Anti-inflammatory Natural Products

Anti-inflammatory glycosides from plants: Identification of cellular targets and studies on structure-function relationships

Anti-inflammatory properties of saponins are gaining increasing interest. Over 25% of related scientific articles have appeared in the last 4 years. Although there is no doubt about the anti-inflammatory effect, mostly crudely purified saponin mixtures were used and the results are descriptive. In addition, structure-function relationships are lacking, and intracellular targets have not been identified. It is hypothesized that the anti-inflammatory effects are due to specific interactions between targets and defined subsets of saponins with specific chemical functionalities. Our goal is to first identify cellular targets for commercially available saponins with known structure and demonstrated anti-inflammatory effects and to deduce structure-function relationships. Specifically, we aim to determine how interactions between saponins and targets lead to changes in cytokine composition by performing labeling studies, binding assays, localization studies, inhibition experiments, and membrane assays after confirmation of anti-inflammatory effects, as well as by tracing cellular activation pathways. The identification and structural elucidation of new saponins will then be used to elucidate further details and to establish generally valid theses on the effects of saponins. Important structural features (aglycone, sugar composition, sugar linkage, configuration of stereoisomers) will be elucidated by MALDI and NMR. In the long term, the molecular mechanisms of the anti-inflammatory effect will also be investigated in vivo.