Wound healing potential of naringin ointment formulation via regulating the expression of inflammatory, apoptotic and growth mediators in experimental rats

Pharm Biol. 2016;54(3):419-32. doi: 10.3109/13880209.2015.1038755. Epub 2015 Apr 20.

Abstract

Context: Wound healing is a consequence of a complex process involving inflammatory, proliferative, and remodeling phases. Naringin, a flavanone glycoside, is associated with modulation of various oxido-inflammatory and growth factors.

Aim: The aim of this study is to evaluate the wound-healing activity of naringin ointment formulation (NOF) on experimental wound models.

Materials and methods: A soft paraffin-based cream containing 1, 2, and 4% (w/w) naringin was formulated and evaluated for physicochemical characters. Excision wounds and incisions wounds were used to study the topical effect of NOF for 20 d (once a day) on various biochemical, molecular, and histological parameters.

Results: NOF (2 and 4%, w/w) treatment showed a significant decrease (p < 0.05) in wound area and epithelization period whereas the rate of wound contraction increased significantly (p < 0.05). The altered levels of oxido-nitrosative stress (SOD, GSH, MDA, MPO, and NO) were significantly (p < 0.05) restored by NOF. Treatment produced a significant increase (p < 0.05) in tensile strength, hydroxyproline content, and protein content. TNF-α, IL-1β, IL-6, IL-8, NF-κB, smad-7, and Bax mRNA expression were significantly down-regulated (p < 0.05) by NOF, whereas polymerase gamma (pol-γ), smad-3, VEGF and TGF-β, and collagen-1 mRNA expressions were significantly up-regulated (p < 0.05) by NOF. Histological alterations in wound skin were also restored by NOF.

Conclusion: NOF exerts wound healing potential via down-regulated expression of inflammatory (NF-κB, TNF-α, and ILs), apoptotic (pol-γ and Bax), and up-regulated growth factor (VEGF and TGF-β) expression, thus modulating collagen-1 expression to induce angiogenesis leading to wound healing.

Keywords: Collagen-1; NF-κB; TGF-β; VEGF; pol-γ; smad-3; smad-7.

MeSH terms

  • Administration, Topical
  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Chemistry, Pharmaceutical
  • Flavanones / administration & dosage*
  • Inflammation Mediators / antagonists & inhibitors*
  • Inflammation Mediators / metabolism*
  • Lymphotoxin-alpha / agonists
  • Lymphotoxin-alpha / biosynthesis
  • Male
  • Ointments
  • Rats
  • Rats, Wistar
  • Vascular Endothelial Growth Factor A / agonists
  • Vascular Endothelial Growth Factor A / biosynthesis*
  • Wound Healing / drug effects*
  • Wound Healing / physiology

Substances

  • Flavanones
  • Inflammation Mediators
  • Lymphotoxin-alpha
  • Ointments
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat
  • naringin