Wound healing activity of Triterpenes from birch bark – insights into the molecular mechanism
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 . 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.
 Metelmann et al., in preparation.
Acknowledgement: Financial support from the Federal Ministry of Economics and Technology is gratefully acknowledged.