing bacterium. Not surprisingly, the inhibitory properties of southern African traditional medicine plants against E. coli were particularly well studied. Indeed, 82 species (96% of the total plant species screened) have previously been reported to inhibit E. coli growth at a noteworthy concentration. Notably, the majority of the plant species that have been screened against E. coli have also been screened against one or more other UTI-causing bacteria. Screening of southern African plants against P. aeruginosa has also received substantial attention, with 36 southern African plants reported to have noteworthy activity against this species. This is important as P. aeruginosa is resistant to many conventional antibiotics. Therefore, plant species with activity against this bacterium may be particularly promising, not only against UTIs, but also against other diseases in which P. aeruginosa causes pathogenesis, including multiple sclerosis [89] and cystic fibrosis [84]. Particularly, good P. aeruginosa inhibitory activity was reported for two Terminalia spp. (T. phanerophlebia and T. sambesiaca), with MICs of 80 and 60 μg/mL, respectively [79]. Proteus spp. and K. pneumoniae were each screened against 14 southern African plant species. Nearly all of the plants screened against those bacteria were tested in two separate studies that used the same panels of plant species [40, 41]. Both of those studies screened a larger panel of South African medicinal plants than listed here, and only those plant species with appreciable activity are reported herein. Notably, we were only able to find reports of S. saprophyticus inhibitory activity for two closely related South African plants of the genus Alchornea (A. cordifolia and A. laxiflora) [74]. As this bacterium is responsible for approximately 6% of uncomplicated UTIs, screening of South African plants for this bacterium is a priority for future studies.

Notably, 46 of the bacterial screening studies reported herein did not test toxicity within the same study, and it is therefore not possible to determine therapeutic indexes. Therefore, whilst the plant species examined in those studies may have noteworthy antibacterial activity, it is not possible to comment on their safety and therefore their potential as therapies to treat UTIs. Of the plants that were screened for toxicity alongside antibacterial activity, LC50 values that indicate a lack of toxicity were reported for 28 plant species. Of concern, 11 plant species (A. laxiflora, Bolusanthus speciosus, Calpurnia aurea, Cremaspora triflora, E. croceum, Heteromorpha arborescens, Hypericum roeperianum, Maesa lanceolata, Morus mesozygia, Pittosporum viridiflorum, and Tulbaghia violacea) were reported to have appreciable toxicity, and therefore caution is recommended for their use. Of particular concern, LC50 values of 2–14 μg/mL were reported for C. triflora, E. croceum, and M. lanceolata. Given the MIC values of these plant species against E. coli, the therapeutic indexes (as low as 0.008) can be calculated, indicating that these extracts are extremely unsafe for therapeutic use as the extracts are toxic at ∼1% of the concentration required to achieve the therapeutic effect. However, it is noteworthy that all of these low LC50 values in Vero cells were determined in a single study [77]. That study also reported low LC50 values (lower than 100 μg/mL) for every plant species that was tested in that study, and therefore the results may be an anomaly of that study. The toxicity of these plant species needs to be verified in future studies to evaluate their safety for therapeutic use.

4. Discussion and Conclusion

Urinary tract infections are one of the most widespread classes of infectious diseases globally, yet the development of new therapies to treat these infections remains relatively neglected. Whilst UTIs cause discomfort, they rarely cause mortality or serious morbidity except in immune-compromised individuals. It is likely that the relative lack of severity of these infections may contribute to the low number of studies into the effects of southern African plants specifically targeted at bacteria that cause these infections. Indeed, most of these studies have occurred in the most recent 15-year period. Interestingly, the increase in research in this field coincides with increases in the incidence of antibiotic resistance. Several studies have already screened some South African plants for the ability to inhibit UTI-causing bacteria. Indeed, Table 2 summarises studies screening 85 plant species against UTI-causative bacteria.

Surprisingly, despite 153 plant species identified with documented uses to treat UTIs, only 85 species have been reported to have noteworthy inhibitory activity against the main UTI-causative bacteria species. Furthermore, most of the tested plants were not selected for screening based on their traditional use to treat UTIs. Instead, in many cases, the plant species were screened against the bacteria based on their involvement in other diseases. Escherichia coli is a common gastrointestinal bacterium, and several studies screened plant extracts against this bacterium to examine its potential to treat diarrhoea. The studies described in this review focussed on the main bacterial species that can cause UTIs (E. coli, K. pneumoniae, P. aeruginosa, P. mirabilis, and S. saprophyticus). Combined, these bacteria account for >90% of the cases of uncomplicated UTIs, highlighting their importance to those studies [11]. However, for these pathogens, we were only able to locate a single study that tested South African plants against S. saprophyticus [74], and future studies screening plants against this bacterium are required. Furthermore, other bacterial species are also responsible for a significant proportion of UTIs. In particular, unspecified Enterococcus spp. account for approximately 6% and 11% of uncomplicated and complicated UTIs, respectively [11], and therefore future studies screening South African plants against these pathogens are warranted. Furthermore, our review focussed on the bacterial causes of UTIs as they account for nearly all reported cases. However, C. albicans, as well as some viruses and protozoa, may also cause UTIs and should not be neglected in future studies. Further studies are required to screen those species against the other major causes of UTIs. Additionally, all the previous studies have screened plant species against UTI-causative bacteria that are susceptible to conventional antibiotic therapies. To date, screening plants against antibiotic-resistant bacterial strains has been largely neglected. As there have been substantial increases in the prevalence of antibiotic-resistant bacterial pathogens in recent years, it is important that the plants identified herein are also screened against resistant bacterial strains to further evaluate the potential in clinical environments. Furthermore, when examining antimicrobial efficacy, it must be noted that UTIs are very often biofilm-borne, and this aspect has been neglected in the screening. Only one study [78] focussed on 14 plant species utilising bacterial communication systems via antiquorum sensing signalling and in biofilm studies. Clearly, this area remains untapped, and there is a possibility for plant species to not only act on planktonic bacterial cells, but also inhibit or prevent biofilm formation.

It appears that plant species selection for several studies was based more on plant availability rather than ethnobotanical use. Another aspect of the previous studies is that the plant part tested does not always correlate with the part traditionally used. It is likely that availability may also have been a significant factor in selection of plant part in those studies. However, the chemistry may differ substantially between different plant parts, and they may therefore induce completely different biological activities. Where possible, screening and evaluation studies should test the plant part used traditionally, as well as an approximation of how it was processed for use. These factors may have significant impacts on the toxicity of the preparation. Future studies testing an approximation of the traditional plant preparations are therefore required to validate the traditional use of these plants to treat UTIs.

To be useful in the treatment of UTIs, an extract (or purified compound derived from an extract) must have relatively low toxicity. This is particularly true for the treatment of recurrent infections. Surprisingly, many of the plant species screened for inhibitory activity against UTI-causative bacteria were not tested for toxicity in the same studies. This may be because many of these plants have been used in traditional healing systems for hundreds of years without reported toxicity and are therefore assumed to be safe. However, some plant species are prepared by different methods to test bioactivity from the preparation method used by traditional medicine practitioners. Different preparation methods may dramatically alter the phytochemical composition of different preparations and therefore may also affect their toxicity profiles. Indeed, several studies reported toxic, carcinogenic, and mutagenic effects for extracts prepared from plants traditionally used as medicines [33]. Several of the studies highlighted in this review have also investigated the toxicity of southern African plant species traditionally used to treat UTIs [40, 41, 71, 73, 77, 80]. Whilst most of those studies reported that the plant extracts were nontoxic, one study reported very low LC50 values against Vero cells for several plant species, indicating that those species may not be safe to use medicinally. However, the results of that study may be erroneous as all the plant species tested had low LC50, and verification of these results is required. Of further note, several different toxicity assays (human cell lines, Vero monkey kidney cells, Artemia nauplii assays) were used to screen the plant species in different studies, making comparisons difficult between studies. Ideally, toxicity studies should incorporate more than one toxicity assay to allow for better comparisons between studies.

Ethnobotanical records have already identified several promising plant species used in traditional South African medicinal systems to treat UTIs, and several of those species (as well as multiple species for which a traditional use against UTIs was not recorded) have already been tested against one or more UTI-causative bacteria. Further research is required to screen all identified species against each of the UTI-causative bacteria (rather than just one or two of them) and against antibiotic-resistant bacterial strains that are becoming increasingly common. Additionally, all previous studies have tested the plant extracts in vitro. As considerably different effects may be seen in vivo due to bioavailability differences, studies in animal models are also required.

Overall, there is evidence that southern African medicinal plants have potential to treat UTIs and, with further in-depth analysis, could be the new alternative to cranberry juice which is internationally recognised as a safe natural alternative for treating infections of the urinary tract.

Acknowledgments

The authors are thankful for the financial support provided by the Department of Pharmacy and Pharmacology, University of the Witwatersrand, South Africa, and by the Environmental Futures Research Institute, Griffith University, Australia.

Data Availability

All data are included within this study and are also available from the corresponding author on request.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  • 1.Medina M., Castillo-Pino E. An introduction to the epidemiology and burden of urinary tract infections. Therapeutic Advances in Urology. 2019;11 doi: 10.1177/1756287219832172.1756287219832172 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Flores-Mireles A. L., Walker J. N., Caparon M., Hultgren S. J. Urinary tract infections: epidemiology, mechanisms of infection and treatment options. Nature Reviews Microbiology. 2015;13(5):269–284. doi: 10.1038/nrmicro3432. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Storme O., Tirán Saucedo J., Garcia-Mora A., Dehesa-Dávila M., Naber K. G. Risk factors and predisposing conditions for urinary tract infection. Therapeutic Advances in Urology. 2019;11 doi: 10.1177/1756287218814382.1756287218814382 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Chu C. M., Lowder J. L. Diagnosis and treatment of urinary tract infections across age groups. American Journal of Obstetrics and Gynecology. 2018;219:40–51. doi: 10.1016/j.ajog.2017.12.231. [DOI] [PubMed] [Google Scholar]
  • 5.Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. American Journal of Medicine. 2002;113:5S–11S. doi: 10.1016/s0002-9343(02)01054-9. [DOI] [PubMed] [Google Scholar]
  • 6.Cek M., Tandoğdu Z., Wagenlehner F., Tenke P., Naber K., Bjerklund-Johansen T. E. Healthcare-associated urinary tract infections in hospitalized urological patients-a global perspective: results from the GPIU studies 2003–2010. World Journal of Urology. 2014;32(6):1587–1594. doi: 10.1007/s00345-013-1218-9. [DOI] [PubMed] [Google Scholar]
  • 7.Choe H. S., Lee S. J., Cho Y. H., et al. Aspects of urinary tract infections and antimicrobial resistance in hospitalized urology patients in Asia: 10-year results of the Global Prevalence Study of Infections in Urology (GPIU) Journal of Infection and Chemotherapy: Official Journal of the Japan Society of Chemotherapy. 2018;24:278–283. doi: 10.1016/j.jiac.2017.11.013. [DOI] [PubMed] [Google Scholar]
  • 8.Ebana R., Edet U., Ekanemesang U., Etok C., Ikon G., Noble M. Phytochemical screening and antimicrobial activity of three medicinal plants against urinary tract infection pathogens. Asian Journal of Medicine and Health. 2016;1(2):1–7. doi: 10.9734/ajmah/2016/29460. [DOI] [Google Scholar]
  • 9.Johansen T. E. B., Botto H., Cek M., et al. Critical review of current definitions of urinary tract infections and proposal of an EAU/ESIU classification system. International Journal of Antimicrobial Agents. 2011;38:64–70. doi: 10.1016/j.ijantimicag.2011.09.009. [DOI] [PubMed] [Google Scholar]
  • 10.Tan C. W., Chlebicki M. P. Urinary tract infections in adults. Singapore Medical Journal. 2016;57(9):485–490. doi: 10.11622/smedj.2016153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 11.Cock I. E., Van Vuuren S. F. A review of the traditional use of southern African medicinal plants for the treatment of fungal skin infections. Journal of Ethnopharmacology. 2020;251 doi: 10.1016/j.jep.2019.112539.112539 [DOI] [PubMed] [Google Scholar]
  • 12.Zida A., Bamba S., Yacouba A., Ouedraogo-Traore R., Guiguemdé R. T. Anti- Candida albicans natural products, sources of new antifungal drugs: a review. Journal de Mycologie Médicale. 2017;27(1):1–19. doi: 10.1016/j.mycmed.2016.10.002. [DOI] [PubMed] [Google Scholar]
  • 13.Vikrant P., Priya J., Nirichan K. B. Plants with anti-Candida activity and their mechanism of action: a review. Journal of Environmental Research and Development. 2015;9(4):p. 1189. [Google Scholar]
  • 14.Salvatore S., Salvatore S., Cattoni E., et al. Urinary tract infections in women. European Journal of Obstetrics & Gynecology and Reproductive Biology. 2011;156(2):131–136. doi: 10.1016/j.ejogrb.2011.01.028. [DOI] [PubMed] [Google Scholar]
  • 15.Cheesman M. J., Ilanko A., Blonk B., Cock I. E. Developing new antimicrobial therapies: are synergistic combinations of plant extracts/compounds with conventional antibiotics the solution? Pharmacognosy Reviews. 2017;11(22):57–72. doi: 10.4103/phrev.phrev_21_17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 16.Foxman B., Gillespie B., Koopman J., et al. Risk factors for second urinary tract infection among college women. American Journal of Epidemiology. 2000;151(12):1194–1205. doi: 10.1093/oxfordjournals.aje.a010170. [DOI] [PubMed] [Google Scholar]
  • 17.Brumbaugh A. R., Mobley H. L. Preventing urinary tract infection: progress toward an effective Escherichia colivaccine. Expert Review of Vaccines. 2012;11(6):663–676. doi: 10.1586/erv.12.36. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Foxman B., Buxton M. Alternative approaches to conventional treatment of acute uncomplicated urinary tract infection in women. Current Infectious Disease Reports. 2013;15(2):124–129. doi: 10.1007/s11908-013-0317-5. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19.Meier S., Weber R., Zbinden R., Ruef C., Hasse B. Extended-spectrum β-lactamase-producing Gram-negative pathogens in community-acquired urinary tract infections: an increasing challenge for antimicrobial therapy. Infection. 2011;39(4):333–340. doi: 10.1007/s15010-011-0132-6. [DOI] [PubMed] [Google Scholar]
  • 20.Fennell J., Vellinga A., Hanahoe B., et al. Increasing prevalence of ESBL production among Irish clinical Enterobacteriaceae from 2004 to 2008: an observational study. BMC Infectious Diseases. 2012;12(116) doi: 10.1186/1471-2334-12-116. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 21.Dethlefsen L., Huse S., Sogin M. L., Relman D. A. The pervasive effects of an antibiotic on the human gut microbiota, as revealed by deep 16S rRNA sequencing. PLoS Biology. 2008;6 doi: 10.1371/journal.pbio.0060280.e280 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 22.Trautner B. W., Gupta K K. The advantages of second best: comment on “Lactobacilli vs antibiotics to prevent urinary tract infections”. Archives of Internal Medicine. 2012;172:712–714. doi: 10.1001/archinternmed.2012.1213. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23.Baerheim A. Empirical treatment of uncomplicated cystitis. Scandinavian Journal of Primary Health Care. 2012;30(1):1–2. doi: 10.3109/02813432.2012.649629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.World Health Organization. WHO Traditional Medicine Strategy: 2014–2023. Geneva, Switzerland: World Health Organization; 2013. https://www.who.int/medicines/publications/traditional/trm_strategy14_23/en/ [Google Scholar]
  • 25.Street R. A., Prinsloo G. Commercially important medicinal plants of South Africa: a review. Journal of Chemistry. 2013;2013:16. doi: 10.1155/2013/205048.205048 [DOI] [Google Scholar]
  • 26.Dold A. P., Cocks M. L. The trade in medicinal plants in the Eastern Cape province, South Africa. South African Journal of Science. 2002;98:589–597. [Google Scholar]
  • 27.Mander M., Breton G. Overview of the medicinal plants industry in Southern Africa. In: Diederichs N., editor. Commercialising Medicinal Plants—A Southern African Guide. Stellenbosch, South Africa: Sun Press; 2006. [Google Scholar]
  • 28.Mander M., McKenzie M. Southern African Trade Directory of Indigenous Natural Products. Stellenbosch, South Africa: Commercial Products from the Wild Group; 2005. [Google Scholar]
  • 29.Rates S. M. K. Plants as source of drugs. Toxicon. 2001;39(5):603–613. doi: 10.1016/s0041-0101(00)00154-9. [DOI] [PubMed] [Google Scholar]
  • 30.Sheriffs P. Truths and tradition. Femina. 1996;113:62–65. [Google Scholar]
  • 31.De Jong J. Traditional Medicine in Sub-saharan Africa: Its Importance and Potential Policy Options. Washington, DC, USA: Report for World Bank; 1991. [Google Scholar]
  • 32.Boukandou Mounanga M., Mewono L., Aboughe Angone S. Toxicity studies of medicinal plants used in sub-Saharan Africa. Journal of Ethnopharmacology. 2015;174:618–627. doi: 10.1016/j.jep.2015.06.005. [DOI] [PubMed] [Google Scholar]
  • 33.Fennell C. W., Lindsey K. L., McGaw L. J., et al. Assessing African medicinal plants for efficacy and safety: pharmacological screening and toxicology. Journal of Ethnopharmacology. 2004;94(2-3):205–217. doi: 10.1016/j.jep.2004.05.012. [DOI] [PubMed] [Google Scholar]
  • 34.Bodeker G. Medicinal; plant biodiversity and local healthcare–sustainable use and livelihood development. Proceedings of the 17th Commonwealth Forestry Conference; March 2005; Colombo, Sri Lanka. Forestry Commission; [Google Scholar]
  • 35.Van Vuuren S., Holl D. Antimicrobial natural product research: a review from a South African perspective for the years 2009-2016. Journal of Ethnopharmacology. 2017;208:236–252. doi: 10.1016/j.jep.2017.07.011. [DOI] [PubMed] [Google Scholar]
  • 36.van Vuuren S. F., Nkwanyana M. N., de Wet H. Antimicrobial evaluation of plants used for the treatment of diarrhoea in a rural community in northern Maputaland, KwaZulu-Natal, South Africa. BMC Complementary and Alternative Medicine. 2015;15(1):1–8. doi: 10.1186/s12906-015-0570-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37.de Wet H., Nkwanyana M. N., van Vuuren S. F. Medicinal plants used for the treatment of diarrhoea in Northern Maputaland, KwaZulu-Natal Province, South Africa. Journal of Ethnopharmacology. 2010;130(2):284–289. doi: 10.1016/j.jep.2010.05.004. [DOI] [PubMed] [Google Scholar]
  • 38.Orchard A., van Vuuren S. Commercial essential oils as potential antimicrobials to treat skin diseases. Evidence-based Complementary and Alternative Medicine. 2017;2017:92. doi: 10.1155/2017/4517971.4517971 [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Mabona U., Van Vuuren S. F. Southern African medicinal plants used to treat skin diseases. South African Journal of Botany. 2013;87:175–193. doi: 10.1016/j.sajb.2013.04.002. [DOI] [Google Scholar]
  • 40.Cock I. E., Van Vuuren S. F. Anti-proteus activity of some South African medicinal plants: their potential for the prevention of rheumatoid arthritis. Inflammopharmacology. 2014;22(1):23–36. doi: 10.1007/s10787-013-0179-3. [DOI] [PubMed] [Google Scholar]
  • 41.Cock I. E., Van Vuuren S. F. The potential of selected South African plants with anti-Klebsiella activity for the treatment and prevention of ankylosing spondylitis. Inflammopharmacology. 2015;23(1):21–35. doi: 10.1007/s10787-014-0222-z. [DOI] [PubMed] [Google Scholar]
  • 42.Watt J. M., Breyer-Brandwijk M. G. The Medicinal and Poisonous Plants of Southern and Eastern Africa Being an Account of Their Medicinal and Other Uses, Chemical Composition, Pharmacological Effects and Toxicology in Man and Animal. Edinburgh, UK: Livingstone Publishing; 1962. [Google Scholar]
  • 43.Hutchings A., Scott A. H., Lewis G., Cunningham A. B. Zulu Medicinal Plants: An Inventory. Pietermaritzburg, South Africa: University of Natal Press; 1996. [Google Scholar]
  • 44.Van Wyk B. E., van Oudtshoorn B., Gericke N. Medicinal Plants of South Africa. 2nd. Pretoria, South Africa: Briza Publications; 2009. [Google Scholar]
  • 45.Van Wyk B.-E., Gorelik B. The history and ethnobotany of Cape herbal teas. South African Journal of Botany. 2017;110:18–38. doi: 10.1016/j.sajb.2016.11.011. [DOI] [Google Scholar]
  • 46.Koenen E. Von. Medicinal, Poisonous, and Edible Plants in Namibia. Windhoek, Namibia: Klaus Hess Publishers; 2001. [Google Scholar]
  • 47.Mhlongo L. S., Van Wyk B.-E. Zulu medicinal ethnobotany: new records from the Amandawe area of KwaZulu-Natal, South Africa. South African Journal of Botany. 2019;122:266–290. doi: 10.1016/j.sajb.2019.02.012. [DOI] [Google Scholar]
  • 48.Aston Philander L. An ethnobotany of Western Cape Rasta bush medicine. Journal of Ethnopharmacology. 2011;138(2):578–594. doi: 10.1016/j.jep.2011.10.004. [DOI] [PubMed] [Google Scholar]
  • 49.Thring T. S. A., Weitz F. M. Medicinal plant use in the bredasdorp/elim region of the southern overberg in the Western Cape province of South Africa. Journal of Ethnopharmacology. 2006;103(2):261–275. doi: 10.1016/j.jep.2005.08.013. [DOI] [PubMed] [Google Scholar]
  • 50.Hulley I. M., Van Wyk B. –E. Quantitative medicinal ethnobotany of Kannaland (Western Little Karoo, South Africa): non-homogeneity amongst villages. South African Journal of Botany. 2017;122:225–265. [Google Scholar]
  • 51.De Beer J. J. J., Van Wyk B.-E. An ethnobotanical survey of the Agter-Hantam, Northern Cape province, South Africa. South African Journal of Botany. 2011;77(3):741–754. doi: 10.1016/j.sajb.2011.03.013. [DOI] [Google Scholar]
  • 52.De Wet H., Van Wyk B.-E. An ethnobotanical survey of southern African Menispermaceae. South African Journal of Botany. 2008;74(1):2–9. doi: 10.1016/j.sajb.2007.07.001. [DOI] [Google Scholar]
  • 53.Kling H. Die Sieketrooster. Cape Town, South Africa: Van de Sandt de Villiers; 1923. [Google Scholar]
  • 54.Maliehe E. B. Medicinal Plants and Herbs of Lesotho. Maseru, Lesotho: Mafeteng Development Project; 1997. [Google Scholar]
  • 55.Mulaudzi R. B., Ndhlala A. R., Van Staden J. Ethnopharmacological evaluation of a traditional herbal remedy used to treat gonorrhoea in Limpopo province, South Africa. South African Journal of Botany. 2015;97:117–122. doi: 10.1016/j.sajb.2014.12.007. [DOI] [Google Scholar]
  • 56.Nortje J. M., Van Wyk B.-E. Medicinal plants of the Kamiesberg, Namaqualand, South Africa. Journal of Ethnopharmacology. 2015;171:205–222. doi: 10.1016/j.jep.2015.04.049. [DOI] [PubMed] [Google Scholar]
  • 57.Van Wyk B.-E., de Wet H., Van Heerden F. R. An ethnobotanical survey of medicinal plants in the southeastern Karoo, South Africa. South African Journal of Botany. 2008;74(4):696–704. doi: 10.1016/j.sajb.2008.05.001. [DOI] [Google Scholar]
  • 58.Bryant A. T. Zulu medicine and medicine-men. Southern African Humanities. 1909;2(1):1–3. doi: 10.1097/00007611-190910000-00022. [DOI] [Google Scholar]
  • 59.Gebashe F., Moyo M., Aremu A. O., Finnie J. F., Van Staden J. Ethnobotanical survey and antibacterial screening of medicinal grasses in KwaZulu-Natal Province, South Africa. South African Journal of Botany. 2019;122:467–474. doi: 10.1016/j.sajb.2018.07.027. [DOI] [Google Scholar]
  • 60.Gebashe F., Aremu A. O., Finnie J. F., Van Staden J. Grasses in South African traditional medicine: a review of their biological activities and phytochemical content. South African Journal of Botany. 2019;122:301–329. doi: 10.1016/j.sajb.2018.10.012. [DOI] [Google Scholar]
  • 61.Ngwenya M. A., Koopman A., Williams R. Ulwazi lwamaZulu Ngezimila: Isingeniso (Zulu Botanical Knowledge: An Introduction. Durban, South Africa: National Botanical Institute (NBI); 2003. [Google Scholar]
  • 62.Moteetee A., Van Wyk B. E. The medical ethnobotany of Lesotho: a review. Bothalia. 2011;41(1):209–228. doi: 10.4102/abc.v41i1.52. [DOI] [Google Scholar]
  • 63.Moteetee A., Moffett R. O., Seleteng-Kose L. A review of the ethnobotany of the basotho of Lesotho and the free state province of South Africa (South Sotho) South African Journal of Botany. 2019;122:21–56. doi: 10.1016/j.sajb.2017.12.012. [DOI] [Google Scholar]
  • 64.Moffett R. Sesotho Plant and Animal Names and Plants Used by the Basotho. 1st. Bloemfontein, South Africa: Sunpress; 2010. [Google Scholar]
  • 65.Pooley E. Trees of Natal, Zululand and the Transkei. Durban, South Africa: Natal Flora Publications Trust; 1993. [Google Scholar]
  • 66.Mogale M. M. P., Raimondo D. C., VanWyk B.-E. The ethnobotany of central Sekhukhuneland, South Africa. South African Journal of Botany. 2019;122:90–119. doi: 10.1016/j.sajb.2019.01.001. [DOI] [Google Scholar]
  • 67.Gerstner J. A preliminary checklist of Zulu names of plants with short note. Bantu Studies. 1939;13(2):131–150. doi: 10.1080/02561751.1939.9676095. [DOI] [Google Scholar]
  • 68.Scott G., Springfield E. P., Coldrey N. A pharmacognostical study of 26 South African plant species used as traditional medicines. Pharmaceutical Biology. 2004;42(3):186–213. doi: 10.1080/13880200490514032. [DOI] [Google Scholar]
  • 69.Ferreira F. H. The Trees and Shrubs of South Africa 2. Pretoria, South Africa: Ferreira (Roneod); 1952. [Google Scholar]
  • 70.Finnie J. F., Drewes F. E., Van Staden J. Medicinal and Aromatic Plants VII. Berlin, Germany: Springer; 1994. Bowiea volubilis Harv. ex hook.f. (sea onion): in vitro culture and the production of cardiac glycosides; pp. 84–97. [DOI] [Google Scholar]
  • 71.Cock I. E., Van Vuuren S. F. South African food and medicinal plant extracts as potential antimicrobial food agents. Journal of Food Science and Technology. 2015;52(11):6879–6899. doi: 10.1007/s13197-015-1806-3. [DOI] [Google Scholar]
  • 72.Eldeen I. M. S., Elgorashi E. E., Van Staden J. Antibacterial, anti-inflammatory, anti-cholinesterase and mutagenic effects of extracts obtained from some trees used in South African traditional medicine. Journal of Ethnopharmacology. 2005;102(3):457–464. doi: 10.1016/j.jep.2005.08.049. [DOI] [PubMed] [Google Scholar]
  • 73.Hübsch Z., Van Zyl R. L., Cock I. E., Van Vuuren S. F. Interactive antimicrobial and toxicity profiles of conventional antimicrobials with Southern African medicinal plants. South African Journal of Botany. 2014;93:185–197. doi: 10.1016/j.sajb.2014.04.005. [DOI] [Google Scholar]
  • 74.Siwe-Noundou X., Ndinteh D. T., Olivier D. K., et al. Biological activity of plant extracts and isolated compounds from Alchornea laxiflora: anti-HIV, antibacterial and cytotoxicity evaluation. South African Journal of Botany. 2019;122:498–503. [Google Scholar]
  • 75.Luseba D., Elgorashi E. E., Ntloedibe D. T., Van Staden J. Antibacterial, anti-inflammatory and mutagenic effects of some medicinal plants used in South Africa for the treatment of wounds and retained placenta in livestock. South African Journal of Botany. 2007;73(3):378–383. [Google Scholar]
  • 76.Adamu M., Naidoo V., Eloff J. N. The antibacterial activity, antioxidant activity and selectivity index of leaf extracts of thirteen South African tree species used in ethnoveterinary medicine to treat helminth infections. BMC Veterinary Research. 2014;10(1):52–57. doi: 10.1186/1746-6148-10-52. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 77.Elisha I. L., Botha F. S., McGaw L. J., Eloff J. N. The antibacterial activity of extracts of nine plant species with good activity against Escherichia coli against five other bacteria and cytotoxicity of extracts. BMC Complementary and Alternative Medicine. 2017;17(1):133–210. doi: 10.1186/s12906-017-1645-z. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 78.Baloyi I. T., Cosa S., Combrinck S., Leonard C. M., Viljoen A. M. Anti-quorum sensing and antimicrobial activities of South African medicinal plants against uropathogens. South African Journal of Botany. 2019;122:484–491. doi: 10.1016/j.sajb.2019.01.010. [DOI] [Google Scholar]
  • 79.Shai L. J., McGaw L. J., Masoko P., Eloff J. N. Antifungal and antibacterial activity of seven traditionally used South African plant species active against Candida albicans. South African Journal of Botany. 2008;74(4):677–684. doi: 10.1016/j.sajb.2008.04.003. [DOI] [Google Scholar]
  • 80.Oyedeji-Amusa M. O., Van Vuuren S., Van Wyk B. E. Antimicrobial activity and toxicity of extracts from the bark and leaves of South African indigenous Meliaceae against selected pathogens. South African Journal of Botany. 2020;133:83–90. doi: 10.1016/j.sajb.2020.06.032. [DOI] [Google Scholar]
  • 81.Nkala B. A., Mbongwa H. P., Qwebani-Ogunleye T. The in vitro evaluation of some South African plant extracts for minimum inhibition concentration and minimum bactericidal concentration against selected bacterial strains. International Journal of Scientific and Research Publications. 2019;9(7):996–1004. doi: 10.29322/ijsrp.9.07.2019.p91132. [DOI] [Google Scholar]
  • 82.Mathabe M. C., Nikolova R. V., Lall N., Nyazema N. Z. Antibacterial activities of medicinal plants used for the treatment of diarrhoea in Limpopo province, South Africa. Journal of Ethnopharmacology. 2006;105(1-2):286–293. doi: 10.1016/j.jep.2006.01.029. [DOI] [PubMed] [Google Scholar]
  • 83.Kebede B., Shibeshi W. Evaluation of in-vitro antibacterial and antifungal activities of crude extracts and solvent fractions of methanol extract of leaves of Ricinus communis Linn (Euphorbiaceae) against selected pathogens. Research Square. 2020 doi: 10.21203/rs.3.rs-63537/v2. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 84.Malhotra S., Hayes D., Wozniak D. J. Cystic fibrosis and Pseudomonas aeruginosa: the host-microbe interface. Clinical Microbiology Reviews. 2019;32(3) doi: 10.1128/cmr.00138-18. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 85.Aremu A. O., Moyo M., Amoo S. O., Van Staden J. Ethnobotany, therapeutic value, phytochemistry and conservation status of Bowiea volubilis: a widely used bulbous plant in Southern Africa. Journal of Ethnopharmacology. 2015;174:308–316. doi: 10.1016/j.jep.2015.08.009. [DOI] [PubMed] [Google Scholar]
  • 86.Chaurasia S., Sharma P. Evaluation of antibacterial and antimutagenic potential of Acokanthera oppositifolia and Leucaena leucocephala. American Journal of Pharmacy and Health Research. 2015;3(1):246–258. [Google Scholar]
  • 87.Ponsankar A., Sahayaraj K., Senthil-Nathan S., et al. Toxicity and developmental effect of cucurbitacin E from Citrullus colocynthis L. (Cucurbitales: Cucurbitaceae) against Spodoptera litura Fab. and a non-target earthworm Eisenia fetida Savigny. Environmental Science and Pollution Research. 2020;27(19):23390–23401. doi: 10.1007/s11356-019-04438-1. [DOI] [PubMed] [Google Scholar]
  • 88.Khalil I. A., Troeger C., Blacker B. F., et al. Morbidity and mortality due to shigella and enterotoxigenic Escherichia coli diarrhoea: the global burden of disease study 1990–2016. The Lancet Infectious Diseases. 2018;18(11):1229–1240. doi: 10.1016/s1473-3099(18)30475-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 89.Cock I. E., Cheesman M. Bioactive Food as Dietary Interventions for Arthritis and Related Inflammatory Diseases. Amsterdam, Netherlands: Elsevier; 2019. The potential of plants of the genus Syzygium (Myrtaceae) for the prevention and treatment of arthritic and autoimmune diseases; pp. 401–424. [DOI] [Google Scholar]
  • 90.Mzamane G. I. M. Some medicinal, magical and edible plants used among some Bantu Tribes in South Africa. Fort Hare Papers. 1945;1:29–35. [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

All data are included within this study and are also available from the corresponding author on request.


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