<i>Pyropia yezoensis</i> Extract Attenuates Osteoarthritis Progression <i>In Vitro</i> and <i>In Vivo</i>

Osteoarthritis (OA), a degenerative disease characterized by cartilage degradation and inflammation, occurs due to trauma caused by external stimuli or cartilage aging. <i>Pyropia yezoensis</i> is a red alga that belongs to the Porphyra family and is consumed as food in Asia, especially Korea, Japan, and China. <i>P. yezoensis</i> contains various bioactive substances, including carotenoids, flavonoids, and vitamins, that exert anti-inflammatory, antioxidant, and anti-photoaging effects. In the present study, the anti-osteoarthritic effects of 30% fermented alcohol extract of <i>P. yezoensis</i> (30% FEPY) on interleukin-1 beta (IL-1β)-stimulated chondrocytes and a destabilization of the medial meniscus (DMM)-induced OA rat model were investigated. The results showed that pretreatment with 30% FEPY significantly reduced the IL-1β-induced expression of inflammatory factors (e.g., inducible nitric oxide synthase and cyclooxygenase-2) and cartilage-degrading enzymes [matrix metalloproteinase (MMP) 1, MMP3, MMP13, a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 4, and ADAMTS5], which was analyzed using Griess reaction, enzyme-linked immunosorbent assay, and Western blot analysis. The anti-osteoarthritic effects of 30% FEPY, which were mediated through mitogen-activated protein kinase and nuclear factor kappa-light-chain-enhancer of activated B cell signaling, were analyzed using Western blot analysis. In an <i>in vivo</i> study, Safranin O staining and immunohistochemistry analysis revealed that treatment with 30% FEPY significantly increased cartilage degradation and collagen type II protein expression in the DMM group. These findings collectively suggest that 30% FEPY is a promising candidate for alleviating OA progression and developing new therapeutic drugs.