Abstract
Over the decades, plant-derived phytochemicals have attracted attention as potential therapeutics for wound healing. Moringa oleifera Lam. (M. oleifera) has been traditionally used as herbal remedy in wound healing. To our knowledge, there is a lack of a comprehensive synthesis of evidence on M. oleifera’s wound healing properties. This review aimed to identify literatures that evaluated the pharmaceutical applications of M. oleifera plant in wound healing through in vivo and in vitro studies. Following the PRISMA-ScR guideline, a comprehensive scoping review was conducted on four major electronic databases (ScienceDirect, PubMed, Academic Search Complete, and Semantic Scholar) from 2014 to June 2025 for in vivo or in vitro studies, that evaluated the effects of M. oleifera on wounds. The search on four databases produced 47 studies. Findings revealed that M. oleifera exhibited wound healing activity, through cell proliferation and wound contraction, particularly the leaves of M. oleifera extract also demonstrated increased tensile strength and proliferation rate of wound, and exhibited anti-inflammatory, antioxidant, anti-diabetic, and anti-bacterial properties. Further research should investigate the bioactive compounds in M. oleifera, and the molecular healing mechanisms of M. oleifera.
Keywords
Introduction
A wound is referred to as a breakage or injury to the integrity of the skin epithelium due to physical, chemical, or microbiological harm, typically resulting in contusion, hematoma, lacerations, or abrasions. 1 The wound healing process is described as a natural mechanism that comes into place to restore normal skin integrity, and to prevent exsanguination. This natural process consists of four dynamic overlapping phases: hemostasis, inflammation, proliferation, and remodeling. A disruption or prolongation of these phases will result in delays in the wound healing process. Therefore, over the centuries, various methods have been employed to treat wounds, yet modern wound healing practices have only been ventured in the twentieth century. 2
In the United States alone, annual expenditure on wound care had been estimated to increase significantly from $2.8 billion to $3.5 billion by 2021. 3 Similarly, Monika et al. found that approximately 6.5 million patients were affected by chronic wounds, with an estimated annual expenditure of $25 billion on chronic wound care. 4 Additionally, individuals with concomitant lifestyle diseases are at higher risk for developing chronic wounds. Yazarlu et al. found that chronic wounds were highly associated with hyperglycemia, poor diet, poor blood circulation, trauma, autoimmune diseases, and insufficient wound care in the early stages of injury. 5 If a wound is left untreated, chronic wounds can develop, resulting in serious complications such as amputation, which significantly impairs quality of life. Chronic wounds require a longer time to heal as the wound healing stages are disrupted and do not progress normally. On top of that, chronic wounds are more prone to microbial infections as the exposure to bacteria is prolonged. Some common pathogens which invade chronic wound are Staphylococcus aureus as well as common fungi such as Candida albicans. Chronic wounds such as non-healing traumatic wounds, diabetic foot ulcers, and pressure ulcers could contribute to significant economic burden, deterioration of health-related quality of life, and increased emotional stress of the patient. Thus, proper wound care such as regular debridement of wounds and appropriate wound dressing is essential. For instance, the absorptive capacity of the wound dressing should correspond to the volume of wound exudate. 6
Locally known as “pokok kelor” (Malay), the Moringa oleifera Lam. (M. oleifera) plant is a fast-growing medicinal plant of the Moringaceae family. It is typically known as the drumstick tree, horseradish tree, miracle tree, or mother’s best friend tree. 7 This plant is commonly found indigenous to North India, Bangladesh, Pakistan, and Afghanistan. It is widely distributed in many tropical and subtropical countries, including Malaysia. It is extensively cultivated throughout the world owing to its ability to adapt to extreme conditions such as mild frost and bad droughts. Additionally, M. oleifera has always been recognized and appreciated since most parts of the plant can be used in treating various ailments. 8
Every part of the M. oleifera tree including seeds, oils, fruits, leaves, and roots is valuable for commercial and nutritional purposes due to the presence of various nutraceutical and pharmacological functions. M. oleifera is rich in nutrients such as proteins, minerals, vitamins, and carotenoids that are essential for humans and animals. For instance, the leaves of M. oleifera are used as vegetables and nutritional supplements while the seeds of M. oleifera are consumed fresh, dried, or as roasted tea. For decades, M. oleifera has been used as anti-diabetic, anti-microbial, and anti-inflammatory agent. 9
It remains a global challenge to design and develop an adequate wound dressing which could effectively manage both acute and chronic wounds by facilitating the wound healing process. In light of the many traditional uses of M. oleifera in wound healing, the aim of this scoping review is to identify and present the literatures that evaluated the pharmaceutical applications of M. oleifera and their bioactive compounds in wound healing through in vivo or in vitro studies.
Methodology
This scoping review aimed to answer the research question “What are the pharmaceutical applications of M. oleifera plant in wound healing?” This scoping review was carried out in compliance with the criterion set in Preferred Reporting Items for Systematic reviews and Meta-analyses extension for Scoping Reviews (PRISMA-ScR) guideline and the Joanna Briggs Institute (JBI). 10 The comprehensive review of evidence in this study focused on evaluating the effects of M. oleifera on wound healing, incorporating in vitro and in vivo studies, along with evaluating the bioactive compounds identified in the studies.
Data Sources and Search Strategy
The search for studies evaluating the pharmaceutical application of M. oleifera in wound healing was carried out on four major electronic databases: ScienceDirect, PubMed, Academic Search Complete, and Semantic Scholar from 2014 until June 2025. The reference list of retrieved articles was examined manually to locate additional relevant literatures that were not found during database searches.
The Population Concept Context (PCC) framework was used to construct the search terms which included keywords relevant to M. oleifera, and wound healing. The keywords were combined using Boolean operators (“OR” and “AND”) to form structured search strategies including (“Moringa oleifera” OR “M. oleifera”) AND (“chronic wound healing” OR “wound healing” OR “wound dressing” OR “dressing” OR “wound” OR “wounds”) (Appendix A). During the pilot search on two prominent databases namely ScienceDirect and PubMed, the search strategies used were evaluated and analyzed with a second reviewer, for validation of search strategies before their implementation across other databases.
Selection Criteria
All publications were screened for the following criteria for inclusion: (a) Original research reporting the wound healing efficacy of M. oleifera; (b) Studies published from 2014 to 2025; (c) Full-text articles in English language. Studies were excluded from the review if they (a) did not evaluate M. oleifera; and (b) reported outcomes other than wound healing.
Selection of Articles
All citations obtained from the database searches were imported into a reference management software, Mendeley Reference Manager, for deduplication. The search results were then independently screened by two reviewers (CSM and CCY). The study selection process involved two stages of screening: first, the screening of title and abstract; and second, the screening of the full text of the articles. The screening of title and abstract was blinded to both reviewers using the online screening tool, Rayyan.ai, where both reviewers will independently sort the literatures in accordance with the pre-defined eligibility criteria. Based on the title and abstract, each article was categorized as either “Excluded,” “Maybe” (requires more information to make inclusion decision), and “Included.” Finally, full texts of “Maybe” and “Included” articles were obtained for a second blinded screening for inclusion into the study. Any discrepancies in the inclusion decision were resolved through mutual consensus between the reviewers.
Data Extraction
The information on study characteristics and demographics including the author, year of publication, country, type of study model, plant part analyzed, extract formulation, controls, chemical constituents investigated, type of wound model, and wound healing activity of M. oleifera were independently extracted by one reviewer (CSM) and verified by a second reviewer (CCY). A standardized data extraction table was formed and piloted to improve the relevance of data extraction in meeting the purpose of this scoping review.
Results
Study Selection
The search for literature across four major electronic databases has produced 2393 records, of which 215 were excluded as duplicates. The title and abstract of 2178 articles were screened, of which 89 were included for the subsequent step of screening. As two articles were unable to be retrieved, 87 full-text articles were assessed for eligibility, of which 40 articles were further excluded leaving 47 articles included in this scoping review. The overall flowchart of the literature search was presented in Figure 1.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) Flow Diagram. Flow Diagram of the Search for Eligible Literature Regarding the Pharmaceutical Application of M. oleifera Plant on Wound Healing.
Characteristics of Included Studies and Evidence of Wound Healing Activity
The 47 articles included in this scoping review were published between 2014 to June 2025. The studies were carried out in Malaysia (n = 7), India (n = 10), Indonesia, (n = 7), Nigeria (n = 5), Brazil (n = 3), Pakistan (n = 3), Egypt (n = 3), Morocco (n = 1), Saudi Arabia (n = 1), Iraq (n = 1), Mexico (n = 1), Bangladesh (n = 1), China (n = 1), Algeria (n = 1), and the Philippines (n = 2). The plant parts of M. oleifera used in the included studies were leaves (n = 33), seeds (n = 7), twigs (n = 1), roots (n = 1), and aerial parts (n = 5). All studies were non-clinical research, encompassing 36 in vivo experiments studies, eight in vitro experiments, and three mixed experiments. A total of 45 studies evaluated the effects of topical M. oleifera extract application. One of the other two studies reported the oral administration of aqueous-based M. oleifera extract (Azevedo et al., 2018), while another reported the dual application of both topical and oral formulations (Eyarefe et al., 2015). The summary of the main characteristics and findings of the included studies is outlined in Tables 1, 2, 3, 4, and 5.
Characteristics of the Included Studies and Application of M. oleifera Leaves in Wound Healing.
Characteristics of the Included Studies and Application of M. oleifera Seeds in Wound Healing.
Characteristics of the Included Studies and Application of M. oleifera Twigs in Wound Healing.
Characteristics of the Included Studies and Application of M. oleifera Aerial Parts in Wound Healing.
Characteristics of the Included Studies and Application of M. oleifera Roots in Wound Healing.
The majority (n = 35, 74.47%) of the included studies implemented a similar approach in measuring wound healing activity which was the percentage or rate of wound closure. Subsequently, fibroblast proliferation was reported in terms of period of epithelialization and mean fibroblast count.11–21 To investigate the potential toxicity of M. oleifera, cell viability and signs of toxicity were reported, as well (Chin et al., 2019; Gothai et al., 2017; Gothai et al., 2016; Lim et al., 2019). Pro-wound healing properties such as antioxidant,15,20 anti-inflammatory,17,22,23–26 anti-bacterial,15,27,28 and anti-diabetic 29 were extracted and analyzed in this study. Moreover, four studies reported the tensile strength of restored wounds.25,30–32 Lastly, three studies did not specify the wound healing measures used and have only indicated whether wound healing was improved with M. oleifera intervention.33–35
Discussion
Principal Findings
The present scoping review evaluated 47 studies published from 2014 to 2025. To our knowledge, this is the first scoping review which investigated both in vivo and in vitro studies of wound healing pharmaceutical applications of M. oleifera extracts. The findings from this study suggested that the leaves, seeds, twigs, roots, and aerial parts of the M. oleifera plant are effective in facilitating the wound healing process when administered topically. The therapeutic potential of M. oleifera includes wound contraction, fibroblast proliferation, and increased collagen density, and properties such as anti-microbial, anti-inflammatory, and antioxidant. M. oleifera was also found to be non-toxic and safe to use on wounded skin in cell viability tests. Our evidence synthesis highlights the potential role of M. oleifera as a wound healing agent, particularly the leaves of the plant, based on preclinical data. It is noteworthy that only non-clinical research was included in this review; hence, the translation of findings from this study to real-life settings requires more clinical evidence.
Nutritional Characteristics and Bioactive Compounds of M. oleifera
Various phytocomponents of the M. oleifera plant, specifically the leaves, have served as a vital source for essential nutrients and therapeutics. According to Zarina et al., the nutritive components in M. oleifera include vitamin A (1.28 mg), vitamin B1 (0.06 mg), vitamin B2 (0.05 mg), vitamin B3 (0.8 mg), vitamin C (220 mg), vitamin E (448 mg), and chlorophyll (80 mg). 36 Additionally, polyunsaturated fats such as oleic acid, linoleic acid, and linolenic acid were found to be abundant in the M. oleifera plant, which makes the plant a potential healthy alternate for olive oil. 77 Other bioactive compounds of the M. oleifera leaf includes glucosides such as isothiocyanate, alkaloids such as saponin, carotenoids such as beta-carotene, phenolic compounds such as phenolic acid, polyphenols such as flavonoids and non-flavonoids. Phenolic compounds have a hydroxyl group directly attached to the aromatic ring which gives them their potent scavenging properties. 37 Our findings confirmed the presence of the bioactivity of these compounds. Several examples of phenolic acid present include chlorogenic acid, gallic acid, and caffeic acid. Additionally, the examples of flavonoids include vicenin-2, hesperidin, rutin, quercetin, kaempferol, and myricetin. Flavonoids constitute the largest portion of phenolic compounds found in the leaves. 38 Since the leaves of the M. oleifera plant contain a wide array of phytochemicals, the leaves are the most commonly studied part of the plant for wound healing properties.
Wound Healing Mechanisms of M. oleifera
Wound Closure
Among the 47 studies included in this review, wound contraction or wound closure outcomes were reported in the study of leaves (n = 25), seeds (n = 6), roots (n = 1), and aerial parts (n = 3) of the M. oleifera plant. Based on the 35 studies which reported this outcome, topical treatment with M. oleifera leaves and seeds extract exhibited a high rate of wound contraction or percentage of wound closure compared to positive and untreated controls. For instance, the study by Benkiran et al. observed that both ethanol-based and aqueous-based M. oleifera leaves extract ointment achieved nearly complete burn wound closure on the 14th day of treatment compared to standard (1% silver sulfadiazine; 47.42% wound contraction). 23 Similarly, another in vivo study found that the rate of wound contraction in excision wounds of diabetic rats was significantly higher with aqueous-based M. oleifera leaves extract ointment compared to no treatment. 17 The improvement in wound contraction and tissue granulation with M. oleifera leaves extract could be attributed to the presence of gluconic acid, rosmarinic acid, chlorogenic acid, rutin, quercetin, kaempferol, and vicenin-2. 39 The accelerated wound healing with M. oleifera extracts treatment could be due to the potential synergistic activity between the bioactive compounds present in the extract. This is further supported by the study conducted by Muhammad et al. who concluded that vicenin-2, one of the major bioactive compounds in M. oleifera leaves, is responsible for the upregulation of vascular endothelial growth factor (VEGF) suggesting enhanced angiogenesis. 17 Similarly, Chin et al. observed a significant increase in epidermal growth factors (EGF) and VEGF in 0.5% M. oleifera leaves extract compared to no treatment. 22 Since EGF and VEGF are critical for early-stage fibroblast activation and angiogenesis, the increase in their expression helps accelerate wound healing.
On the other hand, one study conducted by Eyarefe et al. found that oral treatment with aqueous-based M. oleifera leaf extract (5.600 ± 0.84) exhibited lesser wound closure and lower granulation tissue compared to no treatment (5.150 ± 1.05) on the fifth day of treatment. 40 The same study reported that oral administration of M. oleifera extract and antibiotic tetracycline were not effective as anti-microbial agents in Staphylococcus aureus-infected wounds. This could be associated with an increase in oxidative stress induced during biotransformation of oral M. oleifera extract which impairs wound healing. 41 Hence, this suggested that topical administration of M. oleifera extract is more effective in wound healing compared to oral route. To reinforce these findings, Panchatcharam et al. who studied the topical application of curcumin in wound healing, concluded that topical wound healing products are more effective in facilitating wound closure due to greater local effect at the site of injury. 42 The topical route was found to be superior to oral route in wound healing owing to the lower potential for systemic toxicity.
One study incorporated M. oleifera seeds extract into silver nanoparticles. 43 In this study, treatment with silver nanoparticles of M. oleifera seed extract demonstrated higher rate of wound contraction (91%) compared to positive control, betadine ointment (42%) (p < .005). A molecular mechanism study on the treatment with silver nanoparticles with M. oleifera seed scaffold found upregulation of interleukin-10 (IL-10) and VEGF. Expression of transforming growth factor beta (TGF-β) and small mothers against decapentaplegic homolog 3 (SMAD-3) were significantly reduced indicating the promotion of cell migration with minimal scar formation. 43 In line with these findings, higher rate of wound closure was observed in healthy, immunocompromised, and diabetic Swiss mice groups when treated with M. oleifera seed extract oil compared to controls. 44 This highlights the wound healing potential application of M. oleifera seed extract oil in different disease groups.
In addition, Fernandes et al. found that the flower extract of the M. oleifera plant achieved wound closure in a shorter period compared to leaf extract of M. oleifera and control (Phosphate buffer solution). 45 Nevertheless, Dilawar et al. who evaluated various aerial parts of the M. oleifera plant concluded that the leaves demonstrated superior wound healing efficacy compared to other aerial parts (stem, bark, flower, fruit, and seed) and control. 34 It was noted in the same study that leaf and bark extracts significantly decreased epidermal thickness when exposed to UVB radiation. This indicated that these extracts could impede the hyperproliferation of keratinocytes which occurs during skin exposure to UVB radiation.
Additionally, the bark extract of the M. oleifera plant were studied in two included studies. One formulation study from India found higher rate of burn wound contraction 11 days post-treatment in 5% and 10% hydroalcoholic M. oleifera bark extract ointment (75%–80%) compared to untreated control (p < .001). 46 The presence of a wide array of metabolites in the bark may be responsible for the underlying mechanisms facilitating wound healing. Phytochemical analysis of the same study revealed the total phenolic content was 52.56 ± 0.76 mg/gm gallic acid equivalent and total flavonoid content was 84.33 ± 0.44 mg/gm quercetin. Similarly, in diabetic excision-type wound rat model, Manhas and Malairaman (2024) found significant wound healing effects of M. oleifera hydroalcoholic bark extract compared to untreated controls, indicating M. oleifera bark’s potential use for chronic wounds such as diabetic foot ulcers. 47
Fibroblast Proliferation and Cell Viability
Extracts of M. oleifera leaves and seeds demonstrated significant increase in mean fibroblast count and rate of proliferation and decrease in epithelialization period.11–21 The accelerated wound healing with M. oleifera treatment may be attributed to the presence of flavonoids. One systematic review focusing on the mechanisms of action of flavonoids discovered that flavonoids are responsible in the activation of the Ras/Raf/MEK/ERK pathway which stimulates proliferation, maturation of keratinocytes, and upregulation of matrix metalloproteinase-9 (MMP-9) for re-epithelialization. 48 On the other hand, Chin et al. reported that only the lowest concentration of M. oleifera leaves extract (12.5 μg/mL) tested were effective in improving wound healing, contrasting with concentrations ranging from 25 μg/mL to 100 μg/mL. 39 Similarly, Rodríguez-García et al. found that the highest tested concentration of M. oleifera leaves extract exhibited anti-proliferative activity. 13 The findings were in line with the Arndt-Schulz Law where a lower dose of substance would stimulate growth while a higher dose would inhibit cell growth. 39
Moreover, one study on oral wound healing unveiled that the application of 2% (24 ± 3) and 4% (32 ± 5) M. oleifera leaves extract gel resulted in higher fibroblast count compared to povidone-iodine standard treatment (18 ± 3) (p < .00). 12 Given the difficulty in sterilizing the oral cavity, thereby higher exposure to oral pathogens and plaque formations, oral wounds require a longer time to heal, typically ranging from approximately two to four weeks. However, treatment with M. oleifera leaves extract gel has reduced wound healing time to within two weeks. This suggested that the potential wound healing benefits of M. oleifera leaves extract extend beyond skin wounds encompassing oral wounds, such as in periodontal surgery treatment.
Several studies have investigated the toxicity of M. oleifera leaves extract.20–22,49 The M. oleifera leaves extract are generally safe and non-toxic up to specific concentrations. For instance, Gothai et al. found that all concentrations of ethyl acetate-based M. oleifera leaves extract (15.62–500 μg/mL) were non-toxic in normal human dermal fibroblast (HDF) cells. 21 However, when tested on diabetic HDF, a concentration-dependent inhibition of cell growth was found where concentrations above 125 μg/mL increased cytotoxicity by 40% by 24 hours. Similarly, Chin et al. observed that treatment with 0.1%, 0.5%, and 1.0% M. oleifera leaves extract did not show any signs or symptoms of toxicity on animal skin at all point of treatment (24 hours, seven days, 14 days). 22 On the other hand, Lim et al. observed a decrease in cell viability at higher concentrations (>1.5 mg/mL) of aqueous-based M. oleifera leaves extract-loaded phytophospholipid complex (MOPCT) compared to filtered formulations of MOPCT. 49 This may be attributed to the presence of free compounds in the unfiltered formulation which cause toxicity.
Antioxidant Activity
Numerous findings from this review suggested that M. oleifera leaves extract possessed antioxidant activities.15,20 A recent study conducted by Al-Ghanayem et al. echoed similar sentiments when they observed significantly higher levels of antioxidant enzymes, SOD, and catalase, with treatment of methanol-based M. oleifera leaves extract ointment in MRSA-infected wounds compared to control (p < .001). 15 This was attributed to the presence of phenolic compounds in the M. oleifera leaves extract which increases oxidative stress tolerance and prevents cellular damage. 20 In vitro antioxidant activity showed that M. oleifera leaves extract wound dressing reduced oxidative stress at wound site by possessing hydrogen peroxide, hydroxyl, 2,2-Diphenyl-1-picrylhydrazyl (DPPH), and nitric oxide radical-scavenging activity and reducing power. 20 This was further supported by Akanji and Sonibare who concluded that flavonoids and tannins in M. oleifera leaves extract are responsible for their antioxidant activity, whereas quercetin possessed both antioxidant and anti-inflammatory properties through the stimulation of keratinocyte growth. 18 As acute wounds become infected, the inflammatory phase is prolonged causing production of tissue oxidants which impairs wound healing and causes further cellular damage. Hence, antioxidant properties are essential in wound healing products as they contribute to reducing free scavenging radicals resulting in improvement in regeneration and organization of wounds.
Anti-inflammatory Activity
Moreover, the leaves and seeds of M. oleifera demonstrated anti-inflammatory effect in various studies.17,22,23–26 Pro-inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) are crucial mediators for the initiation of the repair process by recruiting keratinocytes and fibroblasts to the wound site. However, prolonged high concentrations of pro-inflammatory cytokines would induce high concentrations of proteases such as matrix metalloproteinases (MMPs) resulting in impaired wound healing. 50 Hence, upregulation of cytokines at the early stages and downregulation of pro-inflammatory cytokines at the later stages of wound healing are essential to ensure appropriate wound healing. This is in accordance with a study which reported that expression of IL-6 (p < .001) and TNF-α were significantly increased in 0.1%, and 0.5% M. oleifera leaves extract group in abrasion wounds compared to no treatment at day 3 post wound. 22 At day 21 post treatment, Muhammad et al. observed that the expression of IL-6, interleukin-1β (IL-1β) and TNF-α were significantly downregulated in 0.5%, 1%, and 2% M. oleifera leaves extract group compared to untreated diabetic control (p < .05). 17 The anti-inflammatory mechanism of M. oleifera may be attributed to the presence of bioactive compounds such as β-sitosterol, vanillin, and 4-hydroxymellein. 51 These findings suggest that M. oleifera leaves extract are capable of preventing a prolonged inflammatory state thereby potentially averting the chronicity of wounds. However, it is noteworthy that the inflammatory state in animal models does not fully represent human wounds due to the immunological differences; thus, it is essential to study the anti-inflammatory effects of M. oleifera on human wounds. 52
Only two studies investigated the anti-inflammatory effects of M. oleifera seed extract.24,26 Meziou-chebouti et al. found that aqueous-based M. oleifera seed extract significantly reduced percentage of edema and are comparable to the standard used (D-clofenal→), a type of non-steroidal anti-inflammatory drug (NSAID). 24 Gene expression analysis found that inflammatory markers including TNF-α and IL-1β were significantly down-regulated with methanol-based M. oleifera seed extract oil. 26 The same study found that the bioactive compounds, quercetin, caffeic acid, and kaempferol, exhibited highest inhibitory potential toward pro-inflammatory cytokine interleukin-6 (IL-6), and matrix metalloproteinases I and II. Hence, M. oleifera seed and leaves extract is a promising novel anti-inflammatory agent replacement for NSAID. The M. oleifera plant extract is a promising source to prevent the prolongation of the inflammatory phase in wound healing.
Anti-bacterial Activity
Contamination of the wound is a common occurrence when the wound is exposed to the external environment. Some common pathogens found in skin wounds include Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. 53 Fayemi et al. revealed that M. oleifera leaves extract were effective in inhibiting the growth of S. aureus and E. coli. 27 Additionally, Al-Ghanayem also found that M. oleifera leaves extract ointment were effective in inhibiting both methicillin-resistant S. aureus (MRSA) and to P. aeruginosa; however, susceptibility of MRSA to the antibacterial effects of M. oleifera were more prominent compared to P. aeruginosa. 15 The terpenoid, alkaloid, and phenolic compounds in the plant extract disrupt the structural integrity of the microorganism’s cell membrane by interacting with proteins and enzymes, thereby inducing cell death. 54 In contrast to these findings, Natarajan et al. found that M. oleifera leaves extract did not possess anti-bacterial effect against all three pathogens (E. coli, S. aureus, and P. aeruginosa). 28 It is noteworthy this study was the only one that found opposite effects of M. oleifera extract in antimicrobial activity. This indicated that the pro-wound healing effects of M. oleifera may result from a synergy of various mechanisms such as anti-inflammatory and antioxidant activity rather than solely relying on a single mechanism.
Since wound infections can delay wound healing and increase morbidity, prevention, and management of these infections remains a crucial step in wound healing. Modern treatment which includes antibiotics tend to give rise to antibacterial resistance and toxicity. For instance, silver sulfadiazine, a topical antibiotic, could impede wound healing by inhibiting cytokine IL-6 which is critical in macrophage activation. 16 Therefore, M. oleifera extract is a potential plant with anti-bacterial and wound healing properties with minimal side effects.
Tensile Strength
Four studies reported the tensile strength outcome. 55 First, Ali et al. evaluated the hexane-based M. oleifera seed extract hydrogel and reported that treatment with extract gel reported higher tensile strength in incision wounds compared to standard (5% povidone-iodine). 31 Moreover, Moura et al. evaluated the hexane-based M. oleifera leaf extract hydroxyethyl cellulose gel and reported that treatment with the extract gel reported higher collagen maturation index compared to control (AGE ointment). 25 Our findings revealed that the increase in tensile strength was attributed to greater collagen deposition and maturation and better reorganization, leading to stabilization of collagen fibers. This is further supported by Rathi et al. who concluded that treatment with aqueous-based M. oleifera seeds extract in incision and dead space models significantly increased hydroxyproline and collagen content. 56 Similarly, Chin et al. found that hydroxyproline concentration in a diabetic rat wound were significantly higher with treatment of 0.5% M. oleifera leaves extract (63.17 ± 8.69 μg/μL) compared to no treatment at day 21 post treatment (46.85 ± 14.53 μg/μL) (p < .05). 22 The same study found an increase in the expression of collagen type I alpha I (COL1α1), a type of collagen predominantly found in the dermis layer typically in mature healed wounds, with 0.1% (p < .01) and 0.5% (p < .05) M. oleifera leaves extract. This finding suggested that M. oleifera leaves extract improve partial thickness wound healing through the upregulation of COL1α1 expression. Therefore, the M. oleifera leaves and seed extract could accelerate wound healing by increasing collagen deposition and improving the tensile breaking strength of repaired wounds
Anti-diabetic Activity
Another study that investigated oral administration of aqueous-based M. oleifera extract (200 mg/kg) found that blood sugar levels were significantly reduced in streptozotocin-induced diabetic rats when comparing the second day and 10th day of treatment (p < .05). 29 The anti-diabetic effect of M. oleifera may be associated with the presence of bioflavonoids which promotes the uptake of glucose in peripheral tissues and regulates the enzyme expression involved in carbohydrate metabolism. 57 Several previous researches have validated the anti-diabetic properties of the M. oleifera plant extract in vivo experiments.57,58 Therefore, while direct facilitation of wound healing through oral treatment of M. oleifera may not be evident, M. oleifera may be effective in reducing hyperglycemia thereby improving wound healing. This is particularly beneficial in diabetic patients, who often experience impaired wound healing.
Strengths and Limitations
This study is the first that reviews the published experimental findings regarding the pharmaceutical application of M. oleifera on wound healing. It serves as a reference for the researchers for future formulation of wound dressing that can be applied for chronic wound healing. This is of utmost importance as diagnosis of diabetic foot ulcers is expected to increase due to the increasing prevalence of diabetes. Therefore, it is crucial to have a comprehensive scoping review on wound healing properties of M. oleifera to develop an effective, affordable, and non-toxic wound dressing to heal chronic wounds. Additionally, this study adhered to the scoping review guidelines (PRISMA-ScR).
One of the limitations in this scoping review is that it only included studies published in the English language. This may have caused potentially relevant studies published in languages other than English to be missed. In addition, this scoping review only evaluated the pharmaceutical applications of M. oleifera extracts through in vivo (animal models) and in vitro experiments. Hence, the translation of improved wound healing activity of M. oleifera extracts into improved clinical, humanistic, and economic outcomes remains unclear. Further research on the clinical efficacy M. oleifera are warranted to resolve these gaps.
Implications and Future Directions
By evaluating and identifying studies related to M. oleifera on wound healing, M. oleifera, particularly the leaves, appears to be a promising candidate to be incorporated into wound dressing for wound healing applications. Our findings on seed oils and other aerial parts of M. oleifera were insufficient to support the effective wound healing action of those parts. Thus, wound dressing that incorporates M. oleifera is affordable for most people (IDF Diabetes Atlas, 2019). However, only non-clinical research on the M. oleifera plant was carried out. Since the leaves of M. oleifera are produced in substantial amounts in subtropical countries, accessibility to the plant part is convenient and economical. Therefore, further research should be conducted to investigate and confirm the wound healing properties of the leaves of M. oleifera through clinical experiments.
Conclusion
M. oleifera, which is an herbal product, is gaining popularity as people become more aware of the negative consequences of synthetic components. The present review investigated the in vivo and in vitro studies which demonstrated that M. oleifera promotes a more effective wound healing process and is less expensive as compared to the current modern wound therapies. Since this review only included the in vivo studies that are conducted in animal models, the outcomes of animal studies may not be translated into human conditions immediately due to biophysiological differences among the species. However, our findings could point to a more practical application of M. oleifera for wound healing in the future. Our findings found that the leaves of M. oleifera were able to improve wound contraction rate, fibroblast proliferation, and wound tensile strength, and possess anti-inflammatory, antimicrobial, antioxidant, and antidiabetic properties. All in all, the leaves of the M. oleifera are a novel therapeutic approach which could be incorporated into wound dressing for wound healing application.
Footnotes
Acknowledgements
The author expresses gratitude to Dr. Chloe Chin Chai Yee for their guidance and to the Faculty of Health and Medical Sciences at Taylor’s University for providing general academic support.
Authors’ Contribution
The authors was in charge of conception and design, acquisition of data, and the analysis and interpretation of data; drafted the article and revised it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agrees to be accountable for all aspects of the work. The author is eligible to be author as per the International Committee of Medical Journal Editors (ICMJE) requirements/guidelines.
Consent to Participate
Not applicable.
Consent for Publication
Not applicable.
Declaration of Conflicting Interests
The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Ethics Approval
This study does not involve experiments on animals or human subjects.
Funding
The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was supported by the Ministry of Higher Education (MOHE), Malaysia through the Fundamental Research Grant Scheme (FRGS/1/2023/SKK06/TAYLOR/03/1).
Informed Consent
Not applicable.
Use of Artificial Intelligence-assisted Technology
The authors declares that they have not used artificial intelligence (AI)-tools for the writing and editing of the manuscript, and no images were manipulated using AI.
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Appendix
Structured Search Strategies for PubMed Database.
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|
|
“drumstick tree”[tw] |
|
|
|
| 2,379 | |
|
|
|
|
|
|
|
|
“wound healing”[MeSH Terms] |
|
|
“wound healing”[tw] |
|
|
“wounds and injuries”[MeSH Terms] |
|
|
“injury”[tw] |
|
|
“wound”[tw] |
|
|
|
| 2,015,640 | |
|
|
|
|
|
|
|
|
2014/01/01:2024/12/31[dp] |
|
|
|
| 115 | |
