In Silico and In Vitro Therapeutic Effects of Phycocyanin Against Lipid Micelle and/or Endotoxin-Induced Oxidative Damage and Barrier Dysfunction in Human Intestinal Epithelial Cells Model.

Obesity is associated with chronic intestinal inflammation, oxidative stress, and disruption of epithelial barrier integrity. Phycocyanin (PHY), a bioactive pigment from Spirulina platensis, is known for its antioxidant and anti-inflammatory activities. This study was conducted to evaluate the protective effect of PHY on the disruption of the intestinal epithelium induced by repeated lipid micelles (LM) and/or inflammation induced by lipopolysaccharides (LPS) in the Caco-2 cell line. Firstly, we evaluated the protective actions of PHY against cytotoxicity, oxidative stress imbalance, inflammatory response, and epithelial barrier alteration through an in vitro model, the intestinal Caco-2 cells, treated with LPS and/or LM. We also conducted an in silico molecular docking with PHY. In vitro, PHY was not cytotoxic to Caco-2 cells; instead, it improved cell viability, demonstrated antioxidant and inflammation-suppressing effects, preserved tight junction organization, and protected against endoplasmic reticulum (ER) stress, thereby maintaining epithelial barrier integrity. In silico analysis revealed strong binding affinity of PHY to antioxidant enzymes (SOD, CAT) and favorable interactions with pro-inflammatory cytokines (TNF-α, IL-6), supporting its regulatory potential. Taken together, these findings indicate that PHY protects Caco-2 cells, preserving intestinal barrier integrity under oxidative and inflammatory stress, and may serve as a natural therapeutic candidate against obesity-related gut dysfunction.