# Activation of Angiogenic TGF-β1 by Salbutamol Enhances Wound Contraction and Improves Healing in a Streptozotocin-Induced Diabetic Rat Model

**Authors:** Promise M. Emeka, Abdulaziz K. Al Mouslem, Hussien Almutawa, Malek Albandri, Hussain Alhmoud, Mohammed Alhelal, Zakaria Alhassan, Abdullah Alhamar

PMC · DOI: 10.3390/cimb47100820 · Current Issues in Molecular Biology · 2025-10-03

## TL;DR

This study shows that applying salbutamol improves wound healing in diabetic rats by boosting blood vessel growth and reducing inflammation.

## Contribution

The study demonstrates that topical salbutamol activates TGF-β1 to enhance wound healing in diabetic conditions.

## Key findings

- TS treatment led to 100% wound contraction in 14 days in diabetic rats.
- TS increased TGF-β1 and NO activity while reducing inflammatory markers like IL-1β and TNF-α.
- Sympathetic nerve stimulation via salbutamol supports angiogenesis in diabetic wounds.

## Abstract

Wound healing is impaired under diabetic conditions due to reduced angiogenesis, thereby increasing the risk of wound-healing complications. Studies have shown that inhibition of α- and β-adrenoceptors delays wound healing. This study investigates the effects of topical salbutamol (TS) on STZ-induced diabetic wound healing in rats. The rats were divided into two initial groups: non-diabetic and diabetic. Diabetes mellitus was induced in the second group with STZ (65 mg/kg). Excision wounds were inflicted on the dorsal thoracic region, 1–1.5 cm away from the vertebral column on either side, following anesthesia on all groups. Group 2 was subdivided into untreated diabetic wounds, low-dose-TS-treated diabetic wounds (6.25 mg/mL), medium-dose-TS-treated diabetic wounds (12.5 mg/mL), and high-dose-TS-treated diabetic wounds (25 mg/mL), and were monitored for 14 days. Percentage wound contraction and the time required for complete wound closure were observed and recorded. In addition, oxidative stress and inflammatory markers such as NO, CRP, MPO, TGF-β1, TNF-α, IL-6, IL-1β, NO, and hexosamine were estimated in wound exudates and tissue over 14 days. TS treatment resulted in 100% wound contraction in all treated wounds within 14 days compared to untreated non-diabetic and diabetic wounds. Increased NO, TGF-β1, and hexosamine activity was observed in TS-treated wounds when compared to untreated diabetic wounds. In addition, TS treatment decreased the activity of IL-1β, TNF-α, IL-6, CRP, and MPO, all of which were elevated in the untreated diabetic wounds. The current study shows that the application of TS significantly improved diabetic wound contraction and aided the healing process. Angiogenic markers, such as TGF-β1 and NO, were prominently increased, supporting the role of sympathetic nerve stimulation in angiogenesis.

## Linked entities

- **Proteins:** TGFB1 (transforming growth factor beta 1), Nos1 (nitric oxide synthase 1, neuronal), CRP (C-reactive protein), MPO (myeloperoxidase), TNF (tumor necrosis factor), IL6 (interleukin 6), IL1B (interleukin 1 beta)
- **Chemicals:** salbutamol (PubChem CID 2083), hexosamine (PubChem CID 739)
- **Diseases:** Diabetes mellitus (MONDO:0005015)
- **Species:** Rattus norvegicus (taxon 10116)

## Full-text entities

- **Genes:** Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, Il6 (interleukin 6) [NCBI Gene 24498] {aka ILg6, Ifnb2}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Crp (C-reactive protein) [NCBI Gene 25419] {aka Aa1249, Ab1-341, Ab2-196, Ac1-114, Ac1262, Ac2-069}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 59086] {aka Tgfb}, Mpo (myeloperoxidase) [NCBI Gene 303413]
- **Diseases:** inflammatory (MESH:D007249), Diabetes mellitus (MESH:D003920)
- **Chemicals:** STZ (MESH:D013311), NO (MESH:D009614), TS (-), hexosamine (MESH:D006595), Salbutamol (MESH:D000420)
- **Species:** Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12564531/full.md

## References

40 references — full list in the complete paper: https://tomesphere.com/paper/PMC12564531/full.md

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Source: https://tomesphere.com/paper/PMC12564531