African Medicinal Plants in Cutaneous Wound Repair: A Comprehensive Analysis of the Role of Phytochemicals

ABSTRACT

Chronic and non‐healing wounds are a global health issue with limited effective treatments. Wound care costs continue to rise, highlighting the need for new therapies. Medicinal plants, particularly African species, show promise for enhancing wound healing. This review analysed 93 studies and identified 37 relevant to wound healing, covering 39 plant species. Ten species were identified for their rich phytochemical content, specifically flavonoids, terpenoids, and alkaloids (plant‐derived compounds). These compounds act synergistically, enhancing the wound healing process at each stage. Flavonoids reduce inflammation and support tissue turnover, while terpenoids enhance collagen production and wound closure. Alkaloids offer antimicrobial benefits and support wound contraction. Notable plants include Ageratum conyzoides and Aspilia africana (Asteraceae family); promoting haemostasis by lowering plasma fibrinogen and enhancing platelet‐derived growth factors; Withania somnifera (Solanaceae); and Entada africana (Fabaceae), effectively regulating inflammation. In the proliferative phase, Ocimum gratissimum (Lamiaceae), Calendula officinalis (Asteraceae), and Centella asiatica (Apiaceae) although C. officinalis is native to Southern Europe, and C. asiatica an Asian‐native; they are widely used in African traditional medicine and included here for their relevance in African wound healing practices; Justicia flava (Acanthaceae), Alternanthera sessilis (Amaranthaceae), and Acalypha indica (Euphorbiaceae); play key roles in enhancing collagen production, angiogenesis, and re‐epithelialisation. This comprehensive analysis highlights the role of African medicinal plants in wound healing and their potential to improve wound care therapy.

Abbreviations

2D

2 Dimensional

3D

3 Dimensional

Afr

Afrikaans

B

Bemba

bFGF

Basic fibroblast growth factor

COX

Cyclooxygenase

DPPH

Diphenyl picrylhydrazyl

ECM

Extracellular matrix

Eng

English

ETA

Ethyl acetate

EtOH

Ethanol

GC/MS

Gas chromatography–mass spectrometry

H

Hindi

H₂O

Water

Ha

Hausa

HaCaT

Keratinocytes

I

Ibo

IGF

Insulin‐like growth factor

IL

Interleukin

MAPK/NF‐κB

Mitogen‐activated protein kinase/nuclear factor‐κB pathway

MeOH

Methanol

MMPs

Matrix metalloproteinases

MPO

Myeloperoxidase

NaDES

Natural deep eutectic solvents

NMR

Nuclear magnetic resonance spectroscopy

NO

Nitric oxide

p38 MAPK

p38 Mitogen‐activated protein kinases

PDGF

Platelet‐derived growth factor

PT

Prothrombin time

RAW 264.7

Macrophage cell model

ROS

Reactive oxygen species

S

Sesotho

Sw

Swahili

TGF

Transforming growth factor

TIMPs

Tissue inhibitors of matrix metalloproteinases

TNF‐α

Tumour necrosis factor‐alpha

VEGF

Vascular endothelial growth factor

Y

Yoruba

Z

IsiZulu

Summary.

• Wounds, both acute and chronic, pose significant global health challenges due to their impact on quality of life, high treatment costs, and limited effective therapies. This review discusses the role of African medicinal plants in wound healing, focusing on their phytochemical compositions and mechanisms of action.

• Ninety‐three studies were reviewed; 37 were found relevant, covering 39 African plant species.

• Ten African plant species, containing flavonoids, terpenoids, and alkaloids, contribute to haemostasis, reducing inflammation and accelerating tissue repair.

1. Introduction

Acute wounds are breaches in the epidermal and dermal layers, disrupting cutaneous integrity [1]. The healing process occurs through primary or secondary intention, which typically involves multiple phases: haemostasis, inflammation, proliferation, and remodelling [2]. Chronic wounds, characterised by slow and prolonged healing times, present a significant global health challenge, impacting millions of individuals worldwide [3]. Factors like age and comorbidities, such as chronic diseases, contribute to the exponential rise in chronic wounds [4]. Moreover, the absence of effective pro‐healing agents, including topical medications, further exacerbates the quality of life for individuals with chronic wounds [5].

The anticipated financial strain of wound treatment costs underscores the urgent need for novel topical healing bioactives. Ideally, these would be derived from natural sources like plants and would have a long‐standing and safe record of medicinal use across diverse cultures [6]. Natural compounds derived from plants offer potential advantages, including biological compatibility, fewer side effects, and a diverse array of chemical structures conducive to discovering novel therapeutic agents [7, 8]. However, plant harvesting poses challenges to ecosystems, risking overexploitation and species endangerment; hence, regulations to mitigate exploitation are necessary [9]. While traditional extraction methods such as maceration, percolation, and Soxhlet extraction methods use organic solvents, are laborious, and may result in impurities due to compound heterogeneity, innovative green chemistry methods may offer more sustainable alternatives [10].

Moreover, advanced analytical methods, including liquid chromatography‐high‐resolution mass spectrometry (LC‐HRMS) and nuclear magnetic resonance spectroscopy (NMR), can improve metabolomic screening and analysis, thereby improving product purity [11, 12]. In contrast, synthetic drugs offer high purity, which ensures precise dosage and absorption compared to natural sources. However, although reproducible, they may lack certain active compounds found in natural resources, potentially impacting healing abilities and contributing to drug failures. Meanwhile, semi‐synthetic technology strikes a balance between natural and synthetic drugs by incorporating structural modifications of natural bioactives into synthetic drugs while mitigating ecological concerns [13].

African plants, thriving in diverse climates, contribute significantly to the continent's botanical diversity. Notably, Southern Africa exhibits several unique biodiversity hotspots, including the Cape Floristic Region in South Africa and the Eastern Afromontane region [14]. These regions boast a high concentration of endemic plant species, meaning they are exclusive to these areas and not found anywhere else in the world. Numerous African plant species are exclusive to particular regions, enriching the continent's biodiversity [15].

Southern Africa, particularly the arid regions, is known for its diverse array of succulent plants, such as aloes and euphorbias [16, 17]. These plants have adapted to survive in water‐scarce environments. Moreover, Africa has a rich history of using indigenous plants for medicinal purposes. Traditional healers often rely on a variety of plant species with therapeutic properties, contributing to the continent's distinctive ethnobotanical landscape.

Despite Africa's rich biodiversity, research on medicinal plants lags behind other regions. In 2020, Salmeron‐Manzano et al. conducted a global analysis of research trends on medicinal plants spanning from 1960 to 2019. The study revealed that over the period, no African country exceeded 2000 publications in total, while recording China: 19,846; USA: 7,339; and Brazil: 5993 publications in this field [18]. With over 40, 000 plant species, approximately 5000 of which have been used in traditional medicine for centuries [19], and over 80% of the African population relying on plant preparations for various ailments, further investigations into the pharmacological properties of African medicinal plants are warranted.

Phytochemical compounds found in plants, such as flavonoids, terpenoids, and alkaloids; exhibit potent bioactivities, including stimulating cell proliferation and differentiation; promoting collagen synthesis, and demonstrating antioxidant, antimicrobial and anti‐inflammatory activities crucial for wound healing [20]. These attributes highlight the potential of medicinal plants in traditional medicine and suggest their potential as sources for future therapeutic options.

In this context, we present a comprehensive review of studies discussing the role of African plants and phytochemicals in wound healing. Our literature search, covering publications between 1960 and 2024, has identified African plant species with wound healing properties, providing scientifically validated information for our review. We applied search databases including Google Scholar, Scopus, and PubMed. Search terms included ‘African plants with wound healing properties’; ‘Effect of African plants in wound healing’; ‘African medicine in wound healing’; ‘Effect or action of phytochemicals in wound healing’; and ‘Plants as an alternative medicine for wound healing’. This search resulted in 93 studies, with 37 found relevant to wound healing, covering 39 species, from which 10, namely, Ageratum conyzoides , Aspilia africana, Calendula officinalis (Asteraceae), and Centella asiatica (Apiaceae); although C. officinalis is native to Southern Europe, and C. asiatica an Asian‐native, they are widely used in African traditional medicine, and included here for their relevance in African wound healing practices. Other notable species include Entada africana (Fabaceae); Ocimum gratissimum (Lamiaceae); Withania somnifera (Solanaceae); Centella asiatica (Apiaceae); Justicia flava (Acanthaceae); Alternanthera sessilis (Amaranthaceae); and Acalypha indica (Euphorbiaceae). These species, illustrated in Figure 1a–j, were selected for their rich phytochemical profiles. Their contributions to wound healing are discussed in Sections 3.3, 3.5. Only scientifically validated information on African plants demonstrating wound healing activities was included in our review.

FIGURE 1.

(a–j): Examples of African medicinal plants in wound healing. Illustration of the top ten identified medicinal plant species with direct involvement in the wound healing process; active in wound healing as antioxidants, promoting haemostasis and anti‐inflammatory activity, increasing cell proliferation, and collagen formation. (a) Aspilia a fricana (Haemorrhage plant or Wild sunflower (Eng)) (b) Ageratum conyzoides (Billy‐goat weed (Eng) or Bokkruid (Afr)); (c) Withania somnifera (Winter Cherry (Eng), Ubuvimba (Z), Ashwagandha (H)); (d) Entada africana (African dream herb, African sea‐bean (Eng.), Reuseseeboontjie, Boonbobbejaantou (Afr), Inkwindi, Intindile, Umbhone (Z)); (e) Calendula officinalis (Pot marigold (Eng)); (f) Centella asiatica (Bolila‐balinku (S), Indian Pennywort (Eng), Icudwane (Z)); (g) Justicia flava (Yellow justicia (Eng.), Geelgarnaalbos (Afr.), Impela (Z)); (h) Alternant h era sessilis (Sessile joyweed (Eng)); (i) Acalypha indica (Indian nettle (Eng)); (j) Ocimum gratissimum (mbijazane (Z), Umnandi (Z), Wild Basil (Eng)). Abbreviations: Afr, Afrikaans; Eng, English; H, Hindi; S, Sesotho; and Z, IsiZulu.

2. Wound Pathophysiology and Treatment

In acute wounds, the slightest disruption of the skin triggers a response that facilitates the onset of the wound repair process. The response begins with the activation of the coagulation cascade, inducing the production of growth factors such as platelet‐derived growth factors (PDGF). PDGF recruits platelets to aggregate in the wounded area, achieving haemostasis [21]. Simultaneously, inflammatory cytokines, such as interleukin‐1, 6 and 8 (IL‐1, IL‐6, and IL‐8), along with tumour necrosis factor‐alpha (TNF‐α), and growth factors like transforming growth factor‐α and ‐β (TGF‐α and TGF‐β), insulin‐like growth factor‐1 (IGF‐1), basic fibroblast growth factor (bFGF), and vascular endothelial growth factor (VEGF), are also mobilised to the injured site. Neutrophils and macrophages are recruited to facilitate healing, debridement and removal of bacteria by phagocytosis [22, 23, 24].

Growth factors are released to mediate the activation and migration of adjacent cells, including fibroblasts, epithelial cells, as well as endothelial cells. This promotes capillary regeneration, facilitating oxygen, and blood supply to the wound to accelerate healing [25, 26]. Furthermore, fibroblasts release collagen, forming compact strands of proteins in injured tissues that create a scaffold that holds the wound together, thereby enhancing tensile strength. Activated epithelial cells then migrate to re‐epithelialise the wound surface during the healing process, leading to the eventual remodelling and maturation of the wound [9, 27].

During maturation, collagen is rearranged, and differentiated fibroblasts (myofibroblasts) align along the wound edges to contract and reduce the wound size. This process decreases vascularity, thus forming a scar (remodelling and maturation) [28]. Under abnormal conditions, including chronic diseases, prolonged infection, age, and immunodeficiency; the proper execution of wound healing phases is disrupted. This disruption may result in prolonged inflammation, poor cell migration, and angiogenesis; tissue necrosis from bacterial infiltration, reduced tissue inhibitors of matrix metalloproteinases (TIMPs) resulting in an accumulation of matrix metalloproteinases (MMPs), decreased extracellular matrix (ECM) secretion, and increased oxidative stress [29, 30, 31, 32].

Non‐healing wounds require specialised care and treatment to manage chronicity and promote healing. A broad range of wound‐care products, including dressings and ointments, are available. These include Pentoxifylline, Iloprost (prostacyclin), Nifedipine, Diltiazem, Doxycycline, Deferoxamine, Betneval (Betamethasone), Fucidin, Silverex, Activon, and L‐Mesitran [33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44]. Despite their purported wound‐healing efficacy, limitations such as drug resistance, including microbial resistance, reduced drug efficacy, and drug–drug interactions, have been reported [45]. This necessitates the ongoing search for alternative therapeutic agents. The advantages and limitations of current drugs used for wound healing are listed in Table 1.

TABLE 1.

Current therapeutic products for chronic wounds and limitations.

Drugs	Uses	Mode of action	Type of wounds	Limitations	references
Pentoxifylline	Reduces inflammation, prevents claudication, and improves blood flow	Promotes TIMP‐1 gene expression, reduces MMP‐1, and MMP‐3 production, TNF‐α activity	Venous leg ulcers	Allergies, may cause internal bleeding	[36, 37, 46]
Iloprost (prostacyclin)	Severe limb ischaemia, prevents gangrene	Increases blood flow, reduces TNF‐α activity	Leg ulcers	Causes internal bleeding	[33, 47]
Nifedipine	Calcium blockers are vasodilators, increases blood flow, modulates inflammation	Promotes nitric oxide (NO) production, angiogenesis, epithelialisation, TGF‐β production, and Collagenase production	Vasculitis ulcers	Gingival hyperplasia	[38, 39]
Diltiazem	Calcium blocker, dilates blood vessels to improve blood flow and regulates inflammation	Promotes nitric oxide (NO) production, angiogenesis, epithelialisation, TGF‐β production, and Collagenase production	Vasculitis ulcers	Gingival hyperplasia	[38, 39]
Doxycycline (DOX)	Antimicrobial agent, prevents oxidative stress	Decreases MMPs activity, ROS production, NO production	Chronic wounds	Allergies, microbial resistance	[44, 48]
Deferoxamine (DFO)	Promotes angiogenesis and has antioxidant properties	Reduces ROS production and attracts endothelial cells	Chronic wounds	Drug resistance	[44]
Betneval (Betamethasone)	Regulates inflammation, reduces redness, swelling, and itching	Inhibits protein synthesis, reduces leucocyte and fibroblast migration, and capillary permeability	Chronic wounds	Allergies, increase susceptibility to infections	[40]
Fucidin	Antibacterial agent for bacterial skin conditions	Prevents bacterial protein synthesis and turnover	Infected ulcers, traumatic, and surgical wounds	Allergies, microbial resistance	[41]
Silverex (Silver Sulfadiazine)	Antimicrobial prevention and treatment	Disrupts bacterial cell membranes, and inhibits DNA or RNA replication	3rd degree burns,	Allergies, microbial resistance, epidermal necrolysis	[42, 49]
Activon	Antimicrobial, debridement, regulates inflammation and promotes healing	Autolytic debridement, stimulates angiogenesis, granulation, and epithelialisation	Chronic wounds, Ulcers	Allergies, exudate	[43]
L‐Mesitran	Antimicrobial, debridement	Autolytic debridement, stimulates granulation, neovascularisation, and re‐epithelialisation	Chronic, fungating wounds, pressure ulcers	Allergies, exudate	[35]

Note: Current therapeutic products for chronic wounds and limitations. The therapeutic products shown include Pentoxifylline, Iloprost (prostacyclin), Nifedipine, Diltiazem, Doxycycline, Deferoxamine, Betneval (Betamethasone), Fucidin, Silverex, Activon, and L‐Mesitran. Their uses, mode of action, type of wound they are used in based on site or chronicity and limitations are mentioned here.

Abbreviations: MMPs, Matrix metalloproteinases; NO, Nitric oxide; ROS, Reactive oxygen species; TGF‐β, Transforming growth factor‐ beta; TIMP, Tissue inhibitors of matrix metalloproteinases; and TNF‐α, Tumour necrosis factor alpha.

3. The Role of African Medicinal Plants and Bioactives in Wound Healing

Africa boasts a highly diverse population of plants, used by over 80% of the population for treating various ailments [50, 51, 52]. The use of plants in traditional medicine has ancient roots, dating back to more than 5000 years B.C. Consequently, there is abundant indigenous knowledge regarding the use of these plants in wound healing. This rich tradition has drawn the attention of researchers, leading to efforts to isolate and characterise plant bioactive compounds and evaluate their role in wound healing [53]. Studies have identified specific African medicinal plants and their bioactive compounds that contribute to wound healing. For example, Kigelia africana has been reported to promote wound healing, enhance tissue granulation, and improve glutathione peroxidase activity; it exhibits potent antioxidant properties crucial for neutralising oxidative stress during the wound healing process [54, 55]. Similarly, Elaeis guineensis , known for its antibacterial effects, helps prevent microbial infection at the wound site [56].

Evidence shows that plants contain natural compounds such as phenols, terpenoids, and alkaloids, which are produced as secondary metabolites during photosynthesis. These compounds play vital roles in protecting plants against oxidative stress and microbial infection [57]. Due to the presence of these bioactive compounds, African plants have shown a spectrum of healing properties, including antioxidant, antibacterial, haemostatic, anti‐inflammatory, angiogenic, and proliferative effects. Such activities are crucial in enhancing wound healing [58, 59]. Additional studies illustrating the diverse roles of plants in wound healing are presented in Table 2.

TABLE 2.

Other African medicinal plants and their mechanisms in wound healing.

Medicinal plants	Common name	Geographical distribution	Actions in wound healing	References
Malva parviflora	Cheese weed (Eng)	Northern Africa, Mediterranean and widespread as introduced species globally	Anti‐inflammatory activity via COX‐1 enzyme action, antimicrobial and analgesic properties, promotes wound healing	[60, 61]
Ficus asperifolia	Sandpaper tree, Guardian fig (Eng)	Sub‐Saharan Africa	Antioxidant and anti‐inflammatory activity, promotes epithelialisation and increases wound contraction	[62, 63]
Gossypium arboreum	Wild cotton (Eng), Kotini (X), Umgawuma (Z)	Sub‐Saharan Africa, China	Increase hydroxyproline content, increases wound contraction, possesses antioxidant and anti‐inflammatory properties	[64]
Bulbine natalensis	Ibhucu (Z), Rooiwortel (Afr)	South Africa, Mozambique, Malawi, Zimbabwe	Improve collagen production, promotes wound contraction, increases tensile strength, antioxidant activity	[65, 66]
Bulbine frutescens	Snake flower, Cat's tail (Eng)	South Africa	Antioxidant activity, promotes collagen production and increases tensile strength	[65, 66]
Parkia biglobosa	African locust bean tree (Eng)	Nigeria, West Africa	Antioxidant activity, promotes fibroblast proliferation	[67]
Bridelia ferruginea	Iralodan (Y), Oho (Ibo)	Nigeria, West Africa	Promotes cell proliferation, antioxidant activity	[67]
Achyranthes aspera L.	Chaff‐flower, Devil's horsewhip (Eng)	Ethiopia, Kenya	Promotes wound contraction, neovascularisation, promotes epithelialisation	[68, 69]
Albizia adianthifolia	Flat crown (Eng)	South Africa, West Africa	Antioxidant and antimicrobial activities	[70]
Cissus quadrangularis	Veld grape, Devil's backbone (Eng)	Africa, Asia	Anti‐inflammatory via COX‐1 and 2 inhibitions, increase wound healing rate	[71]
Boerhavia diffusa	Red spiderling, Punarnava hog weed (Eng)	Ghana, India	Promotes cell migration antioxidant activity	[72]
Aloe muth‐muth	—	Africa	Antioxidant activity, increases cell migration	[73]
Aloe vera	Aloe vera , Aloe barbadensis	Native to Arabian Peninsula, widely distributed in Africa, Europe, and elsewhere	Antioxidant, anti‐inflammatory activity, promotes TGF‐β activation, wound contraction, collagen production and decrease scar tissue	[74, 75]
Hypoxis hemerocallidea	African potato (Eng), Inkomfe (Z), Ilabatheka (X)	South Africa	Anti‐inflammatory, antioxidant, and antimicrobial activities	[76]
Ximenia americana	Tallow wood, Yellow plum (Eng)	Native to tropical Africa, Australia, Asia, America	Increases fibroblast proliferation, increases collagen production, promotes angiogenesis	[77]
Terminalia sericea	Silver cluster leaf (Eng)	South Africa	Scavenging and antimicrobial activity anti‐erythmic activity	[78, 79, 80]
Terminalia avicennioides	Kpace, Kpayi, Baushe (Ha)	Western Africa	Promotes wound contraction, reduces wound healing time	[81]
Momordica balsamina	Balsam pear (Eng), Intshungwana yehlathi (Z)	South Africa	Promotes wound healing by reducing wound healing time	[82, 83]
Fagonia schweinfurthii	Desert fagonia (Eng)	Africa, India, Pakistan, Iran	Anti‐inflammatory activity, promotes wound healing	[84]
Alchornea cordifolia	Christmas bush (Eng), Bundzila (Z)	Africa	Antimicrobial, anti‐inflammatory activity, promotes wound contraction	[85]
Zanthoxylum chalybeum	Knob wood (Eng), Mjafari (Sw), Pupwe (B)	Africa	Antioxidant, antibacterial activity, reduces epithelialisation time, promotes wound closure	[86]
Warbugia ugandensis	African green heart (Eng)	Africa	Antioxidant, antibacterial activity, reduces epithelialisation time, promotes wound closure	[86]
Kigelia africana	Sausage tree (Eng)	Africa	Enhances tissue granulation and improve activity of glutathione peroxidase	[87]
Tagetes erecta	African marigold (Eng)	Mexico, Central and South America, Africa	Ulcer protective activity	[88]
Jatropha curcas Linn.	Poison nut, bubble bush (Eng), Purgeerboontjie (Afr)	Mexico, America, Africa	Stimulates wound contraction and increases tensile strength	[89]
Elaeis guineensis	African oil palm (Eng)	West Africa	Antibacterial activity, promotes tissue regeneration and wound closure	[90]
Tamarindus indica	Indian tamarind (Eng)	Africa	promote wound closure, reduces wound healing time	[91]
Blepharis maderaspatensis	Creeping Blepharis Surprise packet (Eng), Skietpitjie (Afr)	Africa, Arabia, Asia	Improves wound repair, collagen synthesis and maturation, wound contraction and epithelialisation	[92]
Azadirachta indica	Neem (Eng)	Africa, India	Increases neo‐vascularisation, antibacterial activity	[93]

Note: Other African medicinal plants and their mechanisms in wound healing. Medicinal plants (Scientific and common names), geographical distribution and their action in wound healing are mentioned here.

Abbreviations: Afr, Afrikaans; B, Bemba; COX, Cyclooxygenase; Eng, English; Ha, Hausa; I, Ibo; Sw, Swahili; X, Xhosa; Y, Yoruba; and Z, IsiZulu.

3.1. African Plants as a Source of Antioxidants

Reactive oxygen species (ROS) are secondary messengers playing pivotal roles in the first line of wound repair. They exhibit bacteriostatic properties and regulate inflammation and angiogenesis in the wound [94]. However, excessive ROS production at hypoxic wound sites can lead to oxidative stress, prolonged inflammation, and impaired angiogenesis and re‐epithelialisation [95]. Several studies have evaluated the antioxidant activities of various plants. For example, a study by Annan and Houghton et al. (2008) investigated the antioxidant properties of Ficus asperifolia and Gossypium arboreum extracts using 2,2′‐diphenylpicrylhydrazyl (DPPH) test and hydrogen peroxide‐induced damage in fibroblasts. The DPPH test revealed antioxidant properties for both extracts at IC₅₀ values of 237 and 35,7 μg/mL respectively, in comparison to L‐Ascorbic acid at 21,1 μg/mL. Furthermore, the extracts exhibited cytoprotective properties, with G. arboreum showing the highest activity (82% at 50 μg/mL) and F. asperifolia showing 58% activity [62].

In another study, ethanolic extracts of Parkia biglobosa and Bridelia ferruginea demonstrated antioxidant activities at concentrations ranging from 3,8–31 μg/mL, compared with ascorbic acid (7,3 μg/mL) [67]. Komakech et al. (2019) reported that A. africana (Figure 1a) is rich in alkaloids, saponins, tannins, flavonoids, phenols, terpenoids, β‐caryophyllene, germacrene D, α‐pinene, carene, phytol, and linolenic acid‐phytochemicals that play a major role in antioxidant and anti‐inflammatory properties [96]. Plant‐based antioxidants exhibit promising potential in addressing ROS‐related challenges in wound healing. However, it is crucial to emphasise that additional research and rigorous clinical validation studies are imperative. These steps are necessary to unlock and maximise the benefits of plant‐based antioxidants, ensuring their effectiveness and safety in therapeutic interventions within the field of wound care.

3.2. African Plant Extracts as Antibacterial Agents

Wounds are highly susceptible to infections, especially when antibiotic‐resistant biofilms develop. These biofilms can lead to the overproduction of inflammatory cytokines, resulting in a prolonged inflammatory phase that hinders cell proliferation, angiogenesis, and re‐epithelialisation [97]. Grierson and Afolayan et al. (1999) investigated the antibacterial activities of acetone, methanol, and water extracts of Grewia occidentalis , Polystichum pungens, Cheilanthes viridis, and Malva parviflora against various Gram‐positive bacteria (e.g., Bacillus cereus , Bacillus subtilis , and Staphylococcus aureus ) and Gram‐negative bacteria (e.g., Pseudomonas aeruginosa , Klebsiella pneumoniae , Enterobacter cloacae, and Escherichia coli ) in vitro. Their findings demonstrated that acetone extracts of P. pungens were effective against five Gram‐positive bacteria, while other extracts showed no activity. Meanwhile, methanolic extracts of G. occidentalis , P. pungens and C. viridis exhibited growth inhibitory activities against both Gram‐positive and Gram‐negative bacteria at 5,0 mg/mL, except for P. pungens, which only inhibited E. coli at higher concentrations. Water extracts showed limited activity against bacterial species compared to those obtained with acetone and methanol. Among the water extracts, C. viridis demonstrated activity against Gram‐positive as well as two Gram‐negative species, E. cloacae and P. aeruginosa. P. pungens was active against four Gram‐negative bacteria and E. cloacae. In contrast, G. occidentalis showed activity against only two species: S. aureus and E. cloacae. None of the M. parviflora extracts showed activity against all tested bacteria [60].

In a study by Kruger et al. (2018), the antibacterial and wound healing properties of Terminalia sericea leaf extract and isolated terminoic acid were investigated in Wistar rats infected with S. aureus . The rats were treated 48 h after infection, with gentamicin as a positive control. Results showed that both the leaf extract and isolated compound reduced wound exudate production and erythema, demonstrating significant antimicrobial effects on S. aureus , surpassing gentamicin, and being slightly more effective than the untreated group [78].

In another study, a methanolic extract of Terminalia avicennioides inhibited the growth of various pathogenic microorganisms, including Streptococcus pyogenes, Mycobacterium tuberculosis, S. aureus , B. subtilis , among others, at concentrations ranging from 78 to 0,4 mg/mL [81].

3.3. The Role of African Plant Extracts During Haemostasis

In a recent study by Ebrahimi et al. (2020), the haemostatic properties of several plants were reported from different families. They identified common bioactives in these plants, including tannins, iridoid glycosides, glycoconjugates, lignans, saponins, and phenolic compounds. These compounds contribute to haemostasis by stimulating coagulation through the activation of coagulation factor XII activity, increasing fibrinogen levels, inducing vascular or muscle constriction, and promoting platelet aggregation. For instance, A. conyzoides (Figure 1b) methanolic extracts, administered at doses of 250, 500 and 750 mg/kg to albino rats for 2 weeks, demonstrated a dose‐dependent decrease in bleeding time, prothrombin time (PT), clotting time, and increased plasma fibrinogen. Furthermore, A. conyzoides reversed the anticoagulant and antiplatelet effects of conventional drugs [98]. A. africana is reported to augment haemostasis by increasing platelet‐derived growth factor, white and red blood cell, and basic fibroblast growth factor production [96, 99].

3.4. African Plant Extracts and the Inflammatory Phase of Wound Healing

Acute inflammation involves a cascade of regulated reactions or pathways, initiated by pro‐inflammatory cytokines like TNF‐α, IL‐6 and IL‐1‐β among others. Cytokines are chemo‐attractants that stimulate angiogenesis during inflammation, signal and promote immune cell influx to the wound site to facilitate debridement and healing [100]. However, in chronic wounds, this signalling is dysregulated, overriding innate anti‐inflammatory responses due to an overpopulation of immune cells and chronic production of cytokines at the wound site, causing tissue necrosis, thereby hindering the progression of the healing process. Therefore, anti‐inflammatory agents are administered to regulate this signalling, but because of current drug limitations, the search for alternatives is necessary [101, 102]. TNF‐α plays a dual role, promoting inflammation and tissue repair in acute wounds but contributing to prolonged inflammation and tissue damage in chronic wounds when dysregulated [100, 101, 102]. Studies have indicated that W. somnifera (Figure 1c) extract possesses anti‐inflammatory properties through the inhibition of the mitogen‐activated protein kinase/nuclear factor‐κB (MAPK/NF‐κB) pathways. This leads to the downregulation of pro‐inflammatory cytokine expression and the promotion of anti‐inflammatory cytokine production in HaCaT keratinocytes [103]. The nuclear factor‐κB (NF‐κB) pathway is known as the central regulator of inflammation, activated by TNF‐α, IL‐1‐β, and toll‐like receptor (TLR) signalling, to drive immune cell recruitment, pro‐inflammatory transcription, and tissue repair. Meanwhile, the mitogen‐activated protein kinase (MAPK) pathway is activated by TNF‐α, IL‐1, stress, and pathogen invasion, facilitating inflammation, cytokine production, apoptosis, cell survival, and subsequent proliferation [104, 105].

Another study by Owona et al. (2013) demonstrated that fraction Ea5 from E. africana (Figure 1d) significantly reduced lipopolysaccharide‐induced nitric oxide (a pro‐inflammatory mediator) production by 89.06% at 100 μg/mL compared to a standard in the RAW 264.7 macrophage cell model. Ea5 further decreased TNF‐α, IL‐6, IL‐1‐β, and p38 MAPK activities by 30% [106].

These findings collectively support the notion that these plant extracts hold promise in modulating the inflammatory phase of wound healing. The identified mechanisms of action, including the regulation of key pathways and cytokine expression, provide valuable insights into the potential therapeutic applications of W. somnifera and Ea5 fraction in promoting a balanced and controlled inflammatory response during the wound healing process.

3.5. African Plant Extracts in the Proliferative and Remodelling Phase

Several studies have documented the effects of plant extracts on the proliferative and remodelling phases of wound healing. For instance, Komakech et al. (2019) reported that A. africana promotes wound healing in Wistar rat excision wounds by improving the rate of re‐epithelialisation and promoting collagen deposition [96]. Moreover, a study by Arulprakash et al. (2012) showed that the topical application of A. conyzoides (Figure 1b) extract on a rat excision wound model (40 mg/kg) promotes cell proliferation and collagen synthesis. The extract improved the rate of epithelialisation, wound contraction, and showed an increase in tissue tensile strength by 40% [107]. In another study, topical applications of W. somnifera paste and gel increased wound contraction, promoted re‐epithelialisation, and increased tensile strength in Wistar Albino rat excision and incision wounds [108]. Notably, W. somnifera was deemed a protease inhibitor, modulating the expression of proteases implicated in the degradation of the ECM in chronic non‐healing wounds. This inhibition creates a balance in the expression of proteases and inhibitors, thereby promoting wound healing [109, 110].

Additionally, Baidoo et al. (2021) showed that topical application of E. africana cream extracts on Wistar rats promotes collagen production, re‐epithelialisation, good scar formation, and increased tensile strength [111]. Muley et al. (2009) demonstrated that C. officinalis (Figure 1e) promotes wound healing by increasing collagen, hydroxyproline, and hexosamine production, reducing acute phase proteins and tissue damage in thermally induced burns in a rat model (200 mg/kg) [112]. Agyare et al. (2016) demonstrated that topical application of C. asiatica (Figure 1f) at 0.2% and 0.4% concentrations promotes wound healing by increasing hydroxyproline, tensile strength, collagen production, and promoting re‐epithelialisation in a delayed‐wound type of guinea pigs. Similarly, the oral administration of J. flava (Figure 1g) and A. sessilis (Figure 1h) extracts reduced wound size and promoted angiogenesis, collagen formation, tensile strength, and re‐epithelialisation [113]. Zahidin et al. (2017) reported that the ethanolic extract of Acalypha indica (Figure 1i) promoted wound closure in Wistar rats (excision and incision wounds) and upregulated the expression of TNF‐α and TNF‐β, the key signals for wound repair [114].

Similarly, Ganeshkumar et al. (2012) showed that topical application of A. indica extract to rat excision wounds (40 mg/kg) promotes TNF‐α expression during the early stages of wound healing, increases cell proliferation, TGF‐β, and collagen type I and III production. This accelerated wound closure and increased tensile strength [115]. Essentially, during the proliferative and remodelling phases, TNF‐α promotes keratinocyte migration, fibroblast proliferation, angiogenesis, ECM production, and remodelling. On the other hand, TNF‐β (Lymphotoxin‐ α), a member of the TNF‐α family, is not well characterised in wound healing, but like TNF‐α, TNF‐β promotes cell proliferation and remodelling. TNF‐α supports tissue repair in acute wounds, but when excessive, in chronic wounds, it impairs fibroblast and keratinocyte function, increases ECM degradation, and delays remodelling [114, 115, 116, 117, 118]. Excessive levels of TNF‐α and TNF‐β in chronic wounds hinder the progression to the proliferative phase, impairing fibroblast and keratinocyte function, increasing ECM degradation, and delaying tissue remodelling [116, 117, 118]. Therefore, understanding the mechanisms of plant extracts is critical to informing the decision‐making process regarding their application, depending on the stage of healing and the type of wound.

In another study, Orafidiya et al. (2003) demonstrated that O. gratissimum (Figure 1j) essential oil promotes cell proliferation and wound contraction in incisional and excisional wounds of adult albino rabbits [119]. Later, Ifedioramma et al. (2022) demonstrated that O. gratissimum crude extract enhances wound healing by increasing the rate of re‐epithelialisation, increasing wound contraction and tensile strength in rabbit excision wounds [120].

These collective findings highlight the multifaceted roles of plant extracts in promoting the crucial proliferative phase of wound healing, offering valuable insights for potential therapeutic applications in clinical settings. However, it is imperative that further research, including clinical trials, be conducted to validate and translate these promising outcomes into safe and effective wound healing interventions for human patients.

3.6. The Action of African Plant Bioactives in Wound Healing

Compounds such as flavonoids, terpenoids, alkaloids, tannins, cannabinoids, germacrene D, α‐pinene, carene, phytol, and linolenic acid have been associated with wound healing due to their anti‐inflammatory, antioxidant, and antimicrobial activities. These properties are crucial for regulating the wound healing process [61, 96].

3.6.1. Flavonoids in Wound Healing

Flavonoids, phenolic compounds abundant in most plants, exhibit excellent anti‐inflammatory properties crucial for wound healing. This effect was substantiated in a study by Majtan et al. (2013), which examined the in vitro effects of flavonoids (Apigenin and kaempferol) isolated from fir honeydew honey on human keratinocytes (HaCaT) with TNF‐α dependent overexpression of metalloproteinase‐9 (MMP‐9) [121, 122]. MMP‐9 belongs to the gelatinase class of the MMP family. Under normal conditions, it degrades and removes excess old extracellular matrix (ECM) during inflammation, facilitating angiogenesis and cell migration during re‐epithelialisation. However, an uncontrolled increase in MMP‐9 production has been implicated in the progression of chronic wounds. This continuous ECM degradation reduces tensile strength, impairs cell migration and angiogenesis, and leads to persistent infiltration of wound sites with pro‐inflammatory cytokines, causing prolonged inflammation (a characteristic of non‐healing wounds).

The demonstrated anti‐inflammatory effects of flavonoids, as highlighted above, present a promising avenue for therapeutic interventions in wound care. By modulating MMP‐9 activity, flavonoids show potential in mitigating chronic inflammation, promoting a balanced ECM turnover, as shown in Figure 2, and ultimately fostering an environment conducive to effective wound healing. As research in this field advances, these findings pave the way for the development of targeted strategies utilising flavonoids to enhance the treatment of chronic wounds.

FIGURE 2.

Action of phytochemicals in wound healing. The illustration delineates mechanisms by which phytochemical compounds promote wound healing. Flavonoids reduce inflammation by preventing the accumulation of reactive oxygen species (ROS) and inhibiting TNF‐α secretion, regulating the production of metalloprotease‐9 overexpression thereby preventing ECM degradation. Terpenoids reduce inflammation by inhibiting oedema caused by the formation of hypochlorous acid through myeloperoxidase (MPO) activity; this in turn prevents ECM degradation catalysed by MPO activity. Alkaloids have antimicrobial properties and promote cell proliferation. Antimicrobial, anti‐inflammatory, antioxidant, and proliferative activities are critical for wound healing. Created in BioRender. BioRender.com/j95t339.

3.6.2. Terpenoids in Wound Healing

Terpenoids are naturally occurring plant compounds from the terpene family, exhibiting remarkable wound healing effects, as demonstrated in various research studies. For instance, Riella and colleagues (2012) isolated and investigated the wound healing effects of thymol, a monoterpene extracted from the essential oil of Lippia gracilis leaves, in rodents. Thymol displayed potent anti‐inflammatory activity by significantly reducing oedema caused by hyperaemia and inhibiting myeloperoxidase (MPO) activity, as illustrated in Figure 2. MPO catalyses the production of hypochlorous acid, which is responsible for excessive degradation of ECM and contributes to tissue damage. Additionally, the use of collagen‐based thymol‐infused wound dressings promotes collagen production and arrangement in the wound area, thereby enhancing wound contraction and promoting wound closure [123, 124].

In essence, these findings not only highlight the specific benefits of thymol but also contribute to the broader understanding of terpenoids as a class of compounds with substantial therapeutic potential in the field of wound healing. As research in this area progresses, the insights gained from studies such as these pave the way for innovative wound care strategies, potentially harnessing the unique properties of terpenoids for improved clinical outcomes.

3.6.3. Alkaloids in Wound Healing

Alkaloids occur naturally and are produced by bacteria, fungi, plants, and animals. Over the years, alkaloids have been found to possess important pharmaceutical characteristics, serving various roles such as analgesics, anti‐malarial agents, anti‐neurodegenerative agents, and wound healing agents, among others [125]. In 2014, Fetse and colleagues demonstrated the antimicrobial and wound healing effects of alkaloid extracts from Alstonia boonei root bark. Using the well diffusion method to test extracts against various microorganisms such as P. aeruginosa , B. subtilis , S. aureus, and E. coli , the extracts demonstrated high antimicrobial potency. Conversely, wound healing effects were elucidated via testing on healthy Sprague‐Dawley rat excisions, and their findings showed significant wound healing properties by accelerating the rate of wound contraction, which also indicated a reduction in the period of re‐epithelialisation [126].

A year later, Gould and co‐workers (2015) demonstrated the wound healing effect of an alkaloid‐rich Senecio serratuloides plant extract in pig models. Upon extract administration and wound monitoring, a significant decrease in wound area was observed, suggesting that the extracts accelerated cell proliferation and promoted wound contraction significantly, with minimal liver toxicity reported [127].

To conclude, the cumulative outcomes of these studies reinforce the potential of alkaloids as promising agents in the field of wound healing. The confirmed antimicrobial effectiveness, combined with the demonstrated capacity to expedite wound contraction and reduce re‐epithelialisation periods, as Figure 2 illustrates, establishes alkaloids as noteworthy contenders for further investigation and possible integration into wound care strategies.

3.7. Preclinical and Clinical Wound Models and Challenges

Preclinical and clinical models play an important role in evaluating wound healing interventions, each offering unique insights at different stages of translational research. Preclinical models include in vitro, ex vivo and in vivo animal models [128]. In vitro assays employ scratch, Transwell/Invasion assays, spheroids, organoids and 3D skin equivalent models. The scratch assay models 2D cell migration but lacks tissue complexity. Transwell/invasion assays, on the other hand, evaluate directional migration or matrix invasion, providing quantifiable data but having limited physiological relevance [129]. Spheroids mimic 3D cell–cell interactions and gradients; they lack full tissue architecture [130]. Although organoids replicate organ‐like structures with multiple cell types, enhancing physiological relevance, they are complex and variable [131]. Meanwhile, 3D skin equivalents closely resemble human skin with layered structure, offering high translatability but are costly and technically demanding [132].

Ex vivo models, including human explants and organotypic cultures [133], provide physiologically relevant data while avoiding systemic variables like immunogenicity. However, they have a short culture span, with donor variability. In vivo animal models range from rodent excisional/incisional, burn and diabetic wounds to rabbit ischemic wounds, which heal primarily by wound contraction, to porcine full‐thickness models, closely mimicking human physiology [134, 135]. Together they enable evaluation of the complete wound healing cascade, including inflammation, angiogenesis, and matrix remodelling. Several African medicinal plants, such as Ageratum conyzoides , Aspilia africana and Terminalia sericea , have been tested in these models, particularly in rodent and porcine models, to assess their wound healing properties, demonstrating enhanced re‐epithelialisation, collagen production and antimicrobial effects [78, 96, 107].

Clinical models, on the other hand, are essential for assessing efficacy and safety in human subjects, using standard acute wounds or chronic wounds like diabetic foot and venous leg ulcers [136, 137]. Despite their systemic relevance, ethical constraints, interpatient variability, and comorbidities are limiting. Overall, while the complexity and translatability increase from scratch to 3D models, each has trade‐offs in cost, scalability, reproducibility, and physiological fidelity. Nevertheless, together, these models help bridge the gap between laboratory findings and clinical application.

4. Discussion and Future Remarks

Based on the reviewed literature, the extensive diversity and utilisation of medicinal plants in traditional African medicine have captured the attention of researchers. Existing findings indicate that plants contain phenolic compounds, flavonoids, tannins, alkaloids, and terpenes, which play roles in various wound healing stages. In vitro and animal studies have demonstrated that plant extracts and their derivative formulations possess antioxidant, antimicrobial, haemostatic, anti‐inflammatory, proliferative, and angiogenic effects. These attributes enable plants to restore equilibrium in wounds with delayed healing times by regulating oxidative stress, promoting angiogenesis, cell proliferation, collagen formation, and wound contraction, ultimately reducing re‐epithelialisation time, promoting wound closure, and facilitating remodelling, summary is illustrated in Figure 3. These findings suggest that medicinal plants may provide a solution to existing drug limitations, being natural and demonstrating low toxicity and high efficacy. New, naturally based therapeutics have the potential to improve the quality of life for affected individuals as well as alleviate the economic burden.

FIGURE 3.

Medicinal plants and bioactives as prospective agents for wound healing therapy. The illustration summarises the process by which medicinal plant bioactives, obtained from (A): plant sampling, (B): extraction using solvents like methanol (MeOH), ethanol (EtOH), water (H₂O), ethyl acetate (ETA), natural deep eutectic solvents (NADES). Crude extracts are profiled in (C): using analyses like gas chromatography–mass spectrometry (GC/MS), liquid chromatography–high‐resolution mass spectrometry (LC–HRMS), nuclear magnetic resonance spectroscopy (NMR) to identify (D): compounds in extracts which are then screened in (E): current wound models (i) in vitro and (ii) animal models for (F): wound healing activities. Studies have shown that plants containing phenolic compounds such as flavonoids, alkaloids, and terpenoids possess antimicrobial, anti‐inflammatory, proliferative, and angiogenic effects. These attributes allow for the restoration of homeostasis in non‐healing wounds by regulating oxidative stress, promoting angiogenesis, cell proliferation, collagen formation, and wound contraction, reducing re‐epithelialisation time and promoting wound closure. Because current models fail to closely mimic human physiological processes, (G): advanced methods including (i)‐in silico, computational modelling, (ii)‐organoids/organotypic models, (iii)‐ex vivo and ultimately (iv)‐in vivo (human) are needed to improve plant screening for better relatability and application in (H): (i) drug design and (ii) topical wound therapies. This gives a promising insight into the potential of the use of medicinal plants and bioactives in the development of natural‐based wound therapies. Created in BioRender. BioRender.com/z23f517.

The challenge in these studies was poor metabolic profiling and screening models. Several plants that have shown wound healing activities are poorly characterised, leading to a lack of understanding of their mechanisms in wound healing. Current models include in vitro 2D monolayers and animal models, which pose challenges due to their relevance to human physiology. Although 2D models are easy to use and show preliminary potential at a low cost, they do not mimic the physiological environment and lack cell‐matrix interactions crucial for signal transduction in wound healing. On the other hand, the anatomy and physiology of animal wound and scar models differ significantly from those of humans, resulting in erroneous interpretations. Consequently, results obtained using these models may not directly translate to what occurs in human skin wounds, contributing to an inability to translate these animal‐based study findings to clinical use.

In the future, more work is needed to characterise plant metabolites and improve the relevance of medicinal effects of plant extracts and isolated compounds by selecting suitable models to ensure physiological relevance, reliability, and applicability of medicinal actions in humans. The use of more robust preclinical 3D models, such as spheroids, organoids, organotypic, and ex vivo human skin wound models that can mimic the wound physiological environment, could potentially generate reliable and translatable results.

5. Conclusion

Our comprehensive review has identified 10 plant species with tissue repair activity and unveiled their unique contributions to different phases of cutaneous wound healing. The diversity of African medicinal plants and their wound healing attributes has gained considerable attention recently; this will provide an opportunity for continued groundbreaking research to identify novel therapeutic agents for the treatment of wounds. Improving data on plant metabolomics and refining screening models will undoubtedly contribute to a deeper understanding of the mechanistic role of plants in wound healing, ensuring that the results obtained are relevant to human skin healing.

Conflicts of Interest

The authors declare no conflicts of interest.

Molefe P. F., Ghasemishahrestani Z., Mbele M., et al., “African Medicinal Plants in Cutaneous Wound Repair: A Comprehensive Analysis of the Role of Phytochemicals,” International Wound Journal 22, no. 8 (2025): e70742, 10.1111/iwj.70742.

Data Availability Statement

The authors have nothing to report.