<i>Artemisia argyi</i> -enhanced Mesenchymal Stem Cell Exosomes Alleviates Inflammation in C28/I2 Chondrocytes by inhibiting NF-κB

Osteoarthritis (OA) is a degenerative joint disease with chronic inflammation, causing joint damage and function loss. Current treatments relieve symptoms but don't halt disease progression, highlighting the need for new therapies. Research shows mesenchymal stem cells (MSCs) can repair joints and reduce inflammation, but direct MSC injection may cause immune rejection, making MSC-derived exosomes a promising alternative. <i>Artemisia argyi</i> (AA) has antioxidant, anti-inflammatory, and anti-ageing effects that enhance stem cell function and cellular stability, making it a potential therapy for OA. This study explores whether AA extract can enhance exosomes from Wharton's jelly stem cells (WJSCs) for OA treatment. Results revealed that AA promoted WJSCs proliferation and increased both the yield and size of exosomes. Furthermore, AA-enhanced exosomes significantly suppressed NF-κB pathway related proteins (p-IKKα/β and p-NF-κB) and the matrix degrading protein MMP13 while increasing the expression of the cartilage extracellular matrix protein COL2A1, resulting in a greater reduction of NF-κB signaling proteins and MMP13 expression, along with increased COL2A1 levels. Additionally, these exosomes effectively reversed H₂O₂-induced ROS accumulation, with antioxidant effects surpassing those of untreated exosomes. Further studies using NF-κB activators confirmed that the therapeutic effects of these exosomes were primarily mediated by inhibition of the NF-κB signalling pathway. In conclusion, AA-enhanced WJSCs exosomes improved the proliferation, anti-inflammatory, and antioxidant capacities of C28/I2 chondrocytes under oxidative stress. These findings highlight their potential to reduce ROS levels, regulate pro-inflammatory proteins, and inhibit the NF-κB pathway, offering a promising strategy for protecting cartilage against damage caused by inflammatory joint diseases.