Tropical Journal of Pharmaceutical Research

Investigation of the effect of oxidation on keratin obtained from chicken feathers

Emmanuel Agbamu — 2025-03-08

Purpose: To investigate excipient properties of oxidized extracted keratin (OEK) compared to extracted keratin (EK) obtained from chicken feathers.

Methods: Keratin from whole chicken (Gallus gallus domesticus) feathers was extracted under conditions of optimum yield. Oxidation was carried out with hydrogen peroxide (H₂O₂) for 15 mins, washed, filtered, dried and stored in airtight containers. Organoleptic properties, chemical tests, pH, true density, hydration capacity, swelling capacity, flow properties and chemical functionalities using UV/visible spectroscopy, Fourier transform-infrared spectroscopy (FT-IR) and High-performance liquid chromatography (HPLC) were investigated.

Results: The yield of EK was 28 % while that of OEK was 89.2 % (obtained from EK). The EK was dark brown, fine and powdery with a characteristic odour. However, OEK was pale brown, smooth texture and odourless. Furthermore, OEK had significantly lower hydration capacity, and true density as well as significantly higher pH, swelling capacity, and improved flow compared to EK (p < 0.05). UV and FTIR spectra were superimposable. The wavelength of maximum absorption was 244.50 to 306.50 nm (EK) and 269 to 335.50 nm (OEK). The transmission band was attributed to CH3, C=O, N-H, C-H, C-S, and N-H stretching. Furthermore, HPLC analysis revealed varying amounts of amino acids and total amino acid content was higher in EK compared to OEK.

Conclusion: Oxidation of EK from chicken feathers enhances appearance, and flow, and reduces protein content with a significant reduction in cysteine residues. Drug release modulation properties of OEK would need to be investigated in further studies.

Development of double-coated microparticles for improved oral insulin delivery in diabetes management

Josephat I Ogbonna — 2025-03-08

Purpose: To formulate double-coated insulin-loaded polymer-based microparticles (MPs) for oral delivery of insulin.

Methods: Different formulations of insulin-loaded MPs were prepared using polyethylene glycol 4000 (PEG 4000) and chitosan as primary coat and Eudragit® RL 100 as secondary coating agents. Physicochemical characterization, in vitro drug release, toxicological, and in vivo studies in diabetic rats were performed, and the results of the orally administered MPs were compared with those of subcutaneously administered Humulin®.

Results: The developed MPs showed good physicochemical characteristics. In vitro release studies showed that all batches of MPs exhibited sustained insulin release in 12 h with the highest insulin release achieved by MPs formulated using PEG 4000 as primary coating. In vivo, the orally administrated MPs containing 2 % chitosan achieved a reduction in blood glucose level from 100 mg/dL to 15.8 mg/dL after 10 h, compared to subcutaneously administered Humulin® which was 100 mg/dL to 20.60 mg/dL after 24 h. The MPs reduced blood urea (76.25 - 43.21 mg/dL) better than Humulin® (76.25 - 73.11 mg/dL), hence, may prevent development of insulin resistance and/or defective insulin release.

Conclusion: The effects of these formulations on blood glucose were comparable to subcutaneously administered Humulin® in diabetic rats. However, there is need to optimize these polymer blends for improved effectiveness, as well as study the long-term stability of these formulations.

Effect of biosurfactants on the stability of anti-burn ointment of aqueous Morus alba leaf extract

Bouchher Saadia — 2025-03-08

Purpose: To evaluate the anti-burn activity of ointment formulation from Morus alba leaves aqueous extract (MAE) stabilized by a biomolecule product of Marinobacter hydrocarbonoclasticus.

Methods: Phytochemical study conducted on MAE includes moisture content, ash content, and pH. Prepared Morus alba leaf ointment was evaluated for organoleptic, consistency, pH, spreadability, and skin irritation study. The effect of temperature variations and physiological and environmental factors on stability was also determined. Anti-burn effectiveness of MAE ointment (250 mg) was tested on the burn skin model of male Albino rabbits.

Results: Morus alba leaves contain polyphenols, flavonoids, glycosides and tannins as active chemical components that are useful in infection. Flavonoids exhibit antioxidant activity with indirect inhibition of inflammatory markers. The MAE ointment showed good scores in all test parameters that were evaluated including appearance, texture, pH, spreading ability and non-irritant study. The ointment was stable at different temperatures, and physiological and environmental conditions, and was free from any bacterial contaminations that have the capacity to cause allergies, especially after the addition of stabilizers which kept the ointment stable for longer period.

Conclusion: Ointment formulated from MAE is physically, chemically and microbiologically stable and is effective in the treatment of burns in rabbit models. The MAE thus has promising therapeutic potential in the management of skin burns.

Semaglutide ameliorates diabetes-induced steatotic liver disease in rats: Role of AMPK, mTOR, ERK and ABHD6

Sultan A Alfawaz — 2025-03-08

Purpose: To determine whether semaglutide protects rats with diabetes from metabolic dysfunction-associated steatotic liver disease (MASLD), and its underlying molecular mechanisms.

Methods: Fifty-three male Wistar rats were divided into five groups: control, streptozotocin (STZ, 45 mg/kg given intraperitoneally); STZ + low-dose semaglutide (12 μg/kg every 3 days), STZ + high-dose semaglutide (40 μg/kg every 3 days), and STZ + metformin (100 mg/kg/day orally). Rats (except control group) were given 10 % fructose in drinking water from the beginning of the experiment until the 12th week. Blood concentrations of glucose, insulin, liver biomarkers, and lipid profiles were measured. Oxidative stress and inflammatory markers in liver tissues were assessed, along with protein expressions of pAMPK, mTOR, ERK, and ABHD6.

Results: High-dose semaglutide enhanced blood glucose levels, reduced feed and water intake, decreased body weight, and enhanced liver function, when compared to the STZ group. Oxidative stress was reduced, and levels of inflammatory indices (TNF-α and IL-6) were supressed. Additionally, semaglutide decreased the expression levels of mTOR, ERK, and ABHD6, while activating the hepatic AMPK pathway. Reduced histopathological lesions were observed in liver tissues. Conclusion: Semaglutide may be beneficial in preventing MASLD in T2DM, thereby providing new perspectives on its potential therapeutic role.

Accidental myiasis caused by housefly (Musca domestica) in Rock Hyrax (Procavia capensis Jayakari) in Saudi Arabia

Manei M Aljedaie — 2025-03-08

Purpose: To determine the organisms responsible for intestinal infection in rock hyrax (Procavia capensis jayakari), a wild animal in Saudi Arabia, through morphological and molecular characterization.

Methods: Intestinal contents obtained from 20 dead rock hyrax were used to confirm the presence of larvae. Larval morphology was examined using stereo-microscopy and scanning electron microscopy (SEM). For molecular characterization, ribosomal 18S rDNA and mitochondrial DNA (mtDNA) gene sequences in larval DNA were amplified by polymerase chain reaction (PCR).

Results: Four samples of the intestinal contents of dead rock hyrax showed positive response indicative of larval infection (infection rate 20 %) with a slender and creamy larval structure in rock hyrax intestine. For molecular characterization, from the 20 samples, 11 ribosomal 18S rDNA sequences and six mitochondrial DNA (mtDNA) sequences presented positive polymerase chain reaction (PCR) signals. The gene sequences were used to construct an evolutionary tree with other related sequences available in a gene database. The morphological features and the evolutionary trees were developed based on the above two genes, confirming the resemblance between Musca domestica (Housefly) and larvae in this study.

Conclusions: The intestine of rock hyrax is invaded by houseflies. The results obtained could be a first step in understanding the cause of myiasis infection in wild animals. The translational value of these findings raises a serious concern regarding the transmission of this disease in animals with houseflies being the vector for pathogens to enter hosts such as wild animals. This would pose a serious problem in preserving the ecological balance of wild animals in the future.

Antiviral activity of Eucalyptus globulus and Eucalyptus citriodora essential oils against H5N1 avian influenza virus and infectious bronchitis virus

Ni Luh Putu Indi Dharmayanti — 2025-03-08

Purpose: To explore the antiviral potential of Eucalyptus citriodora and Eucalyptus globulus essential oils against zoonotic highly pathogenic avian influenza (HPAI) H5N1 and infectious bronchitis virus.

Methods: The extraction process of eucalyptus leaves was carried out using the steam distillation method. The physicochemical properties of both essential oils were determined by gas chromatography (GC) injection. The essential oils were then tested for toxicity and antiviral activity by liquid phase and vapour phase methods in ovo. In addition to specific pathogen-free (SPF)-egg testing, the infectivity of HPAI H5N1 and effectivity of the essential oils in the vapour phase in inhibiting the growth of H5N1 were also tested using MTT assays.

Results: The result showed 100 % inhibition by both essential oils against 10³ EID₅₀ of H5N1 AI and IBV for all concentrations that were administered through direct contact. In the vapor phase, complete inhibition of 10² EID₅₀ of HPAI H5N1 and IBV viruses was observed at 8 % concentration for both essential oils, as confirmed by the absence of lesions on the embryos and negative HA test result.

Conclusion: Eucalyptus essential oils from E. citriodora and E. globulus may serve as potential alternative natural products for combating zoonotic HPAI H5N1 and infectious bronchitis virus (IBV). Further studies are needed to characterize their phytopharmaceutical activity and pathways as novel antiviral agents against these viruses.

Therapeutic potential of Thai Mucuna pruriens (T-MP) seed aqueous extract on acute ethanol-induced behavioral and motor dysfunction

Jirayut Kaewmor — 2025-03-08

Purpose: To assess the therapeutic potentials of Thai Mucuna pruriens (T-MP) seed aqueous extract in mitigating acute ethanol-induced behavioral and motor dysfunction in mice.

Methods: The mice were orally administered either water or T-MP seed extract (600 mg/kg). One hour after this initial treatment, the mice were given either distilled water or 6 g/kg of 30 % (w/v) ethanol. Thirty minutes following the second treatment, the mice were subjected to behavioral and motor function tests, comprising of the exploratory test, rotarod test, footprint analysis, elevated plus maze (EPM), and tail suspension test (TST), respectively.

Results: Ethanol treatment significantly increased anxiety-like behaviors, as evidenced by the exploratory and EPM tests, and depressive behavior, as indicated by prolonged immobility time in the TST (p < 0.05). It also reduced the time spent on the rod in the rotarod test and heightened gait abnormalities observed in gait analysis, indicating impaired motor functions. Treatment with T-MP significantly alleviated these ethanol-induced behavioral and motor dysfunctions (p < 0.05).

Conclusion: Thai Mucuna pruriens seed extract effectively mitigates neurological and behavioral dysfunctions induced by acute ethanol intoxication in mice, highlighting its potential as a neuroprotective agent. Further studies are required to elucidate T-MP's mechanisms in combating symptoms of acute ethanol intoxication, which is crucial for advancing medical and neuropharmacological treatments.

Antidiabetic potential of seven-herb Thai formula: Effect on blood glucose, lipid profile, and pancreatic islet restoration in diabetic rats

Teeraporn Katisart — 2025-03-08

Purpose: To assess an aqueous extract from a traditional Thai herbal formula for hypoglycemic activity in streptozotocin-induced diabetic rats.

Methods: The rats were divided into six groups, each consisting of 8 animals as follows: normal and diabetic controls, received distilled water (1 mL/kg); a glibenclamide-treated positive control (5 mg/kg); and three groups received orally the herbal extract at doses of 125, 250 or 500 mg/kg body weight. Treatment was for a duration of four weeks, once daily. Changes in body weight, fasting blood glucose levels, hemoglobin (HbA1c) levels, liver and kidney function results before and after the administration of the extracts were observed. Histological examination of the pancreatic cells was also conducted.

Results: Administration of 250 mg/kg of these herbal formula extracts to diabetic rats resulted in a significant reduction in HbA1c levels, a notable decrease in fasting blood glucose, and a significant increase (p < 0.05) in body weight relative to diabetic controls. Organ weights and other hematological values remained unchanged. Significant reductions (p < 0.05) in triglycerides, total cholesterol, and AST/ALT levels were seen, compared to diabetic controls. Histological analysis showed that the treatment dose-dependently restored pancreatic islet architecture, especially at 250 mg/kg, suggesting tissue regeneration.

Conclusion: These promising results support the need for further studies to identify the active compounds and understand the mechanism of action.

Immunohistochemical characterization of pancreatic delta cell as potential target for dibutyl phthalate toxicity in Wistar rats

Ezat A Mersal — 2025-03-08

Purpose: To investigate the endocrine disrupting potential of dibutyl phthalate (DBP) on δ-cells of the pancreas.

Methods: A total of 40 adult Wistar rats comprised of 20 males and 20 females were each grouped into control and study groups. Control groups had spontaneous access to food and water (controlspontaneous), and oral gavage normal saline (3.2 mL/kg; control-forced) every day for 8 weeks. Study group were exposed to DBP in their drinking water (0.8 µg/L; study-spontaneous), and oral gavage 0.8 µg DBP/kg for 8 weeks (study-forced). Blood glucose level was monitored weekly, and oral glucose tolerance test (OGTT) was conducted at the end of the experiment. The animals were sacrificed, pancreas excised, re-sectioned and processed for hematoxylin and eosin (H&E) staining, and immunohistochemical assay for identification of somatostatin (SST) protein.

Results: The H & E-stained pancreatic sections revealed a typical structural pattern of the endocrine and exocrine pancreas. The immunohistochemical assay using an anti-SST antibody indicated δ-cell immunoreactivity, mainly localized at the periphery of the islet population. The cell body of δ-cells exhibited characteristic neuron-like shaped filopodia-like extensions. The DBP-exposed animals demonstrated significant SST immunoreactivity compared to control (p < 0.05). The forced mode of DBP exposure showed a more significant effect on SST absorbance with no sex differences compared to drinking water exposure (p < 0.05).

Conclusion: This study shows that DBP toxicity induces alteration in the pancreatic δ-cells' SST immunoreactivity, which depends on exposure irrespective of sex.

Inhibition and reversal of formaldehyde-induced inflammation in rats by active compounds isolated from leaf extract of Chikadoma plant (Duranta repens)

Sylvester C Ohadoma — 2025-03-08

Purpose: To investigate the anti-inflammatory activity of the leaf extracts of Duranta repens.

Methods: Methanol, ethyl acetate, and hexane fractions from the methanol crude extract of Duranta repens leaves were obtained using gradient mixture elution in bioactivity-guided silica gel column chromatography. A mixture of spectrochemical, infrared (IR), nuclear magnetic resonance (NMR), and gas chromatographic/mass spectroscopic (GC/MS) investigations were used to clarify the structures of the identified active chemicals. A total of 50 Wistar rats randomized into 10 groups (n = 5) were given either 200 mg/kg of Hexane fraction (HFCP) or ethylacetate fraction (EAFCP) intraperitoneally. A subplantar injection of 0.1 mL 2.5 % formaldehyde solution was used to induce inflammation 1 h later, and this procedure was repeated on day three. After five days, the compounds were administered once daily, and then every other day for the next five days. Using a plethysmometer, the rat paw volume was measured every day following a 1 h drug delivery period. Diclofenac was used as the control.

Results: Compounds isolated belong to the following groups: flavonol glycoside, stigmast steroid and triterpenehydroxyl acid. The molecules identified by their structures are ursolic acid, stigmastene 3, 6- dione, and tetrahydroxy flavone-3α-rhamnoside, respectively. In rats, the combination of these compounds showed significant (p < 0.05) biological action against formaldehyde-induced inflammation, exceeding the respective percentage inhibition of individual compounds (62.60, 82.60, and 62.60 %; p < 0.05).

Conclusion: There is a significant anti-inflammatory activity of active compounds from the leaves of Chikadoma plant. The mechanism of this anti-inflammatory activity is through synergism. Clinical studies are necessary to advance the safety and toxicity profiles of these products.

Role of vitamin C in mitigating lead-induced hepatotoxicity in male albino rats

Ukam U Uno — 2025-03-08

Purpose: To investigate the adaptive role of vitamin C (VC) against lead-induced hepatotoxicity in male albino rats.

Methods: Twenty-four male albino rats were randomly assigned to four treatment groups, with each group consisting of six animals, following a completely randomized design. Animals in group I served as the control. Group II was administered 60 mg/kg body weight (BW) of Pb acetate, group III was administered 100 mg/kg BW of VC, while group IV was treated with 60 mg/kg BW of Pb acetate and VC at 100 mg/kg BW. The animals were treated orally for 65 days. Twenty-four hours after treatment, changes in body weight, liver enzymes and histopathological parameters were compared.

Results: Results showed a significant reduction in the body weight of Pb-exposed animals when compared with control group (p < 0.05). The level of Pb residue was significantly higher in the liver of rats administered solely with Pb when compared with the control animals and other treatment groups (p < 0.05). Moreover, Pb-treated animals showed liver histopathological changes such as injured hepatocytes and cytoplasmic swellings which suggest inflammation, in comparison with animals in control group. Notably, vitamin C administration mitigated Pb-induced effects across all evaluated parameters.

Conclusion: The results provided evidence of the adaptive potential of VC in mitigating Pb-induced hepatotoxicity in male albino rats.

Antimicrobial profiles of probiotic lactic acid bacteria isolated from Nigerian fermented spice condiment Okpeye (Prosopis africana)

Dinebari P Berebon — 2025-03-08

Purpose: To investigate the antimicrobial profile of lactic acid bacteria (LAB), also called friendly bacteria or probiotics, found in Nigerian fermented spice condiment Okpeye (Prosopis africana).

Methods: The LAB was isolated by enrichment and serial dilution. Biochemical characterization of isolates was done using standard microbiological protocols and determined using 16S rDNA gene sequencing. The survival of LAB in low pH 2.5 and 0.3 % bile salt media were evaluated. Using the agar well diffusion assay, the cell-free supernatant (CFS) standardized to 0.5 McFarland was evaluated for antibacterial, hydrogen peroxide, and bacteriocin activities to combat multi-drug resistant and foodborne pathogens (MDR-FBPs). Antibiotic susceptibility profile of isolates was profiled against seventeen antibiotics comprising twelve different classes using disk diffusion method.

Results: Isolates identified were Pediococuss pentosaceus, Lactobacillus brevis, and Lactobacillus plantarum, with strong antibacterial activities against S. aureus, moderate activities against L. monocytogenes, and weak activities against P. aeruginosa, B. cereus, and E. coli. The isolate retained viability greater than 80 % at pH 2.5 and 0.3 % w/v bile condition after 4 h of exposure. The isolates showed a wide range of activities against MDR-FBPs. Regarding antibacterial activity, all isolates were effective against S. aureus, moderate against L. monocytogenes ATCC 13932, and weak against P. aeruginosa ATCC 27883, Bacillus cereus and E. coli.

Conclusion: Okpeye is not just a spice; it contains high probiotics, which have antibacterial properties against foodborne and multidrug-resistant organisms, making it a beneficial addition to any diet.

Identification of bioactive compounds in red watermelon extract using qualitative liquid chromatography-mass spectrometry

Mochamad Bahrudin — 2025-03-08

Purpose: To qualitatively determine the bioactive compounds in red watermelon fruit extract using LCMS/MS

Methods: Liquid chromatography-mass spectrometry (LC-MS/MS) was used to identify and characterize the bioactive compounds in red watermelon fruit extract, with optimization of chromatographic and MS/MS parameters.

Results: The use of total ion chromatogram (TIC) for extraction of fragmentation products from target m/z revealed the retention times for various compounds. Lycopene compounds had retention time (tR) of 1.08 min; retinol (vitamin A) had tR of 1.14 min, while citrulline had tR of 1.23 min. Ascorbic acid (vitamin C) had tR of 1.35 min, while α-tocopherol (vitamin E) had tR of 9.93 min.

Conclusion: Using LC-MS/MS analysis, lycopene, citrulline, vitamin A, vitamin C and vitamin E have been identified as primary bioactive compounds in red watermelon pulp extract.

Inhibition of carbachol-induced gastrointestinal motility mediates the antidiarrheal activity of Combretum platypetalum (Welw.) Hutch & Dalziel leaf extract

Christopher EC Ugwoke — 2025-03-08

Purpose: To evaluate the mechanism of antidiarrheal activity of the leaves of Combretum platypetalum (Welw.) Hutch & Dalziel (Combretaceae) in Swiss albino mice.

Methods: The study employed bioactivity-guided fractionation of the extract, which was separated using hexane, ethyl acetate, and butanol. Further fractionation was done with vacuum liquid chromatography (VLC). The antidiarrheal activity of the extracts (100 - 400 mg/kg) and fractions (100 - 200 mg/kg) was evaluated using the charcoal meal antimotility and castor oil-induced antisecretory activity models with 3 mg/kg loperamide standard. The antimotility mechanism of the most active VLC fraction was assessed by measuring gastrointestinal transit (GT) and gastric emptying (GE).

Results: Maximum antimotility effect was achieved at 400 mg/kg extract (70.14 %), surpassing loperamide (61.88 %; p < 0.01). In the GT test, the control group's charcoal meal traversed a long distance (peristaltic index, PI: 91.48 %), which was significantly reduced (p < 0.001) with ethyl acetate fraction treatment at 50, 100, and 200 mg/kg, showing PIs of 23.46 %, 20.18 and 51.74 %, respectively. GT significantly increased (p < 0.05) with carbachol and serotonin (10 mg/kg) and 30 mg/kg metoclopramide by 83.5, 69.1 and 68.9 %, respectively, compared to control animals (44.3 ± 5.5 %). Pre-treatment with VLC fraction (200 mg/kg) significantly (p < 0.05) inhibited carbachol's action on GE (75.6 vs 27.6 %) but had no significant impact on metoclopramide and serotonin's actions on GE.

Conclusion: Combretum platypetalum's antidiarrheal activity is mediated by an antimotility mechanism, specifically through the inhibition of carbachol-induced GT and GE.

Potential drug-drug interactions among outpatients with chronic diseases at an Indonesian teaching hospital

Rima Elfitra Rambe — 2025-03-08

Purpose: To determine potential drug-drug interactions (PDDIs) among outpatients with Chronic Diseases and their correlation to patient’s age, number of drug(s), and clinic visited.

Methods: A retrospective cross-sectional study was conducted. The data were collected from prescriptions of outpatients with chronic diseases at Prof Dr Chairuddin P Lubis Universitas Sumatera Utara, an Indonesian teaching hospital in 2023. Interactions were identified by the Lexicomp® Drug Interaction Checker. Data were analyzed statistically and presented as numbers and percentages. Correlation between variables was carried out using the chi-square test in SPSS V22.0.

Results: The results showed 1405 PDDIs from 313 patients. Most PDDIs based on interaction mechanism, severity, and reliability were pharmacodynamic, moderate, and fair. Cardiovascular, internal medicine and psychiatric outpatient clinics contributed the most PDDIs. Statistically, there was no correlation between patient’s age and clinic visits to the number of PDDIs. Meanwhile, the amount of drugs correlated with PDDIs was significantly stated by a p-value of 0.000.

Conclusion: High percentages of PDDIs are found among outpatients with chronic diseases. The more drugs on the prescription, the more PDDIs result. Hence, the healthcare team participates in preventing drug-drug interaction.

Potential effects and mechanistic pathways of sodium-glucose cotransporter 2 inhibitors in diabetic wound healing: A comprehensive review

Dalal Alfawaz — 2025-02-28

Diabetes mellitus (DM) and its associated morbidities embody a significant challenge and considerable strain on healthcare sectors globally. Significantly, impaired wound healing is a common complication associated with poorly managed diabetes, often leading to adverse consequences. The diabetic wound results from a perpetual state of localized inflammation induced by the over-accumulation of proinflammatory cells along with their cytokines and proteases. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors represent one of the classes of novel antidiabetic drugs that have shown promising effects in promoting wound healing, largely due to their anti-inflammatory properties. The findings in this review were synthesized using authoritative sources and advanced research tools. Searches on platforms such as Google Scholar, PubMed, Scopus, and JSTOR yielded high-quality peer-reviewed articles. Furthermore, the use of generic medication names referenced in this study, combined with terms such as "wound healing" and "diabetes," facilitated a precise and comprehensive analysis of their therapeutic implications. Reference materials were sourced from eminent journals like ScienceDirect and The Lancet, providing a robust empirical foundation, while esteemed repositories such as the World Health Organization (WHO) enriched the discourse with authoritative insights. This review focused on the potential impact of SGLT-2 inhibitors, namely, empagliflozin and dapagliflozin, on promoting wound healing. It will also discuss the mechanistic pathways by which this process is thought to occur. The current pool of evidence favors the notion that certain antidiabetic medications possess anti-inflammatory properties that aid in preventing wounds from being in a perpetual inflammatory stage; this is thought to be accomplished by the downregulation of proinflammatory cytokines, upregulation of specific growth factors, reduction of metalloproteinases, promotion of angiogenesis, and enhancement of epithelialization. Nevertheless, this remains a fertile area for further research before these antidiabetic medications may be incorporated into clinical guidelines as therapeutic agents in the management of chronic wounds.