Pharmaceutical Application of Moringa oleifera on Wound Healing: A Scoping Review

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

wound healing bioactive compounds

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.

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.

Table 1.

Characteristics of the Included Studies and Application of M. oleifera Leaves in Wound Healing.

Author, Year	Country	Type of Study (Type of Model)	Dosage/formulation	Controls	Chemical Constituents	Type of Wound	Main Findings
Al-Fathonah et al., 2025⁵⁵	Indonesia	In vivo (male Wistar mice)	10%, 20%, 40% M. oleifera extract gel	Bioplacenton (positive) Na-CMC (negative)	−	Burn	Post 7-day treatment with positive control group (Bioplacenton) exhibited highest collagen density (65.967%) as compared to 10% (50.844%), 20% (51.300%), 40% (62.433%) M. oleifera extract gel, and negative control (Na-CMC) (49.167%). Treatment efficacy of M. oleifera extract gel was not statistically significant (p > .05).
Dutta et al., 2025⁵⁹	India	In vivo (male Wistar Albino rats)	2.5%, 7.5% M. oleifera extract in 7.5% hydroxypropyl methylcellulose (HPMC)-based gel	7.5% HPMC gel (vehicle) USP 10%w/w povidone-iodine ointment (standard) Aloe vera gel (herbal standard)	−	Excision and incision	Treatment with standard group (povidone-iodine) reported the shortest number of days (6.41) to achieve 50% wound contraction, followed by, 5% M. oleifera gel group (7.10), aloe vera gel group (7.15), 2.5% M. oleifera gel group (8.26), and vehicle group (10.46) (p <.001).
Almehayawi et al., 2024⁶⁰	Egypt	In vitro (fibronectin extracellular matrix)	M. oleifera extracted under 15 MPa, 25 MPa, and 35 MPa supercritical CO₂ extraction	No treatment	Gallic acid, chlorogenic acid, catechin, methyl gallate, caffeic acid, syringic acid, pyrocatechol, rutin, ellagic acid, coumaric acid, vanillin, ferulic acid, naringenin, rosmarinic acid, daidzein, quercetin, cinnamic acid, kaempferol, hesperetin	Cell scratch assay	Post 48-hour treatment with M. oleifera extracted under 25 MPa exhibited highest wound contraction (75.053%), compared to untreated group (53.903%), 15MPa (59.082%), and 35MPa (70.876%).
Ashames et al., 2024⁶¹	Pakistan	In vivo (rabbit)	2%, 4%, 8% amniotic fluid-moringa-loaded nanocomposite (AMF-Me.mo)	No treatment (negative) 1% silver sulfadiazine (positive)	−	Burn	Post 21-day treatment on burn infected wound showed that 2% (27.3%), 4% (30.0%), and 8% (73.7%) AMF-Me.mo nanofilms had higher wound contraction compared to untreated model (p <.001).
Fontanilla et al., 2024⁶²	Philippines	In vivo (male piglets)	Ethanolic M. oleifera crude extract	No treatment 0.2% nitrofurazone (positive)	−	Castration	Post 12-day treatment with M. oleifera showed smaller wound surface area (0.86 mm²) compared to untreated control group (1.06 mm²), but larger than nitrofurazone control group (0.68 mm²).
Benkiran et al., 2024²³	Morocco	In vivo (Wistar mice)	10% aqueous, 10% ethanolic Mssisi-grown M. oleifera extract-based ointment 10% aqueous, 10% ethanolic Lamta-grown M. oleifera extract-based ointment	silver sulfadiazine (SSD) (positive)	Flavonoids and tannins	Burn	All groups treated with M. oleifera extracts showed significant reduction in inflammation in comparison to control groups throughout the study. At day 14 post wound, complete wound closure was observed with both aqueous-based and ethanol-based Mssisi-grown M. oleifera extract group.
Mamgain et al., 2024⁶³	India	In vivo (Wistar albino rats)	1.5% w/w aqueous-based M. oleifera extract loaded gel 1.5% w/w aqueous-based M. oleifera extract loaded zein nanoparticles-based gel	5% w/w povidone- iodine ointment USP (positive)	−	Excision	Treatment with M. oleifera loaded zein nanoparticles-based gel showed highest percentage of wound contraction at day 21 post wound (98.17%). Complete wound healing with no scar observed at day 21 post wound, in both treatment groups compared to control group (p <.05).
Kamel et al., 2023⁶⁴	Egypt	In vitro: (human dermal fibroblasts) In vivo: (casper zebrafish embryos)	M. oleifera-leaf-extract-immobilized SA/PVA scaffold (MOE/SA/PVA)	No treatment	Chlorogenic acid, gallic acid, caffeic acid, rutin, coumaric acid, vanillin, naringenin, quercetin, 3,4-dihydroxybenzoic acid, cinnamic acid, kaempferol,ferulic acid, syringic acid	In vitro: Cell scratch assay In vivo: Transected caudal tail fins	In vitro: MOE/SA/PVA scaffold improved cell scratch closure in concentration-dependent manner. In vivo: MOE/SA/PVA scaffold improved cell growth percentage, through regeneration of the caudal tail of zebrafish from 216 ± 42% to 246 ± 69% when concentration increased from 1 mg/ml to 2 mg/ml.
Muzammil et al., 2023⁶⁷	Pakistan	In vitro (human retinal pigment epithelial)	Ethanol-based, methanol-based, acetone-based M. oleifera leaf extract	Platelet-derived growth factor (PDGF)	P-coumaric acid, caffeic acid, chlorogenic acid, vanillic acid, kaempferol, sinapic acid, salicylic acid, coumarin, quercetin, rutin	Cell scratch assay	Cell migration activity is reduced with increasing drying temperature of M. oleifera extraction process. Concentration of polyphenols in M. oleifera decreases with increasing drying temperature of M. oleifera extraction process.
Ramadhany et al., 2023¹¹	Indonesia	In vivo (male Wistar rats)	4%, 15% M. oleifera extract gel	CMC-Na gel, hyaluronic acid	Flavonoids	Gingival wound	The highest mean number of fibroblasts and angiogenesis, and lowest mean number of neutrophils observed in 15% M. oleifera extract gel group at day 7 post wound. Highest mean epithelial thickness found in 4% M. oleifera gel group at day 5 post wound.
Al-Ghanayem et al., 2022¹⁵	Saudi Arabia	In vivo (adult albino in-bred Wistar rats)	10% w/w, 20% w/w, methanolic-based M. oleifera extract ointment	Emulsifying base without extract (control) Antibiotic mupirocin (standard)	3,4-Dihydroxybenzoic acid, quinic acid, o-coumaric acid, methyl-3-caffeoylquinate, isoquercetin, hyperoside, eugenol, chlorogenic acid, 3-butylidene-4,5,6,7-tetrahydro-6,7-dihydroxy-1(3H)-isobenzofuranone, diethyl phthalate, linoleic acid, 5-O-caffeoylquinic acid butyl ester, oleic acid, azelaic acid	Excision	Treatment with M. oleifera extract ointment inhibited bacterial activity; however, MRSA exhibited higher susceptibility to extract compared to Pseudomonas aeruginosa. Uninfected wounds had higher contraction of wound area compared to infected wounds. Wound contraction was higher in 20% M. oleifera extract compared to 10% M. oleifera extract, yet lower than mupirocin group. Epithelialization in MRSA-infected wounds was quicker in M. oleifera extract groups compared to control, but slower than mupirocin group. Level of antioxidant enzyme, SOD, increased in both M. oleifera extract and mupirocin group, with M. oleifera extract group exhibiting highest antioxidant effect.
Andy et al., 2022¹⁶	Indonesia	In vivo (male Wistar rat)	Ethanol-based M. oleifera extract cream	Silver sulfadiazine (SSD)	−	Burn	Significant increase in new capillary blood vessel counts with M. oleifera extract cream group compared to SSD group. Significant increase in collagen density in M. oleifera extract cream group compared to SSD group.
Tofiq et al., 2021³³	Iraq	In vivo (Adult male Wistar albino rats)	3.5%, 5%, 10% ethanol-based M. oleifera leaf extract ointment	Vaseline Gentamicin ointment	Gallic acid, rutin, catechin, quercetin	Laceration wound	Treatment with 10% M. oleifera extract showed enhanced wound healing with lesser scars, brighter skin, greater hair follicles, and sebaceous glands regenerated as compared to 3.5%, 5%, and control groups.
Moura et al., 2020²⁵	Brazil	In vivo (Wistar rats)	5%, 10% hexane-based M. oleifera extract hydroxyethyl cellulose gel	Essential fatty acid ointment (AGE)	−	Incision	Wound contraction was significantly higher in treatment group (5% and 10% M. oleifera extract gel) compared to control (p <.05). At day 21 post wound, extracellular matrix was denser and had lesser inflammatory response in M. oleifera group compared to control.
Rodríguez- García et al., 2021¹³	Mexico	In vitro (human dermal fibroblast)	0.01, 0.1, 1.0, 10, 100, 500 µg/ml methanol-based M. oleifera extract	Untreated	Quercetin, kaempferol, isorhamnetin, apigenin, chlorogenic acid, myricetin, neohesperidin, rutin, vicenin-2, astragelin	Cell scratch assay	Treatment with 0.01 and 0.1 µg/m M. oleifera extract showed higher (17% and 21%) fibroblast proliferation compared to untreated group. Treatment with 500 µg/ml M. oleifera extract exhibited lowest fibroblast proliferation, lesser than control group Treatment with 0.01 and 0.1 µg/m M. oleifera extract achieved 50.1% and 64.4% wound closure at 24 hours compared to control (31.1%).
Lim et al., 2019⁶⁶	Malaysia	In vitro (human dermal fibroblasts)	Aqueous-based M. oleifera extract–loaded phytophospholipid complex (MOPCT)	Vehicle (PCT)	Quercetin, kaempferol, chlorogenic acid, rosmarinic acid, rutin, vicenin-2 ascorbic Acid, succinic acid conjugate, cinnamic acid conjugate, ellagic acid, zeaxanthin, tryptophan, quinic acid	Scratch	Cell viability: MOPCT and PCT exhibited high cell viability >100% at dose up to 1.5 mg/mL. At higher dose (>1.5 mg/mL) of MOPCT, cell viability decreased to 6.2 ± 7.2%. No toxicity was observed with filtered MOPCT (MOPCT(F)). Cell migration: At 1 mg/mL dose of MOPCT(F), shortest wound closure time was observed where contraction was 94.8 ± 2.1% at 24 hours post treatment, compared to MO, PCT, and MOPCT of the same dose. Complete wound closure was achieved at 48 hours in MOPCT and MOPCT(F) unlike in MO group and PCT group.
Amaliya et al., 2019⁶⁷	Indonesia	In vivo (Sprague–Dawley rats)	2%, 4% Eehanol-based M. oleifera extract gel	10% povidone- iodine 4% HPMC gel	Vitamin C, ß-carotene, protein, calcium, potassium flavonoids, phenolics carotenoids	Excision	On day 10 post wounding, treatment with 4% M. oleifera extract exhibited greatest mean fibroblast count and collagen deposition compared to other groups (p <.05).
Chin et al., 2019⁶⁸	Malaysia	In vivo (STZ/HFD-induced diabetic rat)	1%, 0.5%, 0.1%, aqueous-based M. oleifera extract-loaded hydrocolloid film dressing	Commercial dressing (Kaltostat)	Vicenin-2, chlorogenic acid, rosmarinic acid	Excision Abrasion	Excision wound: 0.5% M. oleifera extract exhibited quicker wound closure (77.67 ± 7.28%) compared to Kaltostat (28.67 ± 12.83%) on day 7 post wound. Abrasion: Rate of wound closure was higher in M. oleifera group (81 ± 4.5%) compared to control (28.8 ± 9.85%) and commercial dressing (73.13 ± 8.05%) on day 3 post wound.
Chin et al., 2018⁶⁹	Malaysia	In vitro (human dermal fibroblasts and human epidermal keratinocytes)	Aqueous-based M. oleifera extract loaded with sodium alginate-pectin film dressing Ethanolic-based M. oleifera (50%, 70%, 100%) extract loaded with sodium alginate-pectin film dressing	PBS	Chlorogenic acid, gallic acid, quercetin, kaempferol, vicenin-2, rosmarinic acid, rutin	Wound scratch assay	Aqueous-based M. oleifera extract showed the most prominent cell proliferation and migration, indicating wound closure, at 48 hours. Cell viability: Concentration of M. oleifera up to 100 µg/mL extract were non-toxic to HDF and HEK cells after 24 hours.
Susanto et al., 2018⁷⁰	Indonesia	In vivo (Sprague–Dawley rats)	2%, 4% Ethanol-based M. oleifera extract gel	10% povidone- iodine 4% HPMC gel	Flavonoids, phenolic acid, chlorogenic acid, rutin, quercetin, kaempferol, tannin, saponin, terpenoids, glycosides	Excision	Treatment with M. oleifera showed significant differences compared to control groups in wound closure at day 3 and 14 post wound (p <.05). Highest wound closure was observed in 4% M. oleifera extract gel group.
Coker et al., 2018⁷¹	Nigeria	In vivo (Wistar female albino rats)	3.25% and 5% ethyl acetate-based M. oleifera ointment	Simple ointment base (negative control) Gentamicin ointment (positive control)	Flavonoids, saponins, phlobatannins, alkaloids, anthraquinones, steroids, resins	Excision	Complete wound closure (100%) was observed with dose 3.25% M. oleifera ointment at day 15 post wound, while wound contraction percentage of gentamicin (93%), 5% M. oleifera ointment (89%), and ointment base (37.5%) was lower.
Natarajan et al., 2018²⁸	Malaysia	In vivo (streptozotocin-induced diabetic male Wistar albino rats)	0.5%, 1.0%, 2.0% carbopol-based M. oleifera extract-loaded hydrogel (MO-hydrogel)	Vehicle	Saponins, carbohydrates, alkaloid	Excision	At day 8 post wound, wound contraction of treatment group (MO-hydrogel) was 89.76% whereas control group was 45.75% (p <.05). All concentrations of MO-hydrogel showed no inhibition of E. coli, P. aeruginosa, and S. aureus.
Fayemi et al., 2018²⁷	Nigeria	In vivo (Wistar rats)	0.1, 0.15, 0.2, 0.5 g polyacrylonitrile- M. oleifera extract nanofibers	Polymer nanofibers	−	Incision	Wound closure percentage was highest with dose 0.5 g M. oleifera extract (35%, 87%, and 95%) and lowest in control group (29%, 75%, and 93%) at day 1, 4, and 7 respectively (p <.05). The percentage of wound closure of treatment group increases with treatment time. Treatment with 0.5 g of M. oleifera extract-loaded nanofiber mat showed best antibacterial activity against S. aureus and E. coli.
Islam et al., 2018²⁹	Bangladesh	In vivo (female Wistar rats)	2% M. oleifera gel	No treatment (negative control) Amniotic membrane gel (positive control)	−	Burn	Amniotic membrane group (AM) (23.2 days) and combined treatment (AM+MO) (19.6 days) group showed statistically significant shorter epithelialization period, compared to MO group alone (28.2 days) (p <.05). Combined treatment group (96 ± 1.96%) achieved highest wound contraction (p <.00003667), followed by AM group (67.74 ±1.32%), MO group (63.03 ± 1.32%), and control group (43.45 ± 1.32%).
Azevedo et al., 2018²⁹	Brazil	In vivo (normal and diabetic- induced adult Wistar rats)	Oral: 100 mg/kg aqueous-based M. oleifera extract Topical: 200 µL of 10% aqueous-based M. oleifera extract	Normal saline (NS)	−	Excision	Oral: Treatment with M. oleifera showed significant reduction in glycemia, when comparing day 2 and day 10 of treatment, in both normal and diabetic rats (p <.05). Topical: Rate of wound closure was higher for both diabetic and normal rats in topical M. oleifera group at day 2, 5, 10 post-wound compared to NS group (p <.05).
Gothai et al, 2017²⁰	Malaysia	In vitro (diabetic human dermal fibroblasts)	15.62–500 µg/mL ethyl acetate-based M. oleifera extract	Allantoin	Phenol, flavonoid	Scratch assay	Cell viability: Concentration-dependent inhibition of cell growth was observed. Cell proliferation: Rate of cell proliferation was not concentration dependent. Lower concentrations (15.62, 31.25, 62.5 µg/mL) showed better proliferative effect. Cell migration: Using optimized concentrations (2.5, 25, and 50 µg/mL), cell migration rate in treatment group was significantly higher (82%–87%) than control group at 24 hours. Cell migration effect in treatment group was comparable to allantoin group, with dose 25 µg/mL slightly higher.
Gothai et al, 2016²¹	Malaysia	In vitro (normal human dermal fibroblasts)	15.62–500 µg/mL ethyl acetate-based M. oleifera extract	Allantoin	−	Scratch assay	Cell viability: No significant differences in cell viability percentage across the tested concentrations of M. oleifera extract indicating non-toxic nature of extract. Antioxidant: M. oleifera extract showed moderate antioxidant activity against hydrogen peroxide, and highest antioxidant activity against 1-diphenyl-2-picrylhydrazyl free radical. Cell proliferation: Rate of cell proliferation was significantly increased in concentrations up to 62.5 µg/mL but concentrations above 125 µg/mL showed reduced proliferation rate. Cell migration: Using optimized concentration (12.5 µg/mL, 25 µg/mL and 50 µg/mL), there was a ± 9% significant differences in wound closure rate comparing treatment and control group at 24 hours. Dose 25 µg/mL exhibited higher wound closure rate compared to higher concentration, 50 µg/mL.
Sivaranjani and Philominathan, 2016⁷²	India	In vivo (male albino Wistar rats)	Titanium nanoparticles aqueous-based M. oleifera gel-based ointment	Sulfadiazine + gel	–	Excision	At day 12 post wound, wound contraction was highest in treatment group (92.36 ± 0.5%) (p <.05), compared to sulfadiazine group (83.55 ± 0.57%).
Muhammad et al., 2016¹⁷	Malaysia	In vivo (diabetic-induced adult Wistar rats)	0.5%, 1.0%, 2.0% (w/w) Aqueous-based M. oleifera extract ointment	No treatment	Vicenin-2	Excision	Wound contraction rate was significantly higher in M. oleifera group compared to untreated diabetic group (p <.05). Period of epithelialization was significantly shorter in M. oleifera group (11 ± 1 days) compared to untreated group (15 ± 1 days).
Kumar et al., 2017⁷³	India	In vivo (male Swiss albino rats)	Aqueous-based M. oleifera extract paste	Untreated	Proteins, vitamin A, vitamin C, iron, copper	Excision and incision	Excision: Complete wound closure was achieved on day 14 post wound in treatment group (99.3 ± 0.09%) compared to control (88.0 ± 0.54%). The mean epithelialization period was shorter in treatment group (14.66 days) compared to control group (17.16 days) (p <.001). Incision: In treatment group, the tensile strength was higher (507.5 ± 7.14 g) compared to control group (367.5 ± 6.76 g) (p <.001).
Olaifa et al., 2016⁷⁴	Nigeria	In vivo (adult rabbits)	Aqueous-based M. oleifera extract	0.9% NS	Fatty acids, vitamin E, carotenoids, mineral elements (iron, copper, zinc, cobalt, amino acids)	Excision	Area of wound uncontracted was smaller in treatment group (1.53 ± 0.65) compared to control group (9.64 ± 2.97) at day 12 post wound (p <.005).
Eyarefe et al., 2015⁴⁰	Nigeria	In vivo (male adult Wistar rats)	300 mg/kg/ml aqueous-based M. oleifera oral administration	Untreated (negative control) 9.4 mg/kg tetracycline (positive control)	–	Incision	Differences in area of wound diameter was not significant except at day 5 post wound where untreated group (5.150 ± 1.05) observed higher contraction compared to M. oleifera group (5.600 ± 0.84) and tetracycline group (6.600 ± 1.01) (p = .013). Most granulation tissue was observed in control group at day 5 onwards (p <.005), followed by M. oleifera group, and tetracycline group. At day 5 post wound, wound edge edema was lowest in control group (33.3%), followed by M. oleifera (66%) group, and tetracycline group (83.3%).
Akanji and Sonibare, 2015¹⁸	Nigeria	In vivo (albino Wistar rats)	100 mg/mL ethanol-based M. oleifera extract	NS Gentamicin	–	Excision	Shorter epithelialization period in treatment group compared to NS group and gentamicin group.

Table 2.

Characteristics of the Included Studies and Application of M. oleifera Seeds in Wound Healing.

Author, Year	Country	Type of Study (Type of Model)	Dosage/formulation	Controls	Chemical Constituents	Type of Wound	Main Findings
Shady et al., 2022²⁶	Egypt	In vivo (Adult male New Zealand Dutch strain albino rabbits)	M. oleifera seeds extract	No treatment (negative control) MEBO® (positive control)	Moringyne,, catechin, quercetin, kaempferol, gallic acid, p-coumaric acid, ferulic acid, caffeic acid, protocatechuic acid, cinnamic acid, ellagic acid, vanillic acid, benzylamine	Excision	Treatment with M. oleifera demonstrated almost complete wound healing (96%) compared to MEBO-treated group (91%), and untreated group.
Ali et al., 2021³¹	India	In vivo (male Swiss albino mice)	5%, 10% hydrogel of n-hexane extract of M. oleifera seeds	No treatment (negative control) 5% povidone-iodine (positive control)	−	Excision and incision	Excision: Percentage of wound contraction in 5% M. oleifera hydrogel group (74%) and 10% M. oleifera hydrogel group (69%) was higher compared to povidone-iodine group (26%) and control group (18%), at any point of time. At day 12 post wound, wound contraction reached 97% in 5% M. oleifera hydrogel group and 98% in 10% M. oleifera hydrogel group, compared to the povidone-iodine group (82%) and untreated group (62%). Incision: Treatment with 5% (152 g) and 10% (156 g) M. oleifera hydrogel showed higher tensile strength compared to povidone-iodine group (115 g) and untreated (96 g) (p <.01).
Mehwish et al., 2021⁴³	China	In vivo (male rats) In vitro (fibroblast L929 cells)	Polysaccharide-embedded silver nanoparticles of M. oleifera seed (MOS-PS-AgNPs)	Betadine ointment	Carbohydrates, uronic acid, protein, nucleic acid, sugar moieties	Incision Wound scratch	Incision: Percentage of wound contraction in high-dose MOS-PS-AgNPs (91%) treated group was highest, followed by medium-dose MOS-PS-AgNPs (63%), low-dose MOS-PS-AgNPs (51%), and standard (42%) (p <.005). Cell migration: Treatment with 6.5 ug/mL MOS-PS-AgNPs showed highest cell migration rate (91%) compared to control (27%).
Ventura et al., 2021⁴⁴	Brazil	In vivo (healthy, diabetic, and immunosuppressed female Swiss mice)	M. oleifera seed oil (MOSO)	No treatment (negative control) Mineral oil Oleic acid Dersani©	−	Excision	In healthy mice group, wound closure was achieved earliest by OA group (9 days), followed by MOSO group (11 days), mineral oil group (13 days), untreated group (14 days), and Dersani© group (15 days).
							I n immunocompromised mice group, wound closure was achieved earliest by OA group (12 days), followed by MOSO group and Dersani© group (15 days), mineral oil group (16 days), and untreated group (18 days). In diabetic mice group, wound closure was achieved earliest by OA group (11 days), followed by MOSO group (13 days), mineral oil group (13 days), untreated group (15 days), and Dersani© group (16 days).
Asmawati et al., 2020¹⁴	Indonesia	In vivo (male Wistar rats)	Ethanol-based M. oleifera fruit seed oil	0.5% CMC (negative control) Aspirin (positive control)	−	Incision of gingival mucosa	Treatment with M. oleifera fruit seed oil showed highest mean number of fibroblast (125.33 ± 18.45) followed by aspirin group (105.33 ± 9.29), and CMC group (50.0 ± 2.00), at day 7 post wound (p <.05).
Parwani et al., 2016⁷⁵	India	In vivo (Swiss Albino mice)	Povidone-iodine loaded polysaccharide polymer of M. oleifera seeds and polyvinyl alcohol hydrogel (PVP-I-loaded MSP/ PVA)	No treatment (negative control) 5% w/w povidone-iodine ointment (PVP-I) (positive control)	−	Excision	Treatment with PVP-I-loaded MSP/PVA hydrogel (56.3 ± 3.2%) showed the highest percentage of wound closure, followed by PVP-I ointment group (43.3 ± 4.8%) and untreated group (33.3 ± 5.7%).
Meziou-chebouti, 2015²⁴	Algeria	In vivo (Wistar rats)	0.5 mL M. oleifera polyphenolic ointment 0.5 mL M. oleifera saponins ointment	0.9% saline (negative control) 75 mg D-clofenal (positive control)	−	Incision	Percentage of edema reduction was highest in D-clofenal group (33.467%), followed by extract saponins (28.160%), extract polyphenols (23.614%), and negative control (0.0%). Treatment with saponins and polyphenols M. oleifera extract ((96.82%, 93.20%) show highest percentage of wound closure compared to D-clofenal group (90%).

Table 3.

Characteristics of the Included Studies and Application of M. oleifera Twigs in Wound Healing.

Author, Year	Country	Type of Study (Type of Model)	Dosage/ formulation	Comparison	Chemical Constituents	Type of Wound	Main Findings
Agnes, 2014³⁵	Philippines	In vivo (healthy guinea pigs)	5, 7.5, 10 mg/mL ethanol-based M. oleifera extract patch	Calmoseptine	Glycosides, phenol, sterol, flavonoids, niazirin, niazirinin	Excision	Treatment with 10 mg/mL M. oleifera extract patch stimulated the wound healing (p <.05).

Table 4.

Characteristics of the Included Studies and Application of M. oleifera Aerial Parts in Wound Healing.

Author, Year	Country	Type of Study (Type of Model)	Dosage/formulation	Controls	Chemical Constituents	Type of Wound	Main Findings
Sahu et al., 2024⁴⁶	India	In vivo (Wistar albino rats)	5% and 10% w/w hydroalcoholic M. oleifera bark extract ointment	0.2% silver nitrate ointment (positive) Ointment base	Gallic acid, quercetin	Burn	Post-14-day treatment with standard control, 0.2% silver nitrate showed highest percentage of wound contraction (87.66%), followed by 10% M. oleifera ointment group (83.04%), 5% M. oleifera ointment group (73.79%), and ointment base group (55.61%) (p <.05).
Manhas and Malairaman, 2024⁴⁷	India	In vitro (McCoy fibroblast) In vivo (diabetic Wistar rats)	0.05 and 0.1 mg/mL M. oleifera hydroalcoholic bark extract (MOHE)	0.1 mg/mL calendula cream (positive) Water (negative)	Gallic acid, quercetin	Scratch assay Excision	Scratch: Post 24-hour treatment with 0.1 mg/mL of MOHE showed highest wound closure area (54.85%), followed by calendula cream group (46.3%), 0.05 mg/mL MOHE group (21.59%), and untreated group (13.6%) (p <.05). Excision: Post 14-day treatment with 10uL MOHE showed highest wound closure area (78.81%), compared to calendula cream (65.44%), and negative control group (53.65%) (p <.05).
Baishal et al., 2024³²	India	In vitro (NIH3t3 fibroblast) In vivo (albino Wistar rats)	Polyvinyl alcohol (PVA)/ M. oleifera gum (MO), PVA/MO/graphene oxide (GO), PVA/MO/GO/ naringin (NAR) polymeric patch	No treatment (negative) Hydra heal (positive)	−	Scratch assay Incision	Scratch assay: Post 48-hour treatment with PVA/MO (83%), PVA/MO/GO (88%), and PVA/MO/GO/NAR (94%) showed higher cell migration compared to untreated group. Incision: Full wound closure is observed at day 12 post-treatment with PVA/MO/GO/NAR, compared to untreated group.
Dilawar et al., 2017³⁴	Pakistan	In vivo (male Sprague–Dawley albino rats exposed to UVB radiation)	Methanolic-based M. oleifera aerial parts (leaves, stem, bark, flower, fruit, seed) extract	0.5 mg/kg oral retinoic acid	Moringine, moriginine, oleic acid, thiocarbamates, isocyanate glycosides	Incision	Treatment with M. oleifera leaf extract showed better wound healing compared to other aerial parts, retinoic acid, and untreated group. Treatment with both M. oleifera leaf and bark extract showed significant decrease in epidermal thickness in comparison to control group. Efficacy in decreasing order: Standard > leaf > bark > flower > fruit > seed > stem > control.
Fernandes et al., 2016⁴⁵	India	In vitro (Rat primary fibroblast cells)	100 and 200 µ/ml aqueous-based M. oleifera leaf and flower extract	Phosphate buffer solution (PBS)	−	Wound scratch assay	Dose 200 µg/ml of M. oleifera flower extract showed complete wound closure at 48 hours of incubation while M. oleifera leaf extract and control group achieved complete wound closure at 72 hours.

Table 5.

Characteristics of the Included Studies and Application of M. oleifera Roots in Wound Healing.

Author, Year	Country	Type of Study (Type of Model)	Dosage/formulation	Controls	Chemical Constituents	Type of Wound	Main Findings
Seran et al., 2025⁷⁶	Indonesia	In vivo (Wistar male rats)	5%, 10%, and 15% M. oleifera root extract gel	Bioplacenton® gel for incision wounds and star ag® for diabetic wounds (positive) No treatment Base gel (negative)	−	Incision Diabetic biopsy punch	Incision: Treatment with 15% M. oleifera root extract gel (100.0%) exhibited highest wound contraction, as compared to 10% (94.5%), 5% (74.17%), untreated (42.0%), and base gel group (51.5%) (p <.05); however, there is no significance difference in effectiveness of wound healing compared to positive control (100.0%). Diabetic wound healing: Treatment with 15% M. oleifera root extract gel (100.0%) exhibited highest wound contraction as compared to 10% (97.5%), 5% 91.67%), untreated (−12.5%), and base gel group (−2.5%) (p <.05); however, there is no significance difference in effectiveness of wound healing compared to positive control (100.0%).

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-diabetic²⁹ 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 showed 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

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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).

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Use of Artificial Intelligence-assisted Technology:

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Appendix

Appendix A.

Structured Search Strategies for PubMed Database.

Population: Moringa oleifera
PubMed
#1	“moringa oleifera”[MeSH Terms]
#2	“moringa oleifera”[tw]
#3	“m. oleifera”[tw]
#4	“drumstick tree”[tw]
#5	OR #1-#4
	2,379
Concept: Wound healing
PubMed
#6	“wound healing”[MeSH Terms]
#7	“wound healing”[tw]
#8	“wounds and injuries”[MeSH Terms]
#9	“injury”[tw]
#10	“wound”[tw]
#11	OR #6-#10
	2,015,640
Context: Publication date
PubMed
#11	2014/01/01:2024/12/31[dp]
	#4 AND #10 AND #11
	115

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