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-1ß, 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-ß, 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-ß) expression, thus modulating collagen-1 expression to induce angiogenesis leading to wound healing.
Subject(s)
Apoptosis/drug effects , Flavanones/administration & dosage , Inflammation Mediators/antagonists & inhibitors , Inflammation Mediators/metabolism , Vascular Endothelial Growth Factor A/biosynthesis , Wound Healing/drug effects , Administration, Topical , Animals , Apoptosis/physiology , Chemistry, Pharmaceutical , Lymphotoxin-alpha/agonists , Lymphotoxin-alpha/biosynthesis , Male , Ointments , Rats , Rats, Wistar , Vascular Endothelial Growth Factor A/agonists , Wound Healing/physiologyABSTRACT
The 'classical' NF-kappaB activation pathway proceeds via IkappaB kinase (IKK)-beta/gamma-mediated phosphorylation, induced ubiquitination and the degradation of small IkappaBs. An alternative, NF-kappaB-inducing kinase and IKK-alpha-dependent pathway, which stimulates the processing of NF-kappaB2/p100, has recently been suggested. However, no physiological stimulus has been shown to trigger the activation of this pathway. Here we demonstrate that persistent stimulation with lymphotoxin beta (LT-beta) receptor agonists or lipopolysaccharide (LPS), but not with interleukin-1beta, tumour necrosis factor-alpha or 12-O-tetradecanoylphorbol-13-acetate, induces the generation of p52 DNA-binding complexes by activating the processing of the p100 precursor. Induction of p52 DNA-binding activity is delayed in comparison with p50/p65 complexes and depends on de novo protein synthesis. p100 is constitutively and inducibly polyubiquitinated, and both ubiquitination and p52 generation are coupled to continuing p100 translation. Thus, both LT-beta receptor agonists and LPS induce NF-kappaB/p100 processing to p52 at the level of the ribosome.
