Creating a reliable zebrafish model for studying inflammation: exploring the therapeutic potential of xanthohumol

Inflammation is the body's natural immune response to pathogens, such as viruses, bacteria, and parasites, and is closely linked to oxidative stress caused by an imbalance in reactive oxygen species (ROS) and antioxidants. Chronic inflammation can lead to diseases and cancer. Due to the side effects of synthetic anti-inflammatory drugs such as NSAIDs and corticosteroids, natural compounds such as flavonoids are gaining interest. This study aimed to validate the zebrafish (Danio rerio) as a model for studying inflammation and to compare the anti-inflammatory effects of xanthohumol with ibuprofen and quercetin. Using lipopolysaccharide (LPS) and copper sulfate (CuSO₄) to induce inflammation, zebrafish larvae provided an excellent model. The study determined the lethal doses (LD50) of several substances, with xanthohumol having an LD50 of 2.659 μg/ml, ibuprofen 15 μg/ml, and quercetin 200 μM. Exposure to xanthohumol at 2 μg/ml before LPS administration significantly improved larval survival, maintaining 80% viability compared to 25% with LPS alone. Additionally, xanthohumol reduced IL-1 levels by over twofold and increased IL-10 expression, demonstrating its anti-inflammatory effects. Xanthohumol also protected against oxidative stress induced by CuSO₄, significantly reducing cell damage compared to controls. These results highlight xanthohumol’s strong protective and anti-inflammatory properties.