Ginger-derived nanovesicles attenuate osteoarthritis progression by inhibiting oxidative stress via the Nrf2 pathway

<b>Aim:</b> Osteoarthritis (OA) is a common degenerative joint disease. Previous studies demonstrated ginger-derived exosome-like nanovesicles (GDN) showed therapeutic effects in degenerative diseases. However, it remains unknown whether GDN could alleviate OA progression. <b>Materials &amp; methods:</b> In this study, GDN were obtained and characterized. Then we evaluated the effects of GDN in tert-butyl hydroperoxide (TBHP)-induced chondrocytes, posttraumatic OA rat model and <i>ex vivo</i> cultured human OA cartilage explants. <b>Results:</b> We demonstrated GDN promoted cartilage anabolism and alleviated oxidative stress in TBHP-induced chondrocytes and OA rat. Our results also showed GDN exhibited protective effects in cultured cartilage explants. Furthermore, we verified the Nrf2 pathway was associated with protective effects of GDN. <b>Conclusion:</b> Altogether, our findings demonstrated GDN hold great potential for OA treatment. The therapeutic potential of ginger-derived exosome-like nanovesicles (GDN) in osteoarthritis (OA) treatment has rarely been investigated so far. GDN showed no obvious cytotoxic effects in cultured chondrocytes, synoviocytes and bone marrow MSCs. GDN effectively entered into chondrocytes and promoted proliferation in TBHP-induced chondrocytes. GDN inhibited oxidative stress and inflammatory response in TBHP-induced chondrocytes. GDN alleviated OA-related pain and cartilage degeneration in posttraumatic OA rats. GDN effectively promoted matrix anabolism and inhibited catabolism in <i>ex vivo</i> cultured human OA cartilage explants. GDN inhibited oxidative stress and promoted chondrocyte proliferation <i>in vitro</i> and <i>in vivo</i> by activating Nrf2 pathway. These findings reveal GDN could be a promising therapeutic strategy for OA patients.