Oleanolic acid cubic liquid crystal nanoparticle-based thermosensitive gel attenuates knee osteoarthritis symptoms in rats

OANG exhibited sustained-release properties and improved joint lubrication. Treatment with OANG significantly alleviated KOA-induced pain and depression-like behaviors, reduced cartilage degradation and subchondral bone sclerosis, and downregulated levels of pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6) and cartilage degradation markers (C-terminal cross-linked telopeptide of type II collagen, cartilage oligomeric matrix protein) in synovial fluid. It also enhanced antioxidant capacity (increased superoxide dismutase, glutathione peroxidase; decreased malondialdehyde) and modulated the expression of key cartilage proteins (increased Collagen II; decreased matrix metalloproteinase 13; regulated glycogen synthase kinase-3β/SRY-box transcription factor 9, β-catenin, and Yes-associated protein). Furthermore, OANG ameliorated hippocampal oxidative stress and inflammation (decreased Cleaved caspase-3, Malondialdehyde; increased IL-10). Network pharmacology and docking suggested the involvement of peroxisome proliferator-activated receptor gamma, mitogen-activated protein kinase 3, prostaglandin-endoperoxide synthase 2, and pathways such as estrogen signaling and cyclic adenosine monophosphate signaling.