Submitted on May 21, 2008
Revised on July 14, 2008
Accepted on July 17, 2008
In Vitro and In Vivo Wound Healing-Promoting Activities of 
-Lapachone
Hsiu-Ni Kung, Mei-Jun Yang, Chi-Feng Chang, Yat-Pang Chau, and Kuo-Shyan Lu1*
1 National Taiwan University
* To whom correspondence should be addressed. E-mail: lks{at}ntu.edu.tw.
Impaired wound healing is a serious problem for diabetic patients. Wound healing is a complex process that requires the cooperation of many cell types, including keratinocytes, fibroblasts, endothelial cells, and macrophages. 
-Lapachone, a natural compound extracted from the bark of the lapacho tree (Tabebuia avellanedae), is well known for its anti-tumor, anti-inflammatory, and anti-neoplastic effects at different concentrations and conditions, but its effects on wound-healing have not been studied. The purpose of the present study was to investigate the effects of lapachone on the wound healing and its underlying mechanism. In this study, we demonstrated that a low dose of -lapachone enhanced the proliferation in several cells, facilitated the migration of mouse 3T3 fibroblasts and human endothelial EAhy926 cells through different MAPK signaling pathways, and accelerated scrape-wound healing in vitro. Application of ointment with or without -lapachone to a punched wound in normal and diabetic (db/db) mice showed that the healing process was faster in -lapachone-treated animals than in those treated with vehicle only. In addition, -lapachone induced macrophages to release VEGF and EGF that are beneficial for growth of many cells. Our results showed that -lapachone can increase the cell proliferation including keratinocytes, fibroblasts and endothelial cells and the migration of fibroblasts and endothelial cells and thus accelerate wound healing. Therefore, we suggest that -lapachone may have potential for therapeutic use for wound healing.
