Loganin Attenuates Osteoarthritis in Rats by Inhibiting IL-1β-Induced Catabolism and Apoptosis in Chondrocytes Via Regulation of Phosphatidylinositol 3-Kinases (PI3K)/Akt

Med Sci Monit. 2019 Jun 4:25:4159-4168. doi: 10.12659/MSM.915064.

Abstract

BACKGROUND Chondrocyte apoptosis and catabolism are 2 major factors that contribute to the progression of osteoarthritis (OA). Loganin, an iridoid glycoside present in several herbs, including Flos lonicerae, Cornus mas L, and Strychnos nux vomica, is a valuable medication with anti-inflammatory and anti-apoptotic effects. Our study examines these effects and explores the potential benefits of loganin in the OA treatment. MATERIAL AND METHODS To clarify the roles of loganin in OA and its specific signaling pathway, chondrocytes were administrated with IL-1ß and supplemented with or without LY294002 (a classic PI3K/Akt inhibitor). The apoptotic level, catabolic factors (MMP-3 and MMP-13 and ADAMTS-4 and ADAMTS-5), extracellular matrix (ECM) degradation, and activation of the PI3K/Akt pathway were evaluated using western blotting, PCR, and an immunofluorescent assay. The degenerative condition of the cartilage was evaluated using the Safranin O assay in vivo. The expression of cleaved-caspase-3 (C-caspase-3) was measured using immunochemistry. RESULTS The data suggested that loganin suppressed the apoptotic level, reduced the release of catabolic enzymes, and decreased the ECM degradation of IL-1ß-induced chondrocytes. However, suppressing PI3K/Akt signaling using LY294002 alleviated the therapeutic effects of loganin in chondrocytes. Our in vivo experiment showed that loganin partially attenuated cartilage degradation while inhibiting the apoptotic level. CONCLUSIONS This work revealed that loganin treatment attenuated IL-1ß-treated apoptosis and ECM catabolism in rat chondrocytes via regulation of the PI3K/Akt signaling, revealing that loganin is a potentially useful treatment for OA.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • China
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Inflammation / metabolism
  • Interleukin-1beta / drug effects
  • Interleukin-1beta / metabolism
  • Iridoids / pharmacology*
  • Male
  • Osteoarthritis / drug therapy*
  • Phosphatidylinositol 3-Kinases / drug effects
  • Phosphatidylinositol 3-Kinases / metabolism
  • Primary Cell Culture
  • Proto-Oncogene Proteins c-akt / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects

Substances

  • Interleukin-1beta
  • Iridoids
  • Proto-Oncogene Proteins c-akt
  • loganin