Procyanidin B2 ameliorates the progression of osteoarthritis: An in vitro and in vivo study

Objective: Osteoarthritis (OA) is characterized by cartilage degeneration and inflammation. Procyanidin B2 (PCB2), a natural flavonoid compound, exhibits potential anti-inflammatory and anti-oxidative effects against several diseases. However, its curative effects on OA remain unclear.Purpose: Herein, we explored the anti-arthritic effects of PCB2 on OA onset and progress and its potential mechanism.Methods: CCK-8 assays and EdU staining were used to assess the cytotoxic effects and cell proliferation activity of PCB2. Flow cytometry was used to detect apoptosis in chondrocytes. ELISA, qPCR, and western blotting, were applied to explore the expression of apoptosis and senescence-associated secretion phenotype (SASP) factors. The Nrf2/NF-Kappa B signaling cascade was explored using immunofluorescence and western blotting. Additionally, we silenced the Nrf2 gene using siRNAs to verify its function in PCB2 regulation of senescence and apoptosis phenotypes. Safranin O-Fast Green (SO) and immunohistochemical staining were used to explore the effects of PCB2 on OA model rats.Results: PCB2 dampened interleukin (IL)-18-triggered expression of SASP factors in vitro. Additionally, PCB2 diminished IL-18-triggered destruction of the extracellular matrix (ECM) via downregulating the expression of MMPs, while upregulating the expression of collagen II and aggrecan. In addition, PCB2 treatment reduced IL-18 -induced apoptosis of chondrocytes. Mechanistically, PCB2 could attenuated chondrocyte senescence in vitro via the Nrf2/NF-Kappa B pathway. Moreover, PCB2 exhibited anti-apoptotic properties via the Nrf2/BAX/Bcl-2 pathway. PCB2 alleviated knee cartilage degeneration in an OA rat model.Conclusions: Our results suggest that PCB2 may be used as a therapeutic agent for OA.