Inhibition of PI3K/Akt/mTOR signaling by curcumin: a novel approach to mitigate synovial fibrosis in knee osteoarthritis

Curcumin (CUR) is used in treating knee osteoarthritis (KOA), but its effects on synovial fibrosis and underlying mechanisms remain unclear. <i>In vivo</i>, a rat KOA model was established via anterior cruciate ligament transection (ACLT), followed by CUR administration. Synovial fibrosis, autophagy, and PI3K/AKT/mTOR pathway were assessed. <i>In vitro</i>, TGF-β1-induced fibroblast-like synoviocytes (FLSs) were treated with CUR. Fibrosis markers, autophagy activity, and PI3K/AKT/mTOR pathway proteins were analyzed. CUR alleviated synovial fibrosis in ACLT-induced rats. In FLSs, CUR reduced TGF-β1-stimulated fibrosis, suppressed PI3K/Akt/mTOR signaling, and enhanced autophagy. <i>In vivo</i> results confirmed CUR inhibited PI3K/Akt/mTOR and activated autophagy. CUR attenuated synovial fibrosis by activating protective autophagy via inhibition of the PI3K/Akt/mTOR pathway, elucidating a novel anti-fibrotic mechanism for KOA therapy.