Immunomodulatory and Anti-Inflammatory Effects of Phycocyanin Oligopeptide Combined with Selenium and Zinc in LPS-Induced Mice

Objective: Nutritional modulation of the immune function provides a promising strategy to mitigate systemic inflammation associated with viral and bacterial infections. This study evaluated the immunomodulatory and anti-inflammatory effects of a novel phycocyanin oligopeptide (PC-O) supplement, alone or in combination with selenium (Se) and zinc (Zn), in a lipopolysaccharide (LPS)-induced murine model of inflammation. Methods: Forty-two male BALB/c mice were pretreated with Se, Zn, PC-O or a combination of these for 14 days, followed by LPS administration to induce systemic inflammation. Serum biochemical markers, tissue oxidative stress parameters, pro-inflammatory cytokines, antioxidant enzyme activities, histopathological alterations, Zn transporter expression, and inflammatory signaling proteins were evaluated. Results: LPS administration induced pronounced hepatic and pulmonary inflammation, characterized by elevated IL-1β, IL-6, and TNF-α levels, increased oxidative stress, and disrupted expression of Zn transporters. While PC-O, Se, or Zn alone partially attenuated these effects, combined supplementation produced the most substantial protective response. Notably, the combination group demonstrated significant reductions in rectal temperature, hepatic enzymes (ALT and AST), lipid peroxidation, and cytokine expression, alongside restored antioxidant enzyme activities and normalized Zn transporter levels. Protein expression analyses revealed marked suppression of NF-κB, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in liver and lung tissues. Conclusions: Combined supplementation with PC-O, Se, and Zn provides enhanced protection against LPS-induced inflammation, likely through coordinated antioxidant and anti-inflammatory mechanisms. This nutritional strategy may help strengthen host defense and limit inflammation-driven tissue injury.