Glycyrrhizin, an HMGB1 inhibitor, Suppresses Interleukin-1β-Induced Inflammatory Responses in Chondrocytes from Patients with Osteoarthritis

Cartilage. 2021 Dec;13(2_suppl):947S-955S. doi: 10.1177/1947603520934858. Epub 2020 Jun 30.

Abstract

Background: High mobility group box 1 (HMGB1) is increased in osteoarthritis (OA) tissue and chondrocytes stimulated with interleukin-1β (IL-1β). Suppression of HMGB1 expression is correlated with reduced inflammatory responses induced by IL-1β. This study aimed to investigate how inhibition of HMGB1 by glycyrrhizin might affect inflammatory responses and viability of OA patient-derived chondrocytes treated with IL-1β.

Design: The amounts of HMGB1 in the cartilage tissue and synovial fluid in patients with OA were assessed by Western blot and enzyme-linked immunosorbent assay (ELISA). Chondrocytes were extracted from OA patients and maintained in culture. The impact of glycyrrhizin on IL-1β-induced cell toxicity and inflammatory mediators and cytokines, including prostaglandin E2 (PGE2), nitric oxide (NO), proinflammatory cytokines, and metalloproteases (MMPs), were assessed by ELISA, Western blot, quantitative real-time polymerase chain reaction, and the Griess reagent assay.

Results: We confirmed that HMGB1 was significantly upregulated in specimens acquired from patients with OA. HMGB1 inhibition by glycyrrhizin improved cell viability of chondrocytes treated with IL-1β. Glycyrrhizin suppressed IL-1β-induced upregulation of HMGB1 and inflammatory mediators and cytokines, including PGE2, NO, proinflammatory cytokines, and MMPs.

Conclusion: Our results indicate that glycyrrhizin may be a potential therapy for OA patients and these promising findings warrant further study for clinical application.

Keywords: glycyrrhizin; high mobility group box 1; inflammation; interleukin-1β; osteoarthritis.

MeSH terms

  • Chondrocytes / metabolism
  • Glycyrrhizic Acid / metabolism
  • Glycyrrhizic Acid / pharmacology
  • Glycyrrhizic Acid / therapeutic use
  • HMGB1 Protein* / metabolism
  • HMGB1 Protein* / therapeutic use
  • Humans
  • Interleukin-1beta / metabolism
  • Osteoarthritis* / drug therapy
  • Osteoarthritis* / metabolism

Substances

  • HMGB1 Protein
  • Interleukin-1beta
  • Glycyrrhizic Acid