Therapeutic Effect of Anwulignan on Knee Osteoarthritis and Its Mechanism through Cell Pyroptosis Pathway in Rats

Abstract Anwulignan (AN) is a monomer compound in the lignans of Schisandra chinensis . In this study, the effect of AN on knee osteoarthritis (KOA) in male SD rats was observed and its potential mechanisms were explored. The results showed that AN could significantly increase the number of standing times of rats within the same time, reduce the degree of knee joint swelling in rats, and alleviate the damage of cartilage tissue. AN could increase the activity of superoxide dismutase (SOD), and decrease the contents of malondialdehyde (MDA) and reactive oxygen species (ROS) in the synovial tissue of rats, and reduce the levels of inflammatory factors such as tumor necrosis factor-α (TNF-α), interlukin (IL)-6, IL-1β and IL-18, prostaglandin E2 (PGE2) and nitric oxide (NO) in the serum and synovial tissue of rats. AN could play an antioxidant role by regulating the nuclear factor erythroid E2-related factor 2 (Nrf2) signaling pathway-related proteins, and play anti-inflammatory and anti-pyroptosis roles by regulating pyroptosis pathway-related proteins, including the nuclear factor-k-gene binding (NF-κB) signaling pathway-related proteins and NOD-like receptor family pyrin domain containing 3 (NLRP3). AN could significantly increase the expression level of CollagenII protein in KOA rats and decrease the expression levels of matrix metalloproteinase1 (MMP1) and matrix metalloproteinase13 (MMP13) proteins. The results of immunofluorescence analysis further confirmed the protective effect of AN against KOA in rats, which may be related to the regulation of Nrf2/HO-1 signaling pathway to play an antioxidant role and the regulation of TLR4/NLRP3/Caspase-1 signaling pathway-mediated anti-pyroptosis effect.