Exploring the Human Health Properties of Compounds Derived from Red Seaweed Using Human In Vitro Cell Line Models

Red seaweeds are increasingly recognized as rich sources of bioactive compounds with promising applications in health promotion, yet their mechanisms of action in human systems remain underexplored. This study investigates the safety and immunomodulatory potential of two red seaweed-derived compounds, R-phycoerythrin (R-PE) and floridoside, and phycobiliprotein-rich extracts from two species of red algae, Acrochaetium secundatum and Gracilaria gracilis. In vitro assays were conducted using Caco-2 intestinal epithelial cells and THP-1 macrophages. Assessed endpoints were cell viability (via a panel of three fluorescence-based assays), intracellular reactive oxygen species (ROS) levels, and cytokine secretion (interleukin-6 (IL-6) and interleukin-8 (IL-8)). Both pure compounds and the seaweed extracts exhibited minimal cytotoxicity. R-PE concentration-dependently increased both IL-6 and IL-8 secretion in THP-1 macrophages, starting at our lowest tested concentration of 3.125 µg mL^-1, whereas floridoside had no detectable effect on cytokine levels. Both compounds elevated ROS production in Caco-2 cells under basal conditions at concentrations ≥ 50 µg mL^-1. R-PE content in the seaweed extracts was quantified at 2022 µg g^-1 wet weight (WW) for A. secundatum and 170.6 µg g^-1 WW for G. gracilis. At exposed concentrations of 1000 µg mL^-1, both extracts significantly increased IL-8 secretion in THP-1 macrophages, with A. secundatum inducing a stronger response (127%) compared to G. gracilis (116%) (p = 0.10). These findings suggest limited bioactivity of floridoside under the tested conditions, but support an immunostimulatory potential of R-PE and red seaweed phycobiliprotein extracts. This study emphasizes the value of investigating both isolated compounds and whole seaweed extracts, as seaweed extracts can offer a more accessible, scalable, and cost-effective alternative to purified compounds, particularly for highly abundant bioactives.