Topical application of metformin accelerates cutaneous wound healing in streptozotocin-induced diabetic rats

Tombultürk, Fatma Kübra; Seven, Zeynep Gizem Todurga; Huseyinbas, Onder; Özyazgan, Sibel; Ulutin, Turgut; Kanıgür-Sultuybek, Gönül

doi:10.1007/s11033-021-06843-7

Cited by 8 publications

(10 citation statements)

References 47 publications

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“…Met is a member of the biguanide family and is a first-line hypoglycemic agent in the clinical therapy of patients with type 2 diabetes. The topical application of Met for diabetic wound therapy has been reported as effective [ 152 ]. GB is a sulfonylurea hypoglycemic medication that reduces blood-glucose levels by increasing insulin release from pancreatic cells and blocking hepatic glycogenolysis and glycogen xenobiotic effects [ 153 ].…”

Section: Electrospinning Nanofiber In Diabetic Wound Therapymentioning

confidence: 99%

Advances in the Preparation of Nanofiber Dressings by Electrospinning for Promoting Diabetic Wound Healing

Liu

Feng

et al. 2022

Biomolecules

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Chronic diabetic wounds are one of the main complications of diabetes, manifested by persistent inflammation, decreased epithelialization motility, and impaired wound healing. This will not only lead to the repeated hospitalization of patients, but also bear expensive hospitalization costs. In severe cases, it can lead to amputation, sepsis or death. Electrospun nanofibers membranes have the characteristics of high porosity, high specific surface area, and easy functionalization of structure, so they can be used as a safe and effective platform in the treatment of diabetic wounds and have great application potential. This article briefly reviewed the pathogenesis of chronic diabetic wounds and the types of dressings commonly used, and then reviewed the development of electrospinning technology in recent years and the advantages of electrospun nanofibers in the treatment of diabetic wounds. Finally, the reports of different types of nanofiber dressings on diabetic wounds are summarized, and the method of using multi-drug combination therapy in diabetic wounds is emphasized, which provides new ideas for the effective treatment of diabetic wounds.

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Section: Electrospinning Nanofiber In Diabetic Wound Therapymentioning

confidence: 99%

Advances in the Preparation of Nanofiber Dressings by Electrospinning for Promoting Diabetic Wound Healing

Liu

Feng

et al. 2022

Biomolecules

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“…Topical metformin treatment showed promising results in patients suffering from melasma 21,25 and recalcitrant central centrifugal cicatricial alopecia 19 . Other successful studies in experimental animals included treatment of wounds 26,27 skin cancer 15,24 and ultraviolet skin injury 28 …”

Section: Introductionmentioning

confidence: 99%

“…[15][16][17][18][19][20][21][22][23][24] Topical metformin treatment showed promising results in patients suffering from melasma 21,25 and recalcitrant central centrifugal cicatricial alopecia. 19 Other successful studies in experimental animals included treatment of wounds 26,27 skin cancer 15,24 and ultraviolet skin injury. 28 This split face study was designed to evaluate the efficacy and safety of topical metformin in comparison to placebo in the treatment of patients suffering from acne vulgaris (AV).…”

mentioning

confidence: 99%

Topical metformin 30% gel in the treatment of acne vulgaris in women, a split face, placebo‐controlled study

El-Komy

Abdo²,

Shamma

et al. 2023

Experimental Dermatology

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Acne vulgaris (AV), a widely common disorder, that negatively affects the quality of life. Metformin is a relatively safe, cheap and well tolerated drug that is widely used in the treatment of Diabetes. Systemic metformin has demonstrated promising results in treating acne, while topically it was studied for melasma and recalcitrant central centrifugal cicatricial alopecia. To study the safety and efficacy of topical metformin 30% in the treatment of AV. Twenty‐seven female AV patients were asked to blindly apply metformin and placebo gels to either side of the face for 12 weeks. AV lesion count was performed at baseline, at each visit and 4 weeks after end of treatment. At the end of the treatment period, the treated side showed significant improvement of comedones, papules and nodules but not pustules. Although, lesions count increased 1 month after stopping treatment, comedones and papules numbers were still significantly less on the metformin side compared to placebo. No side effects were reported. The limited number of patients studied and the limited follow‐up period. The metformin effect was not studied on cellular and molecular levels. Topical metformin nanoemulsion gel can be a promising safe and effective treatment of AV.

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“…Nitric oxide (NO) generation, which has a vital role in microvascular homeostasis, angiogenesis, epidermal migration, formation of granulation tissue, and collagen deposition in the wound, is also impaired in diabetes (3). Some existing drugs have been investigated in drug repurposing efforts, such as statins, phenytoin, metformin, propranolol, valsartan, as well as DPP-4 inhibitors, but have limited or no efficacy for wound healing (4)(5)(6)(7)(8)(9). Topical phenytoin was shown to reduce the time for granulation tissue in ulcers as well as promote a reduction in the size of ulcers (4).…”

Section: Introductionmentioning

confidence: 99%

“…Topical mevastatin stimulated epithelialization and angiogenesis in animal models by exhibiting the modulation of GR ligands and c-Myc inhibition ( 6 ). Topically applied metformin applied to diabetic rats suppresses NF-κB p65 activity and diminishes the expression of MMP2 and MMP9 to accelerate wound healing ( 7 ). In diabetic mice, DPP-4 inhibitors have been shown to promote the migration of keratinocytes ( 8 ).…”

Section: Introductionmentioning

confidence: 99%

Novel topical esmolol hydrochloride improves wound healing in diabetes by inhibiting aldose reductase, generation of advanced glycation end products, and facilitating the migration of fibroblasts

Kulkarni

Deshpande²,

Rastogi³

2022

Front. Endocrinol.

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Aims/ObjectivesWound healing in people with diabetes is delayed secondary to impaired nitric oxide generation, advanced glycation end products (AGE), and poor migration of epithelial cells. We developed a novel topical esmolol hydrochloride (Galnobax) and assessed its efficacy for wound healing in streptozocin-induced diabetic hairless rat.MethodsAll experiments were performed at an animal laboratory and tertiary-care research facility. Ex vivo aldose reductase inhibition was assessed from enzymes obtained from a bacterial culture (spectrophotometer), sorbitol content in homogenized red blood cells, and AGE in glucose and bovine serum by fluorometry following the addition of esmolol in varying concentrations. A scratch assay of human fibroblasts, endothelial cells, and keratinocytes was assessed under a high-glucose environment and after esmolol by phase-contrast microscopy. The efficacy evaluation of the topical application of Galnobax (14 and 20%) or vehicle was conducted in streptozotocin-induced diabetic hairless rats, and endogenous nitrite and hydroxyproline from homogenized wound tissue were measured along with pharmacokinetic and dermal toxicity in Hanford miniature swine.ResultsEsmolol inhibited the formation of sorbitol by 59% in erythrocytes in comparison to glucose-induced sorbitol levels. AGE generation in bovine serum albumin was reduced at 1 mM esmolol concentrations (2.6 ± 1.7) compared with control (p < 0.05) and similar to that of diclofenac (2.5 ± 1.3). Esmolol at 1 and 10 µM enhanced the migration of fibroblasts, epithelial cells, and keratinocytes compared with control. The nitric oxide levels (day 7) were 44 and 112% higher with Galnobax (14%) than those of the diabetic group (p < 0.05) and the vehicle control group (p < 0.05), respectively. The days 7 and 14 hydroxyproline in the wound was higher by 22 and 44% following Galnobax (14%) compared with the diabetic and vehicle control groups. The wound area exhibited better reduction with Galnobax at 14% up to day 10 follow-up compared with the controls. The pharmacokinetic and dermal toxicity in miniature swine suggested no significant adverse event with Galnobax.ConclusionsTopical esmolol hydrochloride is a novel, safe, and effective treatment modality that acts through pleotropic mechanisms to hasten wound healing in diabetes.

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Topical application of metformin accelerates cutaneous wound healing in streptozotocin-induced diabetic rats

Cited by 8 publications

References 47 publications

Advances in the Preparation of Nanofiber Dressings by Electrospinning for Promoting Diabetic Wound Healing

Advances in the Preparation of Nanofiber Dressings by Electrospinning for Promoting Diabetic Wound Healing

Topical metformin 30% gel in the treatment of acne vulgaris in women, a split face, placebo‐controlled study

Novel topical esmolol hydrochloride improves wound healing in diabetes by inhibiting aldose reductase, generation of advanced glycation end products, and facilitating the migration of fibroblasts

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