Stilbenes are important components of food, such as peanuts, grapevine and different types of berries. [1] Anti-inflammatory activity have been determined for a number of stilbenes, including the widely known resveratrol, its analogues, e.g., piceatannol [2], and other non-prenylated and prenylated stilbenes. [3]
We investigated 32 different natural and synthetic stilbenes for their effect on the pro-inflammatory nuclear factor-κB (NF‑κB)/activator protein 1 (AP-1) signalling pathway. As a model for determination of anti-inflammatory potential, the THP1-XBlue™-MD2-CD14 cell line (Invivogen; USA) was used. Lipopolysaccharide (LPS) stimulation of Toll-like receptor 4 (TLR4) in this cell line induces a signalling cascade leading to the activation of NF-κB/AP-1. The ability of these compounds to attenuate the production of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-1β (IL‑1β) were evaluated in LPS-stimulated THP-1 macrophages (European Collection of Cell Cultures; UK). The direct inhibiting effect on cyclooxygenase (COX)-1 and COX-2 and 5-lipoxygenase (5-LOX) were also determined. Molecular docking for the most active stilbenoids was performed to elucidate the interaction between compounds and enzymes.
Several compounds (e.g., piceatannol, TTH-16) affected the production of NF-κB/AP-1 and TNF-α. Some compounds isolated from Thailand´s plant Macaranga siamensis S.J.Davies (Euphorbiaceae) affected the activation of NF-κB/AP-1 and secretion of IL-1β more than prednisone, which was used as a positive control for the assay. We observed that prenylated stilbenes are in general more cytotoxic and more active inhibitors of NF-κB/AP-1 than their non-prenylated analogues. Significant anti-COX/LOX activity was also detected for several compounds.
Elucidation of the structure-activity relationship could contribute to develop potent, natural product-based anti-inflammatory drugs.
This project is supported by the Grant agency of the Czech Rublic, grant No° 16-07193S.
References:
[1] Chong J. et al. Plant Sciences 2008; 177: 143-155.
[2] Piotrowska H. Mutation Research 2012; 750: 60-82.
[3] Pailee P. et al. Tetrahedron 2015; 77: 5562-5571.