Chemical composition and anti-osteoarthritis potential of Lolium perenne L. assisted with computational studies

Osteoarthritis (OA) is a serious health issue that lacks a totally effective treatment. In light of the critical need for alternative therapies to halt osteoarthritis and its progress, This study explores the potential of Lolium perenne as a treatment for osteoarthritis for the first time. The research evaluates the plant's protective effects against monosodium iodoacetate (MIA)-induced OA in rats. 24 rats were assigned into 4 groups, group I (sham control), group II (OA), group III (dichloromethane fraction (FrII) + OA), and group IV (ethyl acetate fraction (FrIII) + OA). For 21 days, the samples were given orally at a dose of 40 mg/kg. The obtained results indicated all treatment groups showed a significant decrease in the severity of articular cartilage degradation and in the concentration of Interleukin-1 beta (IL-1β) and Tumor necrosis factor alpha (TNF-α) cytokines compared to the OA-induced group Moreover, eight structurally varied metabolites were isolated and identified from the FrII and FrIII fractions derived from the methanol extract of the aerial part of L. perenne, which were linked with pro-inflammatory cytokines in the computational docking investigation. Interestingly, salcolin B (2b) and calquiquelignan E (4) isolated from FrII fraction, showed prevalent activity for the two tested receptors [salcolin B, IL-1β (-6.7354 kcal/mol) and calquiquelignan E, TNF-α (-6.2038 kcal/mol)] compared to the reference flurbiprofen drug. Finally, the frontier candidates against IL-1β and TNF-α receptors simulated at 100 ns and the MM-GBSA calculations confirming the docking results. These findings highlight L. perenne's potential as a natural therapeutic for OA.