Abstract

Diabetic ulcers are a severe complication in patients with diabetes that often lead to amputation. The etiology of diabetes-induced wound healing impairment is multi-faceted. Persistent inflammation and deficient tissue regeneration have been suggested to impair wound healing in diabetes patients. Although new therapeutic approaches have been developed, many chronic wound treatments remain unsatisfactory, and more promising therapeutics are urgently needed. We thus developed diabetic wounding models with or without bacterial infection in rats that are optimized for testing a traditional Chinese medicine-Zizhu ointment. We observed increased proinflammatory markers and decreased angiogenesis in both non-infected and infected diabetic wounded rats. These changes were normalized by Zizhu ointment. Additionally, activation of Phosphatidylinositol-3-kinase (PI3K), c-Jun N-terminal kinase (JNK), and nuclear factor-kappa B (NF-κB) were observed in diabetic wounded rats, whereas Zizhu ointment significantly inhibited activation of these proteins. Our results suggest that Zizhu ointment promotes wound healing by inhibiting the inflammatory response. Key words: Zizhu ointment, diabetic wounding, inflammation, angiogenesis, nuclear factor-kappa B (NF?κB).

Highlights

  • Diabetes is a complex, chronic illness and has become a global public health problem associated with multifactorial risk-reduction strategies beyond glycemic control (Munhoz and Frode, 2018)

  • We found that the levels of C reactive protein (CRP), IL6, and nitric oxide (NO) were significantly increased in diabetic wounding rats compared to wounding rats or diabetic rats (Figure 2A)

  • A significant reduction in CRP, IL6, and NO levels were observed at different doses of Zizhu ointment treatment as well as in the positive control treatment (b-FGF Spray, group C) compared to vehicle-treated diabetic wounding rats (Figure 2A)

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Summary

Introduction

Chronic illness and has become a global public health problem associated with multifactorial risk-reduction strategies beyond glycemic control (Munhoz and Frode, 2018). A series of factors, including decreased cell and growth factor response as well as sustained chronic inflammation, lead to diminished peripheral blood flow and decreased local angiogenesis, all of which can contribute to lack of healing in persons with diabetic ulcers (Hardwicke et al, 2011; Han and Ceilley, 2017).

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