Model systems for evaluating cellular responses to plant-derived bioactive compounds under conditions of oxidative and inflammatory stress

Chronic inflammatory diseases are among the most common causes of health restrictions and premature mortality worldwide. Oxidative stress and low-grade inflammatory processes play a central role in the development and progression of these diseases. In recent years, interest in plant-based bioactive extracts and compounds as natural agents with protective properties has increased significantly, in both medical and nutritional contexts. The aim of this dissertation was to investigate the health-promoting effects of plant extracts and isolated natural compounds under defined conditions of oxidative and inflammatory stress. The work is based on three independent publications, each reflecting different methodological approaches and stages of research, from initial characterization to functional analysis of potential mechanisms of actions. For this, cell-free chemical assays, more complex in vitro models, and in vivo approaches using alternative model organisms such as Drosophila melanogaster (D. melanogaster) and Caenorhabditis elegans (C. elegans) were applied. In addition, in silico methods were employed for molecular interaction analysis.
In the first publication, numerous extracts derived from locally sourced plants were examined for their antioxidant potential. Individual extracts, for example from Fragaria × ananassa leaves or Helianthus tuberosus, showed pronounced effects on reducing intracellular reactive oxygen species (ROS) and nitric oxide levels in stimulated cell models. The results highlighted the added value of a combined approach using basic chemical assays and cellular functional analysis but also demonstrated that chemical antioxidant capacities cannot always be directly translated to biological systems.
The second study focused on the functional analysis of a fermented multi-herb extract. In intestinal IPEC-J2 cells, treatment with the extract was able to stabilize epithelial barrier function under stress conditions, promote cell migration, and reduce oxidative stress. In THP-1 macrophages, a broad inflammation-modulating effect was observed, with simultaneous reduction of pro-inflammatory cytokines and increase in anti-inflammatory markers. In the model organisms C. elegans and D. melanogaster, treatment with the herbal extract was associated with improved stress resistance, particularly reflected by reduced ROS levels and improved activity levels under stress.
The third research article investigated a natural derivative of the pentacyclic triterpene tormentic acid, in which esterification led to a significant increase in bioactive properties. The derivative inhibited both Toll like receptor 4 (TLR4)-dependent and -independent nuclear factor kappa B (NF-κB) signaling pathways in vitro and reduced the expression of various pro-inflammatory cytokines. Data from C. elegans model further confirmed a functional role of the tormentic acid derivative in modulating the expression of several stress response genes. This activity was isomer-specific, underscoring the importance of structural features for biological efficacy.
Overall, this dissertation demonstrates that plant bioactives can exert promising effects on oxidative and inflammatory stress under defined experimental conditions. The combination of complementary methodological systems enables a preclinical evaluation of both biological efficacy and potential mechanisms of action, which represents important groundwork for the future development or optimization of plant-based therapeutic and preventive strategies.