Naphthoquinones from Handroanthus impetiginosus promote skin wound healing through Sirt3 regulation

• Main Authors: Fayyaz Ahmad, Shaheen Bibi, Mincheol Kang, Mariam Anees, Muhammad Ansar, Muhammad Rizwan Alam, Sun Kim, Hussain Wahedi
• Format: Article
• Language: English
• Published: Mashhad University of Medical Sciences 2020-09-01
• Series: Iranian Journal of Basic Medical Sciences
• Subjects: beta; lapachone dermatology inflammation regeneration tabebuia
• Online Access: http://ijbms.mums.ac.ir/article_16139_c2c8bb6f3e32bc19e9c5dd1f36db3e9f.pdf
• ISSN: 2008-3866; 2008-3874

<em><strong>Objective(s):</strong></em> Lapachone is a natural naphthoquinone-derived compound found in Tabebuia avellanedae. It is well-known for its analgesic, anti-inflammatory, anti-microbial, diuretic, and anti-cancerous effects. However, the wound-healing effects of this compound are not known yet. The aim of this study was to investigate the wound healing activity of naphthoquinones (α-lapachone and β-lapachone) from Handroanthus impetiginosus. <br /><em><strong>Materials and Methods:</strong></em> Expression of Sirt3, migration-related proteins (Rac1, Cdc42, α-Pak) and angiogenesis-related protein of vascular endothelial growth factor (VEGF) was monitored using western blot analysis. Blood vessel formation and tissue development were monitored by angiogenesis assay and hematoxylin & eosin (H & E) staining, respectively on mouse skin tissue samples. Both α-lapachone and β-lapachone increased Sirt3 expression in vivo, but only β-lapachone increased Sirt3 expression in vitro. <br /><em><strong>Results:</strong></em> Both the compounds accelerated wound healing in cultured skin cells as well as mouse skin; however, β-lapachone was more effective at lower concentrations. Both of the compounds increased the expression of migration-related proteins both in vitro and in vivo. Similarly, α-lapachone and β-lapachone increased VEGF expression, tissue development and blood vessel formation in mouse skin.<br /><em><strong>Conclusion:</strong></em> These findings indicated that α-lapachone and β-lapachone are novel Sirt3 activators, and Sirt3 has a role in wound healing. Thus, Sirt3 and its regulators come out as a novel target and potential drug candidates, respectively in the important field of cutaneous wound healing.