Wound healing activity of Triterpenes from birch bark - insights into the molecular mechanism

Abstract

Birch bark extract (TE), which consists of triterpenes such as betulin, lupeol and betulinic acid, was shown to exert promising wound healing effects in patients [1]. Here, we report studies on the underlying molecular mechanisms. We demonstrate that TE and betulin influence the inflammatory phase of wound healing by upregulating varieties of pro-inflammatory cytokines, chemokines and cyclooxygenase-2 (COX-2) in human primary keratinocytes. These mediators play a crucial role in cell migration, proliferation and angiogenesis. We provide evidence with COX-2 that its increase is due to a mRNA stabilizing effect, a process in which p38 MAPK and HuR are essentially involved. In the new tissue formation phase, controlled migration of keratinocytes at the wound edge is a crucial step in wound healing and requires a coordinated reorganization of the actin cytoskeleton. We demonstrate that TE, betulin and lupeol increase the formation of actin filopodia and lamellipodia, a process which is dependent on the activation of Rho GTPases.