Phycocyanin is a typical microalgal active compound with
antioxidant and anti-inflammatory efficacy, and the pigment moiety
phycocyanobilin has been recently proposed as its active structural component. Here, to explore the structural basis for
phycocyanin's intestinal protective action, we evaluated the
therapeutic effects and mechanism of action of
phycocyanin and
phycocyanobilin in
dextran sodium sulphate (DSS)-induced
colitis mice and in Caco-2 and RAW 264.7 cells.
Phycocyanobilin was obtained by solvothermal alcoholysis of
phycocyanin and characterized by spectroscopy and mass spectrometry methods.
Phycocyanin,
phycocyanobilin and a positive
drug mesalazine were intragastrically administered to C57BL/6 mice daily for 7 days during and after 4-day DSS exposure. Clinical signs and colon histopathology revealed that
phycocyanin and
phycocyanobilin had an equivalent anti-
colitis efficacy that was even superior to
mesalazine. Based on biochemical analysis of colonic
tight junction proteins, mucus compositions and goblet cells, and colonic and peripheral proinflammatory
cytokines,
phycocyanin and
phycocyanobilin displayed equivalent intestinal epithelial barrier-protecting and anti-inflammatory potential that was evidently superior to that of
mesalazine. Flow cytometry analysis of
phycocyanobilin fluorescence in Caco-2 cells unveiled a similar uptake efficacy of
phycocyanin and
phycocyanobilin by intestinal epithelial cells. According to lactic
dehydrogenase release,
2',7'-dichlorodihydrofluorescein fluorescence and methylthiazolyldiphenyl-tetrazolium
bromide assay in Caco-2 cells,
phycocyanin and
phycocyanobilin could equally and effectively protect the intestinal epithelial barrier from
oxidant-induced disruption.
Phycocyanin and
phycocyanobilin also showed equivalent anti-inflammatory effects in
tumor necrosis factor-α-stimulated Caco-2 cells and in
lipopolysaccharides- and
tumor necrosis factor-α-activated RAW264.7 cells. Overall, our results demonstrate the
phycocyanobilin-dependent anti-
colitis role of
phycocyanin via
antioxidant and anti-inflammatory mechanisms.