Planta Med 2010; 76 - WSIIL
DOI: 10.1055/s-0030-1264204

Impulse Lecture: Elucidation of the molecular basis of anti-inflammatory natural compounds from traditional medicinal plants

O Werz 1
  • 1University of Tuebingen, Pharmaceutical Institute, Auf der Morgenstelle 8, 72076 Tuebingen, Germany

Although many traditional medicinal plants are used in the therapy of inflammatory disorders, the bioactive ingredients and/or the molecular basis underlying the anti-inflammatory action are often unclear. Numerous plant-derived natural products with anti-inflammatory properties have previously been reported to reduce the biosynthesis of eicosanoids, i.e., prostaglandins (PGs) and leukotrienes (LTs) and this has essentially been attributed to an interference with the respective key enzymes cyclooxygenase (COX) and 5-lipoxygenase (5-LO). The dual inhibition of 5-LO and of microsomal PGE2 synthase-1 (mPGES-1), which forms pro-inflammatory PGE2 from COX-2 derived PGH2, is a novel and promising strategy for the therapy of inflammation being superior over single inhibition in terms of higher anti-inflammatory efficacy but also may cause fewer side effects. We have investigated selected natural products for which either anti-inflammatory efficacy in vivo or inhibition of PG biosynthesis was described. Here we report that many of these compounds (e.g., hyperforin, epigallocatechin gallate, garcinol, curcumin, myrtucommulone, arzanol) are poor inhibitors of COX enzymes but instead efficiently inhibit mPGES-1. Hence, the previously observed reduced PGE2 levels are rather due to inhibition of mPGES-1 than COX-1/2. Of interest, the mPGES-1 inhibitiory effect is often associated with suppression of 5-LO. Finally, analysis of selected compounds in experimental models of inflammation confirm inhibition of PGE2 and LT biosynthesis in vivo and suggest a valuable therapeutic potential for intervention with inflammatory diseases.