title: Wound healing potential of naringin ointment formulation via regulating the expression of inflammatory, apoptotic and growth mediators in experimental rats.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  The aim of this study is to evaluate the wound-healing activity of naringin ointment formulation (NOF) on experimental wound models.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a Department of Pharmacology , Poona College of Pharmacy, Bharati Vidyapeeth Deemed University , Pune , Maharashtra , India.
authors.forename: Amit D
authors.initials: AD
authors.lastname: Kandhare
authors.affiliation: a Department of Pharmacology , Poona College of Pharmacy, Bharati Vidyapeeth Deemed University , Pune , Maharashtra , India.
authors.forename: Javed
authors.initials: J
authors.lastname: Alam
authors.affiliation: a Department of Pharmacology , Poona College of Pharmacy, Bharati Vidyapeeth Deemed University , Pune , Maharashtra , India.
authors.forename: Mithun V K
authors.initials: MV
authors.lastname: Patil
authors.affiliation: a Department of Pharmacology , Poona College of Pharmacy, Bharati Vidyapeeth Deemed University , Pune , Maharashtra , India.
authors.forename: Akanksha
authors.initials: A
authors.lastname: Sinha
authors.affiliation: a Department of Pharmacology , Poona College of Pharmacy, Bharati Vidyapeeth Deemed University , Pune , Maharashtra , India.
authors.forename: Subhash L
authors.initials: SL
authors.lastname: Bodhankar
mesh_terms: D000287:Administration, Topical; D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002626:Chemistry, Pharmaceutical; D044950:Flavanones / Q000008:administration & dosage*; D018836:Inflammation Mediators / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D008233:Lymphotoxin-alpha / Q000819:agonists / Q000096:biosynthesis; D008297:Male; D009824:Ointments; D051381:Rats; D017208:Rats, Wistar; D042461:Vascular Endothelial Growth Factor A / Q000819:agonists / Q000096:biosynthesis*; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D044950:Flavanones; D018836:Inflammation Mediators; D008233:Lymphotoxin-alpha; D009824:Ointments; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; C005274:naringin
keywords: Collagen-1; NF-κB; TGF-β; VEGF; pol-γ; smad-3; smad-7