A Comprehensive Review of Ethnomedicinal Uses, Phytochemistry, Pharmacology, and Toxicity of Prunus africana (Hook. F.) Kalkman from Africa

Prunus africana, a widely utilized medicinal plant in various African ethnic communities, continues to hold significant importance in traditional healing practices. Research has identified phytochemical compounds in this plant, exhibiting diverse pharmacological activities that offer potential for pharmaceutical development. Notably, P. africana is employed in treating various ailments such as wounds, diabetes mellitus, malaria, benign prostatic hyperplasia, chest pain, and prostate cancer. Its pharmacological properties are attributed to a spectrum of bioactive compounds, including tannins, saponins, alkaloids, flavonoids, terpenoids, phytosterols, and fatty acids. Multiple studies have documented the anti-inflammatory, antimicrobial, antiandrogenic, antiangiogenic, antioxidant, antidipeptidyl peptidase-4 activity, analgesic, and astringent properties of P. africana extracts. This review offers a comprehensive compilation of ethnomedicinal applications, phytochemical composition, pharmacological effects, and toxicity assessments of P. africana, serving as a foundation for future preclinical and clinical investigations. By understanding its traditional uses and chemical constituents, researchers can target specific medical conditions with greater precision, potentially expediting the development of safe and effective pharmaceuticals. Moreover, toxicity assessments provide crucial insights into the safety profile of P. africana extracts, ensuring the development of safe pharmaceuticals to treat various diseases.


Introduction
In many developing regions, especially in sub-Saharan Africa, traditional medicine practitioners are the primary healthcare providers, due to their long-standing, often hereditary, ethnomedicinal knowledge about indigenous plants and their utility in treating diseases [1,2].Te World Health Organization (WHO) notes that globally, many diferent plant species are utilized by various communities to treat various diseases [3].Te international focus on researching, recognizing, supporting, and promoting alternative and complementary medicine is expanding, due to an increasing need for efcacious and safe therapeutic alternatives for combating infections and diseases [4].However, herbal medicines trade practices often jeopardize the sustainability of natural resources, as they are overexploited with limited conservation [5,6].Te renewed enthusiasm for natural products as alternative medicines is attributed to concerns about conventional medicines, such as high costs, and adverse efects, limiting their clinical usefulness [7,8].In addition, the heavy global burden of disease coupled with the emergence of antimicrobial resistance further threatens public health and highlights the need for substitute medications, particularly those derived from natural sources [9][10][11].
Prunus africana (Hook.F.) Kalkman, commonly known as African cherry, African plum, African prune, or bitter almond, belongs to the Rosaceae family, subfamily Amygdaloideae syn.Prunoideae, and subgenus Laurocerasus [12,13].Te term "Prunus" denotes the plum-like shape of its fruit, and "africana" signifes its endemic existence in the Afromontane forests where locals utilize it for various medicinal and household purposes [13,14].Prunus africana is commonly used to treat benign prostatic hyperplasia (BPH) and has been reported to contain various secondary metabolites with anticancer, analgesic, anti-infammatory, antimicrobial, and antiviral activities [15,16].It is also utilized in traditional medicine to manage many ailments such as malaria, fevers, mental illness, and gastrointestinal disorders [14][15][16].
Performing an in-depth review of Prunus africana and highlighting its biological activities, toxicity, and phytochemical components is crucial as it provides an understanding of the therapeutic benefts and safety.Tis review consolidates and provides important insights into its ethnopharmacology, phytochemistry, and bioactivity to guide future research and drug development endeavours.

Methodology
2.1.Search Strategy.We conducted a thorough search for relevant information by exploring electronic literature databases, including PubMed, Web of Science, Scopus, Science Direct, US National Library of Medicine, Cochrane Library, and Google Scholar.Te specifc search terms included "P.africana," "African cherry," and "Pygeum africanum," combined with connector terms such as "phytochemicals," "traditional uses," "ethnomedicine," "biological activities," and "toxicity/safety."Additionally, searches were performed for specifc topics such as "phytochemicals in P. africana," "disease treatment," "safety and toxicity," "traditional medicine," and "medicine."Only articles in the English language were considered.Tis search initially yielded 467 articles.

Study Inclusion and Exclusion
Criteria.Tis review included studies that met the following criteria: (i) published in English in peer-reviewed and internationally refereed journals; (ii) in vitro and in vivo experiments examining P. africana extracts or compounds with appropriate controls (positive and negative); (iii) documentation of traditional/ethnomedicinal uses of P. africana; and (iv) scientifc reports of pharmacological/ biological activities of extracts/isolated compounds from P. africana.
Te exclusion criteria included the following: (i) studies whose primary focus was not P. africana; (ii) studies without data regarding traditional uses, phytochemistry, toxicity/ safety, and pharmacological/biological efects; (iii) non-English language publications; and (iv) studies that did not have appropriate control groups.We used a systematic screening process to identify eligible studies for inclusion in our review, adhering strictly to these outlined criteria.

Assessment of Study Quality and Risk of Bias.
Study quality and risk of bias assessments were independently conducted by two investigators, James Ndung'u and Gervason Moriasi, utilizing previously described criteria [17,18].Assessment parameters encompassed the completeness of outcome data, selective reporting, lack of appropriate control experiments, lack of randomization of study subjects, and other sources of bias.Discrepancies were resolved through consultation with the other two investigators, James Nguta and Isaac Mapenay.Data accuracy and appropriateness were ensured through verifcation and collaborative discussions among the authors.Following the verifcation process and removal of duplicate documents, 63 articles were deemed suitable for inclusion in this review (Figure 1).

Results and Discussion
3.1.Ethnomedicinal Uses.Prunus africana is distributed widely in Africa and is renowned for its medicinal properties across its various parts-leaves, roots, and stem bark [19] (Table 1).P. africana stem bark is a key component of treatment for gastrointestinal disorders, respiratory problems, benign prostatic hyperplasia (BPH), and chest pain in South Africa [14,36].Similarly, in East Africa, the plant's potential is harnessed for addressing acquired immunodefciency syndrome (AIDS)-related symptoms, along with managing diverse health concerns such as BPH, respiratory ailments, diabetes, hypertension, kidney diseases, malaria, and prostate cancer [21,23,28].
Previous research by Stewart [14] and Kipkore et al. [28] supports the extensive use of P. africana's roots, leaves, and fruits in East Africa to address various health issues.In West Africa, particularly Cameroon, the ethnomedicinal application of the plant's stem bark is notable in treating respiratory conditions, wound healing, mental health issues, malaria, prostate cancer, and chest pain [14,20,24].
Te ethnomedicinal fndings underscore the plant's remarkable versatility, spanning a spectrum of health conditions from gastrointestinal problems to prostate cancer, high blood pressure, digestive cleansing, skin infections, and beyond [14].Tese applications not only attest to its efcacy but also illuminate its seamless integration into traditional medical practices, rendering it an invaluable resource [26,28,29,37].In addition, this botanical versatility underscores the rich pharmacological reservoir that P. africana represents in traditional African medicine.Its multifaceted application in treating various ailments highlights the profound empirical knowledge embedded in indigenous healing practices [38].Moreover, the diversity of conditions it addresses underscores the potential for further exploration of its bioactive compounds and mechanisms of action, providing opportunities for novel drug development or complementary therapeutic approaches.
However, despite its widespread use and promising therapeutic indications, it is imperative to bridge the traditional and modern realms of medicine through rigorous scientifc investigation [35].Conducting comprehensive studies to elucidate the active constituents, pharmacological mechanisms, and safety profles of P. africana extracts or  Scientifca derivatives can facilitate its integration into mainstream healthcare practices.Additionally, eforts to promote sustainable harvesting and conservation practices are essential to safeguard the ecological balance and ensure the long-term availability of this valuable botanical resource.
Nonetheless, despite the signifcant progress made in understanding the phytochemical profle of P. africana, several gaps remain to be addressed in future studies.For instance, while individual compounds have been identifed, further research is needed to elucidate the synergistic interactions among these constituents and their collective pharmacological efects.Additionally, more comprehensive pharmacological studies, including in vitro and in vivo experiments, are warranted to validate the therapeutic potential attributed to P. africana and its individual constituents.Moreover, investigations into the mechanisms of action underlying the observed bioactivities are crucial for a deeper understanding of its therapeutic efects.Furthermore, given the increasing demand for natural products in pharmaceuticals, studies focusing on sustainable cultivation, extraction methods, and conservation strategies for P. africana are essential to ensure its long-term availability and viability as a medicinal resource.

Biological Activities.
Phytochemicals derived from P. africana exhibit a diverse array of biological activities, encompassing anticancer, anti-infammatory, antimicrobial, and antiviral properties, as summarized in Table 3. Ursolic acid, oleanolic acid, and β-amyrins, prominent terpenoids found in P. africana, have demonstrated notable anticancer efects through various mechanisms, including the induction of apoptosis and inhibition of tumor cell proliferation [39,41].Furthermore, these compounds possess potent antiinfammatory properties, making them promising candidates for the treatment of infammatory conditions [16,41,50].
Additionally, P. africana-derived phytochemicals such as tannins and terpenoids have exhibited antimicrobial and antiviral activities, suggesting their potential in combating infectious diseases [23,46,[53][54][55][56]. Te elucidation of these biological activities not only underscores the therapeutic potential of P. africana but also highlights the importance of further research to explore their mechanisms of action and clinical applications.Te reported biological activities of phytochemicals in P. africana ofer valuable opportunities for the discovery and development of novel therapeutic agents [65,66].By elucidating the mechanisms underlying their anticancer, anti-infammatory, antimicrobial, and antiviral efects, researchers can identify potential drug targets and develop pharmacological interventions with improved efcacy and safety profles [7,67].Furthermore, the identifcation of synergistic interactions among diferent phytochemical constituents of P. africana may pave the way for the development of combination therapies with enhanced therapeutic outcomes [68,69].Moreover, the exploration of structure-activity relationships of these phytochemicals could facilitate the design and synthesis of analogues with improved bioavailability and pharmacokinetic properties [70].Tus, leveraging the biological activities of phytochemicals in P. africana holds immense potential for the development of new therapeutic agents to address unmet medical needs.
Recognizing the therapeutic potential of P. africanaderived phytochemicals may prompt policymakers to support research initiatives aimed at exploring their pharmacological properties and clinical applications.Moreover, integrating evidence from preclinical and clinical studies into healthcare policies may facilitate the inclusion of P. africana-based interventions in clinical practice guidelines, thereby expanding treatment options for various diseases [71,72].Furthermore, promoting the sustainable cultivation and harvesting of P. africana may contribute to the conservation of biodiversity and support local economies in regions where this plant species is endemic [5].Tus, evidence-based policymaking informed by research on the biological activities of P. africana-derived phytochemicals can have far-reaching implications for public health and environmental sustainability.

Antibenign Prostatic Hyperplasia (BPH)
. About half of men who are 50 years of age or older have BPH, a nonmalignant enlargement of the prostate gland.Practitioners in traditional medicine have used P. africana bark decoction as an efective remedy for BPH for many years [19,47].Te stem bark may be rendered into a decoction by powdering and boiling it in water, or alternatively, the powdered bark can be encapsulated and orally administered to manage and treat BPH [16].Ethnobotanical surveys substantiate the prevalence of P. africana in managing BPH.Ethnomedicinal investigation reveals the signifcant utilization of P. africana 4 Scientifca Scientifca in treating prostatic ailments within the Foumban community in Cameroon [73].Likewise, a study by Kipkore et al. [28] highlights the Marakwet community in Kenya employing the decoction of P. africana stem bark for BPH treatment and management.
In vitro studies demonstrate that P. africana stem bark extract inhibits the proliferation of fbroblasts from human hyperplastic prostate and bladder, underscoring the plant's potential in BPH treatment [74].Wavinya Nyamai et al. [16,75] reported that in double-blind, placebo-controlled clinical trials, daily doses between 75 and 200 mg result in favorable outcomes: decreased prostate size, increased urine fow, decreased frequency of urination, and decreased irritative symptoms-all within a six-to three-month timeframe.
Te efectiveness of P. africana in treating BPH has been reported by Jena et al. [74], Wavinya Nyamai et al. [16], and Letoyah [47].Tese studies attribute this to the synergistic actions of various phytochemicals, including ferulic acid and pentacyclic triterpenoids like ursolic acid and phytosterols like β-sitosterone.By inhibiting the alpha-reductase enzyme, these compounds restore testosterone concentration, mitigate infammatory symptoms, and exhibit antioxidant properties, resulting in anti-BPH efcacy [39].
Scientifc investigations reveal P. africana extracts' potent antiandrogenic activity, impeding androgens' (e.g., testosterone and dihydrotestosterone) biological efects [39,76].Additionally, the high myristic acid content in P. africana's stem bark exerts antioxidant efects, curtailing susceptibility to lipid peroxidation and averting oxidative stress, a key contributor to BPH [39,59].Te pharmacological impact of P. africana phytochemicals on BPH validates and demystifes its ethnobotanical application in traditional medicine for BPH treatment and management.Te convergence of ethnobotanical knowledge with scientifc evidence underscores the pharmacological potential of P. africana in BPH treatment, bridging traditional medicine knowledge with modern therapeutic approaches.

Antiprostate Cancer.
Roughly 15% of men have prostate cancer [77].In recent decades, researchers have identifed various plants, including P. africana, as reservoirs for efective chemopreventive and therapeutic agents against prostate cancer, among other cancers [39,78,79].Extensive ethnobotanical evidence supporting the use of P. africana in treating and managing cancers, including prostate cancer, has been presented in the literature by various scholars [14,22,28].Ochwang'i et al. [20] conducted a study and noted that traditional healers in Kakamega County, Kenya, use P. africana bark decoction can be used to treat cancers such as prostate cancer and other urological symptoms.
Te use of P. africana decoction for the treatment of cancer and related conditions was confrmed by another survey conducted by Tugume et al. [31] close to the Mabira Central Forest Reserve in Uganda.
Several key phytochemicals (Table 3) in P. africana are responsible for its anticancer and antitumor properties.Notably, beta-sitosterol and ursolic acid demonstrate antiinfammatory efects on the prostate gland, denoting its antiprostate cancer activity [16].Furthermore, ferulic acid esters along with their derivatives actively contribute to both antitumor function and hypocholesterolemic activities of the P. africana bark extract on prostatic tissues [16,39].Asuzu et al. [58] and Komakech et al. [59] reported that ethanolic stem bark extract of P. africana stem bark signifcantly inhibited the growth of human prostate cancer cell lines (PC-3 and LNCaP) (IC 50 : 2.5 µl/ml), by inducing apoptosis compared to control cells.In vitro studies suggest a promising strategy that the antiprostate activity of P. africana is driven by ursolic acid, which downregulates B-cell lymphoma 2, thereby inducing apoptosis in PC-3 cells [59].Additionally, its beta-sitosterol and ferulic acid trigger apoptosis not only in PC-3 cells but also in LNCaP human prostate cancer cells, demonstrating an expansive range of potentially impactful treatments at our disposal [16,59].
Following a comprehensive review, Komakech et al. [39] concluded that P. africana holds substantial potential in chemoprevention and chemotherapy for prostate cancer--primarily because of its constituent phytochemicals (Table 3), such as atraric acid and N-butylbenzene-sulfonamide, which suppress the androgen receptor, thus reducing PC-3 proliferation [16,59].In other studies, it was demonstrated that oleanolic acid also suppresses the androgen receptor to avert PC-3 cells' proliferation [39,58,59,80].Furthermore, research shows lauric acid inhibits the 5-α-reductase 6 Scientifca enzyme, which blocks the conversion of testosterone to dihydrotestosterone, in turn, preventing prostate cancer [60,81].Moreover, these phytochemicals exert their antitumor activity by activating the 5′-AMP-activated protein kinase (AMPK) enzyme, disrupting key metabolic pathways in prostate cancer cells [55,56].Te synergistic efects of the phytochemical compounds of P. africana lead to a reduction in cancer cell proliferation, early senescence, and senescence-associated betagalactosidase activity [47,82].Ngule and Francis [46] and Letoyah [47] attributed these antiproliferative efects to tannins.Research has shown that tannins provide essential protection against oxidative damage-especially lipid peroxidation-due to their strong antioxidative properties, consequently functioning as potent anticarcinogenic agents with antimutagenic capabilities [83].

Cognitive-Enhancing Efects.
Recently, Ngai et al. [41] have investigated the cognitive-enhancing efects of the methanolic leaf and stem bark extracts of P. africana based on its ethnomedicinal application in managing mental illnesses [22].Te extracts exhibited a considerable anticholinesterase activity and improved cognitive function in scopolamine-induced cognitive-impaired Swiss albino mice [41].Tese efects were attributed to the diverse phytochemicals such as quercetin, β-sitostenone, chlorogenic acid, apigenin, and ursolic acid, among others [16,39,41].Te proposed mechanisms of the bioactivity of these compounds included the inhibition of cholinesterase activity, the remediation of oxidative stress, and antineuroinfammation [39,41].Based on this report, these extracts may be potential sources of lead molecules for developing drugs to treat neurodegenerative diseases, such as AD.
Te identifcation of phytochemicals with robust cognitive-enhancing properties underscores the importance of exploring natural products as reservoirs for drug development.Te presence of compounds such as quercetin and ursolic acid, known for their neuroprotective efects, hints at the rich pharmacological diversity these extracts ofer [16,41].Leveraging such bioactive compounds could lead to the development of innovative therapeutic interventions for neurodegenerative disorders, which continue to pose signifcant challenges in healthcare [86].However, the journey from the natural extract to the clinical drug candidate is arduous and necessitates rigorous preclinical and clinical evaluations.Tus, while the study by Ngai et al. [41] provides a promising foundation, it also underscores the need for further in-depth investigations to elucidate the safety, efcacy, and mechanisms of action of these extracts.Collaborative eforts between traditional medicine practitioners, pharmacologists, and medicinal chemists are imperative to navigate the intricate path towards translating these natural remedies into clinically viable treatments for neurodegenerative diseases.

Antidiabetic Activity. Te International Diabetes
Foundation [88] and the World Health Organization [89] characterize diabetes as a complex and persistent medical condition, resulting from either the pancreas producing insufcient insulin or the body failing to utilize this hormone efectively leading to elevated levels of blood glucose.Among an array of herbal remedies found in local markets, P. africana has gained recognition for its potential in diabetic treatment [90].Studies have shown that extracts from P. africana possess an intriguing ability to reduce the activity of dipeptidyl peptidase-4 enzyme (DPP-4), which plays a vital role in deactivating glucagon-like peptide (GLP-1), to increase insulin production.Tis is a pivotal approach in type 2 diabetes mellitus management and controlling and maintaining blood glucose levels [91][92][93], underscoring its potential efcacy.
In mitigating oxidative stress in the bladders of diabetic patients and decelerating the progression of diabetic cystopathy, preliminary interventions showed remarkable outcomes upon utilizing P. africana.After inducing diabetes in adult Wistar male rats for initial 4 weeks, orally administered 100 mg/kg of P. africana suspended in peanut oil produced suppression hyperglycaemia and diabetes-associated symptoms [94].In the same study, the results demonstrated efectiveness in managing complications associated with diabetes in the rat, by not only reducing bladder-related issues but also addressing potential renal damage via its antioxidative properties.Furthermore, both aqueous and ethanolic extracts from P. africana showed noteworthy hypoglycaemic efects in alloxan-induced diabetic rats [95].
Te observed antidiabetic properties of the P. africana stem bark are due to the presence of certain phytochemicals, notably: alkaloids, tannins, favonoids, and saponins [46].Tannins have a recognized role in diabetes treatment, as they reduce both plasma glucose and lipid profles, hence signifcantly decreasing blood glucose levels without inducing adiposity [85,96,97].Saponins also play an important part in their signifcant antidiabetic efects, as they lower blood glucose levels in diabetic patients according to previous reports [97,98].Flavonoids are responsible for battling diabetic complications, by modulating the efects on blood sugar transporters, enhancing insulin secretion-an action that also mitigates insulin resistance, and alleviating infammation and oxidative stress in muscles [97][98][99][100].Alkaloids in P. africana exhibit antidiabetic efects by targeting a variety of factors, thus leading to the attenuation of glucose-6-phosphatase, signifcantly reducing free glucose levels in the bloodstream [96].Notably, Tiong et al. [101] presented compelling evidence from vitro studies that alkaloids hold considerable therapeutic promise against type 2 diabetes by facilitating glucose uptake by pancreatic beta-TC6 or myoblast C2 C12 cells.Although this review provides a persuasive account of the antidiabetic potential of P. africana, it is imperative to acknowledge that further research is needed to determine the efcacy of these extracts in human subjects and the clinical relevance of the reported fndings.[21].In response to this health burden, various African communities extensively leverage locally available medicinal plants for therapeutic purposes, with P. africana emerging as a cornerstone in malaria treatment [1,19].P. africana's role in malaria treatment has been previously underscored in a comprehensive study exploring the diversity and utilization of antimalarial ethnophytotherapeutic remedies among the 8 Scientifca Kikuyus in Central Kenya [21].A parallel ethnomedicinal survey in Meru District, Kenya, corroborated the usage of P. africana in combating malaria [102,103].Typically, the stem bark powder is used to make an oral decoction or infusion that is used to treat malaria [104][105][106].

Antimalarial Activity. Malaria stands as a prominent global health challenge, contributing to an annual death toll of one to two million individuals in Africa
Te efcacious attributes of P. africana in malaria treatment fnd scientifc validation owing to its potent tannins, saponins, terpenoids, and alkaloids, constituting major antimalarial phytochemicals across a spectrum of plants used in Africa [107].Tannins, recognized for their prophylactic potential, assume signifcance as bioactive chemicals with antimalarial properties [108].Serge et al. [109] observed that alkaloid extracts from P. africana demonstrated a notable in vitro antiplasmodial activity against the P. falciparum strain, with an IC 50 of 2.36 µg/ml at a 24-hour incubation and 2.56 µg/ml after 48 hours.Similarly, Lehane and Saliba [110] highlighted the P. africana favonoids' inhibitory efect on the intraerythrocytic growth of P. falciparum in vitro, underscoring its potential efectiveness in treating malaria infections.
Rodrigues Goulart et al. [111] demonstrated that terpenoids of P. africana not only impeded Plasmodium falciparum but also suppressed isoprenoid biosynthesis.Tis fnding's signifcance becomes even more apparent when we consider that P. falciparum relies heavily on isoprenoid synthesis for its survival during erythrocytic stages; this includes processes such as transfer ribonucleic acid (tRNA) isopentenylation and protein prenylation, as well as generating essential compounds such as vitamin E, carotenoids, dolichols, and ubiquinone [112].Murata et al. [113] reported that terpenoids possess a potent inhibitory efect against various microbes, including P. falciparum, correspondingly suggesting that these compounds could be useful in combating parasitic infections.Moreover, terpenoids in P. africana extracts can hinder the synthesis of crucial biomolecules and, therefore, impede P. falciparum development [114].Overall, the amalgamation of traditional use and scientifc validation underscores the promising role of P. africana in the treatment and management of malaria, emphasizing its potential as a valuable resource in diverse African communities.However, further empirical investigations are required to determine the specifc compounds, mechanisms of actions, and the translation of the in vitro results into clinical practice.

Management of Gastrointestinal Disorders.
Drawing from human and animal models, a correlation between gastrointestinal disorders, such as stomach pain, and alterations in the microbiota resulting from consuming contaminated foods or water has been demystifed with greater profundity [115][116][117][118][119][120].Elsewhere, Stark et al. [121] documented the traditional African use of P. africana stem bark to treat diarrhea and abdominal conditions, highlighting the growing recognition in medical discourse that specifc botanical remedies can address distinct ailments.
Ethnobotanical investigations in the south-west ethnoecological region of Cameroon by Jiofack et al. [24] revealed the use of P. africana bark decoction to address heartburn and gastralgia.Similarly, Amiri and Kisangau [122] reported the administration of P. africana bark decoction to alleviate stomachache in communities near the Kimboza Forest Reserve in Morogoro, Tanzania.Similarly, South African communities use the stem bark decoction of P. africana to treat gastric and abdominal conditions as reported by Eldeen et al. [123].
Te efcacy of P. africana in managing gastrointestinal (GI) disorders is attributed to its potent antibacterial effects, providing protection against bacteria, a signifcant contributor to such ailments [123].Tis claim was later supported by Chrispus Ngule et al. [124], who demonstrated robust antibacterial activities in the hydromethanolic stem bark extract of P. africana.Further examination revealed that tannins, found in P. africana, demonstrate inhibitory efects on the growth of microbial populations in various environments, including the human gastrointestinal tract [83,[125][126][127].Based on this, Chrispus Ngule et al. [124] linked the presence of tannins in P. africana to astringency agreeing with earlier assertions by Ashok and Upadhyaya [128] that this is an important feature in preventing diarrhea and managing hemorrhage.Research indicates that these compounds achieve this by precipitating proteins and mucus as well as constricting blood vessels [126,129,130].In addition, favonoids may also alleviate both acute and chronic diarrhea through their ability to suppress intestinal motility and excessive mucus secretion, and their potential in alleviating the chronic infammation of the gastrointestinal tract, by protecting against oxidative stress and preserving proper mucosal functioning [131].Further research indicates that favonoids exhibit remarkable therapeutic capabilities and can ameliorate infammatory bowel disease efectively by preventing distressing symptoms such as bloody diarrhea and gastrointestinal pain [131].De Lira Mota et al. [132] elucidated the pharmacological attributes of favonoids in gastroprotection, antisecretory, cytoprotective, and antioxidant actions.Tese play a substantial role not only in treatment but also in controlling gastrointestinal disorders at large [131].Further extensive studies aimed at identifying and characterizing specifc compounds with the reported efcacies and establishing their mechanisms of bioactivity and safety are imperative to foster the translation of these results into clinical practice.
3.10.Antimicrobial Activity.Many communities utilize herbal remedies, renowned for potent antimicrobial properties, to manage skin infections, among other prevalent health maladies primarily attributable to bacteria, viruses, and fungi [19,133,134].For instance, local communities around Nandi Forest in Kenya have for a long time utilized preparations derived from P. africana as topical applications for the treatment and mitigation of various adverse skin conditions, owing to the robust antifungal activity exhibited by the plant's tannins [19,130].Bii et al. [23] found that the methanolic stem bark extract of P. africana signifcantly combated dermatophytes, pathogenic fungi, that thrive on skin and other bodily surfaces to cause conditions such as Scientifca ringworm-this aligns with traditional utilization of P. africana for its remarkable efcacy against these infections.
Research illuminates that tannins can hinder a wide range of microorganisms' growth including fungi, yeasts, viruses, and bacteria [83,129].In addition, Akiyama et al. [135] reported that galloyl catechins and ellagic acid derivatives derived from traditional Japanese medicines possess signifcant antimicrobial efects against these pathogenic agents.Mabhiza et al. [136] observed signifcant inhibitory efects of tannins and alkaloids on Staphylococcus aureus and Pseudomonas aeruginosa growth, which are a major cause of skin and soft tissue infections and were comparable to that of ampicillin (reference antibiotic).Henceforth, owing to its inherent antifungal and antibacterial properties-particularly in the stem bark where tannins are found-the phytochemicals within P. africana substantiate why diverse communities have utilized this plant for treating and managing various types of skin infections.

Chest Pain and Respiratory
Conditions.African communities prevalently utilize a decoction derived from the bark of Prunus africana to treat and manage chest pain and respiratory ailments such as asthma, allergies, and infammatory conditions [137].Similarly in the Kwazulu-Natal region of South Africa, the stem bark decoction of P. africana is used to treat intercostal pain [138], a claim that was later confrmed by Stark et al. [82,121].In a parallel ethnobotanical investigation.Bii et al. [23] reported a potent in vitro pharmacological activity of methanolic extract derived from P. africana against Streptococcus pneumoniae, underscoring its efcacy and potential clinical relevance.
Te potential efectiveness of P. africana in alleviating chest pain is attributed to its potent anti-infammatory properties, which are inherent in the plant's phytochemicals; however, we must note that defnitive scientifc studies on this are lacking.Considerable antinociceptive and antiinfammatory activities have been observed in the tannins of P. africana [73].Likewise, due to their potent antiinfammatory and analgesic activities, saponin compounds present may contribute to the analgesic efects of P. africana [139].Borgi et al. [140] underscored the signifcant analgesic potential of saponins, noting their ability to suppress paw edoema, algesia, and nitrite production while maintaining cell viability.In vivo studies employing model animals have demonstrated that alkaloids from P. africana possess potent analgesic properties [141].Consequently, the diverse classes of phytochemicals within P. africana might partially validate its efcacy in alleviating chest pain.While these fndings suggest a plausible mechanism for P. africana's efcacy in alleviating chest pain, it is imperative to conduct additional empirical studies to validate these claims conclusively.
3.12.Wound-Healing Efects.Te historical application of medicinal plants to facilitate wound healing and prevent infections without signifcant adverse efects is welldocumented [142,143].Notably, P. africana is frequently employed in the treatment of wounds within various African communities.Simbo [144] conducted an ethnobotanical study in Babungo, Northwest Region, Cameroon, and observed that P. africana is ethnomedicinally used to treat wounds and burns.Tis could potentially be due to the presence of secondary metabolites, such as tannins, alkaloids, favonoids, and saponins, which confer wound-healing properties [124].
Te substantial concentration of tannins in medicinal plants characterises their wound-healing and antiinfammatory efects [142].In addition, physiological effects such as accelerated blood coagulation, reduced blood pressure, and modulation of immune responses by tannins contribute to the wound-healing properties of this plant [33,83].Furthermore, the astringent properties of tannins in P. africana are known to expedite wound healing [128].Tannins' antibacterial activity and their ability to enhance NIH3 T3 cell proliferation have been noted to promote wound shrinkage, improve healing rates, and facilitate the recovery of infectious wounds [125,126].Moreover, tannins have been shown to reduce Staphylococcus aureus colonization in wounds, contributing to improved quality of healing [130,135,145].
Alkaloids, recognized for their potent wound-healing activities, have demonstrated efcacy in dermal healing when topically applied [141,[146][147][148]. Flavonoids, as antioxidants, actively scavenge free radicals, preventing oxidative damage, and exhibit remarkable anti-infammatory activities [149].Teir astringent nature, along with antimicrobial attributes, boosts the rates of epithelialization and wound contraction, thus promoting the healing process [33].Moreover, previous reports show that favonoids enhance collagen synthesis, by facilitating cross-linking in collagen fbres, shortening infammation periods, and bestowing resistance to infections [150].Tese are all critical components for amplifying the wound-healing continuum.Notably, Geethalakshmi et al. [151] reported that favonoids, indeed, exhibit a wound-healing potential surpassing that of silver sulfadiazine-a reference drug for burn infection treatment.
Elsewhere, research demonstrated that saponins actively contribute to the treatment and management of various diseases, notably wound healing [140,152].Teir unique ability to precipitate and aggregate red blood cells serves as a crucial factor in wounds' therapeutic process, by efectively halting bleeding [152,153].Moreover, studies indicate that saponins promote enhanced wound healing by stimulating wound contraction and facilitating increased collagen deposition [151,154].Te persistent utilization of P. africana in traditional medicinal practices for wound healing fnds its rationale in the pharmacological efects it possesses on promoting wound closure, largely due to the presence of specifc phytochemicals.Nevertheless, extensive studies to unearth the full potential of this plant in wound healing, identifcation and characterization of the specifc responsible compounds, and their action mechanisms may provide important insights into this plant's pharmacological potential and safety.Tis will, in turn, aid to translate the reported results into clinical applications upon thorough validation.
10 Scientifca 3.13.Safety and Toxicity.While traditional medicinal plants are commonly perceived as safe, it is imperative to recognize the potential for toxicity, necessitating caution [155,156].Numerous scientifc investigations consistently afrm the nontoxic characteristics of P. africana bark extract in humans, even at higher doses [157].A previous study by Karani et al. [158] noted that P. africana bark extract did not cause adverse when administered at a dose of 1000 mg/kg body weight to BALB/c mice.Elsewhere, repeated daily doses of aqueous extract of P. africana bark (1000 mg/kg body weight), administered orally for eight weeks, caused mild toxicity in rats [159,160].
Conversely, an in vivo experiment, conducted over 4 weeks with a dosage of 300 mg/kg/day, demonstrated no observable efects as reviewed previously [73].Although the probity analysis method calculated the lethal dose (LD 50 ) for P. africana as up to 2201.207 mg/kg body weight [158].A recent study proposed a relatively higher LD 50 exceeding 5000 mg/kg body weight for P. africana extracts, denoting its safety [161].Despite these complexities, the collective evidence underscores the overall nontoxic nature of the P. africana bark extract, providing a foundation for its continued exploration as a therapeutic agent.Nevertheless, cautious optimism and rigorous scrutiny remain paramount in leveraging traditional medicinal plants for therapeutic purposes, ensuring both efcacy and safety in clinical applications.

Limitations
Tis review has certain limitations.Firstly, the exclusion of unpublished information in the review process may introduce publication bias.Secondly, there is a possibility of overlooking studies or crucial information published on platforms beyond the scope of our focus.Nonetheless, this review signifcantly underscores the ethnopharmacological potential of P. africana in treating various ailments.

Conclusions and Future Directions
Tis comprehensive review ofers valuable insights into the utilization of Prunus africana, highlighting its signifcance as a potent and versatile medicinal plant deeply rooted in traditional medicine.Te plant's efectiveness extends across a wide range of medical conditions, both locally and worldwide, including benign prostatic hyperplasia, prostate cancer, chest discomforts, diabetes, wound management, malaria, gastrointestinal problems, and skin infections.
Despite numerous scientifc studies documenting the phytochemical composition and therapeutic applications of P. africana stem bark, equivalent investigations for its leaves and roots are lacking, although their use is documented in traditional medicine.Hence, we recommend future research to undertake comparative analyses of the phytochemical composition and medicinal potential of the plant's stem bark, roots, and leaves.Furthermore, additional preclinical and clinical studies are imperative to validate the efcacy and safety of these P. africana phytochemicals, whether used individually or in combination, for potential integration into drug research and development.
Despite the plant's considerable therapeutic potential, unsustainable practices such as improper stem bark harvesting and illegal logging have rendered P. africana, a vulnerable species.Urgent eforts are essential to ensure its sustainable utilization and conservation throughout its distribution range.

Figure 1 :
Figure 1: Schematic fowchart showing the search strategy and selection of eligible studies.

Table 1 :
Summary of ethnomedicinal uses of P. africana.

Table 3 :
Summary of biological/pharmacological activities of notable P. africana phytochemicals.