Protective effect of glycyrrhizin on osteoarthritis cartilage degeneration and inflammation response in a rat model

Abstract

This study was conducted to investigate the protective effects of glycyrrhizin on a rat model of osteoarthritis and elucidate the underlying mechanism. Rat osteoarthritis was established by using medial meniscectomy (MMx) and an anterior cruciate ligament transaction (ACLT). Glycyrrhizin (2, 4, and 10mg/kg) was administered by intra-articular knee injection for 12weeks. Incapacitance test was performed to determine mechanical hyperalgesia. Enzyme-linked immunosorbent assay (ELISA) was performed to measure cartilage degradation and inflammation-related markers. Quantitative reverse transcription PCR (RT-qPCR) and Western blot were performed to determine the mRNA and protein levels of genes, respectively. The results demonstrated that treatment with glycyrrhizin ameliorated mechanical hyperalgesia and bilateral joints oedema in a rat model of osteoarthritis. Treatment with 10mg/kg glycyrrhizin also suppressed serum enzymes including matrix metalloproteinase (MMP)-1, MMP-3, prostaglandin E2, and C-telopeptide of type II collagen (CTX-II). In addition to inhibition of cartilage matrix catabolic related markers, treatment with glycyrrhizin also decreased the levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and iNOS in serum and cartilage. The underlying mechanism study demonstrated that treatment with glycyrrhizin inhibited HMGB1 and the TLR4/NF-κB signaling pathway. In summary, treatment with glycyrrhizin ameliorated cartilage degeneration and inflammation in osteoarthritis rats by the regulation of HMGB1 and the TLR4/NF-κB signaling pathway.