Anti-arthritic and cartilage damage prevention via regulation of Nrf2/HO-1 signaling by glabridin on osteoarthritis

Abstract

Osteoarthritis is a common degenerative disease linked with inflammatory disorders and oxidative stress. Glabridin is an isoflavonoid and major active constituent of licorice. This study aims to investigate the anti-arthritic effects of glabridin on nuclear factor erythroid 2 – related factor 2 (Nrf2) signaling pathway, inflammatory responses, and cartilage degeneration in in-vitro and in-vivo models. Studies on IL-1β-induced chondrocyte model was performed to evaluate matrix metalloproteinase (MMP), Nrf2 signaling pathway. Glabridin was orally administered in monosodium-iodoacetate (MIA)-induced osteoarthritic (OA) rats for in-vivo evaluation. Pain and swelling of limbs were observed, oxidative stress markers and inflammatory cytokines were measured. Histomorphological changes in the joint cartilage were analyzed. Glabridin significantly reduced the arthritic score and paw swelling along with improved body weight, and organ index of rats. Histopathological score showed significant prevention of joint cartilage degeneration by glabridin. Expressions of TNF-α, IL-6, IL-10, and IL-1β were attenuated by glabridin (p < 0.05) in MIA-induced rats. Protein expressions of iNOS, COX-2, ADAMTS5, MMP-3, and MMP-13 were suppressed (p < 0.05) whereas the Nrf2/HO-1 signaling was activated by glabridin (p < 0.05) in osteoarthritic chondrocytes. Therefore, anti-arthritic and chondroprotective activity of glabridin is suggested by the inhibition of MMP expression and regulation of Nrf2/HO-1 signaling.

Keywords

• Glabridin
• MMP
• Inflammatory cytokines
• Nrf2/HO-1
• Monosodium-iodoacetate