title: Topical delivery of 4-hexylresorcinol promotes wound healing via tumor necrosis factor-α suppression.
abstract: OBJECTIVE
  The objective of this study was to evaluate (1) the effect of 4-hexylresorcinol (4HR) application on TNF-α expression in RAW264.7 cells and (2) the effect of 4HR ointment on burn wound healing in a rat burn wound model.
  
  
  METHODS
  RAW264.7 cells were cultured in the presence of different concentrations of 4HR, and the attached cells were sampled for western blot analysis at each time point. Animal studies were conducted on male Wistar rats (n=24). Three treatment groups were evaluated in this study: (1) treatment with ointment alone (negative control), (2) treatment with ointment containing 0.2wt% 4HR, and (3) treatment with ointment containing 2wt% 4HR. For the assessment of wound healing, digital photographs were taken at 1, 5, and 14 days. Animals were sacrificed at 1, 5, and 14 days for histological examination or ELISA analysis.
  
  
  RESULTS
  Western blot analysis showed that TNF-α protein levels were reduced following treatment with 4HR at concentrations between 1 and 10μg/mL. In animal studies, the average denuded area 14 days after burn was smaller in the 2wt% 4HR treatment group compared with the control group (P=0.022). Immunohistochemical analysis revealed lower TNF-α expression in the 2wt% 4HR treatment group compared with the control group 14 days after burn (P=0.027).
  
  
  CONCLUSIONS
  4HR reduced TNF-α expression in RAW264.7 cells and in the burn wounds of rats. Burn wounds dressed with ointment containing 4HR also exhibited rapid epithelization and collagen regeneration.
authors.affiliation: Department of Dentistry, College of Medicine, Hallym University, Chuncheon, Republic of Korea.
authors.forename: Janghoon
authors.initials: J
authors.lastname: Ahn
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University, Gangneung, Republic of Korea. Electronic address: kimsg@gwnu.ac.kr.
authors.forename: Seong-Gon
authors.initials: SG
authors.lastname: Kim
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University, Gangneung, Republic of Korea.
authors.forename: Min-Keun
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Oral Biochemistry, College of Dentistry, Gangneung-Wonju National University, Gangneung, Republic of Korea.
authors.forename: Dae-Won
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University, Gangneung, Republic of Korea.
authors.forename: Jang-Ha
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Oral and Maxillofacial Surgery, College of Dentistry, Gangneung-Wonju National University, Gangneung, Republic of Korea.
authors.forename: Hyun
authors.initials: H
authors.lastname: Seok
authors.affiliation: Department of Biochemistry & Cell Biology, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Je-Yong
authors.initials: JY
authors.lastname: Choi
mesh_terms: D000279:Administration, Cutaneous; D000287:Administration, Topical; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D015153:Blotting, Western; D002056:Burns / Q000188:drug therapy* / Q000378:metabolism; D006604:Hexylresorcinol / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D009824:Ointments; D000067996:RAW 264.7 Cells; D051381:Rats; D017208:Rats, Wistar; D062326:Re-Epithelialization / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects* / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
chemical_list: D000871:Anthelmintics; D009824:Ointments; D014409:Tumor Necrosis Factor-alpha; D006604:Hexylresorcinol
keywords: 4-Hexylresorcinol; Burn; Epithelization; TNF-α