Phillygenin protects against osteoarthritis by repressing inflammation via PI3K/Akt/NF-κB signaling: In vitro and vivo studies
Siqi Zhou, Haiyan Wen, Xiaotao Han, Haohuan Li
Abstract
Osteoarthritis (OA), which is characterized by the destruction of articular cartilage and reactive hyperplasia of bone, has been regarded as the main cause of disability worldwide. Joint inflammation accompanied by the release of inflammatory factors and matrix degrading enzymes is involved in the destruction of articular cartilage. Phillygenin (PHI), extracted from Forsythiae Fructus, is a lignan compound. Previous researchers have found that PHI has the anti-oxidant and anti-inflammatory effect on various diseases. However, whether PHI has anti-inflammatory effect on osteoarthritis has not been reported. In current study, we treated rat chondrocytes with interleukin (IL)-1β (10 ng/ml) in the presence of PHI to investigate PHI’s chondroprotective effect in vitro. We also established an OA model of rat by anterior cruciate ligament transection (ACLT) to study whether PHI could alleviate OA progression in vivo. Our results showed that PHI inhibited the production of IL-1β-induced prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), IL-6, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) and nitric oxide (NO) in rat chondrocytes. In addition, the expression of matrix degrading enzymes that mediated by IL-1β was also down-regulated after the treatment with PHI. Moreover, PHI reduced the phosphorylation of Pi3k and the translocation of P65 from cytoplasm to nucleus. In vivo study, our results revealed that PHI could attenuate cartilage destruction of OA. Taken together, the current study may provide a potential candidate drug for the treatment of OA.