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Updated: Jan 17, 2026
A Protocol for Constructing a Rat Wound Model of Type 1 Diabetes
Published on: February 17, 2023
Empagliflozin targeting STAT3/Akt/Nrf2 axis promoting diabetic wound healing in rat model
Rania Magadmi1, Dalal Alfawaz1, Ahmed Bakhshwin2
1Department of Clinical Pharmacology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
Background:
Diabetes mellitus (DM) and its complications pose a major global health challenge, with impaired wound healing leading to severe outcomes. Chronic inflammation, excessive proinflammatory cells, and high reactive oxygen species contribute to diabetic wound complications. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor, has antioxidant and anti-inflammatory properties, but its impact on wound healing remains unclear.
Objective:
To investigate the effects of empagliflozin on wound healing in diabetic rats and explore its underlying molecular mechanisms.
Methodology:
Fifty male Wistar rats were divided into five groups: untreated diabetic rats (STZ group), STZ + plain hydrogel, STZ + empagliflozin hydrogel (1%), STZ + oral empagliflozin (20 mg/kg), and STZ + MEBO®. Wounds were created 2 weeks post-STZ injection and treated for 21 days. Assessments included wound contraction, histopathology, fasting blood glucose (FBG), oxidative stress parameters, and inflammatory biomarkers in skin homogenates. Mechanistic markers, including phosphorylated STAT3, Akt, nuclear factor erythroid 2-related factor 2 (Nrf2), sirtuin 1 (SIRT1), and β-catenin, were analyzed.
Results:
Empagliflozin-treated animals had significant wound healing improvements, confirmed by macroscopic and histological assessments, with oral administration being the most effective. Inflammatory markers, including tumor necrosis factor-alpha (TNF- α) and interleukin-6 (IL-6), were markedly reduced, alongside decreased oxidative stress. Both oral and topical empagliflozin significantly upregulated key proteins involved in healing, including phosphorylated STAT3, Akt, Nrf2, SIRT1, and β-catenin.
Conclusion:
Empagliflozin accelerates wound healing in diabetic rats through its anti-inflammatory and antioxidant properties. Oral empagliflozin exhibited superior efficacy, suggesting systemic effects that extend beyond glycemic control. These findings offer insights into its molecular mechanisms of empagliflozin as a promising therapeutic agent for diabetic wound management.
Insights
Empagliflozin significantly improves diabetic wound healing in rats by reducing inflammation and oxidative stress. Oral empagliflozin showed the best results, highlighting its potential for managing diabetic wounds.
Area of Science:
- Pharmacology
- Wound Healing Research
- Diabetology
Background:
- Diabetes mellitus (DM) complications include impaired wound healing, driven by chronic inflammation and oxidative stress.
- Empagliflozin, an SGLT2 inhibitor, possesses known antioxidant and anti-inflammatory properties.
- The specific effects of empagliflozin on diabetic wound healing require further investigation.
Purpose of the Study:
- To evaluate the efficacy of empagliflozin in promoting wound healing in diabetic rats.
- To elucidate the molecular mechanisms underlying empagliflozin's effects on diabetic wound repair.
Main Methods:
- Fifty diabetic rats (STZ-induced) were assigned to five groups, including controls and treatments with hydrogel or oral empagliflozin.
- Wound healing was assessed via macroscopic and histological analysis over 21 days.
- Key molecular markers related to inflammation, oxidative stress, and cellular signaling pathways (e.g., STAT3, Akt, Nrf2, SIRT1, β-catenin) were quantified.
Main Results:
- Empagliflozin treatment significantly enhanced wound contraction and histological healing in diabetic rats, with oral administration showing superior effects.
- Marked reductions in inflammatory cytokines (TNF-α, IL-6) and oxidative stress markers were observed.
- Empagliflozin upregulated crucial proteins (p-STAT3, Akt, Nrf2, SIRT1, β-catenin) involved in the healing process.
Conclusions:
- Empagliflozin accelerates diabetic wound healing by mitigating inflammation and oxidative stress.
- Oral empagliflozin demonstrates superior efficacy, suggesting systemic benefits beyond glucose control.
- Empagliflozin presents a promising therapeutic strategy for managing diabetic wound complications.
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