Planta Med 2012; 78 - PD72
DOI: 10.1055/s-0032-1320430

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

S Ebeling 1, G Schmidt 2, K Naumann 1, M Laszczyk 3, A Scheffler 3, I Merfort 1
  • 1Dept. of Pharmaceutical Biology and Biotechnology, University Freiburg, Germany
  • 2Dept. of Experimental and Clinical Pharmacology and Toxicology, University Freiburg, Germany
  • 3Birken AG, Niefern-Öschelbronn, Germany

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.

[1] Metelmann et al., in preparation.

Acknowledgement: Financial support from the Federal Ministry of Economics and Technology is gratefully acknowledged.